Use of the 'Accountability for Reasonableness' Approach to Improve Fairness in Accessing Dialysis in a Middle-Income Country

Universal access to renal replacement therapy is beyond the economic capability of most low and middle-income countries due to large patient numbers and the high recurrent cost of treating end stage kidney disease. In countries where limited access is available, no systems exist that allow for optimal use of the scarce dialysis facilities. We previously reported that using national guidelines to select patients for renal replacement therapy resulted in biased allocation. We reengineered selection guidelines using the 'Accountability for Reasonableness' (procedural fairness) framework in collaboration with relevant stakeholders, applying these in a novel way to categorize and prioritize patients in a unique hierarchical fashion. The guidelines were primarily premised on patients being transplantable. We examined whether the revised guidelines enhanced fairness of dialysis resource allocation. This is a descriptive study of 1101 end stage kidney failure patients presenting to a tertiary renal unit in a middle-income country, evaluated for dialysis treatment over a seven-year period. The Assessment Committee used the accountability for reasonableness-based guidelines to allocate patients to one of three assessment groups. Category 1 patients were guaranteed renal replacement therapy, Category 3 patients were palliated, and Category 2 were offered treatment if resources allowed. Only 25.2% of all end stage kidney disease patients assessed were accepted for renal replacement treatment. The majority of patients (48%) were allocated to Category 2. Of 134 Category 1 patients, 98% were accepted for treatment while 438 (99.5%) Category 3 patients were excluded. Compared with those palliated, patients accepted for dialysis treatment were almost 10 years younger, employed, married with children and not diabetic. Compared with our previous selection process our current method of priority setting based on procedural fairness arguably resulted in more equitable allocation of treatment but, more importantly, it is a model that is morally, legally and ethically more defensible

Quality of pilot trial abstracts in heart failure is suboptimal: a systematic survey

Background: Pilot trials are miniature researches carried out with the sole aim of acting as the precursor for larger more definitive studies. Abstracts are used to summarize and introduce the findings to the reading audience. There is substantive empirical evidence showing that abstracts, despite their important roles, are not informative enough, lacking the necessary details. This systematic survey was designed to assess the quality of reporting of heart failure pilot trial abstracts. The quality of reporting was defined as the completeness of reporting based on adherence to the CONSORT extension for reporting of pilot trial abstracts. We also identified factors associated with reporting quality. Methods: We searched MEDLINE (PubMed), Cochrane Controlled Trials Register, Scopus, and African-wide information databases for abstracts from heart failure pilot trials in humans published from 1 January 1990 to 30 November 2016. These were assessed to determine the extent of adherence to CONSORT extension checklist for reporting of abstracts of pilot trials. We screened identified studies for inclusion based on title and abstract. Data were independently extracted by two reviewers using the checklist. We used regression analysis to assess the association between completeness of reporting (measured as the number of items in the CONSORT extension checklist for reporting of abstracts in pilot trials contained in each abstract) and factors influencing the quality of the reports. Results: Two hundred and twenty-eight (228) articles were retrieved, of which 92 met the inclusion criteria. The mean CONSORT extension score was 8.3/16 (standard deviation 1.7); the least reported items were the source of funding (1% [1/92]), trial registration (13% [12/92]), randomization sequence (13% [12/92]), number randomized to each arm (16% [15/92]), and number analyzed in each arm (16% [15/92]). Multivariable regression analysis showed that pharmacological intervention pilot trials [incidence rate ratio (IRR) = 0.88; 95% confidence interval (CI), 0.81–0.97] were significantly associated with better reporting. Other factors such as structured abstract (IRR = 1.10; 95% CI, 0.99–1.23) and CONSORT endorsement (IRR = 1.10; 95% CI, 0.99–1.23) only showed minimal relationship with better reporting quality. Conclusion: The quality of reporting of abstracts of heart failure pilot trials was suboptimal. Pharmacological intervention was significantly associated with better reporting. These findings are consistent with previous research on reporting of trials

Assessment of quality of obstetric care in Zimbabwe using the standard primipara

Background To improve maternity services in any country, there is need to monitor the quality of obstetric care. There is usually disparity of obstetric care and outcomes in most countries among women giving birth in different obstetric units. However, comparing the quality of obstetric care is difficult because of heterogeneous population characteristics and the difference in prevalence of complications. The concept of the standard primipara was introduced as a tool to control for these various confounding factors. This concept was used to compare the quality of obstetric care among districts in different geographical locations in Zimbabwe. Methods This was a substudy of the Zimbabwe Maternal and Perinatal Mortality Study. In the main study, cluster sampling was done with the provinces as clusters and 11 districts were randomly selected with one from each of the nine provinces and two from the largest province. This database was used to identify the standard primipara defined as; a woman in her first pregnancy without any known complications who has spontaneous onset of labour at term. Obstetric process and outcome indicators of the standard primipara were then used to compare the quality of care between rural and urban, across rural and across urban districts of Zimbabwe. Results A total of 45,240 births were recruited in the main study and 10,947 women met the definition of standard primipara. The maternal mortality ratio (MMR) and the perinatal mortality rate (PNMR) for the standard primiparae were 92/100000 live births and 15.4/1000 total births respectively. Compared to urban districts, the PNMR was higher in the rural districts (11/1000 total births vs 19/ 1000 total births, p < 0.001). In the urban to urban and rural to rural districts comparison, there were significant differences in most of the process indicators, but not in the PNMR. Conclusions The study has shown that the standard primipara can be used as a tool to measure and compare the quality of obstetric care in districts in different geographical areas. There is need to explore further how the quality of obstetric care can be improved in rural districts of Zimbabwe

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis

Aims: Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker). Methods: We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [Cmax]: 7.4 vs 8.3 μg mL–1, P =.223; 3.6 vs 3.5 μg mL–1, P =.569; 50.1 vs 46.8 μg mL–1, P =.081; area under the concentration–time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L–1, P = 0.290; 13.5 vs 12.4 mg h L–1, P =.630; 316.5 vs 292.2 mg h L–1, P =.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L–1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival

Effect of rifampicin and efavirenz on moxifloxacin concentrations when co-administered in patients with drug-susceptible TB.

CAPRISA, 2017.Abstract available in pdf

Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations.

BACKGROUND: Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization-recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. METHODS: Children weighing 4.0-7.9, 8.0-11.9, 12.0-15.9, or 16.0-24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0-36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. RESULTS: In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4-6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1-45.1), 16.7 (9.2-25.9), 317 (263-399), and 9.5 (7.5-11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0-7.9-, 8-11.9-, and ≥25-kg weight bands, isoniazid in the 4.0-7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. CONCLUSIONS: Recommended weight band-based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization-recommended doses requires further evaluation

ZIMBABWE (2010): MATERNAL AND CHILD HEALTH TRaC STUDY EVALUATING MALARIA PREVENTION BEHAVIORS AMONG ADULTS AGED 15-49 IN ZIMBABWE SECOND ROUND

This sub-study is part of a series of TRaC studies on Maternal and Child Health (MCH) that provides evidence for decision making on interventions to reduce exposures to health hazards among women and children. Results of this study will reveal most effective ways of reaching populations with malaria prevention messages as well as identification of areas that require additional interventions. The study utilized a two stage cluster design. In the first stage, enumeration areas (EAs) were randomly selected using probability proportionate to size. EAs are geographic areas used for sampling purposes. In the second stage, households within the selected EAs were selected using simple random sampling. In the selected households, a Kish grid was used to select one participant in cases where the number of eligible respondents was more than one. A total of 1509 and 950 individual interviews were completed during the baseline and follow-up respectively. UNIANOVA command in SPSS version 17 was used to test for differences in means or proportions between baseline and follow-up study. The same command was also used to test for differences among channels of communicati ng malaria prevention messages that were used. The following demographic characteristics were controlled for in the analyses; age, sex, religion, Socio-Economic Status (SES), education, marital status and occupation

Quality of abstracts of pilot trials in heart failure : a protocol for a systematic survey

CITATION: Isiguzo, G., et al. 2017. Quality of abstracts of pilot trials in heart failure : a protocol for a systematic survey. Contemporary Clinical Trials Communications, 8:258-263, doi:10.1016/j.conctc.2017.11.004.The original publication is available at https://www.sciencedirect.comIntroduction: Pilot trials are initial small-scale studies done to inform the design of larger trials. Their findings like other studies are usually disseminated as peer-reviewed journal articles. Abstracts are used to introduce the contents to readers, and give a general idea about the full reports and sometimes are the only source of information available to readers. Despite their importance, the contents of abstracts of trial reports are usually not informative enough and lack the essential details. Methods and analysis: This is a protocol for a planned systematic survey with a primary aim of analyzing the reporting quality measured as the completeness of the reporting of pilot trial abstracts in heart failure. The secondary aim will be to explore factors associated with better reporting quality. Abstracts of heart failure pilot trials in humans (journal and conference abstracts) published in the English language from 1 January 1990 to 30 November 2016 will be assessed to determine the reporting quality, based on the CONSORT 2010 statement extension to randomized pilot and feasibility trials. All non-pilot/feasibility trials and non-human pilot trials will be excluded. We will search Medline (PUBMED), Cochrane controlled trials register, Scopus and African wide information databases for pilot trials in heart failure. Title and abstracts of identified studies will be screened for inclusion and data extracted independently by two reviewers in duplicate without using the full text. Reported and unreported items on the abstracts will be presented as frequencies and percentages, a descriptive analysis will be used to interpret the reporting quality and regression analysis used for characteristics associated with greater statistical reporting at 95% confidence interval.https://www.sciencedirect.com/science/article/pii/S2451865417301242?via%3DihubPublisher's versio