Perspectives for glycaemic control in type 2 diabetes in Kinshasa, Democratic Republic of the Congo.

Glycaemic control is a significant problem in the Democratic Republic of the Congo (DRC), the perspectives associated with glycaemic control are not fully known as previous studies rarely explored patients' perspectives and lived experiences. This qualitative study described the perspectives regarding glycaemic control among persons with type 2 diabetes in Kinshasa, DRC. A total of 23 participants were purposively selected in seven health centres in Kinshasa. In-depth interviews were used for data collection. The study used a phenomenology approach, and deductive, constructionist and thematic analysis. Data analysis was performed using the MAXQDA 2022. Five themes were identified as perspectives for glycaemic control in Kinshasa: financial constraints, limited social and relational support, difficulties with lifestyle changes, beliefs and practices about diabetes and ability to adapt for caring for the illness. Themes were integrated using social cognitive theory. Participants expressed that they were unable to achieve better glycaemic control due to financial constraints, limited social and relational support and difficulty in changing their lifestyle. Their beliefs and practices about diabetes also constituted a barrier. Our results showed that lack of adequate funding is a major determinant of glycaemic control and therefore it is crucial to integrate a consistent and reliable funding system for care of people living with diabetes. Persons with diabetes must be empowered to successfully adapt to the requirements of diabetes care. In this process, support for people living with type 2 diabetes is also essential and should involve their families as well as healthcare providers.

Consensus on potential interventions for improving glycaemic control among patients with type 2 diabetes in Kinshasa, Democratic Republic of the Congo: a Delphi study.

BACKGROUND: Poor glycaemic control is a multifactorial and complex problem with dire clinical and economic implications. In the Democratic Republic of the Congo, recent studies have shown alarming poor control rates. There is no policy framework to guide corrective actions. OBJECTIVES: To build a consensus on interventions to improve glycaemic control among patients with type 2 diabetes in Kinshasa, Democratic Republic of the Congo. METHODS: This was a two-round electronic Delphi study involving 31 local and 5 international experts. The experts rated proposed interventions from previous studies on glycaemic control in sub-Saharan Africa and Kinshasa on a 4-Likert scale questionnaire. Additionally, the experts were asked to suggest other recommendations useful for the purpose. The mode, mean and standard deviation of each statement were calculated for each round. RESULTS: Participants reached consensus in five domains that included 39 statements on how to improve glycaemic control in Kinshasa: strengthening the health system, enhancing the awareness of diabetes, alleviating the financial burden of diabetes, enhancing the adoption of lifestyle modifications, and reducing the proportion of undiagnosed diabetes. CONCLUSIONS: Improved glycaemic control needs to be considered within the broader framework of managing noncommunicable diseases in a more integrated, coordinated and better financed healthcare system. Further studies are needed to operationalise the interventions identified for successful implementation.

Diagnosis and management of a urethral prolapse in a 6-year-old girl: a case report.

Urethral prolapse is a very rare disease, which is most often found in prepubescent girls. It occurs in about one over 5000 girls in the context of a chronic cough or any situation that increases abdominal pressure. It is often associated with diagnostic confusion, which delays management. We report the case of a 6-year-old child brought in urgently by her parents for a minimal genital hemorrhage and presence of a mass protruding from the vulva. In the hypothesis of a urethral prolapse, a medical treatment (conservative) was prescribed. After two weeks, the mass decreased significantly in volume and disappeared completely after 2 months.

Oral fexinidazole for late-stage African Trypanosoma brucei gambiense trypanosomiasis: a pivotal multicentre, randomised, non-inferiority trial.

BACKGROUND: Few therapeutic options are available to treat the late-stage of human African trypanosomiasis, a neglected tropical disease, caused by Trypanosoma brucei gambiense (g-HAT). The firstline treatment is a combination therapy of oral nifurtimox and intravenous eflornithine that needs to be administered in a hospital setting by trained personnel, which is not optimal given that patients often live in remote areas with few health resources. Therefore, we aimed to assess the safety and efficacy of an oral regimen of fexinidazole (a 2-substituted 5-nitroimidazole with proven trypanocidal activity) versus nifurtimox eflornithine combination therapy in patients with late-stage g-HAT. METHODS: In this randomised, phase 2/3, open-label, non-inferiority trial, we recruited patients aged 15 years and older with late-stage g-HAT from g-HAT treatment centres in the Democratic Republic of the Congo (n=9) and the Central African Republic (n=1). Patients were randomly assigned (2:1) to receive either fexinidazole or nifurtimox eflornithine combination therapy according to a predefined randomisation list (block size six). The funder, data management personnel, and study statisticians were masked to treatment. Oral fexinidazole was given once a day (days 1-4: 1800 mg, days 5-10: 1200 mg). Oral nifurtimox was given three times a day (days 1-10: 15 mg/kg per day) with eflornithine twice a day as 2 h infusions (days 1-7: 400 mg/kg per day). The primary endpoint was success at 18 months (ie, deemed as patients being alive, having no evidence of trypanosomes in any body fluid, not requiring rescue medication, and having a cerebrospinal fluid white blood cell count ≤20 cells per µL). Safety was assessed through routine monitoring. Primary efficacy analysis was done in the modified intention-to-treat population and safety analyses in the intention-to-treat population. The acceptable margin for the difference in success rates was defined as 13%. This study has been completed and is registered with ClinicalTrials.gov, number NCT01685827. FINDINGS: Between October, 2012, and November, 2016, 419 patients were pre-screened. Of the 409 eligible patients, 14 were not included because they did not meet all inclusion criteria (n=12) or for another reason (n=2). Therefore, 394 patients were randomly assigned, 264 to receive fexinidazole and 130 to receive nifurtimox eflornithine combination therapy. Success at 18 months was recorded in 239 (91%) patients given fexinidazole and 124 (98%) patients given nifurtimox eflornithine combination therapy, within the margin of acceptable difference of -6·4% (97·06% CI -11·2 to -1·6; p=0·0029). We noted no difference in the proportion of patients who experienced treatment-related adverse events (215 [81%] in the fexinidazole group vs 102 [79%] in the nifurtimox eflornithine combination therapy group). Treatment discontinuations were unrelated to treatment (n=2 [1%] in the fexinidazole group). Temporary nifurtimox eflornithine combination therapy interruption occurred in three (2%) patients. 11 patients died during the study (nine [3%] in the fexinidazole group vs two [2%] in the nifurtimox eflornithine combination therapy group). INTERPRETATION: Our findings show that oral fexinidazole is effective and safe for the treatment of T b gambiense infection compared with nifurtimox eflornithine combination therapy in late-stage HAT patients. Fexinidazole could be a key asset in the elimination of this fatal neglected disease. FUNDING: Drugs for Neglected Diseases initiative.

Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies.

BACKGROUND: Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. METHODS: The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. FINDINGS/CONCLUSION: Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3.

Efficacy and Safety of Pafuramidine versus Pentamidine Maleate for Treatment of First Stage Sleeping Sickness in a Randomized, Comparator-Controlled, International Phase 3 Clinical Trial.

BACKGROUND: Sleeping sickness (human African trypanosomiasis [HAT]) is a neglected tropical disease with limited treatment options that currently require parenteral administration. In previous studies, orally administered pafuramidine was well tolerated in healthy patients (for up to 21 days) and stage 1 HAT patients (for up to 10 days), and demonstrated efficacy comparable to pentamidine. METHODS: This was a Phase 3, multi-center, randomized, open-label, parallel-group, active control study where 273 male and female patients with first stage Trypanosoma brucei gambiense HAT were treated at six sites: one trypanosomiasis reference center in Angola, one hospital in South Sudan, and four hospitals in the Democratic Republic of the Congo between August 2005 and September 2009 to support the registration of pafuramidine for treatment of first stage HAT in collaboration with the United States Food and Drug Administration. Patients were treated with either 100 mg of pafuramidine orally twice a day for 10 days or 4 mg/kg pentamidine intramuscularly once daily for 7 days to assess the efficacy and safety of pafuramidine versus pentamidine. Pregnant and lactating women as well as adolescents were included. The primary efficacy endpoint was the combined rate of clinical and parasitological cure at 12 months. The primary safety outcome was the frequency and severity of adverse events. The study was registered on the International Clinical Trials Registry Platform at www.clinicaltrials.gov with the number ISRCTN85534673. FINDINGS/CONCLUSIONS: The overall cure rate at 12 months was 89% in the pafuramidine group and 95% in the pentamidine group; pafuramidine was non-inferior to pentamidine as the upper bound of the 95% confidence interval did not exceed 15%. The safety profile of pafuramidine was superior to pentamidine; however, 3 patients in the pafuramidine group had glomerulonephritis or nephropathy approximately 8 weeks post-treatment. Two of these events were judged as possibly related to pafuramidine. Despite good tolerability observed in preceding studies, the development program for pafuramidine was discontinued due to delayed post-treatment toxicity.