Key programmatic and policy considerations for introducing multipurpose prevention (MPT) methods: reflections from healthcare providers and key stakeholders in South Africa.

Introduction: Multipurpose prevention technologies (MPTs) simultaneously prevent HIV, other sexually transmitted infections, and/or unintended pregnancy. Key gatekeepers, [healthcare providers (HCPs) and key stakeholders] require proactive engagement before product implementation. This manuscript identifies HCP demand creation strategies, key stakeholder considerations for the adoption of MPTs in South Africa. Methods: Formative research was conducted in three districts in three South African provinces (July to November 2022). Nurses initiating oral PrEP at facility and mobile study sites participated in 4-hour participatory workshops, exploring HIV prevention, including MPTs, demand creation strategies, and preferred MPTs training packages. Activities were observed, transcribed, and thematically analysed. Five online in-depth interviews (IDIs) with Key informants (KIs) (National/district programme implementers and technical leads) and one in person, exploring key programmatic and policy considerations for MPT adoption. IDIs were approximately 40 min long, audio recorded, transcribed, and thematically analysed. Results: Twenty-one Professional Nurses completed workshops: 19 female. Six IDIs were conducted with 4 Facility Managers, 1 NDoH representative and 1 DoH Provincial Deputy Director. All participants were females, aged 30-60+ years with >10 years' in SRH/HIV policy/advocacy/research. Community conversations and information at the clinic were the best MPT demand creation methods among HCPs. KIs identified five considerations for future MPT implementation: HCP training; demand creation and messaging; existing PrEP policy amendments; preparing users for additional choice; and sustaining MPT provision. Conclusion: Contraceptive implant and oral PrEP implementation lessons learned should be proactively considered when preparing for MPT introduction. HCP training and demand creation are of particular importance before MPT introduction.

Assessment of weight gain in adult patients living with HIV receiving first-line dolutegravir-based or efavirenz-based ART regimens in routine care clinics in Tshwane district, South Africa: An observational study.

INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m2 (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m2, and CD4 counts <200 cells/µL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/µL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.

Factors influencing the uptake of a mono-PrEP implant for the prevention of HIV: Males' perspectives from three South African provinces.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention method; however, males over 15 years face challenges with its effective use. Long-acting prevention products could address barriers to effective PrEP use. This study aimed to estimate the potential uptake of a mono-PrEP implant and the factors influencing uptake among males in South Africa. The study also examined messaging and demand creation tactics that males perceive will improve HIV prevention uptake. METHODS: We conducted a mixed methods study comprising participatory workshops and a self-administered survey among 142 PrEP-eligible males (18-40 years) in three provinces (Gauteng, Eastern Cape, and Kwa-Zulu Natal) in South Africa from July to November 2022. Logistic regression was used to assess the relationship between the potential uptake of a hypothetical, non-biodegradable mono-PrEP implant and socioeconomic and behavioural factors. Workshop data were analysed using content analysis. RESULTS: The top three HIV prevention products that males would consider using were the monthly pill (74.6%), the mono-PrEP implant (62.7%), and event-driven oral PrEP (59.2%). If one prevention option was available, 31.7% of participants stated that they would use the monthly oral pill, 28.2% would use the six-monthly injection, and 19.7% the mono-PrEP implant. Four key themes were noted as influential to potential mono-PrEP uptake: "Health Over Everything", "Mono-PrEP Implant Concerns", "Potential Disclosure of Mono-PrEP Use", and "Information Distribution Channels". Participants preferred social and mainstream media as information distribution channels to receive information on HIV prevention services, including the mono-PrEP implant. CONCLUSION: In this study among predominantly heterosexual men in South Africa, there was interest in long-acting HIV prevention methods but concerns about the mono-PrEP implant. A comprehensive and participatory introduction will be needed for the implant, to improve acceptability and address potential concerns. Demand-creation strategies utilising social media and health campaigns should be considered to engage and reach males.

Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

STUDY OBJECTIVE: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. DESIGN: Retrospective analysis. SETTING: Multisite integrated health system throughout Minnesota and Wisconsin. PATIENTS: Adult patients with lymphoma who received HDMTX as a 4-h infusion. MEASUREMENTS AND MAIN RESULTS: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Implementation preferences for the management of sexually transmitted infections in the South African health system: a discrete choice experiment.

OBJECTIVES: Despite strengthening HIV prevention with the introduction of pre-exposure prophylaxis (PrEP), STI services have remained relatively unchanged and the standard of care remains syndromic management. We used a discrete choice experiment to investigate service users' preferences for the diagnosis and treatment of STIs in South Africa. METHODS: Between 1 March 2021 and 20 April 2021, a cross-sectional online questionnaire hosted on REDCap was administered through access links sent to WhatsApp support groups for HIV PrEP users and attendees of two primary healthcare clinics and two mobile facilities in the Eastern Cape and Gauteng provinces aged between 18 and 49 years. Participants either self-completed the questionnaire or received support from a research assistant. We used a conditional logit model for the initial analysis and latent class model (LCM) to establish class memberships, with results displayed as ORs and probabilities. RESULTS: We enrolled 496 individuals; the majority were female (69%) and <30 years (74%). The LCM showed two distinct groups. The first group, comprising 68% of the participants, showed a strong preference for self-sampling compared with no sampling (OR 2.16, 95% CI 1.62 to 2.88). A clinic follow-up appointment for treatment was less preferable to same-day treatment (OR 0.78, 95% CI 0.63 to 0.95). Contact slip from index patient (OR 0.86, 95% CI 0.76 to 0.96) and healthcare professional (HCP)-initiated partner notification (OR 0.63, 95% CI 0.55 to 0.73) were both less preferable than expedited partner treatment (EPT). The second group included 32% of participants with a lower preference for self-sampling compared with no sampling (OR 0.65, 95% CI 0.41 to 1.04). There was no treatment option that was significantly different from the others; however, there was a strong preference for HCP-initiated partner notification to EPT (OR 1.53, 95% CI 1.10 to 2.12). CONCLUSIONS: Our results suggest that service users preferred STI testing prior to treatment, with the majority preferring self-taken samples and receiving aetiology-based treatment on the same day.

Eita! Reaching Communities and Young People to Drive Demand for Oral Pre-Exposure Prophylaxis in South Africa.

PURPOSE: This paper describes a holistic but flexible demand creation strategy for pre-exposure prophylaxis (PrEP) in national public health-care settings in low-income to middle-income countries. METHODS: We describe the development and implementation of a model to drive demand for oral PrEP uptake and use as part of comprehensive sexual and reproductive health services in South Africa: The Eita! MODEL: The project adapted two existing response hierarchy models (marketing models used to describe the stages individuals move through from being unaware to using a product), to formulate the Eita! MODEL: Using the RE-AIM framework, we report on the reach, effectiveness, adoption, implementation, and maintenance of the Eita! RESULTS: More than 34 million connections were made from December 2018 to 2021 through a variety of channels: social media and websites, at events and mobile clinic outreach, and radio and community dialogs. There were 42,447 adolescent girls and young women reached in-person during this time, 16,823 adolescent girls and young women presented for sexual and reproductive health services, and of those 14,637 (87%) initiated on PrEP. The model was implemented in eight health-care facilities and four mobile clinics in three provinces in South Africa. A total of 26 trainings were delivered to project staff implementing the strategy. Various demand creation resources, such as materials and online platforms, have since been adopted by the National Department of Health as national tools. DISCUSSION: The Eita! model was successfully implemented to support the uptake of HIV prevention services and rollout of biomedical prevention products, and can be adapted by other low-income to middle-income countries.

Implementing Differentiated and Integrated HIV Prevention Services for Adolescent Girls and Young Women: Experiences From Oral PrEP Rollout in Primary Care Services in South Africa.

PURPOSE: In South Africa, adolescent girls and young women (AGYW, aged 15-24 years) are disproportionately affected by human immunodeficiency viruses (HIV). Oral pre-exposure prophylaxis (PrEP) has been available in South Africa since 2016; however, there is limited evidence on oral PrEP implementation and integration in real-world settings, particularly among AGYW. Project PrEP is an implementation science project that sought to inform the introduction and integration of oral PrEP as part of combination HIV prevention and sexual and reproductive health services (SRH) in South Africa. The project focused on AGYW, as a priority population in need of HIV prevention. This paper presents strategies Project PrEP employed to increase oral PrEP and SRH service access and utilization. METHODS: We present strategies employed to increase oral PrEP and SRH services uptake. Using routine monitoring data, facility assessments, stakeholder engagement, training and progress reports, and observations, we share implementation lessons learned and describe how strategies can be adapted by HIV prevention programs in different contexts. RESULTS: Approximately 22, 000 people initiated on oral PrEP (December 2018-December 2021) across eight facilities and four mobile clinics. Two-thirds (67%) of initiated clients were AGYW. DISCUSSION: Lessons are to be learned from the introduction of oral PrEP as implementers prepare for the introduction of new PrEP methods. Stakeholders must be continuously engaged to ensure buy-in, and social mobilization and demand creation should be contextual, focused, and innovative. Continuous staff training is needed to reinforce knowledge, and AGYW service delivery models must be local context relevant.

Comparing the Integration of Syndromic versus Etiological Management of Sexually Transmitted Infections Into HIV Pre-Exposure Prophylaxis Services for Adolescent Girls and Young Women, in South Africa.

South Africa has a high incidence of human immunodeficiency virus and sexually transmitted infections (STIs), particularly among adolescent girls and young women. National and global guidelines recommend varied strategies for integrating STI and pre-exposure prophylaxis (PrEP) services. PURPOSE: This paper describes the implementation of a syndromic compared to an etiological approach to STI integration within PrEP services in South Africa. METHODS: We analysed program data from eight fixed and four mobile clinics to describe a cascade of STI care and integration of syndromic management among clients accessing PrEP services. Diagnostic testing was conducted in a subset of clients to determine the prevalence of STIs and estimate the burden of disease missed using a syndromic approach. RESULTS: Between December 2018 and December 2021, 22,505 clients sought services and a high proportion (92.9%) was screened for STI symptoms. Of these, 9% of females and 3% of males had symptoms and 89.5% had recorded treatment. In a subset of PrEP clients (406 females, 70 males) screened through laboratory testing, chlamydia was identified in 25.7% of female and 20.0% of male samples, gonorrhea in 14.1% of female and 18.6% of male samples, and syphilis in 2.3% of female and 1.4% of male samples. Highest prevalence was found among females aged 18-20 years. DISCUSSION: Syndromic STI screening and management can be integrated into routine PrEP service delivery and can identify symptomatic STIs, but misses asymptomatic infections. PrEP clients have a high prevalence of treatable STIs. Etiologic approaches can identify more infections than syndromic screening, but cheap point-of-care tests are needed.

Mental Health Needs of Adolescent and Young Adult PrEP Users in South Africa: Implications for Sexual and Reproductive Health Programming.

PURPOSE: Poor mental health is associated with sexual and reproductive health (SRH) risks, including human immunodeficiency virus (HIV) and pre-exposure prophylaxis discontinuation. Adolescents and young people (AYP) are vulnerable to HIV and depression. This paper describes the prevalence and severity of depression and associated factors in AYP accessing SRH services in South Africa. METHODS: A cross-sectional analysis of enrollment data (January 2019 to December 2021) from a cohort of individuals receiving pre-exposure prophylaxis services at eight clinics in three provinces in South Africa was conducted. Females (n = 1,074) and males (n = 231) aged 15-24 years were included. Interviewer-administered questionnaires were conducted, and the prevalence and severity of depression assessed using the Patient Health Questionnaire-9. Multivariate analysis was used to identify factors associated with depression. RESULTS: Over 40% of participants had experienced any depression symptoms (43.7% of females, 38.5% of males). For males, experiencing intimate partner violence was the only predictor of depression symptoms (adjusted odds ratio (AOR) 8.81, 95% confidence intervals (CI) 1.03-75.44). For females, living with both parents (AOR 1.70, 95% CI 1.15-2.51), having transactional sex (AOR 1.63, 95% CI 1.00-2.65), experiencing any intimate partner violence (AOR 1.96, 95% CI 1.34-2.89), and using drugs (AOR 1.78, 95% CI 1.03-3.11) were all positively associated with depression symptoms. Resilience was a protective factor against depression symptoms for both sexes (males: AOR 0.96, 95% CI 0.93-0.98; females: AOR 0.96, 95% CI 0.95-0.97). DISCUSSION: There is a high burden of depression among AYP accessing SRH services in South Africa. Mental health screening should be integrated into SRH and HIV prevention programs for AYP.

Patterns of HIV Pre-exposure Prophylaxis use Among Adolescent Girls and Young Women Accessing Routine Sexual and Reproductive Health services in South Africa.

PURPOSE: This study describes the patterns of pre-exposure prophylaxis (PrEP) use among adolescent girls and young women (AGYW) initiated on daily oral PrEP for the prevention of HIV, within routine sexual and reproductive health services in South Africa. METHODS: We analysed clinical and survey data from a nested cohort of 967 AGYW initiated on oral PrEP between January 2019 and December 2021 in four geographical clusters in South Africa. We describe the periods of PrEP use, and the proportion who discontinued and subsequently restarted PrEP. Logistic regression analyses were conducted to determine factors associated with early PrEP discontinuation, PrEP use for ≥4 months and PrEP restart. RESULTS: PrEP use for ≤1 month was high (68.6%), although 27% returned and restarted PrEP; and 9% restarted more than once. Initiating PrEP at a mobile clinic (AOR 2.10, 95% CI 1.51 - 2.93) and having a partner known to be HIV negative or whose HIV status was unknown (AOR 7.11, 95% CI 1.45 - 34.23; AOR 6.90, 95% CI 1.44 - 33.09) were associated with PrEP use for ≤1 month. AGYW receiving injectable contraceptives were more likely to restart PrEP (AOR 1.61, 95% CI 1.10 - 2.35). Compared to those aged 15-17 years, participants 18 - 20 and 21 - 24 years were less likely to restart PrEP (AOR 0.51, 95% CI 0.35 - 0.74; AOR 0.60, 95%, CI 0.41 - 0.87), as were those initiating PrEP at a mobile clinic compared to a fixed facility (AOR 0.66, 95% CI 0.47 - 0.92). DISCUSSION: Although early PrEP discontinuation was high, it appears that PrEP use is frequently cyclical in nature. Further research is needed to determine if these cycles of PrEP correlate to periods of perceived or actual vulnerability to HIV, which may also be cyclical. PrEP delivery presents a unique opportunity to address multiple unmet health needs of young people.

The Use of HIV Pre-exposure Prophylaxis Among Men Accessing Routine Sexual and Reproductive Health Services in South Africa.

PURPOSE: This study describes a cohort of men seeking oral pre-exposure prophylaxis (PrEP) services and explores their patterns of PrEP use within an implementation project seeking to integrate PrEP provision within sexual and reproductive health services in public health clinics in South Africa. METHODS: Routine program and survey data from 364 males initiated on oral PrEP between July 2020 and May 2022 were analyzed. PrEP use was examined, including time to first discontinuation and restart patterns. Factors associated with early PrEP discontinuation and PrEP restart were analyzed. RESULTS: Despite primarily focusing on access for adolescent girls and young women, PrEP services reached males with HIV prevention needs. PrEP use for ≤1 month (early discontinuation) was high at 58%; however, 18% restarted on PrEP, with 4% restarting repeatedly. Having depression symptoms was associated with early PrEP discontinuation (adjusted odds ratio [AOR]: 1.71, 95% CI [confidence interval]: 1.06-2.78). Those ≥25 years were less likely to discontinue early, as were those with a partner treated for a sexually transmitted infection in the preceding three months (AOR: 0.33, 95% CI: 0.13-0.84) and those who had been circumcised (AOR: 0.59, 95% CI: 0.36-0.96). Those 18-20 years old were less likely to restart PrEP than those ≥25 years (AOR: 0.43, 95% CI: 0.19-0.97), as were those whose partner's HIV status was unknown (AOR: 0.33, 95% CI: 0.12-0.88). DISCUSSION: This study identified interest and uptake of oral PrEP among an underrepresented population of predominantly heterosexual males seeking sexual and reproductive health services. It found high rates of early PrEP discontinuation, with a subset returning to restart PrEP. Further research is needed to determine whether these periods of PrEP use are associated with periods of HIV risk.

Preferences, educational messaging, and demand creation channels for multipurpose-prevention technologies (MPTs) among women in South Africa.

BACKGROUND: South African women, including female sex workers (FSWs), are disproportionately affected by HIV, experience a high unmet need for contraception and high rates of sexually transmitted infections (STIs). Products that address the interlinked risk between HIV, unplanned pregnancy, and other STIs are needed. There are several multipurpose-prevention technologies (MPTs) in development, aimed at preventing both HIV and pregnancy. This study aimed to explore educational messaging and demand creation channels to improve the potential uptake of a hypothetical MPT implant, using participatory action research. It also aimed to look at product and service provision attributes preferred by potential end users. METHODS: Between July and August 2022, 303 PrEP-eligible adolescent girls and young women (AGYW) (18-24 years), women > 24 years, and FSW's (≥ 18 years) participated in 4-hour workshops, where they were asked about their ideal messaging and demand creation channels and their preferences for different attributes of an MPT implant. Quantitative descriptive analysis was conducted to determine the frequency and ranking for each demand creation message, channel, and each product and service provision attribute, by population group. A chi-square test was used to assess MPT implant characteristics associated with age. Qualitative data were analysed using deductive and thematic analysis. RESULTS: A total of 104 AGYW, 157 women > 24 years, and 42 FSWs participated in the PAR workshops. Participants preferred demand creation messages that were empowering, motivational and encouraged body autonomy. The use of slang was popular. Community radio stations and newspapers, social media, and information at hospitals and clinics were participants' preferred MPT demand creation channels because they were easily accessible. Providing long-term and dual HIV and pregnancy protection, receiving implant services at the local clinic, manageable side effects, discreet and private implant, and numbing the area before insertion and removal, were the most preferred product and service provision attributes. CONCLUSION: Early considerations for women's product preferences are key to product development. Educational messaging around the MPT implant should be empowering and in local languages, this may motivate women to learn more about it and use it. Multiple demand creation channels should be used to engage both young and older populations, which may ensure better reach.

Integrated access to care and treatment (I ACT) support groups for adolescents living with HIV in public healthcare facilities in South Africa: feasibility and acceptability for scaling up.

Integrated Access to Care and Treatment (I ACT) for adolescents is an educational support group initiative conducted monthly by trained healthcare providers (counsellors/health promoters). It follows a defined educational curriculum of six topics including, HIV/AIDS, disclosure, sexual and reproductive and mental health. Qualitative assessments, conducted midway of I ACT implementation at four primary healthcare facilities in North West province, South Africa, aimed to explore the perceptions of healthcare providers and the experiences of adolescents living with HIV (ALHIV). Face-to-face interviews were conducted with healthcare providers (n = 4), Facility Managers (n = 4) and ALHIV 15-19 years (n = 15). Interviews were recorded, transcribed, translated, verified and a content analysis performed. ALHIV reported the benefit and educational value of I ACT support groups. Healthcare providers shared their experience with initiating the groups and Facility Managers highlighted implementation challenges. In this study I ACT for adolescents supported ALHIV needs and promoted engagement with healthcare providers and peers. Sustaining I ACT for adolescents will require additional health system strengthening like provision of human and material resources.

Critical factors in gene expression in postmortem human brain: Focus on studies in schizophrenia.

BACKGROUND: Studies of postmortem human brain are important for investigating underlying pathogenic molecular mechanisms of neuropsychiatric disorders. They are, however, confounded by pre- and postmortem factors. The purpose of this study was to identify sources of variation that will enable a better design of gene expression studies and higher reliability of gene expression data. METHODS: We assessed the contribution of multiple variables to messenger RNA (mRNA) expression of reference (housekeeping) genes measured by reverse transcriptase-polymerase chain reaction (RT-PCR) by multiple regression analysis in a large number (N = 143) of autopsy samples from the hippocampus and white and grey matter of the dorsolateral prefrontal cortex (DLPFC) of patients with schizophrenia and normal control subjects. RESULTS: The strongest predictor of gene expression was total RNA quality. Other significant factors included pH, postmortem interval, age and the duration of the agonal state, but the importance of these factors depended on transcript measured, brain region analyzed, and diagnosis. The quality of RNA obtained from the DLPFC white matter was also adversely affected by smoking. CONCLUSIONS: Our results show that normalization of expression data of target genes with a geometric mean of multiple housekeeping genes should be used to control for differences in RNA quality between samples. The results also suggest that accurate assessment of other confounding factors and their inclusion as regressors in the analysis is critical for obtaining reliable and accurate quantification of mRNA expression.

Reliability of psychiatric diagnosis in postmortem research.

BACKGROUND: Postmortem human brain research is an important approach for identifying the cellular, molecular, and genetic pathways involved in the pathophysiology of psychiatric disorders. One critical component in postmortem research is the reliability of psychiatric diagnoses used to define study cohorts. Finding reliable methods for assessing lifetime psychiatric diagnoses in subjects after death is extremely challenging. METHODS: Two commonly used approaches were compared: psychiatric record reviews and postmortem family interviews. We hypothesized that these two methods would lead to more diagnostic agreement for subjects with schizophrenia than those with mood disorders. For 37 cases, psychiatric records were reviewed retrospectively using the Diagnostic Evaluation After Death, and family members were interviewed using the Structured Clinical Interview for DSM-IV. RESULTS: Comparison of diagnoses derived from these two approaches generated an overall kappa coefficient of .67. Kappa coefficients for the schizophrenia cohort were .94, .68 for the major depressive disorder cohort, and .58 for the bipolar disorder cohort. CONCLUSIONS: Thus, although it may be sufficient to establish the postmortem diagnosis of schizophrenia using one of the two methods, the best method for reaching an accurate postmortem diagnosis for mood disorders is more difficult to determine and requires further study.

Smoking, gender, and dietary influences on erythrocyte essential fatty acid composition among patients with schizophrenia or schizoaffective disorder.

BACKGROUND: Prior reports of decreased levels of essential fatty acids among schizophrenic patients have generated several hypotheses proposing inherent abnormalities in phospholipid and fatty acid metabolism and have provided the basis for treatment trials; however, these essential fatty acid aberrations may be attributable to uncontrolled factors, such as smoking, rather than abnormalities inherent to schizophrenia. METHODS: Erythrocyte fatty acid compositions were quantified in 72 medicated schizophrenic or schizoaffective patients both at baseline and after 16 weeks of supplementation with 3 g/day of either ethyl-eicosapentaenoic acid or placebo. Current smoking status, gender, dietary survey, and Montgomery Asburg Depression Rating Scale, Repeatable Battery for the Assessment of Neuropsychological Status, Abnormal Involuntary Movement Scale, and Positive and Negative Syndrome Scale scores were assessed. RESULTS: Schizophrenic patients who smoked had lower baseline erythrocyte docosahexaenoic acid percent (2.98 +/-.7 vs. 3.59 +/- 1.2, p <.005) and eicosapentaenoic acid (EPA) percent (.39 +/-.13 vs. 47 +/-.22, p <.05), compared with nonsmokers, with a significant gender interaction (p <.01) in multivariate analyses of variance. Baseline arachidonic acid did not differ. Smokers reported lower dietary intake (percent total fat) of linolenic acid (F = 10.1, p <.003) compared with nonsmokers. Nonsmoking women reported greater dietary intake of EPA compared with smoking men or nonsmokers of either gender. CONCLUSIONS: Smoking status, gender, and dietary intake significantly predicted erythrocyte polyunsaturated fatty acid status among schizophrenic patients. No evidence was found for subgroups of schizophrenia or relationships to specific symptom severity on the basis of erythrocyte fatty acids. Prior reports of abnormalities of essential fatty acid metabolism among schizophrenic patients may have been an artifact of patients' smoking behavior and differences in dietary intake of omega-3 fatty acids.

Contact with mental health and primary care providers before suicide: a review of the evidence.

OBJECTIVE: This study examined rates of contact with primary care and mental health care professionals by individuals before they died by suicide. METHOD: The authors reviewed 40 studies for which there was information available on rates of health care contact and examined age and gender differences among the subjects. RESULTS: Contact with primary care providers in the time leading up to suicide is common. While three of four suicide victims had contact with primary care providers within the year of suicide, approximately one-third of the suicide victims had contact with mental health services. About one in five suicide victims had contact with mental health services within a month before their suicide. On average, 45% of suicide victims had contact with primary care providers within 1 month of suicide. Older adults had higher rates of contact with primary care providers within 1 month of suicide than younger adults. CONCLUSIONS: While it is not known to what degree contact with mental health care and primary care providers can prevent suicide, the majority of individuals who die by suicide do make contact with primary care providers, particularly older adults. Given that this pattern is consistent with overall health-service-seeking, alternate approaches to suicide-prevention efforts may be needed for those less likely to be seen in primary care or mental health specialty care, specifically young men.