Can context justify an ethical double standard for clinical research in developing countries?

BACKGROUND: The design of clinical research deserves special caution so as to safeguard the rights of participating individuals. While the international community has agreed on ethical standards for the design of research, these frameworks still remain open to interpretation, revision and debate. Recently a breach in the consensus of how to apply these ethical standards to research in developing countries has occurred, notably beginning with the 1994 placebo-controlled trials to reduce maternal to child transmission of HIV-1 in Africa, Asia and the Caribbean. The design of these trials sparked intense debate with the inclusion of a placebo-control group despite the existence of a 'gold standard' and trial supporters grounded their justifications of the trial design on the context of scarcity in resource-poor settings. DISCUSSION: These 'contextual' apologetics are arguably an ethical loophole inherent in current bioethical methodology. However, this convenient appropriation of 'contextual' analysis simply fails to acknowledge the underpinnings of feminist ethical analysis upon which it must stand. A more rigorous analysis of the political, social, and economic structures pertaining to the global context of developing countries reveals that the bioethical principles of beneficence and justice fail to be met in this trial design. CONCLUSION: Within this broader, and theoretically necessary, understanding of context, it becomes impossible to justify an ethical double standard for research in developing countries

Analisis dan Perancangan Sistem Informasi Pendistribusian Gas Lpg Bersubsidi dengan Metodologi Object Oriented Studi Kasus PT. Xyz

Kemajuan peradaban dan populasi manusia, serta revolusi industri telah membawa manusia pada era eksploitasi Sumber Daya Alam(SDA) sehingga persediaannya terus berkurang secara signifikan. SDA mutlak diperlukan untuk menunjang kebutuhan manusia. Indonesia merupakan negara dengan tingkat biodiversitas tertinggi kedua di dunia setelah Brazil. Berdasarkan sifatnya dapat digolongkan menjadi SDA yang dapat diperbaharui dan SDA tak dapat diperbaharui seperti tumbuhan, hewan, mikroorganisme, sinar matahari, angin, dan air. Minyak bumi, emas, besi, Gas dan berbagai bahan tambang lainnya adalah SDA tak dapat diperbaharui yang jumlahnya terbatas karena penggunaanya lebih cepat daripada proses pembentukannya. LPG adalah kependekan dari Liquefied Petroleum Gas. LPG merupakan gas hasil produksi dari kilang minyak atau kilang gas, yang komponen utamanya adalah gas propane (C3H8) dan butane (C4H10) yang dicairkan. Menimbang bahwa dalam rangka untuk menjamin penyediaan dan pengadaan bahan bakar di dalam negeri dan mengurangi subsidi Bahan Bakar Minyak (BBM) guna meringankan beban keuangan negara, perlu dilakukan substitusi penggunaan minyak tanah ke LPG maka keluar Peraturan Presiden Republik Indonesia Nomor 104 Tahun 2007 tentang penyediaan, pendistribusian, dan penetapan harga LPG. PT. XYZ menjadi salah satu Badan Usaha yang menyelenggarakan penyediaan dan pendistribusian LPG bersubsidi. Dalam prosesnya dibutuhkan laporan – laporan mengenai pendistribusian, terutama pada data penerima subsidi. Data ini sangat banyak sehingga menyulitkan jika dilakukan secara manual. PT. XYZ membantu proses pendistribusian untuk menghindari kecurangan – kecurangan yang mungkin dilakukan pada saat pendistribusian. PERTAMINA sebagai pemberi subsidi mengharapkan distribusi merata di seluruh wilayah Indonesia. Untuk mengurangi kesalahan dan kecurangan pada saat distrubisi Gas maka dibutuhkan Sistem informasi, dengan sistem informasi proses pendistrubusian Gas akan lebih cepat dan akurat sehingga Perusahaan dapat bekerja secara baik, efektif, dan efisien. Anaisis dan perancangan sistem menggunakan Metodologi Object Oriented dan UML, database yang digunakan adalah Mysql Server dengan Microsoft Visual Studio 2005 sebagai bahasa program nya

No Difference in Growth Outcomes up to 24 Months of Age by Duration of Exposure to Maternal Antiretroviral Therapy Among Children Who Are HIV-Exposed and Uninfected in Malawi

BACKGROUND: With the implementation of lifelong antiretroviral therapy (ART) for HIV treatment and prevention, the proportion of children exposed to ART in utero from conception is increasing. We estimated the effect of timing of ART exposure on growth of children HIV-exposed and uninfected (CHEU) up to Up to 24 months of age in Malawi. METHODS: Data were collected from a prospective cohort of infants HIV-exposed aged 1–6 months (enrollment) and their mothers with HIV enrolled in the National Evaluation of Malawi’s Prevention of Mother-to-Child Transmission of HIV Programme (2014–2018). Anthropometry was measured at enrollment, visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) were calculated using the WHO Growth Standards. Multivariable mixed-effects models with linear splines for age were used to examine differences in growth by timing of ART exposure (from conception, first/second trimester, or third trimester/postpartum). Models were adjusted for confounders selected a priori guided by a conceptual framework. Hypothesized interactions and potential mediators were explored, and interactions with splines were included in final models if P 1.0). CONCLUSION: Reassuringly, ART exposure from conception was not associated with decreased WAZ or LAZ in CHEU Up 24 months of age. Overall growth trajectories suggest CHEU experience growth faltering after 12 months of age and may need support through and beyond the first 2 years of life

Tackling challenges of global health electives: Resident experiences of a structured and supervised medicine elective within an existing global health partnership

Background: The Toronto-Addis Ababa Academic Collaboration in Emergency Medicine (TAAAC-EM) deploys teaching teams of Canadian EM faculty to Addis Ababa to deliver a longitudinal residency curriculum. Canadian trainees participate in these teams as a formally structured and supervised elective in global health (GH) and EM, which has been designed to enhance the strength of GH electives and address key challenges highlighted in the literature.Methods: The purpose of this qualitative study was to identify, describe, and evaluate strengths and weaknesses of this elective in relation to its purposeful structure. Residents who completed the elective were invited to participate in face-to-face interviews to discuss their experiences.Results: The findings show that the residents both chose this elective because of its purposefully designed features, and that these same features increased their enjoyment and the educational benefit of the elective. Supervised bedside teaching, relationships shared with Ethiopian residents, and the positive impact the experience had on their clinical practice in Canada were identified as the primary strengthsConclusion: Purposeful and thoughtful design of global health electives can enhance the resident learning experience and mitigate challenges for trainees seeking global health training opportunities

Risk factors for stunting in children who are HIV-exposed and uninfected after Option B+ implementation in Malawi

Evidence suggests children HIV-exposed and uninfected (CHEU) experience poor growth. We analysed child anthropometrics and explored factors associated with stunting among Malawian CHEU. Mothers with HIV and their infants HIV-exposed were enroled in a nationally representative prospective cohort within the National Evaluation of Malawi's Prevention of Mother-to-Child HIV Transmission Programme after Option B+ implementation (2014-2018). Anthropometry was measured at enrolment (age 1-6 months), visit 1 (approximately 12 months), and visit 2 (approximately 24 months). Weight-for-age (WAZ) and length-for-age (LAZ) z-scores were calculated using World Health Organization Growth Standards; underweight and stunting were defined as WAZ and LAZ more than 2 standard deviations below the reference median. Multivariable logistic regression restricted to CHEU aged 24 months (±3 months) was used to identify factors associated with stunting. Among 1211 CHEU, 562/1211 attended visit 2, of which 529 were aged 24 months (±3 months) and were included. At age 24 months, 40.4% of CHEU were stunted and/or underweight, respectively. In multi-variable analysis, adjusting for child age and sex, the odds of stunting were higher among CHEU with infectious disease diagnosis compared to those with no diagnosis (adjusted odds ratio = 3.35 [95% confidence interval: 1.82-6.17]), which was modified by co-trimoxazole prophylaxis (p = 0.028). Infant low birthweight was associated with an increased odds of stunting; optimal feeding and maternal employment were correlated with reduced odds. This is one of the first studies examining CHEU growth since Option B+. Interventions to improve linear growth among CHEU should address their multi-faceted health risks, alongside maternal ART prescription, and follow-up of mother-child pairs

The effectiveness of interventions to improve uptake and retention of HIV-infected pregnant and breastfeeding women and their infants in prevention of mother-to-child transmission care programs in low- and middle-income countries: protocol for a systematic review and meta-analysis

Abstract Background Despite recent improvements, uptake and retention of mothers and infants in prevention of mother-to-child transmission (PMTCT) services remain well below target levels in many low- and middle-income countries (LMICs). Identification of effective interventions to support uptake and retention is the first step towards improvement. We aim to complete a systematic review and meta-analysis to evaluate the effectiveness of interventions at the patient, provider or health system level in improving uptake and retention of HIV-infected mothers and their infants in PMTCT services in LMICs. Methods/Design We will include studies comparing usual care or no intervention to any type of intervention to improve uptake and retention of HIV-infected pregnant or breastfeeding women and their children from birth to 2 years of age attending PMTCT services in LMICs. We will include randomized controlled trials (RCTs), cluster RCTs, non-randomized controlled trials, and interrupted time series. The primary outcomes of interest are percentage of HIV-infected women receiving/initiated on anti-retroviral prophylaxis or treatment, percentage of infants receiving/initiated on anti-retroviral prophylaxis, and percentage of women and infants completing the anti-retroviral regimen/retained in PMTCT care. The following databases will be searched from inception: Ovid MEDLINE and EMBASE, The WHO Global Health Library, CAB abstracts, EBM Reviews, CINAHL, HealthSTAR and Web of Science databases, Scopus, PsychINFO, POPLINE, Sociological Abstracts, ERIC, AIDS Education Global Information System, NLM Gateway, LILACS, Google Scholar, British Library Catalogue, DARE, ProQuest Dissertation & Theses, the New York Academy of Grey Literature, Open Grey, The Cochrane Library, WHO International Clinical Trials Registry, Controlled Clinical Trials, and clinicaltrials.gov. Reference lists of included articles will be hand searched and study authors and content experts contacted to inquire about eligible unpublished or in progress studies. Screening, data abstraction, and risk of bias appraisal using the Cochrane Effective Practice and Organization of Care criteria will be conducted independently by two team members. Results will be synthesized narratively and a meta-analysis conducted using the DerSimonian Laird random effects method if appropriate based on assessment of clinical and statistical heterogeneity. Discussion Our findings will be useful to PMTCT implementers, policy makers, and implementation researchers working in LMICs. Systematic review registration PROSPERO CRD4201502082

Towards elimination of mother-to-child transmission of HIV: performance of different models of care for initiating lifelong antiretroviral therapy for pregnant women in Malawi (Option B+).

INTRODUCTION: Malawi introduced a new strategy to improve the effectiveness of prevention of mother-to-child HIV transmission (PMTCT), the Option B+ strategy. We aimed to (i) describe how Option B+ is provided in health facilities in the South East Zone in Malawi, identifying the diverse approaches to service organization (the "model of care") and (ii) explore associations between the "model of care" and health facility-level uptake and retention rates for pregnant women identified as HIV-positive at antenatal (ANC) clinics. METHODS: A health facility survey was conducted in all facilities providing PMTCT/antiretroviral therapy (ART) services in six of Malawi's 28 districts to describe and compare Option B+ service delivery models. Associations of identified models with program performance were explored using facility cohort reports. RESULTS: Among 141 health facilities, four "models of care" were identified: A) facilities where newly identified HIV-positive women are initiated and followed on ART at the ANC clinic until delivery; B) facilities where newly identified HIV-positive women receive only the first dose of ART at the ANC clinic, and are referred to the ART clinic for follow-up; C) facilities where newly identified HIV-positive women are referred from ANC to the ART clinic for initiation and follow-up of ART; and D) facilities serving as ART referral sites (not providing ANC). The proportion of women tested for HIV during ANC was highest in facilities applying Model A and lowest in facilities applying Model B. The highest retention rates were reported in Model C and D facilities and lowest in Model B facilities. In multivariable analyses, health facility factors independently associated with uptake of HIV testing and counselling (HTC) in ANC were number of women per HTC counsellor, HIV test kit availability, and the "model of care" applied; factors independently associated with ART retention were district location, patient volume and the "model of care" applied. CONCLUSIONS: A large variety exists in the way health facilities have integrated PMTCT Option B+ care into routine service delivery. This study showed that the "model of care" chosen is associated with uptake of HIV testing in ANC and retention in care on ART. Further patient-level research is needed to guide policy recommendations

Baseline characteristics of study sites and women enrolled in a three-arm cluster randomized controlled trial: PMTCT uptake and retention (pure) Malawi

Abstract Background Malawi introduced an ambitious public health program known as “Option B+” which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of WHO clinical stage or CD4 cell count. The PMTCT Uptake and REtention (PURE) study aimed at evaluating the effect of peer-support on care-seeking and retention in care. Methods/design PURE Malawi was a three-arm cluster randomized controlled trial that compared facility-based and community-based models of peer support to standard of care under Option B+ strategy. Each arm was expected to enroll a minimum of 360 women with a total minimum sample size of 1080 participants. 21 sites (clusters) were selected for inclusion in the study. This paper describes the site selection, recruitment, enrollment process and baseline characteristics of study sites and women enrolled in the trial. Results Study implementation was managed by 3 partner organizations; each responsible for 7 study sites. The trial was conducted in the South East, South West, and Central West zones of Malawi, the zones where the implementing partners operate. Study sites included 2 district hospitals, 2 mission hospitals, 2 rural hospitals, 13 health centers and 1 private clinic. Enrollment occurred from November 2013 to November 2014, over a median period of 31 weeks (range 17–51) by site. A total of 1269 HIV-infected pregnant (1094) and breastfeeding (175) women, who were eligible to initiate ART under Option B+, were enrolled. Each site reached or surpassed the minimum sample size. Comparing the number of women enrolled versus antenatal cohort reports, sites recruited a median of 90% (IQR 75–100) of eligible reported women. In the majority of sites the ratio of pregnant and lactating women enrolled in the study was similar to the ratio of reported pregnant and lactating women starting ART in the same sites. The median age of all women was 27 (IQR 22–31) years. All women have ≥20 months of possible follow-up time; 96% ≥ 2 years (24–32 months). Conclusion The PURE Malawi study showed that 3 implementing partner organizations could successfully recruit a complex cohort of pregnant and lactating women across 3 geographical zones in Malawi within a reasonable timeline. Trial registration This study is registered at clinicaltrials.gov - ID Number NCT02005835 . Registered 4 December, 2013

Pregnancy intention and contraceptive use among HIV-positive Malawian women at 4-26 weeks post-partum: A nested cross-sectional study.

BACKGROUND: Avoiding unintended pregnancies through family planning is a WHO strategy for preventing mother to child transmission of HIV (PMTCT) and maternal morbidity/mortality. We investigated factors associated with unintended index pregnancy, unmet contraceptive need, future pregnancy intention and current contraceptive use among Malawian women living with HIV in the Option B+ era. METHODS: Women who tested HIV positive at 4-26 weeks postpartum were enrolled into a cross-sectional study at high-volume Under-5 clinics. Structured baseline interviews included questions on socio-demographics, HIV knowledge, partner's HIV status/disclosure, ART use, pregnancy intention and contraceptive use. Logistic regression was used to determine factors associated with outcomes. RESULTS: We enrolled 578 HIV-positive women between May 2015-May 2016; median maternal age was 28 years (y) (interquartile-range [IQR]: 23-32), median parity was 3 deliveries (IQR: 2-4) and median infant age was 7 weeks (IQR: 6-12). Overall, 41.8% women reported unintended index pregnancy, of whom 35.0% reported unmet contraceptive need and 65.0% contraceptive failure. In multivariable analysis, unintended index pregnancy was higher in ≥35y vs. 14-24y (adjusted Odds Ratio [aOR]: 2.1, 95% Confidence Interval [95%CI]: 1.0-4.2) and in women with parity ≥3 vs. primiparous (aOR: 2.9, 95%CI: 1.5-5.6). Unmet contraceptive need at conception was higher in 14-24y vs. ≥35y (aOR: 4.2, 95%CI: 1.8-9.9), primiparous vs. ≥3 (aOR: 8.3, 95%CI: 1.8-39.5), and women with a partner of unknown HIV-status (aOR: 2.2, 95%CI: 1.2-4.0). Current contraceptive use was associated with being on ART in previous pregnancy (aOR: 2.5, 95%CI: 1.5-3.9). CONCLUSIONS: High prevalence of unintended index pregnancy and unmet contraceptive need among HIV-positive women highlight the need for improved access to contraceptives. To help achieve reproductive goals and elimination of MTCT of HIV, integration of family planning into HIV care should be strengthened to ensure women have timely access to a wide range of family planning methods with low failure risk

Uptake and outcomes of a prevention-of mother-to-child transmission (PMTCT) program in Zomba district, Malawi

<p>Abstract</p> <p>Background</p> <p>HIV prevalence among pregnant women in Malawi is 12.6%, and mother-to-child transmission is a major route of transmission. As PMTCT services have expanded in Malawi in recent years, we sought to determine uptake of services, HIV-relevant infant feeding practices and mother-child health outcomes.</p> <p>Methods</p> <p>A matched-cohort study of HIV-infected and HIV-uninfected mothers and their infants at 18-20 months post-partum in Zomba District, Malawi. 360 HIV-infected and 360 HIV-uninfected mothers were identified through registers. 387 mother-child pairs were included in the study.</p> <p>Results</p> <p>10% of HIV-infected mothers were on HAART before delivery, 27% by 18-20 months post-partum. sd-NVP was taken by 75% of HIV-infected mothers not on HAART, and given to 66% of infants. 18% of HIV-infected mothers followed all current recommended PMTCT options. HIV-infected mothers breastfed fewer months than HIV-uninfected mothers (12 vs.18, respectively; <it>p </it>< 0.01). 19% of exposed versus 5% of unexposed children had died by 18-20 months; <it>p </it>< 0.01. 28% of exposed children had been tested for HIV prior to the study, 76% were tested as part of the study and 11% were found HIV-positive. HIV-free survival by 18-20 months was 66% (95%CI 58-74). There were 11(6%) maternal deaths among HIV-infected mothers only.</p> <p>Conclusion</p> <p>This study shows low PMTCT program efficiency and effectiveness under routine program conditions in Malawi. HIV-free infant survival may have been influenced by key factors, including underuse of HAART, underuse of sd-NVP, and suboptimal infant feeding practices. Maternal mortality among HIV-infected women demands attention; improved maternal survival is a means to improve infant survival.</p