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

A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalized and non-hospitalized tuberculosis patients with or without HIV

Background. Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups. Methods. Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM® was used to analyze the data. Results. Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin’s absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid’s clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide’s clearance was more variable among hospitalized patients. The variability in clearance among patients was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients. Conclusion. We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underexposed compared to their outpatient counterparts

Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and formulations

Background: Dispersible paediatric fixed dose combination (FDCs) tablets delivering higher doses of first-line antituberculosis drugs in WHO-recommended weight-bands were introduced in 2015. We report the first pharmacokinetic data for these FDCs in Zambian and South African children in the treatment-shortening SHINE trial. // Methods: Children weighing 4.0-7.9 kg, 8.0-11.9 kg, 12.0-15.9 kg and 16.0-24.9 kg had 1, 2, 3 and 4 tablets daily (rifampicin/isoniazid/pyrazinamide 75/50/150 mg, with or without 100 mg ethambutol, or rifampicin/isoniazid 75/50 mg), respectively. Children 25.0-36.9 kg received doses recommended for adults <37kg (300, 150, 800, 550 mg daily for rifampicin, isoniazid, pyrazinamide, ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. // Results: Of 77 children evaluated, median (IQR) age was 3.7 (1.4-6.6) years, 40 (52%) were male and 20 (26%) HIV-positive. AUC24 for rifampicin, isoniazid, pyrazinamide and ethambutol were 32.5 (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 compared to adults for rifampicin in 4.0-7.9 kg, 8-11.9kg and ≥25kg weight-bands, isoniazid in 4.0-7.9kg and ≥25kg, and ethambutol in all five weight-bands. Pyrazinamide exposures were similar to adults. // Conclusions: Recommended weight-band based FDC doses result in lower drug exposures in children in lower weight-bands and in those ≥25kg (on adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current WHO-recommended doses requires further evaluation

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

An assessment of the maternal death notification system in Zimbabwe - 2006

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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

Impact of Xpert MTB/RIF on Antiretroviral Therapy-Associated Tuberculosis and Mortality: A Pragmatic Randomized Controlled Trial.

GeneXpert® MTB/RIF (Xpert) is now widely distributed in high human immunodeficiency virus (HIV)/tuberculosis (TB)-burden countries. Yet, whether the test improves patient-important outcomes within HIV treatment programs in limited resource settings is unk

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 antituberculosis 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 antituberculosis therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed. Results: Pharmacokinetic data was collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient twelve-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (Cmax:7.4 vs. 8.3 μg·mL-1, p=0.223; 3.6 vs. 3.5 μg·mL-1, p=0.569; 50.1 vs. 46.8 μg·mL-1, p=0.081; AUC0-8:41.0 vs. 43.8 mg·h·L-1, p= 0.290; 13.5 vs. 12.4 mg·h·L-1, p=0.630; 316.5 vs. 292.2 mg·h·L-1, p=0.164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid Cmax were below recommended ranges in 61% and 39% inpatients and 44% and 35% outpatients. Rifampicin exposure was higher in patients with lactate >2.2mmol·L-1. Conclusion: Mortality in hospitalized HIV-TB patients was high. Early antituberculosis drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid Cmax were sub-optimal 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

Consequences of polyparasitism on anaemia among primary school children in Zimbabwe

The effect of concomitant infection with schistosomes, Plasmodium falciparum and soil transmitted helminths (STHs) on anaemia was determined in 609 Zimbabwean primary school children. P. falciparum, haemoglobin levels and serum ferritin were determined from venous blood. Kato Katz, formal ether concentration and urine filtration techniques were used to assess prevalence of Schistosoma mansoni, STHs and Schistosoma haematobium infections. The prevalence of S. haematobium, S. mansoni, P. falciparum, hookworm, Trichuris trichiura and Ascaris lumbricoides were 52.3%, 22.7%, 27.9%, 23.7%, 2.3% and 2.1%, respectively. The overall prevalence of anaemia and iron deficiency anaemia (IDA) were 48.4% (277/572) and 38.1% (181/475). Haemoglobin levels among children who had P. falciparum, S. haematobium and hookworm were lower than negative individuals, p\u3c0.001, p\u3c0.001 and p = 0.030, respectively. The prevalence of anaemia and IDA in co-infections was almost double that in single infection. Children with P. falciparum/STHs/schistosome and schistosomes/. P. falciparum co-infections recorded higher prevalence of anaemia and IDA (80.8% and 57.4%, respectively) than other combinations, p\u3c0.001. Logistic regression revealed that, age group. ≥ 14years,P. falciparum,S.haematobium light and heavy infections, and S.mansoni moderate and heavy infection, hookworm light infection were predictors of anaemia. This study suggests that integrated school based de-worming and malaria control have the potential to reduce the burden of anaemia. © 2010