Effect of HIV infection on time to recovery from an acute manic episode

E Nakimuli-Mpungu1,2,3, B Mutamba2,3, S Nshemerirwe2,3, MS Kiwuwa4, S Musisi21Mental Health Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA; 2Department of Psychiatry, Makerere College of Health Sciences, School of Medicine, Kampala; 3Butabika National Referral Mental Hospital, Ministry of Health, Kampala; 4Clinical Epidemiology Unit, Makerere College of Health Sciences, School of Medicine, Kampala, UgandaIntroduction: Understanding factors affecting the time to recovery from acute mania is critical in the management of manic syndromes. The aim of this study was to determine the effect of HIV infection on time to recovery from acute mania.Methods: We performed a retrospective study in which medical charts of individuals who were treated for acute mania were reviewed. Survival analysis with Cox regression models were used to compare time to recovery from an acute manic episode between human immunodeficiency virus (HIV)-positive individuals and HIV-negative individuals.Results: Median survival time was one week for HIV-positive individuals and more than four weeks for HIV-negative individuals (Χ2 = 18.4, P value = 0.000). HIV infection was the only marginally significant independent predictor of survival probability on the acute admission ward (hazards ratio 2.87, P = 0.06).Conclusion: Acute mania in HIV-infected persons responds faster to psychotropic drugs compared with that in HIV-negative persons.Keywords: HIV-related mania, bipolar disorder, HIV infection, Uganda, immunodeficiency viru

The global pendulum swing towards community health workers in low- and middle-income countries: A scoping review of trends, geographical distribution and programmatic orientations, 2005 to 2014

BACKGROUND: There has been a substantial increase in publications and interest in community health workers (CHWs) in low- and middle-income countries (LMIC) over the last years. This paper examines the growth, geographical distribution and programmatic orientations of the indexed literature on CHWs in LMIC over a 10-year period. METHODS: A scoping review of publications on CHWs from 2005 to 2014 was conducted. Using an inclusive list of terms, we searched seven databases (including MEDLINE, CINAHL, Cochrane) for all English-language publications on CHWs in LMIC. Two authors independently screened titles/abstracts, downloading full-text publications meeting inclusion criteria. These were coded in an Excel spreadsheet by year, type of publication (e.g. review, empirical), country, region, programmatic orientation (e.g. maternal-child health, HIV/AIDS, comprehensive) and CHW roles (e.g. prevention, treatment) and further analysed in Stata14. Drawing principally on the subset of review articles, specific roles within programme areas were identified and grouped. FINDINGS: Six hundred seventy-eight publications from 46 countries on CHWs were inventoried over the 10-year period. There was a sevenfold increase in annual number of publications from 23 in 2005 to 156 in 2014. Half the publications were reporting on initiatives in Africa, a third from Asia and 11 % from the Americas (mostly Brazil). The largest single focus and driver of the growth in publications was on CHW roles in meeting the Millennium Development Goals of maternal, child and neonatal survival (35 % of total), followed by HIV/AIDS (16 %), reproductive health (6 %), non-communicable diseases (4 %) and mental health (4 %). Only 17 % of the publications approached CHW roles in an integrated fashion. There were also distinct regional (and sometimes country) profiles, reflecting different histories and programme traditions. CONCLUSIONS: The growth in literature on CHWs provides empirical evidence of ever-increasing expectations for addressing health burdens through community-based action. This literature has a strong disease- or programme-specific orientation, raising important questions for the design and sustainable delivery of integrated national programmes.Scopu

Deletion of individual Ku subunits in mice causes an NHEJ-independent phenotype potentially by altering apurinic/apyrimidinic site repair

Ku70 and Ku80 form a heterodimer called Ku that forms a holoenzyme with DNA dependent-protein kinase catalytic subunit (DNA-PKCS) to repair DNA double strand breaks (DSBs) through the nonhomologous end joining (NHEJ) pathway. As expected mutating these genes in mice caused a similar DSB repair-defective phenotype. However, ku70-/- cells and ku80 -/- cells also appeared to have a defect in base excision repair (BER). BER corrects base lesions, apurinic/apyrimidinic (AP) sites and single stand breaks (SSBs) utilizing a variety of proteins including glycosylases, AP endonuclease 1 (APE1) and DNA Polymerase β (Pol β). In addition, deleting Ku70 was not equivalent to deleting Ku80 in cells and mice. Therefore, we hypothesized that free Ku70 (not bound to Ku80) and/or free Ku80 (not bound to Ku70) possessed activity that influenced BER. To further test this hypothesis we performed two general sets of experiments. The first set showed that deleting either Ku70 or Ku80 caused an NHEJ-independent defect. We found ku80-/- mice had a shorter life span than dna-pkcs-/- mice demonstrating a phenotype that was greater than deleting the holoenzyme. We also found Ku70-deletion induced a p53 response that reduced the level of small mutations in the brain suggesting defective BER. We further confirmed that Ku80-deletion impaired BER via a mechanism that was not epistatic to Pol β. The second set of experiments showed that free Ku70 and free Ku80 could influence BER. We observed that deletion of either Ku70 or Ku80, but not both, increased sensitivity of cells to CRT0044876 (CRT), an agent that interferes with APE1. In addition, free Ku70 and free Ku80 bound to AP sites and in the case of Ku70 inhibited APE1 activity. These observations support a novel role for free Ku70 and free Ku80 in altering BER. © 2014 Choi et al

Mapping services at two Nairobi County primary health facilities: identifying challenges and opportunities in integrated mental health care as a Universal Health Coverage (UHC) priority

Abstract: Introduction There is a need to scale-up mental health service provision in primary health care. The current extent of integration of mental health in primary care is pertinent to promoting and augmenting mental health at this level. We describe a facility mapping exercise conducted in two low-income/primary health facilities in Kenya to identify existing barriers and facilitators in the delivery of mental health services in general and specifically for peripartum adolescents in primary health care as well as available service resources, cadres, and developmental partners on the ground. Method and measures This study utilized a qualitative evidence synthesis through mapping facility-level services and key-stakeholder interviews. Services-related data were collected from two facility in-charges using the Nairobi City County Human Resource Health Strategy record forms. Additionally, we conducted 10 key informant interviews (KIIs) with clinical officers (Clinicians at diploma level), Nurses, Community Health Assistants (CHAs), Prevention of Mother-to-child Transmission of HIV Mentor Mothers (PMTCTMs), around both general and adolescent mental health as well as psychosocial services they offered. Using the World Health Organization Assessments Instrument for Mental Health Systems (WHO-AIMS) as a guideline for the interview, all KII questions were structured to identify the extent of mental health integration in primary health care services. Interview transcripts were then systematically analyzed for common themes and discussed by the first three authors to eliminate discrepancies. Results Our findings show that health care services centered around physical health were offered daily while the mental health services were still vertical, offered weekly through specialist services by the Ministry of Health directly or non-governmental partners. Despite health care workers being aware of the urgent need to integrate mental health services into routine care, they expressed limited knowledge about mental disorders and reported paucity of trained mental health personnel in these sites. Significantly, more funding and resources are needed to provide mental health services, as well as the need for training of general health care providers in the identification and treatment of mental disorders. Our stakeholders underscored the urgency of integrating mental health treatment, prevention, and well-being promotive activities targeting adolescents especially peripartum adolescent girls. Conclusion There is a need for further refining of the integrated care model in mental health services and targeted capacity-building for health care providers to deliver quality services

Community acceptability of use of rapid diagnostic tests for malaria by community health workers in Uganda

<p>Abstract</p> <p>Background</p> <p>Many malarious countries plan to introduce artemisinin combination therapy (ACT) at community level using community health workers (CHWs) for treatment of uncomplicated malaria. Use of ACT with reliance on presumptive diagnosis may lead to excessive use, increased costs and rise of drug resistance. Use of rapid diagnostic tests (RDTs) could address these challenges but only if the communities will accept their use by CHWs. This study assessed community acceptability of the use of RDTs by Ugandan CHWs, locally referred to as community medicine distributors (CMDs).</p> <p>Methods</p> <p>The study was conducted in Iganga district using 10 focus group discussions (FGDs) with CMDs and caregivers of children under five years, and 10 key informant interviews (KIIs) with health workers and community leaders. Pre-designed FGD and KII guides were used to collect data. Manifest content analysis was used to explore issues of trust and confidence in CMDs, stigma associated with drawing blood from children, community willingness for CMDs to use RDTs, and challenges anticipated to be faced by the CMDs.</p> <p>Results</p> <p>CMDs are trusted by their communities because of their commitment to voluntary service, access, and the perceived effectiveness of anti-malarial drugs they provide. Some community members expressed fear that the blood collected could be used for HIV testing, the procedure could infect children with HIV, and the blood samples could be used for witchcraft. Education level of CMDs is important in their acceptability by the community, who welcome the use of RDTs given that the CMDs are trained and supported. Anticipated challenges for CMDs included transport for patient follow-up and picking supplies, adults demanding to be tested, and caregivers insisting their children be treated instead of being referred.</p> <p>Conclusion</p> <p>Use of RDTs by CMDs is likely to be acceptable by community members given that CMDs are properly trained, and receive regular technical supervision and logistical support. A well-designed behaviour change communication strategy is needed to address the anticipated programmatic challenges as well as community fears and stigma about drawing blood. Level of formal education may have to be a criterion for CMD selection into programmes deploying RDTs.</p

High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: the randomized phase III NeoTN trial

Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23–1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03–0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30–3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24–87%), 71% (95% CI 48–100%) and 88% (95% CI 74–100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069

The chicken IL-1 family: evolution in the context of the studied vertebrate lineage

The interleukin-1 gene family encodes a group of related proteins that exhibit a remarkable pleiotropy in the context of health and disease. The set of indispensable functions they control suggests that these genes should be found in all eukaryotic species. The ligands and receptors of this family have been primarily characterised in man and mouse. The genomes of most non-mammalian animal species sequenced so far possess all of the IL-1 receptor genes found in mammals. Yet, strikingly, very few of the ligands are identifiable in non-mammalian genomes. Our recent identification of two further IL-1 ligands in the chicken warranted a critical reappraisal of the evolution of this vitally important cytokine family. This review presents substantial data gathered across multiple, divergent metazoan genomes to unambiguously trace the origin of these genes. With the hypothesis that all of these genes, both ligands and receptors, were formed in a single ancient ancestor, extensive database mining revealed sufficient evidence to confirm this. It therefore suggests that the emergence of mammals is unrelated to the expansion of the IL-1 family. A thorough review of this cytokine family in the chicken, the most extensively studied amongst non-mammalian species, is also presented. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00251-014-0780-7) contains supplementary material, which is available to authorized users