Limitations and potential bias in vital registration data and tuberculosis mortality reporting in South Africa.

Tuberculosis (TB) is a curable disease, but continues to contribute to large numbers of deaths globally and remains among the leading causes of death in South Africa (SA). Evaluating trends in TB deaths and progress towards the End TB strategy target of zero deaths is particularly important to guide policy and practice in SA. TB deaths are complicated by its relationship with HIV, and SA's initial slow response to HIV compounded this. In considering the reported deaths in SA that identify TB as the underlying cause of death, it is important to be aware of potential limitations and sources of bias. We have examined the relationship between TB and HIV and the recording of underlying and contributing causes of death, and clarified the World Health Organization's methodology for estimating TB deaths.

Estimated dates of detectable infection (EDDIs) as an improvement upon Fiebig staging for HIV infection dating.

Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the 'Fiebig staging system' has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying 'sensitivity'. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define 'stages' of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.

Quality of life in schizophrenia and bipolar disorder: The impact of symptomatic remission and resilience.

BACKGROUND: Health-related quality of life (HRQOL) is significantly affected in individuals with schizophrenia or bipolar I disorder (BD-I). The current study investigated whether symptomatic remission and resilience might differently impact HRQOL in these patients. METHODS: Fifty-two patients with schizophrenia and 60 patients suffering from BD-I from outpatient mental health services as well as 77 healthy control subjects from the general community were included into a cross-sectional study. HRQOL and resilience were assessed using the WHOQOL-BREF and the Resilience Scale. In patients, psychopathology was quantified by the Positive and Negative Syndrome Scale or the Montgomery Asberg Depression Rating Scale and the Young Mania Rating Scale, respectively. RESULTS: Notably, both patient groups showed lower HRQOL and resilience compared to control subjects, non-remitted patients indicated lower HRQOL than remitted ones. The effect of remission on HRQOL was significantly larger in patients with BD-I than in those with schizophrenia but did not explain the difference in HRQOL between groups. Resilience predicted HRQOL in all three groups. When accounting for the effect of resilience among remitted patients, only the difference in HRQOL between schizophrenia patients and control subjects was significant. CONCLUSION: These findings demonstrate the impact of symptomatic remission and resilience on HRQOL of both patients suffering from schizophrenia and BD-I and indicate that these factors are especially relevant for HRQOL of patients with BD-I.

Moving towards a reliable HIV incidence test - current status, resources available, future directions and challenges ahead.

In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.

Emotional intelligence and non-social cognition in schizophrenia and bipolar I disorder.

BACKGROUND: The different patterns of Emotional Intelligence (EI) deficits in schizophrenia and bipolar I disorder are are not yet well understood. This study compares EI levels among these groups and highlights the potential impact of non-social cognition on EI. METHOD: Fifty-eight schizophrenia and 60 bipolar outpatients were investigated using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) and the Brief Assessment of Cognition in Schizophrenia (BACS). Analyses of covariance were performed with adjustment for the BACS composite score. RESULTS: Compared to bipolar subjects, schizophrenia patients showed significantly lower levels in both EI and non-social cognition. After adjustment for the BACS composite score, the difference in EI was lost. The mediation analysis revealed that differences between schizophrenia and bipolar patients in strategic EI are almost fully attributable to the mediating effect of non-social cognition. CONCLUSIONS: Our findings suggest that in both schizophrenia and bipolar patients EI is strongly influenced by non-social cognitive functioning. This has to be taken into account when interpreting MSCEIT data in comparative studies in serious mental illness and emphasizes the importance of cognitive remediation.

[Systematic Review of the Application of Complementary and Alternative Medicine and their Potential Therapeutic Benefits in the Treatment of Ophthalmology Patients]. / Ergebnisse eines systematischen Reviews zu Einsatz und berichtetem therapeutischem Nutzen komplementärmedizinischer Methoden in der Augenheilkunde.

Purpose A systematic review was carried out of the reported therapeutic effects of complementary and alternative medicine methods as supplementary or primary treatments for patients suffering from glaucoma, cataract or age-related macular degeneration (AMD). Material and Methods For the years 1990 to 2013, the following databases were screened for reports of the application of complementary and alternative treatments: PubMed, Cochrane Library, EMBASE, CAMbase and AMED. Both randomised and prospective non-randomised patient trials were included in the review; results were evaluated in the following classes: "phytotherapy", "acupuncture/acupressure", "biofeedback" and "other alternative treatments". The studies were evaluated by measures of clinical effect, statistical significance (p value and/or confidence interval) and the underlying trial design. Results 30 clinical trials were included, including 13 on glaucoma, 5 on cataract and 12 on AMD patients. These trials were based on patient numbers of 6 - 332, 27 - 157 and 6 - 328 patients, respectively. Phytotherapy was applied in 14 trials, including 6 on glaucoma patients (all 6 with a controlled design, and 3 of which reporting statistically significant results); 5 trials were on cataract patients (3 with a controlled design and 2 with a significant result) and 3 on AMD patients (only 1 with a controlled design, with a significant result). Acupuncture/acupressure was investigated in 9 trials, 5 on glaucoma patients (3 with a controlled design, 1 with a significant result); no acupuncture/acupressure trial was found in cataract patients, but 4 trials in AMD patients (none with a controlled design). Biofeedback was studied in 4 trials, all on AMD patients (only one with a controlled design, without statistically significant findings). Conclusion Despite its rigorous inclusion criteria, this review identified several clinical trials on complementary and alternative medicine in ophthalmological patients. Phytotherapeutic methods gave significant results in half of the reported controlled trials, whereas there were few significant benefits with acupuncture or acupressure.

Quality of life in stabilized patients with schizophrenia is mainly associated with resilience and self-esteem.

OBJECTIVE: Improving quality of life (QoL) is an important objective in the treatment of schizophrenia. The aim of the current study was to examine to what extent resilience, self-esteem, hopelessness, and psychopathology are correlated with QoL. METHOD: We recruited 52 out-patients diagnosed with schizophrenia according to DSM-IV criteria and 77 healthy control subjects from the general community. In patients, psychopathology was quantified by the Positive and Negative Syndrome Scale. The following scales were used in both patients and control subjects: the Berliner Lebensqualitätsprofil, the Resilience Scale, the Rosenberg Self-Esteem Scale, and the Beck Hopelessness Scale to assess QoL, resilience, self-esteem, and hopelessness respectively. RESULTS: Patients with schizophrenia presented with significantly less QoL, resilience, self-esteem, and hope compared to healthy control subjects. In patients, QoL correlated moderately with resilience, self-esteem, and hopelessness and weakly with symptoms. With respect to the latter, particularly depression and positive symptoms were negatively correlated with QoL. CONCLUSION: Our results highlight the complex nature of QoL in patients suffering from schizophrenia. They underscore that significant efforts are necessary to enhance resilience and self-esteem and to diminish hopelessness as well as affective and positive symptoms in patients with schizophrenia.

Key issues in the clinical development and implementation of TB vaccines in South Africa.

Significant progress has been made in advancing the development pipeline for a new and more effective TB vaccine with some candidate vaccines now in late stage clinical evaluation. However, progress has been hampered by an incomplete understanding of the components of a protective immune response and limited animal models, rendering the field unable to reliably predict vaccine efficacy earlier in preclinical development, including by evaluation in animal models, and limiting the predictive utility of comparing immunogenic effects across vaccine candidates in phase I/II studies. Consequently, new candidate vaccines have to be evaluated for efficacy in large-scale phase II/III trials using clinical endpoints. Apart from the technical challenges of characterising TB incidence in target populations at high risk of acquiring TB disease and standardising case definitions in order to improve both the sensitivity and more importantly the specificity of trial endpoints, there is an urgency in expanding and supporting the considerable trial infrastructure that will be required to evaluate and ultimately license a new TB vaccine. In the longer term, implementation strategies are dependent on what policy makers most value. Economic analyses will be essential to guide policy and implementation. This paper outlines the gaps and challenges and identifies solutions for effectively developing and efficiently introducing a new TB vaccine.

Using tests for recent infection to estimate incidence: problems and prospects for HIV.

Tests for recent infection (TRIs), such as the BED assay, provide a convenient way to estimate HIV incidence rates from cross-sectional survey data. Controversy has arisen over how the imperfect performance of a TRI should be characterised and taken into account. Recent theoretical work is providing a unified framework within which to work with a variety of TRI- and epidemic-specific assumptions in order to estimate incidence using imperfect TRIs, but suggests that larger survey sample sizes will be required than previously thought. This paper reviews the framework qualitatively and provides examples of estimator performance, identifying the characteristics required by a TRI to estimate incidence reliably that should guide the future development of TRIs.