Diagnosis and management of cryptococcal meningitis in HIV-infected adults.

Cryptococcal meningitis is a leading cause of morbidity and mortality globally, especially in people with advanced HIV disease. Cryptococcal meningitis is responsible for nearly 20% of all deaths related to advanced HIV disease, with the burden of disease predominantly experienced by people in resource-limited countries. Major advancements in diagnostics have introduced low-cost, easy-to-use antigen tests with remarkably high sensitivity and specificity. These tests have led to improved diagnostic accuracy and are essential for screening campaigns to reduce the burden of cryptococcosis. In the last 5 years, several high-quality, multisite clinical trials have led to innovations in therapeutics that have allowed for simplified regimens, which are better tolerated and result in less intensive monitoring and management of medication adverse effects. One trial found that a shorter, 7-day course of deoxycholate amphotericin B is as effective as the longer 14-day course and that flucytosine is an essential partner drug for reducing mortality in the acute phase of disease. Single-dose liposomal amphotericin B has also been found to be as effective as a 7-day course of deoxycholate amphotericin B. These findings have allowed for simpler and safer treatment regimens that also reduce the burden on the healthcare system. This review provides a detailed discussion of the latest evidence guiding the clinical management and special circumstances that make cryptococcal meningitis uniquely difficult to treat.

"Most of the cases are very similar.": Documenting and corroborating conflict-related sexual violence affecting Rohingya refugees.

BACKGROUND: In August 2017, a large population of Rohingya from northern Rakhine state in Myanmar fled to Bangladesh due to "clearance operations" by the Myanmar security forces characterized by widespread and systematic violence, including extensive conflict-related sexual violence (CRSV). This study sought to document the patterns of injuries and conditions experienced by the Rohingya, with a specific focus on sexual violence. METHODS: Qualitative interviews were conducted with 26 health care professionals who cared for Rohingya refugees after their arrival in Bangladesh between November 2019 and August 2020. RESULTS: Health care workers universally reported hearing accounts and seeing evidence of sexual and gender-based violence committed against Rohingya people of all genders by the Myanmar military and security forces. They observed physical and psychological consequences of such acts against the Rohingya while patients were seeking care. Health care workers shared that patients faced pressure not to disclose their experiences of CRSV, likely resulted in an underreporting of the prevalence of sexual violence. Forced witnessing of sexual violence and observed increases in pregnancy and birth rates as a result of rape are two less-reported issues that emerged from these data. CONCLUSIONS: Healthcare workers corroborated previous reports that the Rohingya experienced CRSV at the hands of the Myanmar military and security forces. Survivors often revealed their experiences of sexual violence while seeking care for a variety of physical and psychological conditions. Stigma, cultural pressure, and trauma created barriers to disclosing experiences of sexual violence and likely resulted in an underreporting of the prevalence of sexual violence. The findings of this research emphasize the importance of offering universal and comprehensive trauma-informed services to all refugees with the presumption of high rates of trauma in this population and many survivors who may never identify themselves as such.

Health professionals' perspectives on the impact of COVID-19 on sexual and gender-based violence (SGBV) and SGBV services in Rohingya refugee communities in Bangladesh.

BACKGROUND: The COVID-19 pandemic has acutely affected Rohingya refugees living in camps in Cox's Bazar, Bangladesh. Reported increases in sexual and gender-based violence (SGBV) were attributed in part to pandemic-related public health measures. In addition, the Government of Bangladesh's restrictions to prevent the spread of COVID-19 have impacted the provision of comprehensive care for survivors of sexual violence. This study sought to understand how the COVID-19 pandemic affected SGBV and the provision of services for Rohingya survivors in Bangladesh. METHODS: Interviews were conducted with 13 professionals who provided or managed health care or related services for Rohingya refugees after the onset of the COVID-19 pandemic in March 2020. RESULTS: At the outset of the COVID-19 pandemic, organizations observed an increase in the incidences of SGBV. However, health care workers noted that the overall number of survivors formally reporting or accessing services decreased. The pandemic produced multiple challenges that affected health workers' ability to provide essential care and services to Rohingya survivors, including access to the camps, initial designation of SGBV-related services as non-essential, communications and telehealth, difficulty maintaining confidentiality, and donor pressure. Some emerging best practices were also reported, including engaging Rohingya volunteers to continue services and adapting programming modalities and content to the COVID-19 context. CONCLUSIONS: Comprehensive SGBV services being deemed non-essential by the Government of Bangladesh was a key barrier to providing services to Rohingya survivors. Government restrictions adversely affected the ability of service providers to ensure that comprehensive SGBV care and services were available and accessible. The Government of Bangladesh has not been alone in struggling to balance the needs of displaced populations with the necessary precautions to prevent the spread of COVID-19 and its response can provide lessons to others overseeing the provision of services during epidemics and pandemics in other humanitarian settings. The designation of comprehensive services for survivors of SGBV as essential is vital and should be done early in establishing disease prevention and mitigation strategies.

Assessing Knowledge and Acceptability of a Trauma-Informed Training Model to Strengthen Response to Conflict and Gender-Based Violence in the Democratic Republic of Congo.

BACKGROUND: Conflict-related sexual and gender-based violence is common in the eastern Democratic Republic of Congo, but there are few evaluations of multisectoral training interventions in conflict settings. We conducted high-quality, trauma-informed medicolegal trainings amongst multisectoral professionals, and sought to describe changes in knowledge after training and perceived training acceptability. METHODS: Participants were health, law enforcement, and legal professionals who completed training at one of four sites from January 2012 to December 2018. Twelve trainings were randomly selected for evaluation. We conducted pre- and post-training assessments and semi-structured interviews of participants within 12 months of index training. FINDINGS: Forty-six trainings of 1,060 individuals were conducted during the study period. Of the randomly selected trainings, 368 questionnaires were included in the analysis (36% health, 31% legal, 12% law enforcement, 21% other). The mean knowledge scores (standard deviation) significantly improved after training: 77.9 (22.9) vs. 70.4 (20.8) (p <0.001). Four key benefits were identified: 1) improved cross-sector coordination; 2) enhanced survivor-centered care; 3) increased standardization of forensic practices; and 4) higher quality evidence collection. CONCLUSION: Participants completing the training had improved knowledge scores and perceived several key benefits, suggesting the multisectoral training was acceptable in this under-resourced, conflict region.

The little tissue that couldn't - dispelling myths about the Hymen's role in determining sexual history and assault.

Conclusions about women's and girls' sexual history are made in some settings based on assumptions about the hymen, a small membranous tissue with no known biological function, which typically occupies a portion of the external vaginal opening in females. Clinicians, however, continue to refer to changes in the hymen to assess for a history of consensual or nonconsensual sexual intercourse. We reviewed published evidence to dispel commonly held myths about the hymen and its morphology, function, and use as evidence in cases of sexual violence.An examination of the hymen is not an accurate or reliable test of a previous history of sexual activity, including sexual assault. Clinicians tasked with performing forensic sexual assault examinations should avoid descriptions such as "intact hymen" or "broken hymen" in all cases, and describe specific findings using international standards and terminology of morphological features.We call on clinicians to consider the low predictive value of a hymen examination and to: 1) avoid relying solely on the status of the hymen in sexual assault examinations and reporting; 2) help raise awareness of this issue among their peers and counterparts in law enforcement and the judicial system; and 3) promote fact-based discussions about the limitations of hymenal examinations as part of clinical education for all specialties that address the sexual or reproductive health of women and girls.

5-Flucytosine Longitudinal Antifungal Susceptibility Testing of Cryptococcus neoformans: A Substudy of the EnACT Trial Testing Oral Amphotericin.

Background: The EnACT trial was a phase 2 randomized clinical trial conducted in Uganda, which evaluated a novel orally delivered lipid nanocrystal (LNC) amphotericin B in combination with flucytosine for the treatment of cryptococcal meningitis. When flucytosine (5FC) is used as monotherapy in cryptococcosis, 5FC can induce resistant Cryptococcus mutants. Oral amphotericin B uses a novel drug delivery mechanism, and we assessed whether resistance to 5FC develops during oral LNC-amphotericin B therapy. Methods: We enrolled Ugandans with HIV diagnosed with cryptococcal meningitis and who were randomized to receive 5FC and either standard intravenous (IV) amphotericin B or oral LNC-amphotericin B. We used broth microdilution to measure the minimum inhibitory concentration (MIC) of the first and last cryptococcal isolates in each participant. Breakpoints are inferred from 5FC in Candida albicans. We measured cerebral spinal fluid (CSF) 5FC concentrations by liquid chromatography and tandem mass spectrometry. Results: Cryptococcus 5FC MIC50 was 4 µg/mL, and MIC90 was 8 µg/mL. After 2 weeks of therapy, there was no evidence of 5FC resistance developing, defined as a >4-fold change in susceptibility in any Cryptococcus isolate tested. The median CSF 5FC concentration to MIC ratio (interquartile range) was 3.0 (1.7-5.5) µg/mL. There was no association between 5FC/MIC ratio and early fungicidal activity of the quantitative rate of CSF yeast clearance (R2 = 0.004; P = .63). Conclusions: There is no evidence of baseline resistance to 5FC or incident resistance during combination therapy with oral or IV amphotericin B in Uganda. Oral amphotericin B can safely be used in combination with 5FC.

Evaluating the effectiveness of a mobile application to improve the quality, collection, and usability of forensic documentation of sexual violence.

BACKGROUND: Survivors of sexual violence deserve timely and high-quality forensic examination, evidence collection, and documentation as part of comprehensive care. However, in many countries, the quality of medical-legal documentation is severely limited. MediCapt is an innovative digital application that enables clinicians to document forensic medical evidence as well as capture and securely store forensic photographs of injuries. This study evaluated the effectiveness and usability of MediCapt to document forensic medical evidence of sexual violence. METHODS: This mixed-methods evaluation involved key-informant interviews, usability questionnaires, and forensic record reviews. Participants included clinicians, medical records personnel, information technology personnel, and health facility administrators, as well as law enforcement and legal professionals in Kenya. RESULTS: The Physicians for Human Rights (PHR) data quality checklist found that using MediCapt led to significantly higher data-quality scores compared to paper-based forms. MediCapt forms scored higher on 23 of 26 checklist items. While a wide difference in quality was seen among paper-based forms, MediCapt appeared to both standardize and improve quality of documentation across sites. MediCapt strengths included data security and confidentiality, accuracy and efficiency, and supplemental documentation with photography. Weaknesses included infrastructure challenges, required technological proficiencies, and time to learn the new system. Although it is early to assess the impact of MediCapt on prosecutions, providers and law and justice sector professionals were optimistic about its usefulness. They identified MediCapt as appropriate for use with survivors of sexual violence and reported MediCapt's legibility and photography features had already been commended by the court. CONCLUSION: MediCapt was well-received across all sectors, its use was perceived as feasible and sustainable, and it significantly improved the quality of collected forensic data. It is anticipated this improvement in forensic documentation will increase successful prosecutions, strengthen accountability for perpetrators, and improve justice for survivors.

To confront sexual violence, we must train non-forensic experts to perform medico-legal evaluations.

Sexual violence is a global crisis. Forensic evaluations are critical for obtaining evidence and increasing the likelihood of accessing justice, as many cases fail due to lack of evidence or poor evidence. In some countries, only board-certified forensic specialists are authorized to conduct forensic evaluations. However, the high number of sexual violence cases coupled with the shortage of forensic physicians make that restriction a fundamental impediment to a rights-based response to sexual violence crimes. Governments and regulatory bodies should expand the pool of those capable of conducting forensic sexual violence evaluations by partnering with clinicians of different specialties and facilitating their training.

Multiyear, Multisectoral Training Program in Kenya to Enhance Medical-Legal Processes in Response to Sexual and Gender-Based Violence.

Sexual and gender-based violence (SGBV) leads to severe sequelae for individuals and communities. Lack of cross-sector coordination inhibits effective medical-legal support and justice for survivors. Multisectoral trainings for health, legal, and law enforcement professionals on survivor-centered SGBV care were conducted in Kenya during 2012-2018. Evaluation utilized objective structured clinical examinations, standardized patients, knowledge assessments, and interviews. A total of 446 professionals participated in 18 trainings. Mean knowledge scores increased from 75.6% to 84.7% (p < .001). Thirty interviews revealed improved survivor confidentiality, increased specialized hospital care, more comprehensive forensic care, and greater cross-sector collaboration. Participants reported survivors feeling more comfortable pursuing legal action and increased perpetrator convictions.

The Effect of Insurance on Appropriate Hospital Discharge Antibiotics for Patients With Staphylococcus aureus Bacteremia.

BACKGROUND: Inappropriate antimicrobial therapy of Staphylococcus aureus bacteremia (SAB) is associated with worsened outcomes. The impact of insurance coverage on appropriate selection of antibiotics at discharge is poorly understood. METHODS: We used a retrospective cohort design to evaluate whether patients with SAB at a large academic medical center over 2 years were more likely to receive inappropriate discharge antibiotics, depending on their category of insurance. Insurance was classified as Medicare, Medicaid, commercial, and none. Logistic regression was used to determine the odds of being prescribed inappropriate discharge therapy. RESULTS: A total of 273 SAB patients met inclusion criteria, with 14.3% receiving inappropriate discharge therapy. In the unadjusted model, there was 2-fold increased odds of being prescribed inappropriate therapy for Medicare, Medicaid, and no insurance, compared with commercial insurance, respectively (odds ratio [OR], 2.08; 95% CI, 1.39-3.13). After controlling for discharge with nursing assistance and infectious diseases (ID) consult, there were 1.6-fold increased odds (OR, 1.57; 95% CI, 0.998-2.53; P = .064) of being prescribed inappropriate therapy for Medicare, Medicaid, and no insurance, compared with commercial insurance, respectively. We found that being discharged home without nursing assistance resulted in 4-fold increased odds of being prescribed inappropriate therapy (OR, 4.16; 95% CI, 1.77-9.77; P < .01), and failing to consult an ID team resulted in 59-fold increased odds of being prescribed inappropriate therapy (OR, 59.2; 95% CI, 11.4-306.9; P < .001). CONCLUSIONS: We found strong evidence that noncommercial insurance, discharging without nursing assistance, and failure to consult ID are risk factors for being prescribed inappropriate antimicrobial therapy for SAB upon hospital discharge.

The impact of COVID-19 on services for people affected by sexual and gender-based violence.

Sexual and gender-based violence (SGBV), and particularly intimate partner violence (IPV), has spiked dramatically during the COVID-19 pandemic. At the same time, the pandemic is impacting and interrupting SGBV and IPV services of all kinds. This paper focuses on the impact of the COVID-19 pandemic on clinical care and forensic medical documentation for SGBV survivors, including an analysis of the response in the UK and Kenya, and provides recommendations for safe implementation of these services during the pandemic.

Spatiotemporal Heterogeneity in the Distribution of Chikungunya and Zika Virus Case Incidences during their 2014 to 2016 Epidemics in Barranquilla, Colombia.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently emerged as globally important infections. This study aimed to explore the spatiotemporal heterogeneity in the occurrence of CHIKV and ZIKV outbreaks throughout the major international seaport city of Barranquilla, Colombia in 2014 and 2016 and the potential for clustering. Incidence data were fitted using multiple Bayesian Poisson models based on multiple explanatory variables as potential risk factors identified from other studies and options for random effects. A best fit model was used to analyse their case incidence risks and identify any risk factors during their epidemics. Neighbourhoods in the northern region were hotspots for both CHIKV and ZIKV outbreaks. Additional hotspots occurred in the southwestern and some eastern/southeastern areas during their outbreaks containing part of, or immediately adjacent to, the major circular city road with its import/export cargo warehouses and harbour area. Multivariate conditional autoregressive models strongly identified higher socioeconomic strata and living in a neighbourhood near a major road as risk factors for ZIKV case incidences. These findings will help to appropriately focus vector control efforts but also challenge the belief that these infections are driven by social vulnerability and merit further study both in Barranquilla and throughout the world's tropical and subtropical regions.

Attitudes Toward Sexual Violence Survivors: Differences Across Professional Sectors in Kenya and the Democratic Republic of the Congo.

Sexual violence survivors who decide to report their assault interact with health care, law enforcement, and legal and judicial professionals. Professionals' attitudes about sexual violence and survivors play an important role in caring for survivors and in the pursuit of justice. Despite evidence showing the relationship between service provider beliefs and survivor outcomes, relatively little is known about professionals' beliefs about sexual violence or their attitudes toward sexual violence survivors. Between June 2012 and December 2014, our study examined the beliefs and attitudes of 181 professionals from the health care, legal, and law enforcement sectors in the Eastern Democratic Republic of the Congo (DRC) and the Rift Valley region of Kenya, areas with a high prevalence of sexual violence. To determine correlates of beliefs and attitudes about sexual violence and sexual violence survivors, multiple logistic regression models were adjusted for demographic and occupational characteristics. Respondents who agreed that survivors got what they deserved (7%) or that survivors should feel ashamed (9%) were the minority, while those who would be willing to care for a family member with a history of sexual violence (94%) were the majority. Profession was significantly associated with beliefs and attitudes about sexual violence and survivors. Law enforcement professionals were more likely than health professionals and lawyers to indicate that survivors should feel ashamed. Our findings suggest a need for interventions that adequately address potentially harmful beliefs and attitudes of some professionals serving sexual violence survivors.