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February 2011

CASE REPORT: Neurocognitive Presentation of HIV: HIV-associated Progressive Encephalopathy

A case report and review of the literature explores hiv presenting as a syndrome complex with cognitive, motor, and behavioral features..

Eva Pilcher, MD and Michael J. Schneck, MD

Acute HIV infection often involves neurological symptoms in which patients present with an encephalopathic syndrome with no clear history that might otherwise raise a high index of suspicion for HIV. These patients, during the initial infectious phase, may not have yet underwent seroconversion and so routine HIV antibody testing may not be positive leading to a lost opportunity for treatment as anti-retroviral therapy is most effective in this acute phase of HIV infection. The phenomenon has been previously well-described but remains an under-recognized and under-appreciated presentation of HIV infection.

Case Report A 60-year-old man was admitted to the Loyola University Medical Center in November 2009 because of headache, neck pain, and fever. One week before admission, the patient went on a ship cruise to Puerto Rico. On the first day of the trip, he became ill with development of a headache accompanied by fever and chills. He was evaluated by the cruise physician and prescribed azithromycin. He was also advised to take ibuprofen. The patient continued this treatment for five days without improvement; his fever continued, the headache worsened, and he developed neck pain. He became progressively fatigued, weak, and also developed mild confusion. He returned from the cruise and was brought to our emergency department by concerned family members.

The patient lived at home with his family in another state and was an owner of several restaurants. He had traveled to Chicago two weeks prior to join his family on the aforementioned cruise, and was planning on returning home after the vacation. The patient's admission medical history included borderline hypertension, and admission medications were only acetaminophen. He provided no history of alcohol, tobacco, or illicit drug use. He denied any nausea, vomiting, vision changes, focal neurological symptoms, or loss of consciousness.

On initial examination the patient appeared in mild distress due to the headache. The axillary temperature was 37.1°C. The pulse was regular at 89 beats per minute, the blood pressure was 137/81mm Hg, and the respiratory rate was 20 breaths per minute.

The general examination showed no abnormalities. On neurological examination, however, he was inattentive and distractible; he had difficulty following two-step commands and recalled 2/3 words at five minutes. His speech was fluent.

The cranial-nerve examination was normal. He had some difficulty cooperating with the motor examination due to neck pain, but strength and coordination were otherwise normal. He was not able to stand with both eyes closed, but his gait otherwise appeared to be steady. The sensory and reflex examinations were also normal. The Brudzinski sign was negative, but the Kerning sign was positive.

Laboratory investigations included a normal complete blood count and a complete metabolic panel. The C-reactive protein was elevated at 2.8, and the sedimentation rate was increased at 58. A chest radiograph was also normal except for an old clavicular fracture. Magnetic resonance imaging of the brain, with special attention given to the temporal area, with and without gadolinium contrast, did not reveal any abnormalities. An electroencephalogram showed diffused slowing consistent with encephalopathy but no epileptiform activity. A lumbar puncture demonstrated mild lymphocytic pleocytosis: white blood cell count was 40 with 81 lymphocytes and elevated CSF protein at 63.

Because of the altered mental status and abnormal CSF findings, the possibility of viral encephalitis led to initiation of acyclovir 1000mg twice a day at admission. The HSV CSF titer drawn at admission was 3.01, and the patient was continued on acyclovir for a total of six days, until the HSHV PCR results came back negative. Multiple additional CSF studies were obtained, including West Nile Virus IgM, Varicella Zoster Virus, Cytomegalovirus, fungal cultures, CSF cultures, and Acid Fast Bacilli; these all returned negative.

Additional serum studies were sent for HIV 1 and 2 antibodies, influenza A and B, respiratory syncytial virus assay, blood cultures, Epstein Barr Virus and mononucleosis screen. All of these tests were also negative. A CT of the chest and thorax was obtained to investigate for any infectious or neoplastic process and was also normal.

Throughout the hospitalization, the patient continued to complain of neck pain that later developed into a back and shoulder discomfort, especially on the right side. It was thought that the discomfort might be attributable to muscle spasm, so a trial of cyclobenzaprine, and then low dose diazepam, was attempted without providing relief to the patient. Due to the continued significant pain in the neck, back, and shoulder, an MRI of the cervical spine and brachial plexus was obtained. The images from the initial MRI were suboptimal and the study was repeated again with sedation. The repeat study revealed no cervical spine or brachial plexus etiologies, but demonstrated a bursal surface tear of the right anterior supraspinatus tendon. Orthopedic consultants recommended conservative therapy and the patient was started on a flexor patch and a steroid taper for the rotator cuff injury.

Ultimately, the patient's family arrived from out of state and he was discharged with plan to travel back home and follow up with his primary care physician. It was not until two weeks after discharge that the HIV viral load returned at over 500,000 and the patient's primary physician was subsequently contacted, and retroviral therapy was initiated. Of note, neither the patient nor the family had ever provided a history of HIV risk factors.

Discussion Human immunodeficiency virus (HIV) has infected approximately 33 million individuals worldwide, and the virus is rapidly becoming a world pandemic. Initial presentation of an acute infection often involves neurological symptoms. These individuals present with an encephalopathic syndrome, but no prior suspicion for HIV diagnosis and insufficient HIV antibodies to produce a positive HIV enzyme immunoassay. They present at a crucial time: at initial phase of the infection, and prior to seroconversion, when antiretroviral therapy has been shown to be most effective in reducing mortality and morbidity. HIV infection of the CNS is especially problematic; it causes a barrier to management and eradication of the virus because of the incomplete impermeability to antiretroviral drugs, resulting in sub-therapeutic levels within the CNS. As a result, while the HIV infection goes undiagnosed, the CNS ends up being a reservoir for the virus, providing a safe environment where the virus can replicate and mutate. Early treatment with antiretroviral therapy targets the virus before it has the advantage of sequestration in the CNS. Considering the crucial importance of prompt and accurate diagnosis of an acute HIV infection, it is troublesome that guidelines for management of acute HIV aseptic meningitis are limited to case reports. The need for increased awareness of neurological presentation of acute HIV infection is evident.

On admission to the hospital, our patient was thought to have an acute change in mental status accompanied by headache, neck pain and fever along with CSF lymphocytosis and elevated CSF protein. In this patient, the absence of clinical and laboratory evidence of electrolyte or organ function abnormalities ruled out metabolic or toxicologic etiologies. Instead, given the abnormal cerecerebrospinal fluid findings, the focus was redirected at infectious causes of meningitis and encephalitis. While the patient was treated with an antiviral agent (acyclovir) because of appropriate concerns of HSV encephalitis, retroviral therapies were not initiated early in the course of therapy. All other tests for viral, bacterial, and fungal pathogens were negative, and symptomatic treatment was ineffective except for a transient improvement in headache that may have been related to the administration of pain medications. It was not until after discharge that the HIV viral load was found to be significantly elevated; previously obtained HIV antibody testing was negative. As such, a missed opportunity for early intervention in HIV infection resulted.

In this context, the diagnostic evaluation was disappointingly inconclusive as to the etiology; it was not until after the patient had been discharged that an HIV viral load of over 500,000 was discovered. While the patient did not disclose any risk factors for HIV infection, his presentation was consistent with acute encephalitis likely due to a recent HIV infection. Unfortunately, it is often difficult to identify patients with primary HIV infection when they fail to disclose risk factors for acquiring the virus and there are no clinical findings indicative of immunosuppression. The presentation is depressingly common. Similarly, in other reports, patients with an underlying diagnosis of primary HIV infection were not initially identified, which resulted in a delay of diagnosis.

Successful identification of a primary HIV infection is fundamental; it offers the patient the opportunity to receive potent antiretroviral therapy prior to the time of virus seroconversion, when one can favorably affect the prognosis of the disease.

Neurological symptoms can occur before HIV diagnosis is suspected, before there are sufficient HIV antibodies to produce a positive HIV enzyme immunoassay. Neurological features of an acute HIV virus infection include aseptic meningitis, meningoencephalitis and encephalitis that can occur in up to 17 percent of patients. These individuals present with fever, headache, stiff neck, photophobia, CSF with mild lymphocytic pleocytosis and slightly elevated protein, but normal glucose. Approximately 40-90 percent of patients with an acute HIV infection present with physical symptoms similar to influenza or mononucleosis. Primary HIV infection is characterized by fever, lethargy, and headache and generalized flu-like symptoms. The HIV virus does not directly invade nerve cells, but rather causes inflammation. It is this persistent infection and inflammation that results in breakdown of the blood-brain barrier, neuronal and axonal injury, neurotoxicity, and clinical symptom such as confusion, forgetfulness, headache and even changes in behavior and cognition.

Unfortunately the management of acute HIV aseptic meningitis is limited to case reports. Our case is consistent with other reports in the literature. One case report described a patient that presented with mild confusion and was not able to follow commands. Another case described a patient that had been well until 13 days prior to presentation, at which time he began having bi-frontal headaches, low-grade fever and began experiencing changes in behavior. Interestingly, another very similar report described a 31 year-old male, which presented with one week of confusion and fever after having returned from a trip to the Caribbean; this patient's provisional diagnosis was viral encephalitis, based on lymphocytic fluid obtained via a lumbar puncture and he was treated with intravenous acyclovir.

It is evident that accurate diagnosis of HIV infection is crucial at time of acute onset. In acute presentation, when suspicion is high, the need for thorough history-taking cannot be forgotten. But patients can fail to disclose risk factors for HIV infection; hence, proper testing is crucial. It is important to remember that a viral load can detect the virus a few days after HIV infection, while a standard HIV antibody test can remain negative for months after the HIV infection.

While starting acyclovir in patients with a clinical picture of meningoencephalitis until an HSV PCR returns negative is an accepted clinical practice, a parallel approach is not considered for acute HIV infection. We suggest therefore, in cases of meningoencephalitis of unclear etiology, where the HIV antibodies are negative and the HIV viral load has been sent but remains pending, it may be reasonable to initiate a short course of retroviral drugs until return of the HIV viral load assay results. Thus, with awareness of the neurological presentations of an acute HIV infection, diligent history taking, proper laboratory testing, and rapid initiation of therapy, failure to identify primary infection can be minimized and crucial delays in antiretroviral therapy can be eliminated.

The author(s) declare that they have no competing interests. An attempt was made to contact the patient, but this unsuccessful. However we have taken adequate steps to keep his identity safe and in no way have we revealed any personal information about the patient in the case report.

• Bruse James Brew. HIV Neurology. N Eng J Med 2001; 1713-1714.
• Hollander H, Schafer PW, Hedley-Whyte ET. Case 22-2005: An 81-Year-Old Man with Cough, Fever, and Altered Mental Status. N Engl J Med 2005; 353: 287-95.
• José Biller. Practical Neurology. Philadelphia: Lippincott Williams & Wilkins, 2009.
• National Institute of Neurological Disorders and Stroke.
• Newton PJ, Newsholme W, Brink NS, Manji H, William IG, Miller RF. Acute meningoencephalitis and meningitis due to primary HIV infection. BMJ 2002; 1225-1227.
• Ropper AH, Brown RH. Adams and Victor's Principles of Neurology. New York: McGraw-Hill, 2005.
• Scully RE, Mark EJ, McNeely WF, Ebeling SH, Phillips LD, Ellender SM. Case 10- 2000. Case Records of the Massachusetts General Hospital 200; 342: 957-965.
• Singer EJ, Valdes-Sueiras M, Commins D, Levine A. Neurological Presentation of AIDS. Neurological Clinics 2010; 253-275.
• Trancoso J, Rubio A, Fowler D. Essential Forensic Neuropathology. Baltimore: Lippincott Williams & Wikins, 2009.

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Confidentiality in the Age of AIDS: A Case Study in Clinical Ethics

Print this case study here:  Case Study – Confidentiality in the Age of AIDS

The Journal of Clinical Ethics, Fall 1993

Martin L Smith, STD, is an Associated in the Department of Bioethics, Cleveland Clinic Foundation, Cleveland, Ohio.

Kevin P Martin, MD is a Child and Adolescent Psychiatrist in the Department of Mental Health, Kaiser Permanente, Cleveland.

INTRODUCTION

AIDS (acquired immunodeficiency syndrome), now in pandemic proportions, presents formidable challenges to health-care professionals. The human immunodeficiency virus (HIV) infection and its related diseases have also raised a number of thorny ethical questions about government and social policy, health-care delivery systems, and the very nature of the physician-patient relationship. This article presents the case of an HIV-positive patient who presented the treating physician, a psychiatrist, with an ethical dilemma. We provide the details of the case, identify the ethical issues it raises, and examine the ethical principles involved. Finally, we present a case analysis that supports the physician’s decision. Our process of ethical analysis and decision making is a type of casuistry,1 which involves examining the circumstances and details of the case, considering analogous cases, determining which maxim(s) should rule the case and to what extent, and weighing accumulated arguments and considerations for the options that have been identified. The goal of this method is to arrive at a reasonable, prudent moral judgement leading to action.

The patient, Seth, is a 32-year-old, HIV-positive, gay, white male whose psychiatric social worker had referred him to a community-mental-health-center psychiatrist for evaluation. He had a history of paranoid schizophrenia that went back several years. He had been functioning well for the last two years as an outpatient on antipsychotic medications and was working full time, socializing actively, and sharing an apartment with a female roommate.

The social worker described a gradual deterioration over several months. Seth had become less compliant with his medication and with his appointments at the mental-health center, had lost his job, had been asked to leave his apartment, and was living on the streets. He was described as increasingly disorganized and paranoid. His behavior was increasingly inappropriate, and he had only limited insight into his condition.

On examination, Seth was thin, casually dressed, slightly disheveled, and with poor hygiene. His speech was spontaneous, not pressured, and loose with occasional blocking. [That is, he spoke spontaneously, he could be interrupted, and his speech was unfocused with occasional interruption of thought sequence.] His psychomotor activity was labile [unstable]. His affect was cheerful and inappropriately seductive, and he described his mood as ”mellow.” He denied having hallucinations, systematized delusions and suicidal or homicidal ideation. He admitted having ideas of reference [incorrect interpretation of casual incidents and external events as having direct reference to himself], was clearly paranoid, and at times appeared to be internally stimulated. He made statements such as: “They’re blaming me for everything,” and “I’m scared all the time,” although he was too guarded or disorganized to provide more detail. His cognitive functioning was impaired, and testing was difficult given his distracted, disorganized state. His judgement was significantly impaired, and his insight was quite limited.

At the time of the evaluation, Seth indiscriminately revealed his HIV-positive status to the staff and other patients. He claimed he had been HIV positive for five years, and he denied that he had developed any symptoms of disease or taken any HIV-related medications. He was not considered reliable, and the staff sought confirmation. After he provided the location and approximate date of his most recent HIV test, the physician confirmed that the patient had been HIV positive at least since the test, about a year earlier.

When asked, Seth stated that the was not currently in a relationship. He appeared to be disorganized and could not name his most recent sexual partner(s). He could not remember whether he had been practicing safer sex and whether he had informed his partners of his HIV positive status.

In addition to the information he obtained during the evaluation, the psychiatrist, by chance, had limited personal knowledge of the patient. Through his own involvement as a member of the local gay community, the psychiatrist had briefly met the patient twice – once while attending an open discussion at the lesbian-gay community center, and later, at a worship service in a predominantly lesbian-gay church. The physician recalled that Seth had seemed to be functioning quite adequately, at least superficially. He was somewhat indiscriminately flirtatious, his behavior was otherwise appropriate, and he did not appear to be psychotic or disorganized in his thinking. He was not overtly paranoid and did not publicly reveal his HIV-positive status.

Through the church, the psychiatrist had also become acquainted with Maxwell and Philip, who were partners in a primary sexual relationship. Before Seth’s decompensation [deterioration of existing defenses, leading to an exacerbation of pathologic behavior], but after he was known to have tested HIV positive, Seth and Maxwell had been lovers. Maxwell left Philip and moved in with Seth for about two months, but then left Seth and returned to Philip around the time of Seth’s decompensation.

The psychiatrist was not privy to details of Maxwell and Seth’s or Maxwell and Philip’s sexual practices. He did not know of the HIV status of Maxwell or Philip, or whether either had ever been tested. In addition, he was unaware of whether Maxwell or Philip know of Seth’s HIVpositive status at the time of Maxwell’s relationship with Seth, or at any time thereafter. During the evaluation, Seth did not recall having met the psychiatrist, nor did he mention his relationship with Maxwell.

Seth agreed to enter a crisis stabilization unit and to resume treatment with antipsychotic medications. Free to come and go at will during daylight hours, he left the unit on day two, failed to return, and was lost to follow-up. His mental status had not changed significantly before he left the crisis unit.

In this case, the physician’s duty to maintain physician-patient confidentiality conflicts with his duty as a psychiatrist to warn third parties at risk. Clearly, a patient’s status as HIV positive is a matter of confidentiality between doctor and patient. Just as clear is the risk for third parties to whom the patient may pass the virus via sexual intercourse. It is unknown whether everyone infected with HIV will develop AIDS, or how many months or years may intervene between infection and the appearance of full-blown AIDS. However, once AIDS develops it is always fatal.2 Therefore, there is a potentially lethal risk to a person having intercourse, particularly without employing safer sex-practices, with another infected with the HIV virus.

This ethical conflict raises two questions. Is it permissible to violate confidentiality to warn a third party at risk? Is there a duty to violate confidentiality to warn a third party at risk? The potential benefit to the third parties must be considered, as well as the strength of the principle of confidentiality in the patient-physician relationship. There is also wider societal consideration as to how breaches of confidentiality, even for good reasons, will affect voluntary testing and seeking of prophylactic treatment by HIV-positive persons. This societal consideration must be weighed against the benefit to the individual third party of knowing the risk and then choosing to be tested and treated and choosing to be tested and treated and choosing to take precautions against infecting others.

In this case, another issue arises from the fact that the physicians of at least one third party who may have been placed at risk possibly without his knowledge, was obtained through personal knowledge, outside the professional relationship. Is it appropriate to bring this information into the clinical setting, particularly because it is so central to the primary ethical issue? Does the physician have an obligation to act on this information?

Finally, two additional sets of issues complicate this case. First, the patient’s decompensation and disappearance necessitate the physician’s choosing a course of action without patient consent or cooperation, and with patient-supplied information that is incomplete and probably unreliable. Second, a breach of confidentiality could greatly damage the physician’s position as a psychiatrist and a trusted member of the gay community, offering assistance directly to some and referral to many others. Given these issues, what should the physician do?

BACKGROUND DISCUSSION

Some background information will be useful in analyzing the ethical issues of the case. This information includes basic ethical values and norms, and legal mandates and opinions about confidentiality, the duty to warn, and HIV/AIDS reporting.

Whether privacy is viewed as a derivative value from the principle of autonomy or as a fundamental universal need with its own nature and importance,3 privacy, and the associated issue of confidentiality, is generally accepted as essential to the relationship between physician and patient. The purpose of confidentiality is to prevent unauthorized persons from learning information shared in confidence.4 Stated more positively, confidentiality promotes the free flow of communication between doctor and patient, thereby encouraging patient disclosure, which in turn should lead to more accurate diagnosis, better patient education, and more effective treatment.

The Hippocratic Oath is evidence of the long-standing tradition of confidentiality in Western though: “What I may see or hear in the course of treatment… I will keep to myself, holding such things shameful to be spoken about.” More recently, the American Medical Association,6 the American Psychiatric Association,7 the American College of Physicians, and the Infectious Diseases Society of America8 have reaffirmed the right of privacy and confidentiality, specifically for HIV-positive patients. Without the informed consent of the patient, physicians should not disclose information about their patient. The Center for Disease Control also recommends that patient confidentiality be maintained, because the organization believes that a successful response to the HIV epidemic depend on research and on the voluntary cooperation of infected persons.9That is, the interests of society seem best served if the trust and cooperation of those at greatest risk can be obtained and maintained.10

Within the complexities of clinical care, should patient confidentiality be regarded as absolute, never to be breached under any circumstances (as claimed by the World Medical Association in its 1949 International Code of Medical Ethics11)? Or should confidentiality be regarded as a prima facie duty? (That is, should it be binding on all occasions unless it is in conflict with equal or higher duties?12)

Most commentators and codes conclude that patient confidentiality is not absolute and, therefore, it could – and even should – be overridden under come conditions.13 In other words, in a specific situation in which patient confidentiality is one value at stake, the health-care provider’s actual duty is determined by weighing the various competing prima facie duties and corresponding values, including confidentiality. (As might be expected, not all authors accept this conditional view of confidentiality and argue for its absolute quality.14) There is less unanimity about the circumstances under which patient confidentiality can be justifiably breached. More specifically for HIV-positive patients, the controversy revolves around the premise that some circumstances might create a duty to warn endangered third parties, even at the expense of confidentiality. The potential for harm to HIV-positive patients through breaches of confidentiality is great. Discrimination, isolation, hospitality, and stigmatization are all too real for these patients when their HIV-positive status has become known to others.15 Further, societal harm is possible if these patients – who might ordinarily seek medical attention voluntarily – refrain from doing so, knowing that professional breaches of confidentiality may ensue. Without ignoring this potential societal harm, the majority opinion of professional codes and of ethical and legal experts16 foresee the possibility of a duty to warn through discrete disclosure, especially if others are in clear and imminent danger if the patient cannot be persuaded to change hi behaviors or to notify those at risk of exposure.

Public health regulations often reflect the same conclusion – that confidentiality can be compromised under certain circumstances – and therefore mandate reporting HIV-positive and AIDS patients to public health authorities. Patient confidentiality is not to be upheld so strictly that it obviates an ethically justified (and usually legally mandated) duty to report such cases to authorized health agencies. Those who support such public policies view society’s right to promote its health and safety, and the need for accurate epidemiological information, to be at least as important as an individual’s right to privacy and confidentiality.

In trying to balance patient confidentiality with other professional values, the California Supreme Court decision in Tarasoff v. Regents of the University of California17 has become a guideline for other courts and health-care professionals (although technically this decision applies to only one state and specifically addresses a unique set of circumstances). In this famous and controversial case heard before the California Supreme Court in 1976, the majority opinion held that the duty of confidentiality in psychotherapy is outweighed by the duty to protect an intended victim from a serious danger of violence. The court explained the legal obligation to protect and the potential duty to warn as follows:

When a therapist determines, or pursuant to the standards of his profession should determine that his patient presents a serious danger of violence to another, he incurs an obligation to use reasonable care to protect the intended victim against such danger. The discharge of this duty may require the therapist to take one or more various steps, depending upon the nature of the case. Thus, it may call for him to warn the intended victim or others likely to apprise the victim of the danger, to notify the police, or to take whatever steps are reasonably necessary under the circumstances.18

Regarding the limits placed on confidentiality under these conditions, the court stated: “The protective privilege ends where the public peril begins.” This “Tarasoff Tightrope” identifies for the professional the dual duties of promoting the well-being and interests of the patient and protecting public and private safety.

Given the general jurisdictional autonomy of each state, the duty to protect and the potential duty to warn as adopted in California has been applied differently in different states.20 Although most commentators assume that Tarasoff is relevant for sorting out the issue of confidentiality relative to HIV-positive patients, this assumption is not universally accepted.21

Without a state statute or court case that specifically addresses the tension between patient confidentiality and the right of others to know whether they may have been exposed to HIV infection, and given the conundrum of legal principles relating to AIDS confidentiality, it is unclear as to who must be warned and under what circumstances.22 This lack of clarity is in indication that, in practice, the professional duty to warn is not absolute but always conditioned by the circumstances of the case (that is, the duty to warn is a prima facie value).

The above paragraphs describe an emerging consensus among health-care professionals who face confidentiality dilemmas, although universal agreement has not been fully achieved. Further, this emerging consensus and its contributing principles by no means provide easy answers to ethical quandaries. Each case, with its own specific set of relevant circumstances, must be analyzed and judged individually. Such an analysis of the presented case now follows.

AN ANALYSIS

Seth’s case, perceived as a dilemma by the psychiatrist, could be brushed aside easily if the information obtained outside the therapeutic relationship was simply ignored. But the lethality of HIV infection makes it difficult to dismiss the information either as irrelevant or inadmissible for serious consideration. Had the information been obtained by unethical means (for example, by coercion or deception), a stronger justification for not using the information might be made. Such is not the situation. Without reason to ignore this information, the psychiatrist must incorporate this “data of happenstance” into his decision. To do so, of course, places him precisely at the crossroads of the dilemma: to uphold confidentiality, to warn the third party, or to create an option that supports the values behind these apparently conflicting duties.

Several factors ethically support both a breach of confidentiality and the physician’s duty to warn and protect the third party: the emerging professional consensus that confidentiality is not absolute; the known identity of a third party who stands in harm’s way; the risk to unknown and unidentified sexual partners of the third party; and the deadliness of AIDS. Such a combination of factors is what the professional statements noted above23 have tried to address in their allowance for limits to patient confidentiality. In this case, the risk to the known third party has already been established, but other people may be at risk, including sexual partners of the patient and those of the third party. Individuals infected and unaware will not benefit from prophylactic therapies.

An additional reason for the psychiatrist to warn the third part is the patient’s mental status, which probably renders him incapable of informing his sexual partner(s) or of consenting to the physician’s informing them. On admission, he was not able to name his partner(s), and he was lost to follow-up without significant change in his mental status. Without the decision-making capacity of the likelihood of action on the part of the patient, any warning to the third party would have to come from the physician or through public health officials notified by the physician.

But the duty to warn, incidental information, and mental status are not the only factors that need to be considered here. Patients are subject to the risks of discrimination when their HIV status is disclosed. But for a patient who has indiscriminately revealed his own HIV-positive status, the physician’s contribution to this risk of discrimination through discreet disclosure to one person may be minimal.

Also, to be considered is the societal risk that testing and prophylactic treatment of HIV-positive persons will decrease if confidentiality is not upheld. Members of the lesbian and gay community are often mistrusting of medical and mental health professionals,24 perhaps with valid reason. Mistrust, fear, and nonparticipation in voluntary programs may increase if confidentiality cannot be assured. Persons will be less likely to come forward voluntarily for education, testing, or other assistance if their well-being is threatened as a result. In Tarasoff, the court declared that protective privilege ends where social peril begins. In this case, overriding the protective privilege of the individual could lead to greater societal peril. Trust in this physician by members of the lesbian and gay community benefits individuals and the community as a whole, by improving access to medical and mental health services. A breach of confidentiality, if it became known, could damage this trust, as well as the physician’s reputation, reducing his professional contributions to the community. This professional loss would be significant.

Also, to be considered is the general knowledge of the higher risk among gay and bisexual men for HIV infection, as well as the information in the gay community as to what constitutes high risk behavior and what precautions can decrease risk of infection. Thus, we can reasonably assume that a gay or bisexual male is already aware of his risk and that of his sexual partner(s) for carrying the HIV virus. Warning a probably knowledgeable third party about the HIV-positive status may be of little benefit to the third party, while it risks the greater individual, societal, and professional harms discussed above. Regarding the risk to unknown sexual partners of the patient, whatever their number, the physician is powerless to change their fate precisely because they are unknown to him.

The duty to maintain patient confidentiality and the duty to warn third parties at risk can both be viewed as prima facie duties. In clinical situations such as the one described here, when one duty must be weighed against another to arrive at an ethically supportable solution, the weighing should take place only in the context of the given case. In this case, we found no solution that upholds all the duties; thus, a choice must be made between the two duties.

We submit that, although there is support for the physician to warn the third party, there is greater support for upholding confidentiality in this case. The individual risk of discriminatory harm from disclosure is possible, although admittedly small. Further, it is reasonable to presume the third party’s awareness of his risk and of the risk to his sexual partner(s) of carrying the HIV virus, and thus, his awareness of the need for appropriate precautions.

Even more persuasive is the peril to the local gay community and the wider society if a breach of confidentiality increases mistrust of the healthcare system and decreases the effectiveness of this particular psychiatrist to provide quality professional care. In this case, the confidentiality of the physician-patient relationship should be maintained.

What has been presented here can serve as a model for ethical decision making within the complexities of clinical care. As cases and their accompanying ethical questions arise, the details of each case should be gathered. Any tendency to label the case prematurely as a particular type (for example, a duty-to-warn case) should be resisted. Such a label can divert attention from relevant details that make each case unique. In examining the facts of the case and judging their significance, the values and duties at stake can be identified. If necessary and practical, background material and analogous cases should be researched. Ethical dilemmas present persons with hard choices. While several solutions may have some ethical support, few can be labeled as perfect solutions. Often, choosing one solution over another leaves behind an ethically significant value and regrettably may even produce harm. The circumstances described here presented the psychiatrist with a hard choice and no easy answer. We have suggested an ethically supported solution, but we found no perfect solution for the dilemma.

1. A.R. Jonsen, “Casuistry as Methodology in Clinical Ethics,” Theoretical Medicine 12 (1991): 295-307. 2. J.W. Curran, H.W. Jaffee, A.M. Hardy, et al., “Epidemiology of HIV Infection and AIDS in the United States,” Science 239 (1988): 610-16. 3. T.L. Beauchamp and J.F. Childress, Principles of Biomedical Ethics (New York: Oxford University Press, 1983). 4. W.J. Winslade, “Confidentiality,” in Encyclopedia of Bioethics, ed. W.T. Reich (New York: Free Press, 1978). 5. L. Walters, “Ethical Aspects of Medical Confidentiality,” in Contemporary Issues in Bioethics,3rd edition, ed. T.L. Beauchamp and L. Walters (Belmont, Calif.: Wadsworth, 1989). 6. Council on Ethical and Judicial Affairs of the American Medical Association, “Ethical Issues Involved in the Growing AIDS Crisis,” Journal of the American Medical Association 259 (1988): 1360-61. 7. American Psychiatry Association, “AIDS Policy: Confidentiality and Disclosure,” American Journal of Psychiatry 145 (1988): 541-42. 8. Health and Public Policy Committee of the American College of Physicians, and lnfectious Diseases Society of America, “A quired Immunodeficiency Syndrome,” Annals of Internal Medicine 104 (1986): 575-81. 9. Centers for Disease Control, “Additional Recommendations to Reduce Sexual and Drug-Related Transmission of Human T-Lymphotropic Virus Type I I1/L y mph adenopathy-Associated Virus,” Morbidity and Mortality Weekly Report 35 (1986a): 152-55. 10. R. Gillan, “AIDS and Medical Confidentiality,” in Contemporary lssues in Bioethics. Code of Ethics, 1949 World Medical Association,” in Encyclopedia of Bioethics. 11. W.O. Ross, The Foundations of Ethics (Oxford, England: Clarendon Press, 1939). 12. Beauchamp and Childress, Principles of Biomedical Ethics; Winslade, “Confidentiality”; Walters, “Ethical Aspects of Medical Confidentiality”; AMA, “Report on Ethical Issues”; APA, “AIDS Policy”; American College of Physicians and Infectious Diseases Society of America, “Acquired Immunodeficiency Syndrome”; S. Bok, “The Limits of Confidentiality,” Hastings Center Re port 13 (February 1983): 24- 31; H.E. Emson, “Confidentiality: A Modified Value,” Journal of Medical Ethics 14 (1988): 87-90. 13. M.H. Kottow, “Medical Confidentiality: An Intransigent and Absolute Obligation,” Journal of Medical Ethics 12 (1986):117-22. 14. R.J. Blendon and K. Donelan, “Discrimination against People with AIDS,” New England Journal of Medicine 319 (1988): 1022-26; L.O. Gostin, “The AIDS Litigation Project: A National Review of Court and Human Rights Commission Decisions, Part II: Dis crimination,” Journal of American Medical Association 263 (1990): 2086-93. 15. G.J. Annas, “Medicolegal Di lemma: The HIV-Positive Patient Who Won’t Tell the Spouse,” Medical Aspects of Human Sexuality 21 (1987):16; T.A. Brennan, “AIDS and the Limits of Confidentiality: The Physician’s Duty to Warn. Contacts of Seropositive Individuals,” Journal of General Internal Medicine 4 (1989): 242-46: B.M. Dickens, “Legal Limits of AIDS, Confidentiality,” Journal of the American Medical Assoclarion 259 (1988):3449-?1; S.L. Lentz. ”Confidentiality and lnformed Consent and the Acquired Immunodeficiency. Syndro111e. Epidemic,” . Archives of Pathology, & Laboratory Medicine 114 (1990):304 8; D. Seiden, “HIV ·Seropositive Patients and Confidentiality,” Clinical Ethics Report (1987): 1-8H.Zomina, “Warning Third 16. Tarasoff v. Regents of the University of California, 11Cat.3d 425,551 P 2d ht (1,976) 17. Ibid. 18. R.D. Mackay, “Dangerous. Patients: Third Party Safety and Psychiatrists’ Duties: Walking the Tarasoff Tightrope,” Medicine, Science & the Law 3Q (1990): 52-56, 19. LA. Gray and A.R. Harding, “Confidentiality Limits with Clients Who Have the AIDS Virus,” Journal of Counseling and Development 6 (1988):219-23. 20. S. Perry, “Warning Third ‘Parties at Risk of AIDS: APA’s Policy is a Barrier to Treatment,” Hospital and Community Psychiatry 40 {1989):’ i5.8-6I. 21. L.O Gostin, The AIDS Litigation Project: A National Review of Court and Human Rights Commission Decisions. Part 1: The Social Impact of AIDS,” Journal of the American Medical Association 263 (1990), ‘961-7Q 22. AMA; “Report on Ethical Issues”; APA, “AIDS Policy”; American College of Physics and Infectious Diseases Society of America” Acquired lmmunodeficiency Syndrome.” 23. L. Dardick and KE Grady, “Openness between·:Gay Persons and Health Professionals,” Annals of Internal Medicine 93 -(1 80): 115-.19; T.A. DeCrescenzo, Homophobia: A Study of the Attitudes of Mental Health Professionals toward Homosexuality. Journal of Social Work and Homosexuality 2 (198):.84): 115-36.

Print this case study here:  Case Study – Gathering Information and Casuistic Analysis

Gathering Information and Casuistic Analysis

Journal of Clinical Ethics By Athena Beldecos and Robert M. Arnold

Athena Beldecos is a graduate student in medical ethics in the Department of History and Philosophy of Science, University of Pittsburgh.

Robert M. Arnold, MD is an Assistant Professor of Medicine, and the Associate Director for Education, Center for Medical Ethics, University of Pittsburgh.

In their article, “Confidentiality in the Age of AIDS,” Martin L. Smith and Kevin P. Martin present a complex case in clinical ethics. Their analysis examines a physician’s quandary when treating a mentally incompetent HIV-positive patient: whether to uphold physician-patient confidentiality or to violate this confidentiality by warning a third party. Out critique focuses on the way the problem is conceptualized and the analytic methods used to resolve the case, rather than on the solution itself. We believe that several problems in the authors’ analysis arise from a misinterpretation of the casuistic method. Furthermore, we argue that Smith and Martin present a case that is insufficiently detailed, thereby precluding the identification of all of the moral problems in the case and the development of creature solutions to the problem(s) identified. We note several reasons why there is a need to gather more information prior to determining the appropriate ethical response. Finally, we suggest ways in which similar problems in clinical ethics might be avoided in the future.

IS THIS CASUISTRY?

The authors conceive of their “process of ethical analysis and decision making” as a “type of casuistry.” Although we agree that casuistry, as outlined by A.R. Josen,1 is a potentially fruitful technique for practical ethical decision making, we believe that certain essential features of such casuistic reasoning are not clearly present in Smith and Martin’s analysis.

The power and scope of casuistry are derived not only from attention to details and careful identification of circumstances in the presentation of individual cases, but – more importantly – from the process of case comparison. Using this method, a case under moral consideration is situated in a family of related cases, whereby the casuist examines the similarities and differences between the cases at hand. The context of an individual case and how its conflicting maxims appear within that particular context are the raw materials of the case-comparison method. The relative weight of conflicting maxims in an individual case is ascertained by comparison to analogous cases. With casuistry, moral judgement does not involve a more traditional retreat to the weighing of conflicting duties or general principles. Rather, moral guidance is provided by an ever-growing body of paradigm cases that represent unambiguous instances in which moral consensus is easily obtained. It is crucial that the casuist place the case under consideration in its proper taxonomic context(s) and that she or he identify the most appropriate paradigm, whether it be real or hypothetical.

The authors do identify a paradigm case, but their analysis departs from casuistry on several interrelated points. The authors do not proceed by analogical reasoning. Had they done so, they might have discovered that their chosen paradigm is inappropriate, due to significant dissimilarities with Seth’s case. Finally, their insufficiently detailed case precludes a thorough measurement of the similarities and differences between the cases at hand. For it is in the details that an individual case may differ from a paradigm case.

The authors’ analytic method has more in common with principle-based ethics2 than casuistry. They do not use a variety of similarly situated cases to point out and balance the relevant moral maxims instead, they extract the conflicting duties and principles from their paradigm, the Tarasoff case,3 and apply them directly to Seth’s case. The authors weigh one prima facie duty “against another to arrive at an ethically supportable solution.” Furthermore, the weighing takes place “only in the context of the given case.” Thus, case comparison, an intrinsic element of casuistry, is not performed. Instead, the authors’ major goal seems to be finding and applying a sufficiently modified principle regarding confidentiality to resolve the case at hand.

WHY TARASOFF IS PROBLEMATIC AS A PARADIGM CASE

By using Tarasoff as a paradigm case in their analysis, Smith and Martin situate their case in the family of “duty-to-warn” (prevention-of-harm) cases. It is reasonable that they identify this particular taxonomy as a starting point for their analysis. However, they do not test the appropriateness of the paradigm by systematically comparing and contrasting it with Seth’s case. The authors note the uniqueness of the circumstances of the Tarasoff case and its limited applicability but nonetheless proceed to use it as a paradigm. Casuistry, however, seeks closest-match paradigms. The use of analogical reasoning would have illuminated the similarities and differences between the two cases and would have helped the authors to determine which morally relevant features a paradigm case should minimally share with its analogous cases.

In the Tarasoff case, the court held that a psychotherapist, to whom a patient had confided a murderous intent, had a duty to protect the intended victim from harm.4 This duty includes warning the third party at risk, among other interventions. The unique circumstances of Tarasoff include the imminence of fatal harm to an identified, yet unsuspecting, individual. Although the authors are correct in noting the precedent-setting value of Tarasoff, the dissimilarities between Tarasoff and Seth’s case are so numerous as to suggest the selection of another paradigm.

First, a critical aspect in Tarasoff is the prevention of future fatal harm. Based on the circumstances of the case, there is no evidence of preventable fatal harm to Maxwell. For this condition to be satisfied, the psychiatrist would have to be assured of Maxwell’s seronegativity and have evidence of a current or an intended sexual relationship between Maxwell and Seth. The preventable harm to Maxwell consists of not allowing him the opportunity to institute early anti-viral therapy or to reconsider his life goals in the face of a fatal disease. A casuist would need to assess, using a series of cases, the moral difference between the fatal harm in Tarasoff and the lesser harms in the case of Seth.

Second, Tarasoff involves a person maliciously intending to harm another person. However, there is no evidence suggesting that Seth intended to harm Maxwell. Here, a casuist might begin the analysis using a paradigm case in which a physician is aware of his HIV-positive patient’s malicious intention to infect a third party from that point, one could progressively change the variables of the case to approach the degree of moral ambiguity and complexity shown in Seth’s case. This process would culminate in a case involving sexual relationship between a patient and his partner.

Third, the notion of harm with respect to HIV transmission is quite different from the harm to be prevented in Tarasoff . One might argue that fatal harm to others is averted by informing Maxwell of his risk for HIV positivity. He can subsequently alter his sexual practices and, thus, prevent the future spread of the virus. Herein lies the problem. In Tarasoff the person warned of the harm is also the person at risk of being harmed. In the case under discussion, however, warning Maxwell might prevent harm to other, yet unnamed individuals. A case analogous to Seth’s should describe a situation in which the possible harm has already occurred and the future harm to be avoided consists of preventing future transmission. An analogous case might involve issues of confidentiality in regard to the (vertical) transmission of a fatal genetic disease that manifests itself after sexual maturity. Imagine, for example, a young man afflicted with a severe and incurable genetic disease who has proceeded to start a family without disclosing his genetic status to his wife. Does his personal physician have a duty to uphold confidentiality in this case, or should he notify the spouse so that she can make informed reproductive decisions?

Fourth, in Tarasoff , the victim was presumably unaware of the intended harm. In Seth’s case, one can argue that Maxwell knows (or can be reasonably expected to know) the potential risk of having sexual relations with a homosexual. The authors mention this factor but do not provide a way to assess its importance. To test the importance of this morally relevant fact, a series of cases in which the third party is more (or less) responsible for knowing about the possibility of risk could be used for comparison. For example, how would our intuitions about physician disclosure in this case differ if Seth were a bisexual male who did not inform his wife of his unprotected extramarital affairs with gay and bisexual men?

Fifth, Seth was reported to have publicly announced his HIV-positive status, whereas the patient in Tarasoff disclosed his intent to kill within a protected doctor-patient relationship. Does the fact that “Seth indiscriminately revealed his HIV-positive status to the staff and other patients” at a community-mental-health-center make it easier for the psychiatrist to justify a violation of confidentiality in the name of protecting potential victims? Unfortunately, there is insufficient information to determine whether Seth’s public disclosure qualifies as a fair warning to potential victims and sanctions a violation of confidentiality. This point is potentially an important difference between Tarasoff and Seth’s case. The authors, however, would need to gather additional information concerning the circumstances of Seth’s public disclosures (when they began, to whom they were addressed, and so forth) before evaluating the weight of this morally relevant feature by comparison to a similar case.

Sixth, Tarasoff does not address the issue of how the duty to uphold confidentiality might be affected when a patient’s mental competence is in question. Seth’s case involves a mentally incompetent patient presumed to be “incapable of informing his sexual partner(s) [of his HIV positivity] or of consenting to the physician’s informing them.” The circumstances of this case raise the question: Does Seth’s physician have the same obligation to respect his patient’s confidences as he would have if Seth were a mentally competent adult patient? Central to this analysis is an understanding of how the underlying justifications for respecting the confidences of incompetent patients might differ from those of competent patients. Although the authors briefly discuss the implications of Seth’s impaired mental status, they could have profitably expanded their analysis of the ethical significance of a patient’s competency in regard to the physician’s duty to maintain confidentiality. The authors neglect to discuss, for example, how the selection of a surrogate to speak on Seth’s behalf might influence the case’s resolution.

Identifying which should be the determining factor(s) in deciding Seth’s case is a difficult moral problem. However, the first step is any casuistic analysis is to determine where the case fits in relation to other cases. Without this basic first step, it is too easy to neglect factors that may be critical in determining the proper course of action or to reply upon ad hoc, intuitive decisions.

THE NEED FOR A RICHLY DETAILED CASE

The casuistic method to which Smith and Martin supposedly subscribe, demands attention to the context of the particular case at hand, so that it may be compared to and contrasted with paradigm cases in which the ethical analysis is clear. A casuist needs sufficiently detailed information to be able to identify all of the moral issues and, thereby, situate an individual case in its appropriate taxonomy.

In Seth’s case, the authors seem to decide prematurely on the ethical issue, inappropriately hindering the search for future data. In the rush to identify and resolve the presumed ethical conflict, the ethicist may neglect to collect critical information.5 Without adequate information, the ethicist is unable to determine accurately what kind of case it is. While obtaining more information might be less interesting than theoretical analysis, often the most prudent course of action is to gather more information from the sources available in order to clarify and embellish the initial facts. Prior to leading the psychiatrist through a philosophical analysis of how to resolve the conflict between the duty to warn and the duty to uphold confidentiality, the authors should have urged the psychiatrist to obtain more information.

It is difficult, for example, to weigh the impact of Seth’s mental incompetency against the duty to maintain confidentiality because of a lack of sufficient information. Information regarding the severity of Seth’s mental illness and the chances of its reversibility would be useful in determining whether Seth should be viewed as only temporarily or permanently incompetent. If Seth is incompetent, it is not clear who should assess the harm done to Seth by a breach of confidentiality. We know too little about Seth’s life to determine who would most appropriately serve as his surrogate. Furthermore, it is not clear that violating Seth’s confidentiality would result in the social harms the authors forecast. In order to make this point, the authors would need to identify a case analogous to Seth’s, in which violating an incompetent person’s confidences is ill-advised because it might lead competent patients to mistrust or fear the health-care system.

In the previous section, we identified a variety of morally relevant factors in Seth’s case and suggested how they might affect one’s analysis. Determining the importance of the various factors in this case, however, requires the ethicist to obtain information concerning the following: the efficacy of antiviral treatment in HIV-positive persons, Seth and Maxwell’s sexual practices, the probability that Maxwell knows of Seth’s seropositivity, the degree to which Maxwell can reasonably be expected to know the risk of homosexual encounters, Seth’s previous comments regarding confidentiality, who is best situated to serve as Seth’s surrogate, and the degree to which violating an incompetent patient’s confidentiality will lead other patients to lose trust in physicians and thus avoid the health-care system. Some of this information might be obtained from Seth’s social worker. Other data, however, can be obtained only by reviewing the empirical literature. We admit that much of this information may be unobtainable. Knowing the limits of one’s knowledge, however, will allow an honest appraisal of how uncertainty regarding various factors affects one’s moral decision making. This is preferable to not attempting to ascertain the information at all.

CREATIVE SOLUTIONS

The failure to gather sufficient information often leads to an impoverished understanding of the ethical issues that a case raises. In Seth’s case, the authors present the case as though there were one question: Is it permissible/obligatory to violate Seth’s confidentiality to warn Maxwell? Asked this way, there appears to be only two resolutions to the case: either a physician protects Seth’s confidentiality by failing to warn Maxwell o the risk, or he violates Seth’s confidentiality by warning Maxwell. Upon collection of sufficient data, one might discover ways to resolve the case that would allow all relevant values to be promoted. In some cases, additional information may provide the ethicist with an “end run” around the presumed ethical problem. For instance, if the ethicist learns that Maxwell is already aware of Seth’s seropositivity, then the ethical quandary vanishes. There is strong pedagogical justification for the authors to provide us with sufficient information to conclude that the quandary could have been resolved by seeking additional information and to help us develop innovative solutions that might promote the competing values.

Even if more information does not allow one to avoid the ethical conflict, it may prove useful in determining how best to resolve the case. It is simplistic to view the outcome of ethical analysis as a hierarchical ranking of two competing values or principles. Intermediate solutions often exist, which allow one to respect both competing values. Even in those cases where it is justified to promote one value over another, one is nevertheless obligated to consider alternative courses of action that respect, as much as possible, the other value. The authors neglect an important step in ethical problem solving – attempting to develop creative solutions that, if they cannot perfectly respect all values, at least cause as little damage as possible. This approach, known in American law as “the least restrictive alternative,”6 recognizes that solutions can be more or less respectful of ethical principles. Thus, for example, one might decide that the risk to Maxwell is sufficiently high so that some violation of Seth’s confidentiality is permissible. A variety of options would still be open. (1) The psychiatrist could call Maxwell (or have the public health department do so) and inform him that he may have been exposed to the HIV virus and thus, he should be tested. (2) The psychiatrist could call Maxwell, identify himself as Seth’s physician, and attempt to ascertain what Maxwell knows about Seth’s serostatus and what the nature of their sexual relationship was. That evidence could then be used to determine whether further actions are in order. (3) The psychiatrist could call Maxwell and tell him that he is Seth’s physician, hat he knows of Maxwell and Seth’s sexual relationship, and that Seth is HIV positive. He could then urge Maxwell to be tested. A similar range of alternatives could be developed if one decides that respecting Seth’s confidentiality is the most important value.

PREVENTIVE ETHICS

A final question is simply why this problem arose. If we assume, as the authors do, that “choosing one solution [in an ethical dilemma] over another leaves behind an ethically significant value and regrettably may even produce harm,” we should attempt to prevent ethical dilemmas from occurring.7 However, typically, case discussions focus on how to “solve” the problem at hand without determining how and why the problem arose, and how it might be avoided in the future. As E. Haavi Morreim points out: “Our moral lives are comprised, not of terrible hypotheticals from which there are no escapes, but of complex situations whose constituent elements are often amenable to considerable alterations.”8 The psychiatrist in this case may not have been able to anticipate Seth’s disappearance, but perhaps he could have asked additional questions on his initial encounter to prevent the resulting ethical quandary. For instance, it would have been useful if the psychiatrist had gathered information about Seth’s values and desires prior to his decompensation. Furthermore, if the physician had asked Seth for permission to talk to his friends, whether others knew of his seropositivity, whether the doctor could release this information to Seth’s sexual partners. or to identify his moral surrogate, this additional information could have ameliorated the quandary that subsequently arose.

In the final analysis, we may well agree with Smith and Martin about how the psychiatrist should handle this case. In this article we have tried to criticize not the answer, but the process by which the answer was reached. We urge ethicists who are dealing with a challenging case to use the process of case comparison in their analysis, examining a variety of analogous cases; to seek sufficient information to be able to identify all the moral issues in a case and situate the case in its proper taxonomic family; to attempt to develop creative, “least-restrictive” alternatives to ethical dilemmas; and to determine if there are ways that the ethical problem can be prevented in the future. Close attention to these points is likely to improve ethical decision making in the clinical setting and ethical analyses of cases presented in the bioethics literature.

ACKNOWLEDGMENTS

We would like to thank our friends and colleagues for their helpful comments on this paper: Lisa Parker, PhD; Joel Frader, MD; Peter Ubel, MD; and Shawn Wright. JD, MPH.

1. A.R. Jonsen, “Casuistry as Methodology in Clinical Ethics,” Theoretical Medicine 12 (1991): 295-307.

2. T.L Beauchamp and J.F. Childress, Principles of Biomedical Ethics (New York: Oxford University Press, 1989).

3. 3c. Tarasoff v. Regents of the University of California, 17 Cal. 3d 425. 551 P.2d 334 (1976}.

5. N. Whitman, Creative Medical Teaching (SaIt Lake City: University of Utah School of Medicine, 1990).

6. Lake v. Cameron. 364 F. 2d 657 (D.C. Cir. 1966).

7. L. Forrow R.M. Arnold and L.S. Parker, “Preventive Ethics: Expanding the Horizons of Clinical Ethics:· The Journal of Clinical Ethics (forthcoming).

8. E.H. Morreim, “Philosophy Lessons from the Clinical Sening.” Theoretical Medicine 7 (1986): 47-63.

TARASOFF: Discussion Questions

1. Traditionally, the Tarasoff case pits two goods or values against each other: confidentiality between therapist and patient vs. protection of an intended victim. Why is each a value?

2. Confidentiality is not only a value, but it has been called a duty which is incumbent on health care professionals to maintain secrecy about information gained in the course of interaction with a patient or client. Confidentiality derives from the more fundamental value of autonomy, the right each person has to be one’s own self-decider, one’s own intentional agent.

Protection of an intended victim likewise becomes a duty. To discharge that duty, the court argued, the therapist is obliged to warn the intended victim or others, to notify the police, or to take steps which are reasonably necessary to guard the intended victim.

Formulate an argument that supports the duty of confidentiality over the duty to warn an intended victim. Then formulate an argument which supports the duty to warn over the duty to protect confidentiality. (Being able to make good cases for each of the values shows the ambiguity involved here. Bring into your arguments the issue of the foreseeability of violence (is violence clearly foreseeable, probably foreseeable or unforseeable?) and the element of control over the patient by the therapist.)

3. One can easily use the Tarasoff decision to show the two principal ways of argument, consequentialist and non-consequentialist. Formulate an argument from a utilitarian (consequentialist) perspective, i.e., emphasize risk over benefit in arguing for safety and again, in arguing for confidentiality.

Next, consider confidentiality and the right to be protected as goods in themselves, regardless of consequences. Show how each value is tied to the meaning of being human and indicate how such a value can be argued for without consideration of consequences.

4. Notice how the arguments being proposed by the committee deny the absolute nature of either value. Rather, the committee is attempting to justify an action that is indicated in favor of one value over another, while acknowledging that both values are human goods. How would one attempt to argue when faced with the position that confidentiality or protection were absolute values?

Further Readings

Beauchamp, Tom and LeRoy Walters (eds.) 1994. “The Management of Medical Information” in Contemporary Issues in Bioethics. Fourth Edition. Belmont, CA: Wadsworth:123-186.

Kleinman, Irwin. 1993. “Confidentiality and the Duty to Warn.” Canadian Medical Association Journal 149: 1783-1785.

Perlin, Michael L. 1992. “Tarasoff and the Dilemma of the Dangerous Patient: New Directions for the 1990’s.” Law and Psychology Review 16: 29-63.

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• 1. The UC San Diego AntiViral Research Center sponsors weekly presentations by infectious disease clinicians, physicians and researchers. The goal of these presentations is to provide the most current research, clinical practices and trends in HIV, HBV, HCV, TB and other infectious diseases of global significance. The slides from the AIDS Clinical Rounds presentation that you are about to view are intended for the educational purposes of our audience. They may not be used for other purposes without the presenter’s express permission. AIDS CLINICAL ROUNDS
• 2. Cases Gigi Blanchard, MD July 19,2013
• 3. DK • DK is a 36yo Indian woman with newly diagnosed HIV who presented w/ fever and progressively worsening back pain • Tested HIV negative in India 2010 prior to her immigration here • Late spring of 2012 developed fevers and anorexia and was diagnosed with HIV by her PCP • Initial CD4 = 162 (7%); VL = 412,652
• 4. Chest imaging 7/12
• 5. 7/12 Admission for pna • Ruled out for TB with 3 negative AFB smear/cx • Cryptococcal Ag & Histo negative • Cocci CF anti-complementary; ID negative • Bronch wash: • AFB smear and cx negative; MTD - • Silver stain negative • Aspergillus Galactomannan neg • CSF remarkable for WBC = 50, 94% L • Defervesced on ceftriaxone
• 6. 7/12 Admission w/ anaphylaxis • Another admission for fever (104.6) and cough • This admission complicated by anaphylaxis • Infectious w/u repeated and still negative • Fever and cough treated with 10 days of IV vanc/aztreonam • Starts RIL/TDF/3TC + RAL
• 7. Outpatient F/U • CD4 = 264 – up from 172 • HIV VL = 207 – down from 400K • CT chest 8/12: • Partial resolution of diffuse B/L GGO and centrilobular nodules compatible with resolving infection • Decrease in mediastinal and axillary lymphadenopathy • ABD CT: Stable to decreased retroperitoneal lymphadenopathy
• 8. 8/12 Admission • Daily fever (102.6), back and leg pain • No weakness but pain is so bad can’t walk and now has a rash to oxycodone • ROS is o/w negative • MEDS: • RIL/TDF/FTC + RAL • Lorazepam • Zolpidem • Oxycodone
• 9. • ALL: • Augmentin • Ceftriaxone • Cipro • Doxycycline • Fluconazole • SMP/TMZ • Azithromycin • Morphine • Micafungin • Shx: • No tob • No etoh • No drugs • Not sexually active • Fhx: • Dad has DM • Aunt with breast cancer
• 10. T 102.5 P 104 BP 118/76 RR 16 • GEN: tearful but in no other distress • HEENT: OP clear; no icterus • PULM: CTA B/L • CV: Tachycardic, no M • ABD: soft, NT, ND, NABS; no HSM • BACK/EXT: No spinal tenderness; tender over L SI joint; no edema • NEURO: Moving all extremities; DTRs WNL
• 11. • Na 131, K 3.9, Cl 99, Bicarb 19, BUN/Cr nl • AST/ALT: 44/45, ALB 3.8 • WBC = 8.9, H/H = 9.9/30; Plt = 384 • S 36 L 51 E 6 • Sed rate = 99; CRP 6.2 • CD4 = 264; VL = 207
• 12. MRI Lumbar Spine
• 14. 8/12 Admission • IR unable to aspirate the SI joint but did do a wash- out • WBC 90 (44% PMNs, 44% Lymphocytes, 4% Eos, 8% maacrophages) • Aerobic Culture: Negative • Anaerobic Culture: Negative • AFB Culture: Negative
• 15. Admission Sacroiliitis • Brucella Ab <1:20 • Bartonella Ab < 1:64 • Strongyloides Ab 0.03 negative • Lyme 0.26 negative • Coxiella burnetti Ab negative • Cryptococcal Ag negative
• 16. 8/12 Admission • 8/13/12 Cocci CF Anticomplementary; ID negative • Numerous bacterial, AFB and fungal cx negative from blood, CSF • Quantiferon negative • TEE negative
• 17. A New Result • 8/18/13 Cocci CF + 1:16 • Total body bone scan negative • CSF studies are normal/negative • Desensitized to fluconazole and started on 400mg bid
• 18. 18 Case DK July 3-5 July 20 Aug 13 Aug 18 Aug 24 Cryptococcal antigen (serum) Negative Negative Negative Histoplasma antigen (urine) <2.0 (neg) <2.0 (neg) <2.0 (neg) Coccidioides immunodiffusio n (ID) Negative Negative Negative Negative Coccidioides complement fixation (CF) Anti- complementar y Anti- complementar y Positive 1:16 Positive 1:16
• 19. Coccidioides
• 20. Coccidioidies: forms
• 21. • Endemic to arid SW • Arizona, California, Nevada, New Mexico & Utah • Parts of Central and South America
• 22. Clinical Manifestations • 50-70% of infections are asymptomatic or so mild that they don’t come to medical attention • Usually self-limited • Complications manifest weeks to 2 years later • The severity of the initial infection does not correlate with the likelihood of complications • Highly infectious (transferring planes in Phoenix) • 1 arthroconidium is enough
• 23. Clinical Manifestations • Early respiratory infection • Sx develop 7-21 days after exposure • Onset is usually subacute but can be abrupt • 70-75% have fever and cough • 30-40% have chest pain (pleurisy), dyspnea and fatigue • Weight loss is common • HA occur ~ 20% of the time • Rash: fine papular rash, e nodusum, e multiforme • Migratory arthralgias are common
• 24. Pulmonary Findings • Unilateral infiltrates, hilar adenopathy & effusions • Nodules – Peripheral & Solitary • Cavities ~ 8% of the time • Usually thin walled • May develop a mycetoma • Diffuse pulmonary (reticulonodular) infiltrates more common in HIV • May mimic septic shock • Chronic Fibrocavitary Pneumonia
• 25. ExtraPulmonary Dissemination • Only 0.5% in general population • Much more common in immunosuppressed • AIDS (CD4 < 100) • Transplant pts • Pts on chronic steroids (prednisone 20mg) • Hodgkin’s lymphoma • More common in men than women (unless she’s pregnant)
• 26. ExtraPulmonary Dissemination • Skin: maculopapular lesions to ulcers to abscesses • Joints and bones – any joint can be involved • Synovitis and effusion • Knee; hands and wrists; feet and ankles and the pelvis • Infection may erode to involve bone as well • Vertebral infection is not uncommon with multiple vertebrae involved & may see paraspinous abscesses • Meningitis (eosinophilia in CSF in add’n to usual abnormalities)
• 27. Diagnosis • Delayed-type hypersensitivity testing • + for life • Anergy: May be negative during active infection • Direct Examination and culture • Serology
• 28. Diagnosis: Direct exam/cx • Identifying spherules in a specimen • Sputum is not infectious • Can’t be detected by Gram Stain • Cytology stains; H&E, silver or PAS stains all work • Grows well on most fungal or bacteriologic media w/in 1 week - • NOTIFY THE LAB - this culture is highly infectious
• 29. Serologic Diagnosis • + Antibodies in serum, CSF or other fluid • Highly specific • Even minimally reactive results are significant • A negative test NEVER excludes infection • Repeat tests over 2 months to increase sensitivity • Titer >1:16 ass’d with dissemination • Does not cross react with Cryptococcus or Blasto and very rarely with Histo
• 30. Immunodiffusion • Antigen is incorporated into the gel or agar • Serum (antibody) is added to wells, which then diffuses through the Antigen containing gel • Precipitate/ring forms • IgM
• 31. 32 Complement Fixation Disease No disease Control (no test antigen) Notes Control (no test antigen) Heat (remove native complement) Add test antigen (coccidioidin) Add standardized complement Incubation Add sensitized sheep RBCs coated with hemolysins Reaction (RBC plug vs Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y Y OK Anticomplementary
• 32. Back to DK • She remains afebrile • Back pain due to anterolisthesis remains severe • Re-admitted 10/12 for out of control pain • Repeat MRI:
• 35. • A diagnostic procedure is performed
• 36. Non-Hodgkin’s Lymphoma!!
• 37. Terry • Terry is a 41yo AA M-to-F with a CD4 = 196 (12%) , VL = 167 in 6/11 who presented to UCSD’s ED 10/12 with several complaints • Had been out of care since 6/11 d/t meth abuse • + dysphagia for solids x 10days; no odynophagia • Abd pain • Chest pain – in the ED, ass’d with EKG abnormalities
• 38. Terry • Abd pain – epigastric x 1 week • + N/V; No D or constipation • Not ass’d with eating; no radiation • Wakes her up at night • Chest Pain in the ED • Substernal, stabbing; No radiation • No palpitations; no DOE; no syncope; no orthopnea • Smoked meth on the day of admission • Resolved with ASA and nitro
• 39. Terry • ROS: • + anorexia with ~ 20lbs weight loss over 2 mo • F x 2 weeks – as high as 110!; NS x 2 week • No HA; No visual problems; no oral lesions/pain • No easy bruising; epistaxis or bleeding gums • + dry cough; no pleurisy • No pedal edema; no DOE; No orthopnea • No rash
• 40. Terry • PMHx • HIV, dx’d in ‘03 • Syphilis • Meds: None • ALL: NKDA • Shx: • on disability • No tob, etoh • Smoked meth 2 weeks ago and on the day of admission • Fhx: mother has DM; Dad A&W
• 41. T 97 P119 BP 106/70 RR 22 100% • GEN: thin AAM in NAD • HEENT: poor dentition but no thrush or lesion • PULM: CTA B/L • CV: tachy, but no M/R/G • ABD: soft, NT, ND, NABS; no HSM • EXT: no edema • LN: no cervical, axillary, inguinal LAD
• 42. Labs • Na = 131, BUN/Cr = 22/0.17 • Cl = 89, Bicarb = 17 • SGOT/SGPT = 53/17; albumin = 2.6 • AG = 27.5; Lactate = 91.1 • Lipase = 16 • CPK-MB = 9.2 (nl <4.8); • Troponin T = 0.53 (nl < 0.01; >0.09 = MI)
• 43. Labs • WBC = 6.8; H/H = 10.9/33.4; Plt = 232 • MCV = 76.1, RDW = 20.9 • S 77; B 3; L 10 • UA: 1.027, 1+ protein; no glu; moderate ketones; 3- 5 WBC; 6-10 RBC; many squames • U tox = + amphetamine; BAL < 9 • Blood cx – pending
• 45. Bedside Echo
• 46. Cardiac Masses • Infections/endocarditis • Bacteria • Mycobacteria • Fungi • Candida • Aspergillus (intracardiac masses have been described) • Cryptococcus
• 47. Cardiac Masses • Thrombi (cluster of grapes; trapped in the chords) • Structural Abnormalities • False tendons (ventricular muscle band that goes from muscle to muscle rather than muscle to valve and it spans the chamber) • Moderator bands (carry the R bundle branch in the RV) • Ruptured chordae tendinae
• 48. Cardiac Tumors • Sx depend on size and location • Chest pain, syncope, heart failure • Arrhythmias, murmurs, pleural effusions • Metastatic disease more common than primary tumors • Melanoma, lymphoma most common by incidence • Lung and breast most common by number • Usually nodules or pericardial involvement; chamber involvement less common
• 49. Primary Cardiac Tumors • Myxoma • Most common benign tumor • 1/3 of all primary cardiac tumors • 75% involve the LA at the fossa ovalis • 15% involve the RA • Usually solitary unless part of a syndrome • Occur typically in the 3rd to 6th decades • Women > men • Sx are those of obstruction, emboli or constitutional sx
• 50. Primary Cardiac Tumors • Sarcoma • Most common malignant primary cardiac tumor • ~ 40% are angiosarcomas • Usually in the RA • Well defined mass • Sx: R sided heart failure or tamponade d/t frequent pericardial involvement • Bloody pericardial fluid usually has no malignant cells • Undifferentiated, rhabdomyosarcoma (arises from valves), osteosarcoma and leiomyosarcoma
• 51. Primary Cardiac Tumors • Kaposi’s Sarcoma • Cardiac involvement much more common when cutaneous disease (20% of an autopsy series) • Similar to cutaneous disease, see violaceous plaques and nodules • Usually multiple sites: • Pericardium, epicardium, subepicardium & myocardium • Usually asymptomatic and only found at autopsy
• 52. Primary Cardiac Tumors • Primary cardiac lymphoma • Usually involves the RA • Pericardial involvement is common but not extension into the valves • Metastatic (secondary cardiac lymphoma) • Typically aggressive B-cell lymphomas • Present anywhere in the heart • Pericardial, epicardial or diffusely infiltrative • Sx: dyspnea, CHF, CP, epigastric pain • Tamponade, arrhythmia • MI simulated by diffuse myocardial infiltration
• 53. More Labs and imaging • LDH: 5640!! uric acid = 11.2 • CT C/A/P: Large ill-defined mass in the LUQ causing mass effect on multiple structures w/o definitive evidence of invasion. The left kidney is displaced inferiorly and the spleen superiorly. • There is mass effect on the splenic vein and artery and the L renal vein and artery w/o evidence of invasion.
• 54. • FNA of RP mass: High grade B-cell lymphoma c/w Burkitt’s Lymphoma • Started on hydration, alkalinazation, and allopurinol • R-EPOCH
• 55. F/U Echo
• 56. F/U Echo
• 57. Ready for a quickie?
• 58. JP • 26yo with no PMHx presented to UCSD’s ED 5/13 with h/o cough and dyspnea since Sept • Intermittent fevers • Seen in urgent care 10days ago and given course of doxycycline • ROS + for 20lb weight loss
• 62. 63 Questions
• 63. Thank you!

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• Rev Inst Med Trop Sao Paulo
• v.55(6); Nov-Dec 2013

Language: English | Portuguese

CASE STUDY OF A PATIENT WITH HIV-AIDS AND VISCERAL LEISHMANIASIS CO-INFECTION IN MULTIPLE EPISODES

Estudo de caso de paciente com múltiplos episódios da coinfecção hiv-aids e leishmaniose visceral, elis dionísio da silva.

1 Postgraduate Course of Biology applied to Health, Federal University of Pernambuco, PE, Brazil. E-mail: [email protected] , [email protected]

2 Graduate Course on Biological Sciences, Institute of Biological Sciences, University of Pernambuco, PE, Brazil

3 Parasitology Department, Aggeu Magalhães Research Center, Oswaldo Cruz Foundation, PE, Brazil. E-mails: rb.zurcoif.maqpc@said , rb.zurcoif.maqpc@eciremla , rb.zurcoif.maqpc@said , rb.zurcoif.maqpc@eciremla

Luiz Dias de Andrade

Paulo sérgio ramos de araújo.

4 Tropical Medicine Department, Clinical Hospital, Federal University of Pernambuco, PE, Brazil. E-mails: rb.zurcoif.maqpc@oigresp , rb.moc.lou@seahlagamev , rb.zurcoif.maqpc@oigresp , rb.moc.lou@seahlagamev

Vera Magalhães Silveira

Carlos eduardo padilha.

5 Service of Infectious and Parasitic Diseases, Clinical Hospital, Federal University of Pernambuco, Brazil. E-mail: moc.liamg@ahlidapgec , moc.liamg@ahlidapgec

Maria Almerice Lopes da Silva

Zulma maria de medeiros.

6 Pathology Department, Institute of Biological Sciences, University of Pernambuco, PE, Brazil. E-mail: rb.zurcoif.maqpc@soriedem , rb.zurcoif.maqpc@soriedem

Report of a 45-year-old male farmer, a resident in the forest zone of Pernambuco, who was diagnosed with human immunodeficiency virus (HIV) in 1999 and treated using antiretroviral (ARV) drugs. In 2005, the first episode of visceral leishmaniasis (VL), as assessed by parasitological diagnosis of bone marrow aspirate, was recorded. When admitted to the hospital, the patient presented fever, hepatosplenomegaly, weight loss, and diarrhea. Since then, six additional episodes of VL occurred, with a frequency rate of one per year (2005-2012, except in 2008). In 2011, the patient presented a disseminated skin lesion caused by the amastigotes of Leishmania , as identified by histopathological assessment of skin biopsy samples. In 2005, he was treated with N-methyl-glucamine-antimony and amphotericin B deoxycholate. However, since 2006 because of a reported toxicity, the drug of choice was liposomal amphotericin B. As recommended by the Ministry of Health, this report emphasizes the need for HIV patients living in VL endemic areas to include this parasitosis in their follow-up protocol, particularly after the first infection of VL.

Relato de caso de paciente masculino de 45 anos, agricultor, residente na zona da mata do Estado de Pernambuco, diagnosticado com HIV em 1999 e em uso de ARV. Em 2005 foi registrada a primeira ocorrência de LV através do diagnóstico parasitológico a partir do aspirado da medula óssea. À admissão no hospital apresentava-se com febre, hepatoesplenomegalia, perda de peso e diarréia. Desde então houve a ocorrência de mais sete episódios de LV, tendo ocorrido em media, um evento a cada ano (2005-2012 exceto em 2008). O paciente apresentou, em 2011, um quadro cutâneo disseminado, sendo realizada biopsia de pele que evidenciou formas amastigotas de Leishmania no exame histopatológico. Em 2005, o tratamento foi realizado com antimoniato de N-metil-glucamina e anfotericina B desoxicolato, mas desde 2006, devido à toxicidade, o medicamento de escolha foi a anfotericina B lipossomal. Como recomendado pelo Ministério da Saúde, esse relato reforça a necessidade de que os casos de HIV residentes em área endêmica de LV deverão ter inserido em seu protocolo de acompanhamento essa parasitose, principalmente após o primeiro episódio.

INTRODUCTION

Cases of visceral leishmaniasis (VL) co-infection with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome AIDS (VL/HIV-AIDS) have been registered in 35 countries, mainly in southwestern Europe. VL/HIV-AIDS co-infections increase in areas where these two diseases coexist, as observed in Asian, African, and Latin American countries. In the latter group, Brazil has the highest number of cases 1 .

In 2011, in Brazil, VL appeared in 22 of the 27 Brazilian states, covering urban and suburban areas. Between 1998 and 2009, the annual average was 3,349 cases 7 . From 1980 to 2011 in Brazil, 608,230 cases of AIDS were reported. This epidemic tends to spread to poorly inhabited macro-regions as well as to medium and small cities 8 . When AIDS and VL databases were correlated, 176 cases of VL/HIV-AIDS co-infection were detected among the Federal States 7 .

Several episodes of VL are frequent in cases of VL/HIV-AIDS co-infection. According to BOURGEOIS et al. , 2010, these patients present a novel nosological entity called ‘active chronic visceral leishmaniasis’. This condition may be termed ‘chronic’ because of the presence of relapses over a period of several years and ‘active’ because of the continuous blood circulation of the parasite. On the other hand, it's impossible to know if repeated episodes are relapses or reinfections by using conventional parasitological and immunological methods 15 . Some studies show that individuals with HIV/AIDS and infected with VL often present atypical clinical manifestations and high incidence of relapse 5 22 24 25 . Molecular methods confirm that more than 90% of these cases are relapses, rather than reinfections 27 . The discrimination between relapses and reinfection can be made by molecular techniques based on restriction fragment length polymorphism (RFLP) analysis. The use of this technology may provide the physician with more information to determine Leishmania infections in patients who do not respond to treatment 20 .

Professionals, who treat patients with HIV/AIDS, report that this co-infection was not prioritized because of the variety of diseases related to immunosuppression, in addition to not being included among the AIDS-defining conditions 11 . To alert healthcare professionals about this association, we describe the case of a patient presenting multiple VL/HIV-AIDS co-infections during the seven years of evolution of this disease.

CASE REPORT

In 1999, a 31-year-old male farmer, who was a resident in the forest zone of Pernambuco, was admitted to the Clinics Hospital of the Federal University of Pernambuco. At the time of admission, he presented with asthenia and headache, and had diarrhea for at least 30 days. He was diagnosed with HIV, and began receiving antiretroviral therapy (ART) with stavudine, lamivudine, and efavirenz. Meanwhile, his 25-year-old partner and 9-month-old daughter were diagnosed with HIV infection.

Five years after initiating ART, the patient presented virological failure; after genotyping, his treatment was changed to tenofovir, lamivudine, and lopinavir/ritonavir. In 2005, he was diagnosed with VL as assessed by directly testing Leishmania in the bone marrow aspirate and initially treated with N-methyl-glucamine-antimony. However, because of pancreatitis, the patient began receiving amphotericin B, which was then replaced by a liposomal formulation because of the onset of renal failure.

In 2011, the patient presented disseminated cutaneous lesions caused by Leishmania , as assessed by histopathological analysis of skin biopsy samples. In July 2012, the patient was readmitted for presenting febrile disease with splenomegaly and pancytopenia, in addition to showing positive results for laboratory tests for leishmaniasis ( Table 1 ). After administration of liposomal amphotericin B deoxycholate, the patient's condition improved, and he was discharged upon recommendation of a secondary prophylaxis by administering liposomal amphotericin B twice a week. Between 2005 and 2012, seven VL infections occurred, as shown in the Table 1 .

HIV, human immunodeficiency virus; N.A., not available; N.D., not done; B.M. aspirate, bone marrow aspirate; d4T, stavudine; 3TC, lamivudine; EFV, efavirenz; TDF, tenofovir; LPVr, lopinavir/ritonavir; DAT, direct agglutination test; PCR, polymerase chain reaction.

This case describes some of the many clinical, diagnostic, and epidemiologic aspects of VL/HIV-AIDS co-infection. Immunosuppression caused by HIV might lead to the development of symptomatic VL 14 . In turn, VL might promote the clinical progression of HIV and of AIDS-defining conditions, thus, reducing the possibility of recovery after treatment and increasing the incidence of relapse 11 . This report showed that individuals with HIV/AIDS and living in endemic areas of VL should include VL assessment in their follow-up protocol. After the first co-infection, by means of clinical and laboratory support, a follow-up protocol of the patient should be created for early detection of relapse and re-infection.

One of the common features of co-infection is the increased tendency of relapse, observed in 37-80% of the patients 22 . Additionally, in some cases a chronic course with multiple occurrences might take place. This can be attributed not only to immunodeficiency but also to re-infection, host deficiencies correlating with ART, secondary prophylaxis, and CD4+ lymphocyte count 16 18 . CD4+ lymphocyte count is one of the most significant prognostic factors for survival 11 22 . VL usually appears as an opportunistic disease in HIV patients when CD4+ cell count is less than 200 cells/mm 3(1,6,12,13,17,25) . During the seven years of follow-up, the patient presented a CD4+ cell count ≤ 170 cells/mm 3 . This represents an important predictor of relapse. Relapses of VL are suggested to occur mainly in individuals with poor responses to antiretroviral treatment who have no improvement in CD4+ counts with a few exceptions 3 9 .

Based on clinical and biological [polymerase chain reaction (PCR)-based] follow-up, an ‘active chronic visceral leishmaniasis’ 5 has been proposed by BOURGEOIS et al. (2010). In our case, only the 6 th and 7 th episodes were able to have the peripheral blood (PB) analyzed by PCR, which showed positive results for Leishmania spp. As PCR-RFLP was only found in the 7 th sample episode, the etiological agent is Leishmania chagasi , according to the pattern of bands defined by SCHONIAN et al. (2003) 26 . Due to the absence of PB samples in previous episodes, the analysis by PCR-RFLP was not made. Therefore, it wasn't possible to distinguish between relapse and reinfection or characterize the case as ‘chronic visceral leishmaniasis’. Despite the medical importance of a clinical and laboratory monitoring of coinfected patients, this practice is still little used 12 19 20 .

ART plays an important role in reducing the effect of opportunistic diseases and in recent studies has shown a reduction in the incidence of VL. Studies in individuals with HIV/AIDS treated using ARV drugs showed a similar incidence of VL relapse when compared to studies of the pre-highly active antiretroviral therapy (HAART) era 11 14 . The increased survival resulting from ART might partially explain the high incidence of relapse observed in this population 18 . In the present study, during the eight years of follow-up, we observed seven VL infections, despite the patient receiving ART before the first infection.

VL manifestations associated with HIV infection might appear in a classical form, particularly in patients from VL-endemic areas, as well as with relatively aggressive symptoms that are sometimes non-specific and difficult to clinically diagnose 11 . In individuals with HIV/AIDS and presenting symptoms such as asthenia, anorexia, and weight loss, VL might be responsible for 7-23% of instances of fever of unknown origin 11 . This patient presented classic clinical manifestations during the study period, although in 2011, we observed the formation of skin lesions because of the parasite, as assessed by histopathological analysis.

Among the previously treated VL cases, several patients present a skin condition characterized by macular, popular, or nodular lesions, called Post-kala-azar dermal Leishmaniasis (PKDL) caused by the amastigotes of Leishmania donovani on the Indian subcontinent (India, Nepal, Bangladesh) and east Africa (Sudan, Ethiopia, Kenya) and caused by Leishmania chagasi in South America where it is rarely reported, as well as its presence in HIV positives 2 4 23 28 . It is worth noticing that exclusive involvement of the skin is an unusual condition, because the simultaneous appearance of skin lesions along with other VL manifestations was more frequently observed 21 . In this case, the skin lesion suggests a clinical PKDL, which developed five years after the first VL episodes, administration of multiple therapeutic regimens, and treatments of discontinuous secondary prophylaxis. Although it has been viewed amastigotes in biopsy specimens obtained from skin lesions, the hypothesis of PKDL can be suggested but not stated categorically because there was no characterization of Leishmania species involved in the cutaneous lesions, and may have been an infection of some sort cutaneous Leshmania endemic to the region as L. braziliensis .

Several studies on co-infected individuals show that they present a decrease in anti- Leishmania antibody levels in the peripheral blood 11 ; that is, in only 40-50% of VL/HIV-AIDS cases, specific antibodies are detected 1 . Conversely, assessment of Leishmania antigen in urine by latex agglutination test showed a sensitivity of 85-100% 1 . Polymerase chain reaction (PCR) in peripheral blood and bone marrow is a useful tool to diagnose, for follow-up, and detect relapses 22 . Although the literature shows that serological analyses are not the most convenient in patients presenting co-infection 1 6 , two serological tests (direct agglutination test and rK39-based rapid immunochromatographic test) performed enabled the diagnosis of such cases in 2011 and 2012. In the same years, latex agglutination test and PCR test showed positive results, thus, confirming the data in the literature. Similar to the finding in our study, CAVALCANTI et al. (2012), described a series of case studies of co-infection in the main hospitals of Recife, Brazil 10 .

There is currently sufficient evidence suggesting that secondary prophylaxis provides some protective effect but does not completely prevent the occurrence of relapse 11 . A meta-analysis study described that the average incidence of relapse in patients who did not receive secondary prophylaxis was 67%, whereas in those who received it was 31% 16 . Current recommendations from the Ministry of Health of Brazil 2 for the diagnosis, treatment, and follow-up of patients presenting co-infection state that the “efficacy of the secondary prophylaxis after the first successfully treated VL infection, was not completely established.” The suggested secondary prophylaxis ( Table 1 ) was poorly adopted, thus, compromising the clinical follow-up. Based on this case study and literature review, it is evident that co-infection presents typical clinical, diagnostic, and therapeutic features, and can be observed in the prognosis of the disease. Therefore, prospective studies are required to clarify gaps such as the efficacy of secondary prophylaxis and need for clinical and laboratory monitoring tools for the early assessment of relapse or re-infection.

Acknowledgments

This study was supported by the FACEPE/MS/CNPq Programme for Research and priority development to unified health system - SUS/ PCT Saúde II (project 03/2004) and CNPq/PIBIC/Fiocruz (process 139172/2012-2).

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From: The effect of late presentation on HIV related mortality among adolescents in public hospitals of north showa zone Oromiya, Ethiopia; 2022: a retrospective cohort study

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BMC Infectious Diseases

ISSN: 1471-2334

• General enquiries: [email protected]

• Open access
• Published: 27 June 2024

Chemotherapy-related cardiotoxicity and its symptoms in patients with breast cancer: a scoping review

• Hyunjoo Kim 1 , 2 ,
• Bomi Hong 3 ,
• Sanghee Kim 4 ,
• Seok-Min Kang 5 &
• Jeongok Park   ORCID: orcid.org/0000-0003-4978-817X 4  

Systematic Reviews volume  13 , Article number:  167 ( 2024 ) Cite this article

Metrics details

Chemotherapy-related cardiotoxicity is a significant concern because it is a major cause of morbidity. This study aimed to provide in-depth information on the symptoms of chemotherapy-related cardiotoxicity (CRCT) by exploring literature that concurrently reports the types and symptoms of CRCT in patients with breast cancer.

A scoping review was performed according to an a priori protocol using the Joanna Briggs Institute’s guidelines. The participants were patients with breast cancer. The concept was the literature of specifically reported symptoms directly matched with CRCT and the literature, in English, from 2010, and the context was open. The search strategy included four keywords: “breast cancer,” “chemotherapy,” “cardiotoxicity,” and “symptoms.” All types of research designs were included; however, studies involving patients with other cancer types, animal subjects, and symptoms not directly related to CRCT were excluded. Data were extracted and presented including tables and figures.

A total of 29 articles were included in the study, consisting of 23 case reports, 4 retrospective studies, and 2 prospective studies. There were no restrictions on the participants’ sex; however, all of them were women, except for one case report. The most used chemotherapy regimens were trastuzumab, capecitabine, and doxorubicin or epirubicin. The primary CRCT identified were myocardial dysfunction and heart failure, followed by coronary artery disease, pulmonary hypertension, and other conditions. Major tests used to diagnose CRCT include echocardiography, electrocardiography, serum cardiac enzymes, coronary angiography, computed tomography, and magnetic resonance imaging. In all case reports, CRCT was diagnosed through an incidental checkup according to the patient’s symptom presentation; however, only 10 of these studies showed a baseline checkup before chemotherapy. The five most common CRCT symptoms were dyspnea, chest pain, peripheral edema, fatigue, and palpitations, which were assessed by patient-reported symptom presentation rather than using a symptom assessment tool. Dyspnea with trastuzumab treatment and chest pain with capecitabine treatment were particularly characteristic. The time for first symptom onset after chemotherapy ranged from 1 hour to 300 days, with anthracycline-based regimens requiring 3–55 days, trastuzumab requiring 60–300 days, and capecitabine requiring 1–7 days.

Conclusions

This scoping review allowed data mapping according to the study design and chemotherapy regimens. Cardiac assessments for CRCT diagnosis were performed according to the patient’s symptoms. There were approximately five types of typical CRCT symptoms, and the timing of symptom occurrence varied. Therefore, developing and applying a CRCT-specific and user-friendly symptom assessment tool are expected to help healthcare providers and patients manage CRCT symptoms effectively.

Peer Review reports

Breast cancer is currently the most common cancer worldwide. Its incidence and mortality rates in East Asia in 2020 accounted for 24% and 20% of the global rates, respectively, and these rates are expected to continue increasing until 2040 [ 1 ]. In the USA, since the mid-2000s, the incidence rate of breast cancer has been increasing by 0.5% annually, while the mortality rate has been decreasing by 1% per year from 2011 to 2020 [ 2 ]. Despite the improved long-term survival rate in patients with breast cancer due to the development of chemotherapy, the literature has highlighted that cardiotoxicity, a cardiac problem caused by chemotherapy, could be a significant cause of death among these patients [ 3 ]. Chemotherapy-related cardiotoxicity (CRCT) can interfere with cancer treatment and progress to congestive heart failure during or after chemotherapy [ 4 ], potentially lowering the survival rate and quality of life of patients with cancer [ 5 ].

The term cardiotoxicity was first used in the 1970s to describe cardiac complications resulting from chemotherapy regimens, such as anthracyclines and 5-fluorouracil. The early definition of cardiotoxicity centered around heart failure, but the current definition is broad and still imprecise [ 6 ]. The 2022 guidelines on cardio-oncology from the European Society of Cardiology (ESC) define cardiotoxicity as including cardiac dysfunction, myocarditis, vascular toxicity, arterial hypertension, and cardiac arrhythmias. Some of these definitions reflect the symptoms. For example, cardiac dysfunction, which accounts for 48% of cardiotoxicity in patients with cancer, is divided into asymptomatic and symptomatic cardiac dysfunction. Asymptomatic cardiac dysfunction is defined based on left ventricular ejection fraction (LVEF), myocardial global longitudinal strain, and cardiac biomarkers. Symptomatic cardiac dysfunction indicates heart failure and presents with ankle swelling, breathlessness, and fatigue [ 7 ]. The ESC guidelines for heart failure present more than 20 types of symptoms [ 8 ]; however, to the best of our knowledge, few studies have been conducted to determine which heart failure symptoms and their characteristics are associated with CRCT in patients with breast cancer. Similarly, there is a lack of information related to vascular toxicity such as myocardial infarction [ 7 ].

Professional societies in cardiology and oncology have proposed guidelines for the prevention and management of cardiotoxicity in patients with cancer. According to the American Society of Clinical Oncology and the ESC, it is recommended to identify high-risk patients, comprehensively evaluate clinical signs and symptoms associated with CRCT, and conduct cardiac evaluations before, during, and after chemotherapy [ 7 , 9 , 10 ]. In addition, guidelines for patients with cancer, including those for breast cancer survivorship care, emphasize that patients should be aware of the potential risk of CRCT and report symptoms, such as fatigue or shortness of breath to their healthcare providers [ 7 , 11 , 12 ]. Although these guidelines encompass cardiac monitoring as well as symptom observation, many studies have focused solely on objective diagnostic tests, such as echocardiography, cardiac magnetic resonance, and cardiac biomarkers [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ], which means that there is little interest in CRCT symptoms in patients under breast cancer care.

This lack of interest in CRCT symptoms may be related to the absence of a specific symptom assessment tool for CRCT. Symptom monitoring of CRCT in patients with breast cancer was conducted through patient interviews and reported using the appropriate terminology [ 23 ]. In terms of interviews, patients with cancer experienced the burden of expressing symptoms between cardiovascular problems and cancer treatment. Qualitative research on patients with cancer indicates that these patients experience a daily battle to distinguish the symptoms they experience during chemotherapy [ 24 ]. To reduce the burden of identifying CRCT symptoms, it is crucial to educate patients with breast cancer undergoing chemotherapy about these symptoms. To report cardiotoxicity, healthcare providers in oncology can use a dictionary of terms called the Common Terminology Criteria for Adverse Events (CTCAE) for reporting adverse events in patients with cancer [ 25 ]. Patients can also use Patient-Reported Outcome (PRO), which allows unfiltered reporting of symptoms directly to the clinical database [ 26 ]. PRO consists of 78 symptomatic adverse events out of approximately 1,000 types of CTCAE [ 27 ]. Basch et al. suggested that PRO could enable healthcare providers to identify patient symptoms before they worsen, thereby improving the overall survival rate of patients with metastatic cancer [ 28 ]. This finding implies that symptoms can provide valuable clues for enhancing the timeliness and accuracy of clinical assessments of CRCT [ 29 ]. Therefore, it is necessary to explore the scope of research focusing on CRCT symptoms for prevention and early detection of CRCT in patients with breast cancer. The detailed research questions are as follows:

What are the general characteristics of the studies related to CRCT in patients with breast cancer?

What diagnostic tools and monitoring practices are used to detect CRCT?

What are the characteristics and progression of symptoms associated with CRCT?

A scoping review is a research method for synthesizing evidence that involves mapping the scope of evidence on a particular topic [ 30 ]. It aims to clarify key concepts and definitions, identify key characteristics of factors related to a concept, and highlight gaps or areas for further research [ 30 ]. This study used a scoping review methodology based on the Joanna Briggs Institute (JBI) framework. The JBI methodology, refined from the framework initially developed by Arksey and O’Malley [ 31 ], involves developing a research question, establishing detailed inclusion and exclusion criteria, and selecting and analyzing literature accordingly [ 32 ]. In contrast to systematic reviews, scoping reviews can encompass a variety of study designs and are particularly suitable when the topic has not been extensively studied [ 33 ]; hence, the decision was made to conduct a scoping review.

Development of a scoping review protocol

To conduct this review, an a priori scoping review protocol was developed to enhance transparency and increase the usefulness and reliability of the results. The protocol included the title, objective, review questions, introduction, eligibility criteria, participants, concept, context, types of evidence source, methods, search strategy, source of evidence selection, data extraction, data analysis and presentation, and deviation from the protocol [ 34 ] (Supplementary File 1).

Eligibility criteria

A participant-concept-context (PCC) framework was constructed based on the following research criteria. The participants were patients with breast cancer. The concept was that studies that specifically reported symptoms directly matched to CRCT in patients with breast cancer and the literature, published in English since 2010, in line with the year the CRCT guidelines were announced by the Cardio-Oncology Society. The context was open. We included all types of research designs. The exclusion criteria were studies that included patients with other types of cancer, involved animal subjects, and reported symptoms not directly related to CRCT.

Search strategy

The keywords consisted of “breast cancer,” “chemotherapy,” “cardiotoxicity,” and “symptoms.” The keywords for “cardiotoxicity” were constructed according to the clinical cardiotoxicity report and ESC guidelines [ 7 , 35 ]. The keywords for “symptoms” included 40 specific symptoms of arrhythmia, heart failure, and cardiac problems [ 36 , 37 ] (Supplementary Table 1). We used PubMed, Embase, and CINAHL.

Source of evidence selection

Duplicate studies were removed using EndNote 21. The titles and abstracts were then reviewed according to the inclusion criteria, the primary literature was selected, and the final literature was selected through a full-text review. Any disagreements were resolved through discussions between the investigators.

Data extraction

The data from the literature included the general characteristics of the study, as well as information on the patients, chemotherapy, cardiotoxicity, and symptoms. The general characteristics of the study included author, publication year, country of origin, study design; patient information including sample size, sex, age, cancer type, and cancer stage; chemotherapy information including chemotherapy regimen; cardiotoxicity information including type of cardiotoxicity, diagnostic tests, and times of assessment; and symptom information including type of symptom, characteristics of symptom worsening or improvement, onset time, progression time, and time to symptom improvement. Information on whether to receive chemotherapy after the diagnosis of cardiotoxicity was explored.

Data analysis and presentation

The contents of the included studies were divided into three categories: (1) general characteristics, which encompassed study designs, patients, and medications; (2) type of CRCT and cardiac assessment for CRCT; and (3) characteristics and progression of the symptoms associated with CRCT. CRCT symptom-related data are presented in tables and figures.

In total, 487 studies were identified through database searches, and 116 duplicates were subsequently removed. After reviewing the titles and abstracts, we excluded 197 studies in which participants had cancers other than breast cancer, no symptoms, or symptom-related expressions. Of the remaining 174 studies, 146 were excluded after full-text review. Among the excluded studies, 79 were mainly clinical trials that the symptoms were not directly related to CRCT, 62 did not report specific symptoms, four were in the wrong population, and one was unavailable for full-text review. An additional study was included after a review of references, bringing the final count to 29 studies included in the analysis (Fig. 1 ).

Preferred reporting items for systematic reviews flowchart

General characteristics of studies including designs, sex and age, chemotherapy regimen, and CRCT criteria

Table 1 presents the general characteristics of the studies included in this review. The majority of these studies were published in the USA ( n =14), with Japan ( n =3), and Romania ( n =2) following. The study designs primarily consisted of case reports ( n =23), retrospective studies ( n =4), and prospective studies ( n =2).

All case reports involved female patients, except for one involving a male patient. Five quantitative studies did not specify or limit the sex of the participants, and one retrospective study included only female patients. In terms of cancer stage, the majority of studies involved patients with advanced breast cancer ( n =13), while a smaller number involved patients with early-stage breast cancer ( n =4). Twelve studies did not specify the cancer stage. Approximately 20 types of chemotherapy regimens are currently in use. Trastuzumab, which is a human epidermal growth factor receptor 2 (HER2) blocker, was mentioned in the majority of studies ( n =8), followed by capecitabine (an antimetabolite) ( n =7), and doxorubicin or epirubicin (anthracycline-based chemotherapy) ( n =6). Current chemotherapy and previous treatment methods were described together, with the exception of eight studies. Six quantitative studies defined the CRCT criteria, five of which were based on decreased LVEF and one of which was based on significant cardiac symptoms and/or electrocardiogram changes. Twenty-three case reports described the cardiovascular diagnosis as CRCT.

Diagnostic tools and monitoring practice for CRCT

Table 2 displays the types of CRCT, diagnostic tools, and times of cardiac assessment according to chemotherapy regimens. The most prevalent CRCT were myocardial dysfunction and heart failure, identified in 12 case studies, respectively. This was followed by coronary artery disease, represented in 8 case studies, pulmonary hypertension in 2 case studies, and a single case study of periaortitis. The most used test for diagnosing CRCT was echocardiography ( n =22), followed by EKG ( n =20), various types of cardiac enzymes ( n =16), coronary angiography (CAG, n =12), computed tomography ( n =6), and magnetic resonance imaging (MRI, n =4). Regarding the CRCT symptom assessment tools, the CTCAE was used in two studies, the New York Heart Association classification for heart failure in two studies, the dyspnea assessment scale in one study, and symptoms of cardiac origin, which consisted of chest pain, dyspnea, and palpitations in one study.

Regarding the times of cardiac evaluation, two studies performed regular cardiac checkups including before, during, and after chemotherapy. There were 10 case studies and six quantitative studies describing cardiac function testing before chemotherapy, of which seven studies performed regular cardiac screening tests and two studies mentioned cardiac screening even after the completion of chemotherapy. The frequency of regular checkups varied from every 3 months to every two to four cycles. In all case reports ( n =23), CRCT were diagnosed through incidental checkups based on patients’ symptom presentation, and in most cases, several tests were performed subsequentially for CRCT diagnosis. In one case study, cardiac evaluation was conducted 3 days after the patient’s initial symptom presentation, when the symptoms became more severe.

Characteristics and progression of symptoms associated with CRCT

Table 3 shows the descriptive scope of the CRCT-related symptoms according to the chemotherapy regimens used in the included studies. The mapping factors included initial symptoms, symptom onset or severity, symptom progression, medical management, and CRCT results. One of the most frequent symptoms associated with CRCT was dyspnea, which was discussed in 19 studies and described as difficulty in breathing, shortness of breath, or New York Heart Association (NYHA) class II or III. When dyspnea appeared as the initial symptom of CRCT, the symptom progression was worsening in eight case studies and persistent in two cases. Chest pain was described in 12 studies as a symptom characterized by a squeezing, tingling, burning, tightened, or atypical feeling that was relieved by rest and exacerbated by exertion. Other symptoms included peripheral edema ( n =6), fatigue ( n =5), and palpitation ( n =2). The symptoms were assessed by patient-reported symptom presentation rather than using a symptom assessment tool.

The symptoms could be categorized based on the type of chemotherapy regimens used. In the case studies involving anthracycline-based regimen and HER2 blockers, dyspnea was the most frequently observed symptom ( n =7), followed by peripheral edema ( n =2), and chest pain or discomfort ( n =2). In case studies where antimetabolites were used, specifically capecitabine, chest pain was a common and prominent symptom. This chest pain typically manifested between 1 and 7 days after drug administration and persisted until treatment. Notably, four out of seven patients reported this symptom on the first day of chemotherapy, according to the case reports. The time for first symptom onset after chemotherapy ranged from 1 hour to 300 days, with anthracycline-based regimens requiring 3–55 days, trastuzumab requiring 60–300 days, and capecitabine requiring 1–7 days. Figure 2 shows the progression of symptoms in case studies, detailing the time of symptom onset, the date of symptom reporting, and the date of treatment completion following the use of chemotherapy. The studies that did not specify any of the dates of symptom onset, reporting, and completion of treatment were excluded from the figure.

Figure 3 shows symptoms according to the main types of chemotherapy regimens reported in case studies. Dyspnea with trastuzumab and chest pain with capecitabine are particularly characteristic. A retrospective study included in this scoping review reported that chest pain was the most common symptom associated with capecitabine, followed by dyspnea and palpitation [ 40 ]. Furthermore, peripheral edema was primarily observed with anthracycline, alkylating, and HER2 blockers, while fatigue was noted with various anticancer drugs, irrespective of the type of chemotherapy regimen.

Ongoing chemotherapy was discontinued after CRCT was detected in 20 case studies. When patients presented symptoms indicative of CRCT, the majority were promptly hospitalized for further evaluation, medication, or interventional treatment. The majority of studies indicated the initiation of cardiac medication ( n =21), with three case studies involving coronary intervention and two involving treatment with wearable devices. Most management procedures were conducted in a general ward or an intensive care unit.

In most case studies, symptoms improved following cardiac treatment, with either complete or partial recovery of LVEF observed in 19 instances. However, a few studies reported a poor prognosis, including two instances of death. LVEF recovered in most patients within 6 months when treated with an anthracycline-based regimen and HER2 blockers (Fig. 2 ). A retrospective study reported that the rates of complete or partial recovery of CRCT following treatment with doxorubicin-based chemotherapy and trastuzumab were 42.9% and 86.1%, respectively [ 39 ]. Another retrospective study noted that the recovery time of CRCT when treated with HER2 blockers increased in correlation with the severity of the NYHA class, ranging from 8 to 80 weeks [ 38 ]. In the case of the antimetabolite capecitabine, all patients recovered within a day to a week, except one patient who did not recover.

This scoping review was conducted to explore the scope of studies focusing on CRCT symptoms, including the general characteristics of the studies, diagnostic tools, monitoring practices related to detecting CRCT, and the characteristics and progression of symptoms associated with CRCT. The primary findings of this review were as follows: (1) common symptoms related to CRCT and differences in symptoms according to the chemotherapy regimens used were identified; (2) the symptoms reported by the patient served as clues to suspect a specific type of CRCT; and (3) regular monitoring practices for CRCT prevention and detection were insufficient.

First, the current study identified common symptoms such as dyspnea, chest pain, peripheral edema, fatigue, and palpitation associated with CRCT, as well as variations in symptoms depending on the chemotherapy regimen used in patients with breast cancer. Among these symptoms, dyspnea, edema, and chest pain were frequently observed in patients receiving anthracycline-based and/or HER2 blocker drugs. These symptoms, which are associated with heart failure, appeared later compared to those observed with capecitabine, as depicted in Fig. 2 . This may be due to the known impact of anthracycline-based and/or HER2 blocker regimens on cardiomyocytes and other cells, leading to myocardial damage [ 42 ]. Therefore, the symptoms are related to heart failure, potentially resulting from the impairment of ventricular filling or ejection in patients undergoing treatment with these regimens [ 43 ].

In a similar vein, Attin et al. (2022) documented the occurrence of symptoms such as lower extremity edema, chest pain, difficulty breathing, and fatigue before the diagnosis of CRCT in women undergoing breast cancer treatment. They conducted a retrospective and longitudinal investigation of the symptoms, signs, and cardiac tests of 15 patients who experienced CRCT, using their electronic medical records. In their study, cardiotoxicity was defined by an echocardiogram or MRI showing a decrease in LVEF of 5 to 10%, with a specialist’s confirmation note. They compared the number of symptom occurrences during the first half of the year with those during the second half of the year prior to the diagnosis of cardiotoxicity. Specifically, the frequency of lower-extremity edema significantly increased from three occurrences in the first half of the year to 17 occurrences in the second half of the year. The frequency of symptoms for dyspnea and chest pain also increased from 10 and 8 times, respectively, to 16 and 14 times in the second half of the year. While there was limited information on the doses or timing of chemotherapy, 87% of the patients received the same chemotherapy regimens, namely anthracyclines and/or HER2 blockers [ 44 ]. This suggests that the increase in symptom occurrence over time may be related to the accumulation of anthracycline and the duration of anti-HER2 therapy [ 45 ].

Salyer et al. (2019) conducted a study on the prevalent symptoms of heart failure and their clustering. They identified three symptom clusters: sickness behavior, gastrointestinal disturbance, and discomfort of illness. Notably, dyspnea, edema, and pain were grouped into the discomfort of illness cluster, which aligns with the symptoms we observed in patients treated with anthracyclines and/or HER2 blockers [ 46 ]. Therefore, it is crucial for patients undergoing treatment with anthracyclines and/or HER2 blockers to be vigilant for symptoms such as dyspnea, edema, or chest pain, as these are indicative of heart failure.

Chest pain caused by vasospasm was a predominant symptom in patients taking antimetabolite regimens such as oral capecitabine, and it manifested as the following types of cardiotoxicities: vasospasm-related arrhythmia, myocardial disease, and ischemia [ 47 ]. Vasospasm can be triggered by endothelial dysfunction, hypersensitive vascular smooth muscle, reactive oxidative stress, or chemotherapy regimens [ 48 , 49 ]. According to previous studies, in patients using antimetabolite drugs such as 5-fluorouracil or capecitabine, chest pain was usually reported to occur from several hours to 72 hours after the first administration [ 47 , 50 , 51 , 52 , 53 ]. To detect chemotherapy-related coronary vasospasm in the early stage, it is recommended to carefully monitor typical or atypical symptoms of chest pain and EKG monitoring during drug infusion [ 54 ]. Muco et al. (2022) reported severe outcomes resulting from delayed management of vasospastic angina symptoms. The patient’s cardiac evaluation was performed 3 days after the onset of symptoms, and unfortunately, she did not recover from brain damage caused by coronary vasospastic sequelae. The authors stressed the importance of medical teams recognizing the symptoms of CRCT through vigilant monitoring and patient education [ 55 ].

As seen in the symptoms of CRCT caused by heart failure and vasospasm, careful observation of symptoms and conducting appropriate tests are crucial to prevent cardiotoxicity and minimize damage. These characteristics of CRCT and the associated symptoms related to chemotherapy regimens can provide crucial educational content for healthcare providers and patients preparing for chemotherapy. In addition, CRCT and symptom progression according to chemotherapy regimens could be used to formulate research questions for future systematic reviews.

Second, the preventive management of CRCT necessitates adherence to recommended guidelines. The 2022 ESC guidelines on cardio-oncology have updated the classification of CRCT and the monitoring protocols based on the chemotherapy regimens used [ 7 ]. The CRCT identified in the current study aligns with the drug toxicity outlined in the 2022 ESC guidelines. These guidelines advocate for regular cardiac monitoring before, during, and after chemotherapy to prevent and manage CRCT induced by anthracycline and HER2 blockers [ 7 , 12 ]. In this scoping review, two of 23 records described cardiac monitoring before, during, and after chemotherapy. An Australian multicenter study revealed that 59% of patients were referred to a cardiologist before CRCT occurred, but only 15% of patients diagnosed with CRCT had consulted a cardiologist before chemotherapy [ 41 ]. Given the declining mortality rates among cancer patients, managing CRCT requires a collaborative approach between oncology and cardiology to minimize mortality and morbidity in patients with breast cancer undergoing chemotherapy [ 7 ]. Therefore, it remains crucial to emphasize adherence to cardiac monitoring guidelines and foster cooperation between oncology and cardiology.

Additionally, symptom assessment is important for the early detection of patients with CRCT. The studies included in the current scoping review assessed whether patients’ symptoms could detect CRCT using interviews with patients, the New York Heart Association classification, a dyspnea assessment scale, and CTCAE tools. The United States National Cancer Institute recommends that healthcare providers use CTCAE and patients with cancer use PRO to report adverse events, including symptoms. CTCAE is a broad and comprehensive terminology that encompasses adverse events related to cancer treatment, has been used since the 1980s [ 25 ], and is not specialized in cardiotoxicity. Additionally, a discrepancy between CTCAE and PRO discovered that healthcare providers often underestimate both the incidence and duration of symptoms compared to the patients [ 56 , 57 , 58 ]. Specifically, healthcare providers tend to report symptom severity as lower than that reported by patients. For instance, there are notable discrepancies between healthcare providers and patients when reporting severe or very severe symptoms of fatigue, dyspnea, and limb edema in patients with early-stage breast cancer undergoing chemotherapy. The reported rates were 8% and 22% for fatigue, 0% and 4% for dyspnea, and 0% and 5% for limb edema, from healthcare providers and patients, respectively. Therefore, it is necessary to develop a user-friendly questionnaire to assess the various symptoms of CRCT.

Finally, we found that once CRCT was confirmed, cardiac treatment was promptly initiated and chemotherapy was frequently halted until CRCT resolution. A Delphi study on the use of anthracycline and trastuzumab proposed altering the treatment schedule or discontinuing treatment until there was an improvement in LVEF [ 59 ]. However, the professional societies did not provide definitive recommendations regarding continuing or ceasing ongoing chemotherapy. Instead, they suggested that the decision to continue or discontinue ongoing chemotherapy should be made based on the patient’s potential risks and benefits [ 60 ]. For example, Polk et al. (2016) reported that out of 22 patients with CRCT resulting from capecitabine, six continued medications with or without cardiac treatment; some of these patients experienced the same symptoms, while others did not exhibit significant symptoms [ 40 ]. Further research is required to explore the continuation or discontinuation of chemotherapy when CRCT is confirmed.

This study has some limitations. First, although we did not restrict the patients’ sex when reviewing the literature, most patients, except for one, were female. This may be related to the lower incidence of breast cancer in men. Second, although this scoping review mapped CRCT symptoms according to chemotherapy regimens, including anthracycline-based drugs, HER2 blockers, and antimetabolites, it did not cover cardiotoxicity related to other types of chemotherapy regimens. Thus, exploring the symptoms by focusing on expanded chemotherapy regimens and cardiovascular toxic diseases will assist in overcoming this limitation. Third, of the 29 studies, 23 were case reports with some grey literature, which may be justified by the nature of scoping reviews that allow for inclusion irrespective of the data source [ 61 ] and the study type. Experimental or observational clinical studies use objective criteria, such as diagnostic tests to generate primary evidence. However, case reports have led to new medical discoveries regarding the prevention and treatment of diseases [ 62 ]. Given the nature of case reports, specific symptoms that could provide clues for evaluating CRCT in patients with breast cancer are most often found in these reports. We incorporated grey literature to gather more comprehensive information on CRCT-related symptoms. However, to mitigate the potential issue of unverified quality in grey literature, we initially organized 16 studies from peer-reviewed literature and subsequently incorporated the grey literature into our findings. This approach helped to clarify the results of the peer-reviewed literature, particularly the types of chemotherapy regimens [ 63 ]. Finally, regarding the literature selection criteria, we examined articles written in English and published since 2010, the year the cardio-oncology guidelines were announced, thereby excluding articles published before 2010.

This scoping review allowed data mapping according to the study design and chemotherapy regimens. The key messages included a type of CRCT, cardiac assessment, and in-depth information regarding the CRCT symptoms. There were approximately five typical CRCT symptoms, including dyspnea, chest pain, peripheral edema, fatigue, and palpitations, and the timing of symptom occurrence varied. The symptoms were assessed by patient-reported symptom presentation rather than using a symptom assessment tool. Therefore, developing and applying a CRCT-specific and user-friendly symptom assessment tool are expected to help healthcare providers and patients manage CRCT symptoms effectively.

Availability of data and materials

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank Nawon Kim, a librarian at the Yonsei University Medical Library, for building search terms and guiding the database searches.

This research is supported by the Brain Korea 21 FOUR Project founded by the National Research Foundation (NRF) of Korea, Yonsei University College of Nursing.

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HK, BH, SK, and JP contributed to the study conception and design. The literature search and record screening were performed by HK and BH under the supervision of JP. Material preparation, data collection, and analysis were performed by HK, BH, and JP. The first draft of the manuscript was written by HK and JP commented on each updated version of the manuscript. The tables and figures were prepared by BH under the instruction of JP. SK helped to interpret the data and provided critical feedback on the manuscript. All authors read and approved the final manuscript.

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Kim, H., Hong, B., Kim, S. et al. Chemotherapy-related cardiotoxicity and its symptoms in patients with breast cancer: a scoping review. Syst Rev 13 , 167 (2024). https://doi.org/10.1186/s13643-024-02588-z

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Comparing times of self-harm presentations to hospital emergency departments in children, adolescents, young adults and adults: a national registry study 2007–2019

• David McEvoy 1 ,
• Mary Joyce 2 ,
• David Mongan 3 ,
• Mary Clarke 1 , 4 &
• Mary Codd 5  

BMC Psychiatry volume  24 , Article number:  474 ( 2024 ) Cite this article

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The few studies that have explored self-harm presentation times at hospital emergency departments (EDs) – an important factor that can determine if a patient receives a mental health assessment – primarily focus on adult samples. This study examined the times of self-harm presentations to EDs, self-harm methods used, mental health assessments, and admission data across different age-groups.

Using data from the National Self-Harm Registry Ireland over a 13-year timeframe (2007–2019), this study compared times, days, seasons, methods of self-harm, and admission data for children (8–12 years), adolescents (13–17 years), young adults (18–25 years) and adults (> 25 years).

The majority of the 152,474 self-harm presentations (78.6%) for all ages occurred out-of-hours (outside the standard working hours or in-hours times of 09:00–17:00, Monday-Friday). The four hours before midnight had the highest proportions of self-harm presentations for adolescents (27.9%) and adults (23.1%), whereas the four hours after midnight had the highest proportion of self-harm presentations for young adults (22.9%). The 16:00-midnight timeframe had highest proportion of self-harm presentations in children (52.3%). Higher proportions of patients received a mental health assessment in-hours compared to out-of-hours among young adults (78.2% vs. 73.3%) and adults (76.1% vs. 72.0%). Self-harm presentations were lowest during summer months in children and adolescents.

Hospitals should ensure that adequate resources are available for individuals presenting with self-harm, especially in the case of overcrowded EDs, and protocols need to be designed for those presenting with self-harm due to intoxication. In line with national policy, protocols for patients presenting during out-of-hours should be designed that can incorporate services from allied health multidisciplinary teams, social work, addiction services and counselling organisations. Given the lower rates of self-harm during school holidays for children and adolescents, the school environment must be considered in the context of mental health and self-harm public health prevention interventions.

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Introduction

Suicide and self-harm are major public health problems globally, especially for young people aged 15–29 years old, for whom suicide is the fourth leading cause of death [ 1 ]. Ireland has a suicide rate of 11.0 per 100,000 population in comparison to the European Union’s standardised rate of 10.1 per 100,000 and the United Kingdom’s rate of 7.4 (based on 2017 data) [ 2 ]. In 2019, suicide was the leading cause of death in males under 25 years old and the third most common cause in females of the same age in Ireland [ 2 ].

Patients who present to hospital emergency departments (EDs) with self-harm are much more likely to die by suicide compared to the general population [ 3 , 4 , 5 ]. Estimates amongst studies examining the risk of dying by suicide for those presenting to EDs with self-harm have been found to be up to 50 times more likely than those not presenting to EDs with self-harm [ 3 , 4 , 5 ]. While male suicides accounted for the majority (77%) of suicides in Ireland in 2019 [ 2 ], the majority (55%) of self-harm presentations to EDs were by females [ 6 ].

All patients that present to EDs should receive a mental health assessment from a trained mental health professional [ 7 , 8 , 9 ]. A mental health (or psychosocial) assessment is an evaluation of the person’s needs, safety considerations and vulnerabilities that is designed to identify those personal, psychological and environmental or social factors that might explain an act of self‑harm [ 10 ]. Furthermore, such assessments should foster building relationships with both the patient and families or other supportive adults and should involve gathering good information on past history and current circumstances to inform a collaborative approach to safety planning [ 9 ]. Mental health assessments and appropriate follow-up care for patients presenting with self-harm are essential but previous studies have shown that such assessments are not always universally completed, ranging from 36 to 82% [ 11 , 12 , 13 , 14 ]. In 2019, 72% of patients attending EDs with self-harm in Ireland received such an assessment [ 6 ].

The time of a self-harm presentation at an ED can be an important factor that determines whether a mental health assessment is conducted [ 11 ]. Studying the profiles of patients who present at hospital EDs with self-harm, and in particular the times of these presentations, can be informative for hospital management teams to allocate adequate services at critical times.

In a previous scoping review, we showed that the majority of studies with data on times of self-harm presentations at EDs indicated that these presentations mainly occur out-of-hours (i.e. outside 09:00–17:00, Monday to Friday) – in particular, in the hours before and after midnight [ 15 ]. For the most part, this scoping review found that time of self-harm presentations tended to be a secondary outcome [ 15 ]. In addition, only two of the included studies [ 16 , 17 ] from this review stratified their data for the time of self-harm presentations at EDs by different age-cohorts: Colman et al. [ 17 ] stratified for adults and children and Bergen and Hawton [ 16 ] used three age groups [ 15 ]. It is possible that, in the other studies that did not stratify for different age-groups, the adult numbers dominated the data, potentially hiding the trends in other age-groups [ 15 ]. Furthermore, there was also a dearth of data on the most common weekdays of self-harm presentations at EDs and seasonal data [ 15 ].

This study used data from the National Self-Harm Registry Ireland (NSHRI), the world’s first national registry of self-harm presenting to hospital EDs across an entire country [ 18 ]. The aim of this descriptive study was to stratify data from the NSHRI database for different age groups and compare the most common times of day, weekdays and seasons for self-harm presentations to EDs. Furthermore, this study compared the following across the different age groups: methods of self-harm; the occurrence of repeat self-harm presentations; whether mental health assessments were carried out; and, admission details.

Study population

This study used data from the NSHRI database for 13 years from 2007 to 2019. NSHRI data have been collected at each ED in the Republic of Ireland since 2006 [ 18 ]. The NSHRI uses an internationally-recognised definition for self-harm: namely, “an act with non-fatal outcome in which an individual deliberately initiates a non-habitual behaviour, that without intervention from others will cause self-harm, or deliberately ingests a substance in excess of the prescribed or generally recognised therapeutic dosage, and which is aimed at realising changes that the person desires via the actual or expected physical consequences” [ 18 , 19 ]. A minimal dataset is used for the purposes of analysis and research [ 18 ]. No individual can be identified from the data [ 18 ].

Patients were stratified into four age groups: children (aged 8–12 years), adolescents or teenagers (aged 13–17 years), young adults (aged 18–25 years), and adults (aged 26 years or older). Children were defined as persons less than age 13 since this is typically the age when children begin puberty and transition between primary school and secondary school in Ireland [ 20 ]. Moreover, onset of self-harm behaviour usually begins in early adolescence between the age of 12 to 14 years [ 21 ]. Any data on children aged below age eight were excluded from the NSHRI file in this study due to small numbers. In addition, numbers of participants less than five in categories were hidden in the tables in this study for de-identification purposes.

The definition of adolescence varies across the literature. Youth has been defined as the age-group up to approximately the age of 25 years old [ 22 , 23 ]. Previously, studies have defined adolescence as the period of life between the start of puberty and the point at which an individual attains a stable, independent role in society; however, the timing of puberty and the transition to adulthood varies across time and cultures [ 24 ]. In Ireland, it has been recommended that the age range for eligibility for child and adolescents mental health services (CAMHS) be increased to 25 years to improve the continuity of care [ 25 ]. Moreover, young people typically leave secondary school, to move onto third level education or work, around the age of 18 years. With all of these considerations in mind, adolescents were defined as being aged 13–17 years and young adults as being aged 18–25 [ 22 ].

This study used NSHRI data on the sex and age of the patient. The primary outcomes for this study were the times of day, weekdays and months of self-harm presentations. Hourly time frames were analysed and the 24-hour clock was also split into four-hour time frames beginning at midnight. Following on from the study conducted prior to this one [ 15 ], in-hours (or standard working hours) were defined as the hours of 09:00–17:00 on Mondays through to Fridays and excluded weekends. Out-of-hours were defined as outside of these hours.

The secondary outcomes included methods of self-harm; the occurrence of repeat self-harm presentations; whether mental health assessments were carried out; and, admission details. Methods of self-harm are coded in the NSHRI database using the WHO International Classification of Diseases (ICD-10) codes for intentional self-injury [ 26 ]. For the purposes of this study, these codes were collapsed into six categories for methods of self-harm: drug overdoses only; self-cutting only; overdoses and self-cutting; attempted hanging only; attempted drowning only; and, other methods. Methods of self-harm under ‘other’ referred to a myriad of self-harm methods such as ingesting chemicals and noxious substances; crashing a motor vehicle; use of petroleum products, other solvents or their vapours; using alcohol; use of a blunt (non-sharp) object; jumping from a height; jumping in front of or lying in front of a moving object; use of fire or flames; and, use of rifles, shotgun and large firearm discharge etc.

Data analysis

After stratifying our data into the four age-groups, the percentage proportions were calculated for the aforementioned primary and secondary outcomes for each age-group. With respect to time, this study examined the differences between the age groups using both hourly time frames, four-hour time frames, and attendances during in-hours and out-of-hours. The analyses mentioned were also conducted for males and females within each of the age groups. Moreover, within each of the four age groups, the chi-square test was used to test statistical differences for whether the patient received a mental health assessment in-hours compared to out-of-hours. Given that we conducted four hypothesis tests, we applied the Bonferroni correction to α = 0.05 and tested at α = 0.0125 level of significance. In very large sample sizes, even small differences between the groups can lead to statistically significant results rendering the practical significance of the standard p -values meaningless. Therefore, effect sizes (phi coefficient) were also calculated to quantify the magnitude of the differences between the groups. All analyses were completed using R.

There were 152,474 self-harm presentations involving n  = 90,333 individuals made to EDs in Ireland between 2007 and 2019. Descriptive data for the primary and secondary outcomes of this study, with stratifications for the four age groups, are presented in Table  1 . Further stratification analysis of the age groups for males and females can be viewed in the supplementary material.

The majority of the self-harm presentations were from adults aged over 25 years (63.1%); followed by young adults (25.6%); then, adolescents (10.9%); and, children (aged 8–12) accounted for less than 1% of these ED presentations. For children, 6.1% of self-harm presentations were repeat self-harm presentations and this percentage increased through the age-groups to 24.8% in adolescents, 38.3% in young adults, and 44.7% in adults. The proportion of males to females varied across age groups; however, for adolescents the proportion of female self-harm presentations versus male was larger (70.9% vs. 29.1%) than in the other three groups. A similar observation was made for children although to a lesser degree (57.8% vs. 42.2%). There were only slightly higher female percentages in both the young adult and adult age groups.

Time of self-harm presentations

The highest proportion of self-harm presentations (23.3%) occurred during the 20:00 to midnight time-frame when all age groups were pooled together. The lowest proportion for all age groups pooled together was 08:00 to midday (9%). The most common time for self-harm presentations involving children occurred between midday and midnight, with the highest proportion (52.3%) of self-harm presentations occurring between 16:00 and midnight. The highest proportion (27.9%) for adolescents occurred during the 20:00 to midnight time-frame and the lowest proportion (5.1%) was during the 4:00–8:00 timeframe. Similarly, the highest proportion (23.1%) for adults also occurred during the 20:00 to midnight time-frame, with the lowest numbers of presentations occurring during the period from 04:00 to midday. The highest proportion of young adult self-harm presentations (22.9%) was during the midnight to 04:00 timeframe and the lowest proportion was from 08:00 to midday.

Pooling all age groups together, the majority (78.6%) of all self-harm presentations occurred out-of-hours (outside 09:00–17:00, Monday to Friday). While more self-harm presentations for children did occur out-of-hours (65.2%), this was lower in comparison to the other three age-groups. The proportions of adolescent, young adult, and adult self-harm presentations during out-of-hours were 77.1%, 81.1% and 77.9%, respectively.

The proportions of self-harm presentations for each hour, stratified for each age group, are displayed in Fig.  1 . For children, the peak hour for self-harm presentations was between midday and 13:00. We can also see the higher proportions of self-harm presentations in this age cohort after midday in comparison to before midday. The peak hour for adolescents was from 23:00 to midnight but was also high from 22:00–23:00 and from midnight to 01:00. There was not a clearly defined peak hour for adults and young adults; rather, the peak times were in the three to four hours before and after midnight.

Proportions of self-harm presentations for the four age groups for times of day

Weekdays of self-harm presentations

The proportions for self-harm presentations for children were typically higher on weekdays, particularly on Wednesdays (17.2%) and Thursdays (16.5%), and lower during weekends. See Fig.  2 . For adolescents, the proportion of self-harm presentations were highest on Mondays (17.6%) and decreased as the week went on, with the lowest proportion on Saturdays (11.7%), but rose again on Sundays. In contrast, young adults had the highest proportions on Sundays (17.2%) and Mondays (15.2%), with lower proportions mid-week. Adult self-harm presentations also followed this trend, but was more evenly spread across the week in comparison to young adults.

Proportions of self-harm presentations for the four age groups for weekdays

Months of self-harm presentations

The highest proportions of self-harm presentations for children occurred during March (14.0%) and October (10.4%), whereas the lowest proportions of self-harm presentations for children occurred during July (5.6%) and August (5.8%). See Fig.  3 . Adolescents’ self-harm presentations proportions were highest in January (9.5%) and March (9.4%), and similar to children, the proportions of self-harm presentations were lowest in the summer months during June (6.7%), July (6.8%) and August (6.9%), and was also low during December (7.3%). The proportions for self-harm presentations in young adults and adults were similar across the 12 months, with a slight increase in the proportions during the summer months for adults. The highest proportion of young adults was in March (8.9%) and May (8.8%). The highest proportion for adults was in July (9.2%).

Proportions of self-harm presentations for the four age groups for months

Methods of self-harm

For adolescents, young adults and adults, drug overdoses accounted for the majority of self-harm presentations with proportions of 55.7%, 53.8% and 63.5%, respectively for the three age-groups. See Fig.  4 (i). For the same three age-groups (in the same order), the next biggest proportion of self-harm presentations were self-cutting presentations, with proportions of 23.2%, 22.5% and 16.3%, respectively. Presentations with a combination of these two methods were lower in adults (3.9%) compared to adolescents and young adults (both over 6%). Other methods of self-harm accounted for approximately 10% and attempted hanging accounted for 4–5% in each of these three age-groups. Attempted drowning was lower in adolescents (less than 1%) compared to over 2% in both young adults and adults.

(i) Proportions of methods used in self-harm presentations for the four age groups (ii) Proportions of methods used in self-harm presentations for the four age groups stratified for sex

While these three age-groups had similar proportions across the different methods of self-harm, they were quite different for children. For children, self-cutting was the most common method (34.3%), which was followed by drug overdoses (28%). Attempted hangings in children self-harm presentations accounted for 16.6% and other methods accounted for 18% of self-harm presentations in children.

When we further stratified data on methods of self-harm by sex (see Fig.  4 (ii) and the supplementary material), attempted hanging was the most common method in male children (nearly 30.7% versus less than 7% in females), whereas self-cutting was the most common method in female children (40.1% compared to 26.4% in male children). Female children had higher proportions of drug overdoses (34.8%) compared to male children (18.8%). For each age group, females had higher proportions of drug overdoses in comparison to males. The highest proportion of drug overdoses in sex and age-groups was in female adults (71%). Males had higher proportion of more lethal methods of self-harm such as attempted hangings, attempted drownings and other methods compared to females across all the age groups.

Mental health assessments and admission details

The percentages for those receiving a mental health assessment were highest in children and adolescents (71.1% and 69.0%, respectively) compared to young adults and adults (66.4% and 65.7%, respectively). The highest proportion (3.6%) for those refusing a mental health assessment was in adults. Likewise, the highest proportions of those refusing admission or leaving against medical advice were in both young adults and adults (14.8% and 15.4%, respectively). For all four age groups, there were higher proportions that received a mental health assessment in-hours compared to out-of-hours. (See supplementary material Table 2 .) These proportions, though not substantially different, were only found to be statistically significant in both the young adult and adult groups. In addition, the proportional variation in those receiving and not receiving mental health assessments in these two age groups was small, as indicated by the small effect sizes. In young adults, 78.2% of those who attended in-hours received a mental health assessment, compared to 73.3% of those who attended out-of-hours. In adults, 76.1% of those who attended in-hours received a mental health assessment, compared to 72% of those who attended out-of-hours.

This study found that most self-harm presentations (78.6%) occurred out-of-hours (outside 9:00–17:00, Monday to Friday), with particularly high proportions in the four hours before and after midnight. This was not the case for children, for whom the rates of self-harm presentations peaked from 16:00 in the evening until midnight. Previous studies have also demonstrated that most self-harm presentations occur out-of-hours, with the peak times usually in the hours before and after midnight [ 15 ]. Children presented more commonly midweek and less often during weekends, whereas the proportions of young adult and adult self-harm presentations were highest on Sundays and Mondays and lower midweek. Adolescent presentations were highest on Mondays and lowest on Saturdays. Higher proportions of patients received a psychiatric review during in-hours compared to out-of-hours, though this was found to be statistically significant only in young adults (78.2% vs. 73.3%) and adults (76.1% vs. 72.0%).

Approximately 3.5% of young adults and adults refused a mental health assessment in comparison to less than 2% in the adolescent and children cohorts. Furthermore, approximately 15% of young adults and adults refused admission or left against medical advice in comparison to only 5.9% and 1.4% in adolescents and children, respectively. Alcohol involvement in the self-harm presentation is one factor that may account for whether the patient was discharged without a mental health assessment [ 8 ]. Previous research has found that self-harm presentations involving alcohol peak after midnight and on Sundays and Mondays in comparison to presentations not involving alcohol, which tend to be more evenly spread out across the week and with a less accentuated peak between 18:00 and midnight [ 27 ]. Hence, it is likely that many of the self-harm presentations accounting for the lower proportions of young adults and adults not receiving mental health assessments are due to the involvement of alcohol [ 8 ]. More comprehensive addiction pathways for patients presenting during out-of-hours have previously been recommended for patients presenting to EDs with self-harm [ 8 ].

Appropriate pathways to voluntary counselling services have also been recommended for patients who present to EDs with self-harm but differences in referrals to these agencies have been found for those presenting in-hours and out-of-hours [ 8 ]. Indeed, the lack of availability of allied services, such as multidisciplinary teams and social work support out-of-hours may be another reason for the lower percentages of mental health assessments being conducted [ 28 ]. Overcrowding is another issue facing Irish EDs, which is associated with poorer patient outcomes including higher mortality rates [ 29 ]. The provision of care for patients presenting to EDs with self-harm and the availability of specialised mental health resources varies across different hospitals [ 30 ]. One of the recommendations from Ireland’s national mental health policy, Sharing the Vision , is that there should be continued investment in, and implementation of, a national critical care programme for the assessment and management of patients presenting to EDs following self-harm [ 25 ]. Health service managers should strive to ensure that adequate resources for patients with self-harm are available for those who need them out-of-hours. In addition to ensuring availability of an in-depth mental health assessment (for example through appropriate multidisciplinary staffing of psychiatric services out-of-hours), this may also involve working closely with other local agencies including voluntary sector organisations (such as crisis counselling).

The data from the current study justify the recommendations from the most recently published National Clinical Programme for Self-Harm and Suicide-related Ideation (NCPSH) [ 9 ]. NCPSH recommends that mental health assessments are provided to patients presenting with self-harm at EDs regardless of the time [ 9 ]. It also mentions that each service should ensure that a procedure is in place to ensure the handover of details of all patients who present out-of-hours and that each patient’s GP should receive immediate secure communication on the patient’s presentation and emergency plan [ 9 ]. This is particularly relevant given that the majority (64.4%) of patients that leave the ED after a self-harm presentation without admission to either a general or psychiatry ward. In addition, the NCPSH mentions that each patient should receive a follow-up phone call from a mental health professional, such as a clinical nurse specialist, within 24 h of discharge from ED [ 9 ]. Developing crisis assessment teams and suicide crisis assessment nurses by mental health services in Ireland who will work with GPs have further been recommended [ 9 ]. Given the association between alcohol and self-harm discussed previously [ 8 ], the NCPSH further recommends opportunistic mental health assessment screening for those presenting at EDs at risk of alcohol or substance misuse [ 9 ].

Males made up a smaller proportion of self-harm presentations at EDs compared to females, especially in adolescents, while paradoxically accounting for the vast majority of deaths by suicide [ 2 ]. As in other studies, this study also found that more lethal means of self-harm, such as attempted hanging or drowning, were more common in males [ 27 ]. In fact, the percentage for attempted hangings was the greatest proportion for any method in male children - nearly 31% in male children compared to less than 6.3% in female children. The proportions of those not receiving a mental health assessment or refusing admission or leaving against medical advice were slightly higher in males also compared to females. (See supplementary material). Therefore, males presenting to EDs with self-harm are potentially a high-risk group.

For adolescents and even more so for children, the rates of self-harm were lowest during the summer months. For adolescents, the rates were lowest in June, July and August; whereas for children the rates were lowest for July and August. These align with secondary school and primary school holidays in Ireland, respectively. In addition, the rates were lower in December, during which schools have a two-week Christmas break. In a Canadian study, Colman et al. also found that self-harm presentations were lower for children during summer months [ 17 ]. There has also been some evidence to show that both suicide rates and mental health presentations to EDs are lower during summer months in the United States [ 31 ]. Furthermore, children’s rates of self-harm ED presentations peaked during weekdays and were lowest on weekends. For adolescents, self-harm ED presentations peaked on Mondays and fell as the weekdays went on, with the lowest rates on Saturdays and rising again on Sundays.

School staff are often the ones to identify young people exhibiting self-harm behaviour [ 32 ], and so the lower rates of self-harm during the school holidays may be attributed to the decrease in detection. On the other hand, there are many risk factors for self-harm in young people that involve the school setting (such as bullying, social contagion of self-harm behaviour in peer groups, truancy, and low academic performance) [ 33 ], and this may also account for the higher levels of self-harm during the school months. While school may not necessarily always be a causative factor for self-harm in young people, it must be considered in the context of mental health and self-harm public health prevention interventions in children and adolescents. Sharing the Vision also sets out that every school in Ireland should have a dynamic wellbeing promotion process [ 25 ]. Furthermore, Sharing the Vision recommends that a liaison process should be in place between schools, mental health services, GPs, primary care services, and specialist mental health services [ 25 ].

For adults, the seasonal data are similar to the existing literature with higher self-harm presentations occurring in the summer months [ 17 , 34 , 35 , 36 , 37 ]. There has been some evidence to suggest that higher temperatures are associated with small increases in hospitalisations due to self-harm [ 38 ]. To our knowledge there has been no credible reason for this phenomenon. Previously, we conjectured that alcohol, longer days, idleness, or loneliness during the holiday season could be factors contributing to the peak rates in self-harm presentations at EDs in summer months [ 15 ].

Strengths and limitations

Using data from a national self-harm registry of all ED presentations for this study is unique in global terms and is a major strength to this study. Moreover, we were able to use 13 years of data. On the other hand, hospital-presenting self-harm data does not accurately describe self-harm in community settings where the individuals do not necessarily present at a hospital ED. Hence, the results of this study should be interpreted with this in mind. The rate of community self-harm has been shown to vastly outnumber hospital-presenting self-harm [ 39 ]. An iceberg model of self-harm has been used to describe this phenomenon whereby hospital presenting self-harm is visible above the surface but community self-harm is vastly bigger below [ 39 ]. While we found that overdosing was the most common method for self-harm in adolescents and young adults for example, it has been hypothesised that self-cutting would actually be the most common method in the community setting [ 40 ].

Data on when the self-harm act occurred prior to arrival at the hospital ED were not available in the NSHRI dataset. There have been some estimations for the time of self-harm versus the self-harm presentation, such as an estimation of four hours between an overdose and the time at which the patient arrives at an ED [ 41 ]. In addition, there was no data on the circumstances of the self-harm presentations. The time of a self-harm presentation to an ED only gives an approximation of the time when the self-harm act occurred, and can be influenced by many factors.

Further research

Given that much of the research from this study justifies the recommendations made in the NCPSH [ 9 ], as previously discussed, it would be imperative for future research to examine to what extent the recommendations have been implemented, and explore the barriers to implementation.

Studies examining the time of the self-harm act itself and the circumstances surrounding the act across the different age-groups could further inform the research from this study. Feasibility of collecting such data and research into the time of self-harm acts compared to the time of self-harm presentations at EDs should be considered in the future. Such data would be useful for both the design of clinical response protocols and the design of public health interventions.

Future studies could examine if these analyses could inform public health messaging around restricting access to means – encouraging parents to keep medications in locked cabinets, for example.

Self-harm presentations involving alcohol are more likely out-of-hours [ 27 ] and the proportions of young adults and adults not receiving a mental health assessment following their self-harm presentation were also higher out-of-hours, albeit not substantially. Therefore, we conjectured that alcohol involvement may be an important factor contributing to whether a mental health assessment is carried out or not. Further studies to examine reasons why some self-harm patients do not receive mental health assessments at EDs, using qualitative explorations with patients and clinicians or otherwise, could help inform service delivery for self-harm patients.

Self-harm presentations during the COVID-19 pandemic (i.e. 2020 NSHRI data) were excluded for this study since it this could have skewed the data – it being a period that was not reflective of the typical trends at EDs. While examining this data was not the focus of this study, further research could compare the same trends found in this study to those during and post the COVID-19 period to understand the effect of the pandemic.

All patients presenting to EDs with a self-harm, regardless of the time, should be given a mental health assessment and referred for appropriate care in order to avoid a repeat self-harm presentation or, indeed, a later death by suicide. Hospitals should ensure that adequate resources are available for individuals presenting with self-harm, especially in the case of overcrowded EDs, and protocols need to be designed for those presenting with self-harm due to intoxication. In line with national policy, pathways for self-harm patients should be designed that can incorporate services from allied health multidisciplinary teams, social work, addiction services and counselling organisations. Future research should examine to what extent such pathways been implemented, and explore the barriers to implementation. Future research should properly investigate other factors, besides alcohol, that lead to some self-harm presenting patients leaving ED without a mental health assessment, and what procedures could be put in place for such patients. Given the lower rates of self-harm during school holidays for children and adolescents, the school environment must be considered in the context of mental health and self-harm public health prevention interventions.

Data availability

The dataset analysed during the current study are not publicly available due to General Data Protection Regulation (GDPR) but are available from the second author on reasonable request.

Abbreviations

Child and adolescent mental health services

Emergency Department

National Clinical Programme for Self-Harm and Suicide-related Ideation

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Acknowledgements

We would like to thank the National Suicide Research Foundation (NSRF) for providing us with the data for conducting this study. We would like to thank Dr. Colm Healy and Dr. Ross Brannigan from the Royal College of Surgeons in Ireland (RCSI) for their help with statistical advice. We would also like to thanks Dr. Fiona Boland and Dr. Valeria Lima Passos from the RCSI Data Science Centre for their help with statistical advice. We would also like to thank Dr. Paul Corcoran from the National Suicide Research Foundation (NSRF), Ireland.

This was funded by the Health Research Board (HRB) Ireland as part of the SPHeRE Programme (Structured Population and Health-services Research Education).

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Concept and design: DME and MCoddData Acquisition: DME and MJ Data Analysis: DME Preparation of tables and figures: DME Initial preparation: DME Reviewing and editing the manuscript: DME MJ MClarke MCodd DMongan.

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National Self-Harm Registry Ireland (NSHRI) data was obtained from the National Suicide Research Foundation (NSRF). Since primary data was not taken for this project, an ethical exemption application was submitted and approved by University College Dublin. Ethical approval has been granted to the Registry by the National Research Ethics Committee of the Faculty of Public Health Medicine. The Registry has also received ethical approval from individual hospital and local ethics committees. In 2020, the Registry received approval from the Health Research Consent Declaration Committee to continue the operation of the Registry utilising a waiver of consent.

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McEvoy, D., Joyce, M., Mongan, D. et al. Comparing times of self-harm presentations to hospital emergency departments in children, adolescents, young adults and adults: a national registry study 2007–2019. BMC Psychiatry 24 , 474 (2024). https://doi.org/10.1186/s12888-024-05921-x

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• http://orcid.org/0000-0003-3918-5869 Mark Davison 1 ,
• Maximos McCune 2 ,
• Nishanth Thiyagarajah 2 ,
• http://orcid.org/0000-0002-2045-972X Ahmed Kashkoush 1 ,
• http://orcid.org/0009-0001-1362-1944 Rebecca Achey 1 ,
• Michael Shost 3 ,
• http://orcid.org/0000-0002-3646-3635 Gabor Toth 2 ,
• Mark Bain 1 , 2 ,
• Nina Moore 1 , 2 , 4
• 1 Department of Neurosurgery , Cleveland Clinic Foundation , Cleveland , Ohio , USA
• 2 Cerebrovascular Center , CCF , Cleveland Heights , Ohio , USA
• 3 Case Western Reserve University School of Medicine , Cleveland , OH , USA
• 4 Department of Biomedical Engineering , Lerner Research Institute , Cleveland , OH , USA
• Correspondence to Dr Mark Davison, Neurological Surgery, Cleveland Clinic Foundation, Cleveland, Ohio, USA; davisom{at}ccf.org

Background Arteriovenous malformation (AVM)-associated aneurysms represent a high-risk feature predisposing them to rupture. Infratentorial AVMs have been shown to have a greater incidence of associated aneurysms, however the existing data is outdated and biased. The aim of our research was to compare the incidence of supratentorial vs infratentorial AVM-associated aneurysms.

Methods Patients were identified from our institutional AVM registry, which includes all patients with an intracranial AVM diagnosis since 2000, regardless of treatment. Records were reviewed for clinical details, AVM characteristics, nidus location (supratentorial or infratentorial), and presence of associated aneurysms. Statistical comparisons were made using Fisher’s exact or Wilcoxon rank sum tests as appropriate. Multivariable logistic regression analysis determined independent predictors of AVM-associated aneurysms. As a secondary analysis, a systematic literature review was performed, where studies documenting the incidence of AVM-associated aneurysms stratified by location were of interest.

Results From 2000–2024, 706 patients with 720 AVMs were identified, of which 152 (21.1%) were infratentorial. Intracranial hemorrhage was the most common AVM presentation (42.1%). The incidence of associated aneurysms was greater in infratentorial AVMs compared with supratentorial cases (45.4% vs 20.1%; P<0.0001). Multivariable logistic regression demonstrated that infratentorial nidus location was the singular predictor of an associated aneurysm, odds ratio: 2.9 (P<0.0001). Systematic literature review identified eight studies satisfying inclusion criteria. Aggregate analysis indicated infratentorial AVMs were more likely to harbor an associated aneurysm (OR 1.7) and present as ruptured (OR 3.9), P<0.0001.

Conclusions In this modern consecutive patient series, infratentorial nidus location was a significant predictor of an associated aneurysm and hemorrhagic presentation.

• Arteriovenous Malformation
• Posterior fossa
• Angiography

https://doi.org/10.1136/jnis-2024-022003

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Contributors All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by MD, MM, and NT. Manuscript preparation was performed by MD and all authors participated in manuscript revisions. All authors reviewed and approved the final manuscript.

Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

Competing interests None declared.

Provenance and peer review Not commissioned; externally peer reviewed.

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