Publications by authors named "Ushma Mehta"

35 Publications

Association between food intake and obesity in pregnant women living with and without HIV in Cape Town, South Africa: a prospective cohort study.

BMC Public Health 2021 08 4;21(1):1504. Epub 2021 Aug 4.

Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, University of Cape Town, Falmouth Building, Anzio Road, Observatory, Cape Town, Western Cape, 7925, South Africa.

Background: Although global nutrition/dietary transition resulting from industrialisation and urbanisation has been identified as a major contributor to widespread trends of obesity, there is limited data in pregnant women, including those living with HIV in South Africa. We examined food-based dietary intake in pregnant women with and without HIV at first antenatal care (ANC) visit, and associations with maternal overweight/obesity and gestational weight gain (GWG).

Methods: In an urban South African community, consecutive women living with (n = 479) and without (n = 510) HIV were enrolled and prospectively followed to delivery. Interviewer-administered non-quantitative food frequency questionnaire was used to assess dietary intake (starch, protein, dairy, fruits, vegetables, legumes, oils/fats) at enrolment. Associations with maternal body mass index (BMI) and GWG were examined using logistic regression models.

Results: Among women (median age 29 years, IQR 25-34), the prevalence of obesity (BMI ≥ 30 kg/m) at first ANC was 43% and that of excessive GWG (per IOM guidelines) was 37% overall; HIV prevalence was 48%. In women without HIV, consumption of potato (any preparation) (aOR 1.98, 95% CI 1.02-3.84) and pumpkin/butternut (aOR 2.13, 95% CI 1.29-3.49) for 1-3 days a week increased the odds of overweight/obesity compared to not consuming any; milk in tea/coffee (aOR 6.04, 95% CI 1.37-26.50) increased the odds of excessive GWG. Consumption of eggs (any) (aOR 0.52, 95% CI 0.32-0.86) for 1-3 days a week reduced the odds of overweight/obesity while peanut and nuts consumption for 4-7 days a week reduced the odds (aOR 0.34, 95% CI 0.14-0.80) of excessive GWG. In women with HIV, consumption of milk/yoghurt/maas to drink/on cereals (aOR 0.35, 95% CI 0.18-0.68), tomato (raw/cooked) (aOR 0.50, 95% CI 0.30-0.84), green beans (aOR 0.41, 95% CI 0.20-0.86), mixed vegetables (aOR 0.49, 95% CI 0.29-0.84) and legumes e.g. baked beans, lentils (aOR 0.50, 95% CI 0.28-0.86) for 4-7 days a week reduced the odds of overweight/obesity; tomato (raw/cooked) (aOR 0.48, 95% CI 0.24-0.96) and mixed vegetables (aOR 0.38, 95% CI 0.18-0.78) also reduced the odds of excessive GWG.

Conclusions: Diet modification may promote healthy weight in pregnant women living with and without HIV.
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http://dx.doi.org/10.1186/s12889-021-11566-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335890PMC
August 2021

Adult medical emergency unit presentations due to adverse drug reactions in a setting of high HIV prevalence.

Afr J Emerg Med 2021 Mar 30;11(1):46-52. Epub 2020 Nov 30.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Introduction: South Africa has the world's largest antiretroviral treatment programme, which may contribute to the adverse drug reaction (ADR) burden. We aimed to determine the proportion of adult non-trauma emergency unit (EU) presentations attributable to ADRs and to characterise ADR-related EU presentations, stratified according to HIV status, to determine the contribution of drugs used in management of HIV and its complications to ADR-related EU presentations, and identify factors associated with ADR-related EU presentation.

Methods: We conducted a retrospective folder review on a random 1.7% sample of presentations over a 12-month period in 2014/2015 to the EUs of two hospitals in Cape Town, South Africa. We identified potential ADRs with the help of a trigger tool. A multidisciplinary panel assessed potential ADRs for causality, severity, and preventability.

Results: We included 1010 EU presentations and assessed 80/1010 (7.9%) as ADR-related, including 20/239 (8.4%) presentations among HIV-positive attendees. Among HIV-positive EU attendees with ADRs 17/20 (85%) were admitted, versus 22/60 (37%) of HIV-negative/unknown EU attendees. Only 5/21 (24%) ADRs in HIV-positive EU attendees were preventable, versus 24/63 (38%) in HIV-negative/unknown EU attendees. On multivariate analysis, only increasing drug count was associated with ADR-related EU presentation (adjusted odds ratio 1.10 per additional drug, 95% confidence interval 1.03 to 1.18), adjusted for age, sex, HIV status, comorbidity, and hospital.

Conclusions: ADRs caused a significant proportion of EU presentations, similar to findings from other resource-limited settings. The spectrum of ADR manifestations in our EUs reflects South Africa's colliding epidemics of infectious and non-communicable diseases. ADRs among HIV-positive EU attendees were more severe and less likely to be preventable.
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http://dx.doi.org/10.1016/j.afjem.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787921PMC
March 2021

Adapting virus filtration to enable intensified and continuous monoclonal antibody processing.

Biotechnol Prog 2021 03 11;37(2):e3088. Epub 2020 Dec 11.

Process Solutions, MilliporeSigma, Burlington, Massachusetts, USA.

Ongoing efforts in the biopharmaceutical industry to enhance productivity and reduce manufacturing costs include development of intensified, linked, and/or continuous processes. One approach to improve productivity and process economics of the polishing step (i.e., anion exchange chromatography) is to preconcentrate the product intermediate using a single-pass tangential flow filtration step before loading on the resin. This intensification of the polishing step consequently leads to changes in product intermediate concentration for subsequent virus filtration operations, potentially impacting filter performance and methods for evaluating viral clearance. The filtrate flux performance of a virus filtration operation was evaluated with monoclonal antibody (mAb) solutions of varying concentrations. These data were used to evaluate the effect on filter sizing for a hypothetical mAb perfusion process. The optimum mAb concentration to minimize the area of the virus filter was a function of the filtration step duration and reflected the competing effects of increasing concentration and decreasing volumetric flux on the membrane productivity. mAb solutions at high and low concentrations were used to evaluate viral clearance with extended filtration times (e.g., 24-72 h) simulating continuous processing conditions. Modifications to more traditional filtration viral clearance study methods were required to avoid experimental artifacts associated with the extended filtration time. No virus passage through the filter was observed under these conditions, similar to previous results for batch processes. These data demonstrate the feasibility of obtaining effective virus removal even when mAb concentration and filtrations times are increased by up to an order of magnitude from current common practices.
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http://dx.doi.org/10.1002/btpr.3088DOI Listing
March 2021

Understanding and Responding to Prescribing Patterns of Sodium Valproate-Containing Medicines in Pregnant Women and Women of Childbearing Age in Western Cape, South Africa.

Drug Saf 2021 Jan;44(1):41-51

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, Western Cape, South Africa.

Introduction: Growing evidence of the teratogenic potential of sodium valproate (VPA) has changed prescribing practices across the globe; however, the impact of this research and the consequent dissemination of a Dear Health Care Professional Letter (DHCPL) in December 2015, recommending avoidance of the teratogen VPA in women of childbearing age (WOCBA) and pregnant women in South Africa, is unknown. We explored trends and reasons for VPA use among pregnant women and WOCBA in the public sector in Western Cape Province from 1 January 2015 to 31 December 2017.

Methods: Using the provincial health information exchange that collates routine electronic health data via unique patient identifiers, we analysed clinical and pharmacy records from 2015 to 2017 to determine prescription patterns of VPA and other antiepileptic drug (AED) and mood-stabilising medicine (MSM) use in WOCBA and pregnant women. Senior clinicians and policy makers were consulted to understand the determinants of VPA use.

Results: At least one VPA prescription was dispensed to between 8205 (0.79%) and 9425 (0.94%) WOBCA from a cohort of approximately 1 million WOCBA attending provincial health care facilities per year. Prescriptions were more likely in HIV-infected women compared with HIV-uninfected women (1.1-1.3% vs. 0.7-0.9%; p < 0.001). VPA use in WOCBA remained stable at 0.8-0.9% over the review period despite the 2016 DHCPL. VPA was the most prescribed AED/MSM, constituting 43.2-45.5% of all WOCBA taking at least one such agent, while lamotrigine, the other recommended first-line agent, was only prescribed in 7.8-8.9% of WOCBA. Over 3 years, approximately 663 pregnancies were exposed to VPA, with a steady rise in the number of exposures each year (n = 204, 214 and 245, respectively).

Conclusion: Despite warnings, VPA remained the most frequently prescribed AED or MSM in WOCBA. Contributing factors are described.
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http://dx.doi.org/10.1007/s40264-020-00987-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813724PMC
January 2021

Outcomes at 18 mo of 37 noma (cancrum oris) cases surgically treated at the Noma Children's Hospital, Sokoto, Nigeria.

Trans R Soc Trop Med Hyg 2020 11;114(11):812-819

Médecins Sans Frontières, Amsterdam, the Netherlands.

Background: Noma is a rapidly progressing infection of the oral cavity frequently resulting in severe facial disfigurement. We present a case series of noma patients surgically treated in northwest Nigeria.

Methods: A retrospective analysis of routinely collected data (demographics, diagnosis and surgical procedures undergone) and in-person follow-up assessments (anthropometry, mouth opening and quality of life measurements) were conducted with patients who had surgery >6 mo prior to data collection.

Results: Of the 37 patients included, 21 (56.8%) were male and 22 (62.9%) were aged >6 y. The median number of months between last surgery and follow-up was 18 (IQR 13, 25) mo. At admission, the most severely affected anatomical area was the outer cheek (n = 9; 36.0% of patients had lost between 26% and 50%). The most frequent surgical procedures were the deltopectoral flap (n = 16; 43.2%) and trismus release (n = 12; 32.4%). For the eight trismus-release patients where mouth opening was documented at admission, all had a mouth opening of 0-20 mm at follow-up. All patients reported that the surgery had improved their quality of life.

Conclusions: Following their last surgical intervention, noma patients do experience some improvements in their quality of life, but debilitating long-term sequelae persist.
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http://dx.doi.org/10.1093/trstmh/traa061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645286PMC
November 2020

The prevalence of noma in northwest Nigeria.

BMJ Glob Health 2020 14;5(4):e002141. Epub 2020 Apr 14.

Operational Center Amsterdam Headquarters, Médecins Sans Frontières, Amsterdam, The Netherlands.

Background: Noma, a rapidly progressing infection of the oral cavity, mainly affects children. The true burden is unknown. This study reports estimated noma prevalence in children in northwest Nigeria.

Methods: Oral screening was performed on all ≤15 year olds, with caretaker consent, in selected households during this cross-sectional survey. Noma stages were classified using WHO criteria and caretakers answered survey questions. The prevalence of noma was estimated stratified by age group (0-5 and 6-15 years). Factors associated with noma were estimated using logistic regression.

Results: A total of 177 clusters, 3499 households and 7122 children were included. In this sample, 4239 (59.8%) were 0-5 years and 3692 (52.1%) were female. Simple gingivitis was identified in 3.1% (n=181; 95% CI 2.6 to 3.8), acute necrotising gingivitis in 0.1% (n=10; CI 0.1 to 0.3) and oedema in 0.05% (n=3; CI 0.02 to 0.2). No cases of late-stage noma were detected. Multivariable analysis in the group aged 0-5 years showed having a well as the drinking water source (adjusted odds ratio (aOR) 2.1; CI 1.2 to 3.6) and being aged 3-5 years (aOR 3.9; CI 2.1 to 7.8) was associated with being a noma case. In 6-15 year olds, being male (aOR 1.5; CI 1.0 to 2.2) was associated with being a noma case and preparing pap once or more per week (aOR 0.4; CI 0.2 to 0.8) was associated with not having noma. We estimated that 129120 (CI 105294 to 1 52 947) individuals <15 years of age would have any stage of noma at the time of the survey within the two states. Most of these cases (93%; n=120 082) would be children with simple gingivitis.

Conclusions: Our study identified a high prevalence of children at risk of developing advanced noma. This disease is important but neglected and therefore merits inclusion in the WHO neglected tropical diseases list.
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http://dx.doi.org/10.1136/bmjgh-2019-002141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199707PMC
June 2021

Language and beliefs in relation to noma: a qualitative study, northwest Nigeria.

PLoS Negl Trop Dis 2020 01 23;14(1):e0007972. Epub 2020 Jan 23.

Médecins Sans Frontières, London, United Kingdom.

Background: Noma is an orofacial gangrene that rapidly disintegrates the tissues of the face. Little is known about noma, as most patients live in underserved and inaccessible regions. We aimed to assess the descriptive language used and beliefs around noma, at the Noma Children's Hospital in Sokoto, Nigeria. Findings will be used to inform prevention programs.

Methods: Five focus group discussions (FGD) were held with caretakers of patients with noma who were admitted to the hospital at the time of interview, and 12 in-depth interviews (IDI) were held with staff at the hospital. Topic guides used for interviews were adapted to encourage the natural flow of conversation. Emergent codes, patterns and themes were deciphered from the data derived from IDI's and FGDs.

Results: Our study uncovered two main themes: names, descriptions and explanations for the disease, and risks and consequences of noma. Naming of the disease differed between caretakers and heath care workers. The general names used for noma illustrate the beliefs and social system used to explain the disease. Beliefs were varied; participant responses demonstrate a wide range of understanding of the disease and its causes. Difficulty in accessing care for patients with noma was evident and the findings suggest a variety of actions taking place before reaching a health center or health worker. Patient caretakers mentioned that barriers to care included a lack of knowledge regarding this medical condition, as well as a lack of trust in seeking medical care. Participants in our study spoke of the mental health strain the disease placed on them, particularly due to the stigma that is associated with noma.

Conclusions: Caretaker and practitioner perspectives enhance our understanding of the disease in this context and can be used to improve treatment and prevention programs, and to better understand barriers to accessing health care. Differences in disease naming illustrate the difference in beliefs about the disease. This has an impact on health seeking behaviours, which for noma cases has important ramifications on outcomes, due to the rapid progression of the disease.
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http://dx.doi.org/10.1371/journal.pntd.0007972DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999908PMC
January 2020

Serious adverse drug reactions at two children's hospitals in South Africa.

BMC Pediatr 2020 01 4;20(1). Epub 2020 Jan 4.

Department of Medicine, Division of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.

Background: The high HIV prevalence in South Africa may potentially be shaping the local adverse drug reaction (ADR) burden. We aimed to describe the prevalence and characteristics of serious ADRs at admission, and during admission, to two South African children's hospitals.

Methods: We reviewed the folders of children admitted over sequential 30-day periods in 2015 to the medical wards and intensive care units of each hospital. We identified potential ADRs using a trigger tool developed for this study. A multidisciplinary team assessed ADR causality, type, seriousness, and preventability through consensus discussion. We used multivariate logistic regression to explore associations with serious ADRs.

Results: Among 1050 patients (median age 11 months, 56% male, 2.8% HIV-infected) with 1106 admissions we found 40 serious ADRs (3.8 per 100 drug-exposed admissions), including 9/40 (23%) preventable serious ADRs, and 8/40 (20%) fatal or near-fatal serious ADRs. Antibacterials, corticosteroids, psycholeptics, immunosuppressants, and antivirals were the most commonly implicated drug classes. Preterm neonates and children in middle childhood (6 to 11 years) were at increased risk of serious ADRs compared to infants (under 1 year) and term neonates: adjusted odds ratio (aOR) 5.97 (95% confidence interval 1.30 to 27.3) and aOR 3.63 (1.24 to 10.6) respectively. Other risk factors for serious ADRs were HIV infection (aOR 3.87 (1.14 to 13.2) versus HIV-negative) and increasing drug count (aOR 1.08 (1.04 to 1.12) per additional drug).

Conclusions: Serious ADR prevalence in our survey was similar to the prevalence found elsewhere. In our setting, serious ADRs were associated with HIV-infection and the antiviral drug class was one of the most commonly implicated. Similar to other sub-Saharan African studies, a large proportion of serious ADRs were fatal or near-fatal. Many serious ADRs were preventable.
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http://dx.doi.org/10.1186/s12887-019-1892-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6942333PMC
January 2020

Safety and Effectiveness of Isoniazid Preventive Therapy in Pregnant Women Living with Human Immunodeficiency Virus on Antiretroviral Therapy: An Observational Study Using Linked Population Data.

Clin Infect Dis 2020 11;71(8):e351-e358

Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.

Background: Isoniazid preventive therapy (IPT) is widely used to protect against tuberculosis (TB) in people living with human immunodeficiency virus (HIV). Data on the safety and efficacy of IPT in pregnant women living with HIV (PWLHIV) are mixed. We used an individual-level, population-wide health database to examine associations between antenatal IPT exposure and adverse pregnancy outcomes, maternal TB, all-cause mortality, and liver injury during pregnancy through 12 months postpartum.

Methods: We used linked routine electronic health data generated in the public sector of the Western Cape, South Africa, to define a cohort of PWLHIV on antiretroviral therapy. Pregnancy outcomes were assessed using logistic regression; for maternal outcomes we applied a proportional hazards model with time-updated IPT exposure.

Results: Of 43 971 PWLHIV, 16.6% received IPT. Women who received IPT were less likely to experience poor pregnancy outcomes (adjusted odds ratio [aOR], 0.83 [95% confidence interval {CI}, .78-.87]); this association strengthened with IPT started after the first trimester compared with none (aOR, 0.71 [95% CI, .65-.79]) or with first-trimester exposure (aOR, 0.64 [95% CI, .55-.75]). IPT reduced the risk of TB by approximately 30% (aHR, 0.71 [95% CI, .63-.81]; absolute risk difference, 1518/100 000 women). The effect was modified by CD4 cell count with protection conferred if CD4 count was ≤350 cells/μL (aHR, 0.51 [95% CI, .41-.63]) vs 0.93 [95% CI, .76-1.13] for CD4 count >350 cells/µL).

Conclusions: This analysis of programmatic data is reassuring regarding the safety of antenatal IPT, with the greatest benefits against TB disease observed in women with CD4 count ≤350 cells/μL.
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http://dx.doi.org/10.1093/cid/ciz1224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643738PMC
November 2020

Birth outcomes following antiretroviral exposure during pregnancy: Initial results from a pregnancy exposure registry in South Africa.

South Afr J HIV Med 2019 30;20(1):971. Epub 2019 Sep 30.

KwaZulu-Natal Department of Health, Pietermaritzburg, South Africa.

Background: In 2013, a pregnancy exposure registry and birth defects surveillance (PER/BDS) system was initiated in eThekwini District, KwaZulu-Natal (KZN), to assess the impact of antiretroviral treatment (ART) on birth outcomes.

Objectives: At the end of the first year, we assessed the risk of major congenital malformations (CM) and other adverse birth outcomes (ABOs) detected at birth, in children born to women exposed to ART during pregnancy.

Method: Data were collected from women who delivered at Prince Mshiyeni Memorial Hospital, Durban, from 07 October 2013 to 06 October 2014, using medicine exposure histories and birth outcomes from maternal interviews, clinical records and neonatal surface examination. Singleton births exposed to only one ART regimen were included in bivariable analysis for CM risk and multivariate risk analysis for ABO risk.

Results: Data were collected from 10 417 women with 10 517 birth outcomes (4013 [38.5%] HIV-infected). Congenital malformations rates in births exposed to Efavirenz during the first trimester (T1) (RR 0.87 [95% CI 0.12-6.4; = 0.895]) were similar to births not exposed to ART during T1. However, T1 exposure to Nevirapine was associated with the increased risk of CM (RR 9.28 [95% CI 2.3-37.9; = 0.002]) when compared to the same group. Other ABOs were more frequent in the combination of HIV/ART-exposed births compared to HIV-unexposed births (29.9% vs. 26.0%, adjusted RR 1.23 [1.14-1.31; < 0.001]).

Conclusion: No association between T1 use of EFV-based ART regimens and CM was observed. Associations between T1 NVP-based ART regimen and CM need further investigation. HIV- and ART-exposed infants had more ABOs compared to HIV-unexposed infants.
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http://dx.doi.org/10.4102/sajhivmed.v20i1.971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6779987PMC
September 2019

Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomised trial (DolPHIN-1 study).

PLoS Med 2019 09 20;16(9):e1002895. Epub 2019 Sep 20.

Department of Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

Background: The global transition to use of dolutegravir (DTG) in WHO-preferred regimens for HIV treatment is limited by lack of knowledge on use in pregnancy. Here we assessed the relationship between drug concentrations (pharmacokinetics, PK), including in breastmilk, and impact on viral suppression when initiated in the third trimester (T3).

Methods And Findings: In DolPHIN-1, HIV-infected treatment-naïve pregnant women (28-36 weeks of gestation, age 26 (19-42), weight 67kg (45-119), all Black African) in Uganda and South Africa were randomised 1:1 to dolutegravir (DTG) or efavirenz (EFV)-containing ART until 2 weeks post-partum (2wPP), between 9th March 2017 and 16th January 2018, with follow-up until six months postpartum. The primary endpoint was pharmacokinetics of DTG in women and breastfed infants; secondary endpoints included maternal and infant safety and viral suppression. Intensive pharmacokinetic sampling of DTG was undertaken at day 14 and 2wPP following administration of a medium-fat breakfast, with additional paired sampling between maternal plasma and cord blood, breastmilk and infant plasma. No differences in median baseline maternal age, gestation (31 vs 30 weeks), weight, obstetric history, viral load (4.5 log10 copies/mL both arms) and CD4 count (343 vs 466 cells/mm3) were observed between DTG (n = 29) and EFV (n = 31) arms. Although DTG Ctrough was below the target 324ng/mL (clinical EC90) in 9/28 (32%) mothers in the third trimester, transfer across the placenta (121% of plasma concentrations) and into breastmilk (3% of plasma concentrations), coupled with slower elimination, led to significant infant plasma exposures (3-8% of maternal exposures). Both regimens were well-tolerated with no significant differences in frequency of adverse events (two on DTG-ART, one on EFV-ART, all considered unrelated to drug). No congenital abnormalities were observed. DTG resulted in significantly faster viral suppression (P = 0.02) at the 2wPP visit, with median time to <50 copies/mL of 32 vs 72 days. Limitations related to the requirement to initiate EFV-ART prior to randomisation, and to continue DTG for only two weeks postpartum.

Conclusion: Despite low plasma DTG exposures in the third trimester, transfer across the placenta and through breastfeeding was observed in this study, with persistence in infants likely due to slower metabolic clearance. HIV RNA suppression <50 copies/mL was twice as fast with DTG compared to EFV, suggesting DTG has potential to reduce risk of vertical transmission in mothers who are initiated on treatment late in pregnancy.

Trial Registration: clinicaltrials.gov NCT02245022.
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http://dx.doi.org/10.1371/journal.pmed.1002895DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754125PMC
September 2019

'I treat it but I don't know what this disease is': a qualitative study on noma (cancrum oris) and traditional healing in northwest Nigeria.

Int Health 2020 01;12(1):28-35

Médecins Sans Frontières-Operational Centre Brussels, Medical Department, 68 Rue de Gasperich, 1617, Luxembourg Operational Research Unit (LuxOR).

Background: Noma, a neglected disease mostly affecting children, with a 90% mortality rate if untreated, is an orofacial gangrene that disintegrates the tissues of the face in <1 wk. Noma can become inactive with early stage antibiotic treatment. Traditional healers, known as mai maganin gargajiya in Hausa, play an important role in the health system and provide care to noma patients.

Methods: We conducted 12 in-depth interviews with caretakers who were looking after noma patients admitted at the Noma Children's Hospital and 15 traditional healers in their home villages in Sokoto state, northwest Nigeria. We explored perceptions of noma, relationship dynamics, healthcare practices and intervention opportunities. Interviews were audiorecorded, transcribed and translated. Manual coding and thematic analysis were utilised.

Results: Traditional healers offered specialised forms of care for specific conditions and referral guidance. They viewed the stages of noma as different conditions with individualised remedies and were willing to refer noma patients. Caretakers trusted traditional healers.

Conclusions: Traditional healers could play a crucial role in the early detection of noma and the health-seeking decision-making process of patients. Intervention programmes should include traditional healers through training and referral partnerships. This collaboration could save lives and reduce the severity of noma complications.
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http://dx.doi.org/10.1093/inthealth/ihz066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964223PMC
January 2020

Investigating the combination of single-pass tangential flow filtration and anion exchange chromatography for intensified mAb polishing.

Biotechnol Prog 2019 09 19;35(5):e2862. Epub 2019 Jun 19.

Department of Process Solutions, MilliporeSigma, Burlington, Massachusetts.

There is growing interest within the biopharmaceutical industry to improve manufacturing efficiency through process intensification, with the goal of generating more product in less time with smaller equipment. In monoclonal antibody (mAb) purification, a unit operation that can benefit from intensification is anion exchange (AEX) polishing chromatography. Single-pass tangential flow filtration (SPTFF) technology offers an opportunity for process intensification by reducing intermediate pool volumes and increasing product concentration without recirculation. This study evaluated the performance of an AEX resin, both in terms of host cell protein (HCP) purification and viral clearance, following concentration of a mAb feed using SPTFF. Results show that preconcentration of AEX feed material improved isotherm conditions for HCP binding, resulting in a fourfold increase in resin mAb loading at the target HCP clearance level. Excellent clearance of minute virus of mouse and xenotropic murine virus was maintained at this higher load level. The increased mAb loading enabled by SPTFF preconcentration effectively reduced AEX column volume and buffer requirements, shrinking the overall size of the polishing step. In addition, the suitability of SPTFF for extended processing time operation was demonstrated, indicating that this approach can be implemented for continuous biomanufacturing. The combination of SPTFF concentration and AEX chromatography for an intensified mAb polishing step which improves both manufacturing flexibility and process productivity is supported.
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http://dx.doi.org/10.1002/btpr.2862DOI Listing
September 2019

Pharmacovigilance: A public health priority for South Africa.

S Afr Health Rev 2017 23;2017:125-133. Epub 2017 Aug 23.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town.

South Africa has been engaged in pharmacovigilance (PV) activities to assess the impact of adverse drug reactions on public safety and health for 40 years. Activities have evolved from passive regulatory reporting to encompass active surveillance systems. The HIV and AIDS and TB epidemics stimulated pharmacoepidemiological research into the risks associated with medicines used in the standardised regimens of mass treatment programmes. Specific safety concerns, supported by robust local cohort data, have prompted major changes to national and international treatment policies. This chapter describes the expanding body of local knowledge and the historical and emergent surveillance systems that address the burden of drug-related harms, noting the challenges to health system responsiveness. The South African context presents a unique opportunity to characterise the scale and nature of such harms in mass HIV and AIDS and TB treatment programmes. The use of complex regimens at scale poses new PV challenges. There is an urgent need to develop cohesive, sustainable systems to support evidence-based decisions on appropriate regimen choices, while minimising medicine-associated risks. The increasing use of computerised clinical, laboratory and dispensing records, with unique patient identifiers facilitating data linkage, will increase PV surveillance capacity. A coherent national PV framework is an essential part of medicines policy, encompassing regulatory, programmatic and individual needs. Key pillars of this framework include: (i) consolidation and expansion of active and passive PV surveillance, optimising existing programmes; (ii) prioritising post-marketing monitoring within the new health products regulatory authority; and (iii) instilling a culture of active risk management in clinical practice through the creation of effective channels of communication and feedback into policy and practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5708547PMC
August 2017

Interrater agreement of two adverse drug reaction causality assessment methods: A randomised comparison of the Liverpool Adverse Drug Reaction Causality Assessment Tool and the World Health Organization-Uppsala Monitoring Centre system.

PLoS One 2017 24;12(2):e0172830. Epub 2017 Feb 24.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Introduction: A new method to assess causality of suspected adverse drug reactions, the Liverpool Adverse Drug Reaction Causality Assessment Tool (LCAT), showed high interrater agreement when used by its developers. Our aim was to compare the interrater agreement achieved by LCAT to that achieved by another causality assessment method, the World Health Organization-Uppsala Monitoring Centre system for standardised case causality assessment (WHO-UMC system), in our setting.

Methods: Four raters independently assessed adverse drug reaction causality of 48 drug-event pairs, identified during a hospital-based survey. A randomised design ensured that no washout period was required between assessments with the two methods. We compared the methods' interrater agreement by calculating agreement proportions, kappa statistics, and the intraclass correlation coefficient. We identified potentially problematic questions in the LCAT by comparing raters' responses to individual questions.

Results: Overall unweighted kappa was 0.61 (95% CI 0.43 to 0.80) on the WHO-UMC system and 0.27 (95% CI 0.074 to 0.46) on the LCAT. Pairwise unweighted Cohen kappa ranged from 0.33 to 1.0 on the WHO-UMC system and from 0.094 to 0.71 on the LCAT. The intraclass correlation coefficient was 0.86 (95% CI 0.74 to 0.92) on the WHO-UMC system and 0.61 (95% CI 0.39 to 0.77) on the LCAT. Two LCAT questions were identified as significant points of disagreement.

Discussion: We were unable to replicate the high interrater agreement achieved by the LCAT developers and instead found its interrater agreement to be lower than that achieved when using the WHO-UMC system. We identified potential reasons for this and recommend priority areas for improving the LCAT.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0172830PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325562PMC
September 2017

Adverse Drug Reactions Causing Admission to Medical Wards: A Cross-Sectional Survey at 4 Hospitals in South Africa.

Medicine (Baltimore) 2016 May;95(19):e3437

From the Department of Medicine, Division of Clinical Pharmacology, University of Cape Town, Cape Town (JPM, CN, NK, AS, UM, MB, MFDS, RDW, GM, KC); Department of Medicine, East London Hospital Complex and Walter Sisulu University, East London (AGP); Department of Medicine, Edendale Hospital, Pietermaritzburg, South Africa (DPKW), US Centers for Disease Control and Prevention, Pretoria (EUI, GA); National Department of Health, Pretoria (MD); and Pharmaceutical Services, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa (MD).

Limited data exist on the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa, which has high HIV and tuberculosis prevalence. We determined the proportion of adult admissions attributable to ADRs at 4 hospitals in South Africa. We characterized drugs implicated in, risk factors for, and the preventability of ADR-related admissions.We prospectively followed patients admitted to 4 hospitals' medical wards over sequential 30-day periods in 2013 and identified suspected ADRs with the aid of a trigger tool. A multidisciplinary team performed causality, preventability, and severity assessment using published criteria. We categorized an admission as ADR-related if the ADR was the primary reason for admission.There were 1951 admissions involving 1904 patients: median age was 50 years (interquartile range 34-65), 1057 of 1904 (56%) were female, 559 of 1904 (29%) were HIV-infected, and 183 of 1904 (10%) were on antituberculosis therapy (ATT). There were 164 of 1951 (8.4%) ADR-related admissions. After adjustment for age and ATT, ADR-related admission was independently associated (P ≤ 0.02) with female sex (adjusted odds ratio [aOR] 1.51, 95% confidence interval [95% CI] 1.06-2.14), increasing drug count (aOR 1.14 per additional drug, 95% CI 1.09-1.20), increasing comorbidity score (aOR 1.23 per additional point, 95% CI 1.07-1.41), and use of antiretroviral therapy (ART) if HIV-infected (aOR 1.92 compared with HIV-negative/unknown, 95% CI 1.17-3.14). The most common ADRs were renal impairment, hypoglycemia, liver injury, and hemorrhage. Tenofovir disoproxil fumarate, insulin, rifampicin, and warfarin were most commonly implicated, respectively, in these 4 ADRs. ART, ATT, and/or co-trimoxazole were implicated in 56 of 164 (34%) ADR-related admissions. Seventy-three of 164 (45%) ADRs were assessed as preventable.In our survey, approximately 1 in 12 admissions was because of an ADR. The range of ADRs and implicated drugs reflect South Africa's high HIV and tuberculosis burden. Identification and management of these ADRs should be considered in HIV and tuberculosis care and treatment programs and should be emphasized in health care worker training programmes.
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http://dx.doi.org/10.1097/MD.0000000000003437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902486PMC
May 2016

Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey.

Br J Clin Pharmacol 2015 Oct 6;80(4):818-26. Epub 2015 Jul 6.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town.

Aims: Fatal adverse drug reactions (ADRs) are important causes of death, but data from resource-limited settings are scarce. We determined the proportion of deaths in South African medical inpatients attributable to ADRs, and their preventability, stratified by human immunodeficiency virus (HIV) status.

Methods: We reviewed the folders of all patients who died over a 30 day period in the medical wards of four hospitals. We identified ADR-related deaths (deaths where an ADR was 'possible', 'probable' or 'certain' using WHO-UMC criteria and where the ADR contributed to death). We determined preventability according to previously published criteria.

Results: ADRs contributed to the death of 2.9% of medical admissions and 56 of 357 deaths (16%) were ADR-related. Tenofovir, rifampicin and co-trimoxazole were the most commonly implicated drugs. 43% of ADRs were considered preventable. The following factors were independently associated with ADR-related death: HIV-infected patients on antiretroviral therapy (adjusted odds ratio (aOR) 4.4, 95% confidence interval (CI) 1.6, 12), exposure to more than seven drugs (aOR 2.5, 95% CI 1.3, 4.8) and increasing comorbidity score (aOR 1.3, 95% CI 1.1, 1.7).

Conclusions: In our setting, where HIV and tuberculosis are highly prevalent, fatal in-hospital ADRs were more common than reported in high income settings. Most deaths were attributed to drugs used in managing HIV and tuberculosis. A large proportion of the ADRs were preventable, highlighting the need to strengthen systems for health care worker training and support.
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http://dx.doi.org/10.1111/bcp.12567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594724PMC
October 2015

Influences on participant reporting in the World Health Organisation drugs exposure pregnancy registry; a qualitative study.

BMC Health Serv Res 2014 Oct 31;14:525. Epub 2014 Oct 31.

Department of Community Health and Behavioural Sciences, Makerere University School of Public Health, Kampala, Uganda.

Background: The World Health Organisation has designed a pregnancy registry to investigate the effect of maternal drug use on pregnancy outcomes in resource-limited settings. In this sentinel surveillance system, detailed health and drug use data are prospectively collected from the first antenatal clinic visit until delivery. Over and above other clinical records, the registry relies on accurate participant reports about the drugs they use. Qualitative methods were incorporated into a pilot registry study during 2010 and 2011 to examine barriers to women reporting these drugs and other exposures at antenatal clinics, and how they might be overcome.

Methods: Twenty-seven focus group discussions were conducted in Ghana, Kenya and Uganda with a total of 208 women either enrolled in the registry or from its source communities. A question guide was designed to uncover the types of exposure data under- or inaccurately reported at antenatal clinics, the underlying reasons, and how women prefer to be asked questions. Transcripts were analysed thematically.

Results: Women said it was important for them to report everything they had used during pregnancy. However, they expressed reservations about revealing their consumption of traditional, over-the-counter medicines and alcohol to antenatal staff because of anticipated negative reactions. Some enrolled participants' improved relationship with registry staff facilitated information sharing and the registry tools helped overcome problems with recall and naming of medicines. Decisions about where women sought care, which influenced medicines used and antenatal clinic attendance, were influenced by pressure within and outside of the formal healthcare system to conform to conflicting behaviours. Conversations also reflected women's responsibilities for producing a healthy baby.

Conclusions: Women in this study commonly take traditional medicines in pregnancy, and to a lesser extent over-the-counter medicines and alcohol. The World Health Organisation pregnancy registry shows potential to enhance their reporting of these substances at the antenatal clinic. However, more work is needed to find optimal techniques for eliciting accurate reports, especially where the detail of constituents may never be known. It will also be important to find ways of sustaining such drug exposure surveillance systems in busy antenatal clinics.
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http://dx.doi.org/10.1186/s12913-014-0525-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229602PMC
October 2014

How experiences become data: the process of eliciting adverse event, medical history and concomitant medication reports in antimalarial and antiretroviral interaction trials.

BMC Med Res Methodol 2013 Nov 14;13:140. Epub 2013 Nov 14.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Background: Accurately characterizing a drug's safety profile is essential. Trial harm and tolerability assessments rely, in part, on participants' reports of medical histories, adverse events (AEs), and concomitant medications. Optimal methods for questioning participants are unclear, but different methods giving different results can undermine meta-analyses. This study compared methods for eliciting such data and explored reasons for dissimilar participant responses.

Methods: Participants from open-label antimalarial and antiretroviral interaction trials in two distinct sites (South Africa, n = 18 [all HIV positive]; Tanzania, n = 80 [86% HIV positive]) were asked about ill health and treatment use by sequential use of (1) general enquiries without reference to particular conditions, body systems or treatments, (2) checklists of potential health issues and treatments, (3) in-depth interviews. Participants' experiences of illness and treatment and their reporting behaviour were explored qualitatively, as were trial clinicians' experiences with obtaining participant reports. Outcomes were the number and nature of data by questioning method, themes from qualitative analyses and a theoretical interpretation of participants' experiences.

Results: There was an overall cumulative increase in the number of reports from general enquiry through checklists to in-depth interview; in South Africa, an additional 12 medical histories, 21 AEs and 27 medications; in Tanzania an additional 260 medical histories, 1 AE and 11 medications. Checklists and interviews facilitated recognition of health issues and treatments, and consideration of what to report. Information was sometimes not reported because participants forgot, it was considered irrelevant or insignificant, or they feared reporting. Some medicine names were not known and answers to questions were considered inferior to blood tests for detecting ill health. South African inpatient volunteers exhibited a "trial citizenship", working to achieve researchers' goals, while Tanzanian outpatients sometimes deferred responsibility for identifying items to report to trial clinicians.

Conclusions: Questioning methods and trial contexts influence the detection of adverse events, medical histories and concomitant medications. There should be further methodological work to investigate these influences and find appropriate questioning methods.
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http://dx.doi.org/10.1186/1471-2288-13-140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3832682PMC
November 2013

Evaluating harm associated with anti-malarial drugs: a survey of methods used by clinical researchers to elicit, assess and record participant-reported adverse events and related data.

Malar J 2013 Sep 16;12:325. Epub 2013 Sep 16.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.

Background: Participant reports of medical histories, adverse events (AE) and non-study drugs are integral to evaluating harm in clinical research. However, interpreting or synthesizing results is complicated if studies use different methods for ascertaining and assessing these data. To explore how these data are obtained in malaria drug studies, a descriptive online survey of clinical researchers was conducted during 2012 and 2013.

Methods: The survey was advertised through e-mails, collaborators and at conferences. Questions aimed to capture the detail, rationale and application of methods used to obtain relevant data within various study designs and populations. Closed responses were analysed using proportions, open responses through identifying repeating ideas and underlying concepts.

Results: Of fifty-two respondents from 25 counties, 87% worked at an investigational site and 75% reported about an interventional study. Studies employed a range of methods to elicit, assess and record participant-reported AEs and related data. Questioning about AEs in 31% of interventional studies was a combination of general (open questions about health) and structured (reference to specific health-related items), 26% used structured only and 18% general only. No observational studies used general questioning alone. A minority incorporated pictorial tools. Rationales for the questioning approach included: standardization of assessment or data capture, specificity or comprehensiveness of data sought, avoidance of suggestion, feasibility, and understanding participants' perceptions. Most respondents considered the approach they reported was optimal, though several reconsidered this. Four AE grading, and three causality assessment approaches were reported. Combining general and structured questions about non-study drug use were considered useful for revealing and identifying specific medicines, while pictures could enhance reports, particularly in areas of low literacy.

Conclusions: It is critical to evaluate the safety of anti-malarial drugs being deployed in large, diverse populations. Many studies would be suitable for contributing to a larger body of evidence for answering questions on harm. However this survey showed that various methods are used to obtain relevant data, which could influence study results. As the best practices for obtaining such data are unclear, anti-malarial clinical researchers should work towards consensus about the selection and/or design of optimal methods.
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http://dx.doi.org/10.1186/1475-2875-12-325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848530PMC
September 2013

Protocol for a drugs exposure pregnancy registry for implementation in resource-limited settings.

BMC Pregnancy Childbirth 2012 Sep 3;12:89. Epub 2012 Sep 3.

Independent Pharmacovigilance Consultant, Cape Town, Kenilworth 7708, South Africa.

Background: The absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy.

Methods/design: Sentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed.

Discussion: In addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improves maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy.
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http://dx.doi.org/10.1186/1471-2393-12-89DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3500715PMC
September 2012

Pregravid body mass index is associated with early introduction of complementary foods.

J Acad Nutr Diet 2012 Sep;112(9):1374-1379

Objective: To determine whether women who entered pregnancy overweight or obese were less likely to follow American Academy of Pediatrics guidelines for introducing complementary foods to infants after 4 months of age. In addition, we explored whether psychological factors accounted for any of the effect of pregravid body mass index on age of complementary food introduction.

Design: A prospective cohort study from 2001 to 2005 that recruited pregnant women between 15 to 20 gestational weeks with follow-up through 12 months postpartum from University of North Carolina hospitals (n=550).

Statistical Analysis: Multinomial models were used to estimate relative risk ratios. The outcome was age of complementary food introduction, categorized as younger than 4 months of age, 4 to 6 months, and 6 months or later (referent). Maternal body mass index was categorized as underweight (<18.5), normal weight (18.5 to 24.9), and overweight/obese (≥25). A series of regression analyses tested mediation by psychological factors measured during pregnancy (depressive symptoms, stress, and anxiety).

Results: More than a third of the study population (35.7% of 550) entered pregnancy overweight/obese. The majority of participants (75.3%) introduced foods to their infants between 4 and 6 months of age. Compared with normal-weight women, those who were overweight/obese before pregnancy were more likely (relative risk ratios=2.22 [95% CI 1.23 to 4.01]) to introduce complementary foods before the infant was 4 months old, adjusting for race, education, and poverty status. Depressive symptoms, stress, and anxiety did not account for any of the effect of pregravid overweight/obesity on early food introduction.

Conclusions: The results suggest that overweight and obese women are more likely to introduce complementary foods early and that psychological factors during pregnancy do not influence this relationship. Future studies need to explore why overweight/obese women are less likely to meet the American Academy of Pediatrics recommendations for the introduction of complementary food.
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http://dx.doi.org/10.1016/j.jand.2012.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433719PMC
September 2012

Pregravid body mass index, psychological factors during pregnancy and breastfeeding duration: is there a link?

Matern Child Nutr 2012 Oct 28;8(4):423-33. Epub 2011 Sep 28.

Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599-7461, USA .

Breastfeeding rates in the United States are low, and one possible reason may be the high prevalence of overweight/obesity among women of childbearing age. This analysis examined the association between pregravid body mass index and breastfeeding duration, and explored whether depressive symptoms, perceived stress and anxiety during pregnancy mediated this relationship. Participants (n = 550) in the Pregnancy, Infection and Nutrition Postpartum Study were recruited through prenatal clinics prior to 20 weeks gestation and followed to 12 months post-partum. Duration of any breastfeeding was categorized as none, less than 4 months, 4-6 months, 7-12 months and more than 12 months (referent). Exclusive breastfeeding was categorized as less than 1 month, 1 to less than 4 months and 4 months or more (referent). Being overweight/obese before pregnancy (35.7% of 550) was inversely associated with the durations of any and exclusive breastfeeding. Women who entered pregnancy overweight or obese were more likely to not initiate breastfeeding [relative risk ratio (RRR)=5.39 (95% confidence interval: 2.41, 12.04)] and to breastfeed less than 4 months [RRR=2.38 (1.33, 4.27)] compared with women of normal weight status. Among women who initiated breastfeeding, being overweight or obese vs. normal weight was related to exclusively breastfeeding less than 1 month [RRR=2.09 (1.24, 3.51)]. We did not find evidence to support mediation by depressive symptoms, perceived stress or anxiety during pregnancy. Future research needs to explore the reasons behind the association between overweight/obesity and breastfeeding duration.
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http://dx.doi.org/10.1111/j.1740-8709.2011.00335.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3329574PMC
October 2012

Reduced surface area chromatography for flow-through purification of viruses and virus like particles.

J Chromatogr A 2011 Jul 6;1218(26):3973-81. Epub 2011 May 6.

EMD Millipore, Purification Product Development, Bedford, MA 01730, USA.

A method for flow-through purification of viruses and virus like nano-particles using a combination of binding and size-exclusion chromatography was developed. This technique relies on minimizing the external surface area per unit volume available for virus binding by increasing the mean diameter of the beads used in the column. At the same time the impurity binding capacity of the column is maximized by utilizing beads with multiple functionalities of the optimum size. Purification of different types of viruses and virus-like-particles could be achieved using this technique. Flow-through purification of influenza virus using this technique yielded virus recoveries greater than 70-80% coupled with impurity removal greater than 80%. Finally an approach to optimize and facilitate process development using this technology is presented. Since the impurity binding occurs via a non-specific mechanism and virus recovery is achieved through reduced surface area, the technique is not limited to specific types of viruses and offers the potential as a universal purification tool.
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http://dx.doi.org/10.1016/j.chroma.2011.04.086DOI Listing
July 2011

A novel primary amine-based anion exchange membrane adsorber.

J Chromatogr A 2011 Aug 4;1218(32):5386-92. Epub 2011 Apr 4.

Millipore Corp., 80 Ashby Road, Bedford, MA 01730, USA.

A novel anion exchange membrane adsorber is presented which shows excellent impurity removal under different buffer conductivities ranging from 2 to 2 7mS/cm. The membrane utilizes a primary amine ligand (polyallylamine) and was designed specifically to bind impurities at high salt concentrations. Studies with DNA, endotoxin, and virus spiked into buffer at varying salt conditions were done, resulting in clearance of >3, 4, and 4 LRV, respectively, with negligible change on increasing salt up to 27 mS/cm conductivities. Verification of virus removal in mAb feedstocks is also shown. The data are compared with other membrane adsorbers and a conventional resin which utilize traditional chemistries to demonstrate improved purification performance with the primary amine ligand. Additional data on scale-up of the membrane adsorber device is discussed. A stacked flat-sheet design was implemented to ensure linear scale-up of performance using bovine serum albumin (BSA) as a model. The linearly scalable device, coupled with the highly effective membrane for virus, DNA, and endotoxin removal, represents a step forward in polishing technology for the purification of monoclonal antibodies and recombinant proteins.
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http://dx.doi.org/10.1016/j.chroma.2011.03.068DOI Listing
August 2011

Maternal obesity, psychological factors, and breastfeeding initiation.

Breastfeed Med 2011 Dec 14;6(6):369-76. Epub 2011 Apr 14.

Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599, USA.

Objective: Maternal obesity has been associated with lower initiation of breastfeeding, but reasons for why this association exists have not been well studied. In this study, we examined associations among prepregnancy obesity, psychological factors during pregnancy, and breastfeeding initiation.

Methods: Data came from the postpartum component of the Pregnancy, Infection, and Nutrition study, a prospective cohort study. Pregnant women were recruited from the University of North Carolina hospitals between January 2001 and June 2005. This analysis used data from 688 women followed from pregnancy to 3 months postpartum. Multivariable binomial regression was used to determine the association between having a body mass index (BMI) >26 kg/m(2) before pregnancy and breastfeeding initiation. We tested for mediation of the association between pregravid BMI and breastfeeding initiation by certain psychological factors during pregnancy (depressive symptoms, perceived stress, anxiety, and self-esteem).

Results: Women who began pregnancy overweight or obese (BMI >26 kg/m(2)) had almost four times the risk of not initiating breastfeeding compared with underweight or normal weight women (BMI ≤26 kg/m(2)) (risk ratio = 3.94 [95% confidence interval 2.17, 7.18]) after adjusting for race, poverty level, education level, and marital status. Depressive symptoms, perceived stress, anxiety, and self-esteem levels during pregnancy were not found to mediate the association between pregravid BMI and breastfeeding initiation.

Conclusions: Women who started pregnancy either overweight or obese were more likely to not initiate breastfeeding. Contrary to expectations, pregnancy-related psychological factors did not influence this relationship.
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http://dx.doi.org/10.1089/bfm.2010.0052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3228590PMC
December 2011

Establishing pharmacovigilance programs in resource-limited settings: the example of treating malaria.

Expert Rev Clin Pharmacol 2010 Jul;3(4):509-25

Independent Pharmacovigilance Consultant, Johannesburg, South Africa.

The unprecedented levels of political, technical and financial support for improved malaria control, and particularly for changes in the malaria treatment policy, have heralded a renewed appreciation of the role of pharmacovigilance, its relationship with other areas of public health and the development of novel approaches to addressing the pharmacovigilance priorities in malaria-endemic countries. In order to become a valuable public health activity in these resource-limited settings, pharmacovigilance needs to be viewed within its broadest definition of detecting, understanding and preventing adverse drug reactions and drug-related problems. Pharmacovigilance in resource-limited settings provides an opportunity to identify and address health system failures that significantly impact on patient morbidity and mortality, particularly those that are drug related. Countries need to establish a national strategy that identifies realistic and relevant objectives that meet the most pressing pharmacovigilance needs, taking into consideration the conditions under which these systems are likely to develop.
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http://dx.doi.org/10.1586/ecp.10.37DOI Listing
July 2010

Effect of body image on pregnancy weight gain.

Matern Child Health J 2011 Apr;15(3):324-32

Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.

The majority of women gain more weight during pregnancy than what is recommended. Since gestational weight gain is related to short and long-term maternal health outcomes, it is important to identify women at greater risk of not adhering to guidelines. The objective of this study was to examine the relationship between body image and gestational weight gain. The Body Image Assessment for Obesity tool was used to measure ideal and current body sizes in 1,192 women participating in the Pregnancy, Infection and Nutrition Study. Descriptive and multivariable techniques were used to assess the effects of ideal body size and discrepancy score (current-ideal body sizes), which reflected the level of body dissatisfaction, on gestational weight gain. Women who preferred to be thinner had increased risk of excessive gain if they started the pregnancy at a BMI ≤26 kg/m(2) but a decreased risk if they were overweight or obese. Comparing those who preferred thin body silhouettes to those who preferred average size silhouettes, low income women had increased risk of inadequate weight gain [RR = 1.76 (1.08, 2.88)] while those with lower education were at risk of excessive gain [RR = 1.11 (1.00, 1.22)]. Our results revealed that body image was associated with gestational weight gain but the relationship is complex. Identifying factors that affect whether certain women are at greater risk of gaining outside of guidelines may improve our ability to decrease pregnancy-related health problems.
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http://dx.doi.org/10.1007/s10995-010-0578-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665282PMC
April 2011

Spontaneous adverse drug reaction reporting in rural districts of Mozambique.

Drug Saf 2008 ;31(10):867-76

Eduardo Mondlane University Medical School, CIMed, Maputo, Mozambique.

Background: The roll out of various public health programmes involving mass administration of medicines calls for the deployment of responsive pharmacovigilance systems to permit identification of signals of rare or even common adverse reactions. In developing countries in Africa, these systems are mostly absent and their performance under any circumstance is difficult to predict given the known shortage of human, financial and technical resources. Nevertheless, the importance of such systems in all countries is not in doubt, and research to identify problems, with the aim of offering pragmatic solutions, is urgently needed.

Objective: To examine the impact of training and monitoring of healthcare workers, making supervisory visits and the availability of telecommunication and transport facilities on the implementation of a pharmacovigilance system in Mozambique.

Methods: This was a descriptive study enumerating the lessons learnt and challenges faced in implementing a spontaneous reporting system in two rural districts of Mozambique - Namaacha and Matutuíne - where remote location, poor telecommunication services and a low level of education of health professionals are ongoing challenges. A 'yellow card' system for spontaneous reporting of adverse drug reactions (ADRs) was instituted following training of health workers in the selected districts. Thirty-five health professionals (3 medical doctors, 2 technicians, 24 nurses, 4 basic healthcare agents and 2 pharmacy agents) in these districts were trained to diagnose, treat and report ADRs to all medicines using a standardized yellow card system. There were routine site visits to identify and clarify any problems in filling in and sending the forms. One focal person was identified in each district to facilitate communication between the health professionals and the National Pharmacovigilance Unit (NPU). The report form was assessed for quality and causality. The availability of telecommunications and transport was assessed.

Results: Fourteen months after the first training, 67 ADR reports involving 74 adverse events were received by the NPU involving 25 separate drugs, 16 of which were causally (certainly, probably or possibly) linked to the reaction. Most reported ADRs were dermatological reactions (83.1%). Antimalarial drugs (chloroquine, amodiaquine, quinine, artesunate and sulfadoxine/pyrimethamine) were mentioned in 33 (50.8%) of the reports. There were 14 reactions classified as serious and no fatal reactions were reported. There were differences in telecommunications and transport facilities between the districts that might have contributed to the different number of reports.

Conclusion: Health professionals of all levels of education (including basic training) from rural areas could contribute to ADR spontaneous reporting systems. Training, quality-assurance visits and the ongoing presence of focal persons can promote reporting and improve the quality of reports submitted.
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http://dx.doi.org/10.2165/00002018-200831100-00005DOI Listing
January 2009

Adverse drug reactions in adult medical inpatients in a South African hospital serving a community with a high HIV/AIDS prevalence: prospective observational study.

Br J Clin Pharmacol 2008 Mar 7;65(3):396-406. Epub 2007 Dec 7.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Observatory 7925, South Africa.

Unlabelled: What is already known about this subject. Studies conducted primarily in developed countries have shown that adverse drug reactions (ADRs) are a significant cause of hospital admission, prolong hospital stay and consequently increase the cost of disease management in patients. Cardiovascular medicines, hypoglycaemic agents, nonsteroidal anti-inflammatory drugs and antibiotics are the most frequently implicated medicines in these studies. A large proportion of these ADRs have been shown to be preventable through improved drug prescribing, administration and monitoring for adverse effects. What this paper adds. This is the first Sub-Saharan African study in the HIV/AIDS era that describes the contribution of ADRs to patient morbidity, hospitalisation and mortality. Cardiovascular medicines and antiretroviral therapy contributed the most to community-acquired ADRs at the time of hospital admission while medicines used for opportunistic infections (such as antifungals, antibiotics and antituberculosis medicines were most frequently implicated in hospital acquired ADRs. ADRs in HIV-infected patients were less likely to be preventable.

Aims: To describe the frequency, nature and preventability of community-acquired and hospital-acquired adverse drug reactions (ADRs) in a South African hospital serving a community with a high prevalence of human immunodeficiency virus (HIV)/ acquired immunodeficiency syndrome.

Methods: A 3-month prospective observational study of 665 adults admitted to two medical wards.

Results: Forty-one (6.3%) patients were admitted as a result of an ADR and 41 (6.3%) developed an ADR in hospital. Many of the ADRs (46.2%) were considered preventable, although less likely to be preventable in HIV-infected patients than in those with negative or unknown HIV status (community-acquired ADRs 2/24 vs. 35/42; P < 0.0001; hospital-acquired ADRs 3/25 vs. 14/26; P = 0.003). Patients admitted with ADRs were older than patients not admitted with an ADR (median 53 vs. 42 years, P = 0.003), but 60% of community-acquired ADRs at hospital admission were in patients <60 years old. Among patients <60 years old, those HIV infected were more likely to be admitted with an ADR [odds ratio (OR) 2.32, 95% confidence interval (CI) 1.17, 4.61; P = 0.017]. Among HIV-infected patients, those receiving antiretroviral therapy (ART) were more likely to be admitted with an ADR than those not receiving ART (OR 10.34, 95% CI 4.50, 23.77; P < 0.0001). No ART-related ADRs were fatal. Antibiotics and drugs used for opportunistic infections were implicated in two-thirds of hospital-acquired ADRs.

Conclusions: ADRs are an important, often preventable cause of hospitalizations and inpatient morbidity in South Africa, particularly among the elderly and HIV-infected. Although ART-related injury contributed to hospital admissions, many HIV-related admissions were among patients not receiving ART, and many ADRs were associated with medicines used for managing opportunistic infections.
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http://dx.doi.org/10.1111/j.1365-2125.2007.03034.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2291259PMC
March 2008
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