Hypoglycemic, Antihyperglycemic, and Toxic Effects of Physalis peruviana L. Aqueous and Methanolic Leaf Extracts in Wistar Rats.

Background: Physalis peruviana L. (Solanaceae) is a plant widely used in traditional medicine systems to manage various diseases, including diabetes mellitus, which remains a global health problem in developing and developed countries. This study aimed to scientifically evaluate its antidiabetic bioactivity and short-term toxicity in rats. Methods: We prepared various doses (100, 200, 400 mg/kg) of aqueous and methanolic leaf extracts for the antidiabetic study, and a dose of 2000 mg/Kg was prepared for the acute toxicity test. The first group that evaluated the hypoglycemic effect consisted of forty normoglycemic Wistar rats aged 7-8 months old with a weighted average of 265.8 ± 24.6 g. The second group consisted of intraperitoneal glucose-loaded male animals to evaluate the antihyperglycemic effect. The third group contained two groups of normoglycemic female rats (n = 3), aged 3 and 4 months old (weight average: 187.45 ± 14.82 g), treated for 14 days with aqueous and methanolic extracts (2 g/kg b.w) to assess mortality and toxic effects. Blood samples were taken at 30, 60, 90, and 120 min post-treatment in hypoglycemic and antihyperglycemic evaluations. Glibenclamide (5 mg/kg) was used as a reference drug. The control animals in each group did not receive the extracts. Results: In hypoglycemic rats, 100 mg/kg of aqueous and methanolic extracts significantly lowered the fasting blood glucose level by 13.92% (p < 0.0001) and 21.95% (p < 0.01), respectively, compared to the control group. In glucose tolerance test group, methanolic extracts significantly reduced hyperglycemia by 54.55% (p < 0.0001), 46.50% (p < 0.0001), 39.78% (p < 0.0001) at 400, 200 and 100 mg/kg b.w, respectively, compared to control; aqueous extract 400 mg/kg reduced hyperglycemia by 39.44% (p < 0.05). At the 2000 mg/kg dose, leaf aqueous and methanolic extracts did not show any signs of intoxication and mortality. Conclusion: Crude aqueous and methanolic leaf extracts of P. peruviana ambrosioides appeared safe at 2000 mg/kg and have bioactivity in controlling the blood glucose levels, supporting their use in treating diabetes.

Effects of the Oral Administration of Aqueous and Methanolic Leaf Extracts of Chenopodium ambrosioides L. (Amaranthaceae) on Blood Glucose Levels in Wistar Rats.

Background: Diabetes mellitus is a metabolic disorder that poses a major global health threat. The current diabetes mellitus uses insulin and oral hypoglycemic agents, which have limitations, including adverse effects and secondary failures. Herbal medicine is being evaluated for its role in the pharmacotherapy of diabetes. This study was aimed to assess the anti-diabetic potential and short-term toxicity level of Chenopodium ambrosioides collected from Bukavu in Democratic Republic of Congo. Methods: Leaves of C. ambrosioides were extracted by infusion and maceration with distilled water and 95% methanol, respectively. Hypoglycemic and antihyperglycemic potentials of the aqueous and methanolic were investigated in normoglycemic and intraperitoneal glucose-loaded rats at 100, 200, and 400 mg/kg body weight. An oral acute toxicity test was carried out on healthy female Wistar rats. Results: Acute toxicity test showed the mean lethal dose (LD50) for both aqueous and methanol extracts of C. ambrosioides to be more than 2000 mg/kg. The group treated with glibenclamide (5 mg/kg b.w) and aqueous extract of the plant (200 mg/kg b.w) showed a significant reduction (p< 0.0001 and p< 0.05) of fasting blood glucose by 46.91% and 16.72%, respectively, compared to control and all other treatment groups. In acute conditions, a single oral administration of the aqueous and methanolic extracts lowered fasting blood glucose in rats. Any manifestation and signs of toxicity and mortality have been recorded for 14 days of observation. Conclusion: Leaf aqueous and methanolic extracts of C. ambrosioides appeared safe at 2000 mg/kg. The plant demonstrated some anti-diabetic potential in rats, explaining its use as an anti-diabetic remedy locally.

Understanding the Effect of a Healthcare Provider-Led Family Planning Support Intervention on Contraception use and Pregnancy Desires among Postpartum Women Living with HIV in Southwestern Uganda.

Modern contraceptive prevalence among women living with HIV (WLWH) in Uganda is still low at 45%, and up to a third of women are likely to discontinue the method within the first year of initiation. This increases risks of unplanned pregnancies, perinatal HIV transmission and pregnancy complications. We aim to explore and explain the mechanism of effect of a family planning support intervention investigated in a randomized controlled trial conducted between October 2016 and June 2018 among 320 postpartum WLWH at a referral hospital in Southwestern Uganda that led to improved uptake, decreased contraception discontinuation and lowered pregnancy rates. Thirty WLWH and 10 of their primary sexual partners who participated in this trial were purposively selected and interviewed in the local language; interviews were digitally recorded. Translated transcripts were generated and coded. Coded data were iteratively reviewed and sorted to derive descriptive categories using an inductive content analytic approach. Up to 83% of women wanted to avoid pregnancy within the first year postpartum. Qualitative data showed that contraception uptake and use were influenced by: 1) Participant awareness and understanding of different methods available; 2) Participant perception of offered health services; 3) Healthcare provider (HCP) socio-cultural sensitivity to individual experiences and (mis)conceptions surrounding contraception; 4) Having tactile engagement, follow-up reminders and a reference to prompt action or discussions with partners. Supportive and culturally sensitive HCPs and systems facilitated information sharing leading to increased patient awareness and understanding of the contraceptive methods, and improved health user experience, care engagement, confidence and willingness to take up and continue using modern contraceptive methods.

Antidiabetic Medicinal Plants Used in Democratic Republic of Congo: A Critical Review of Ethnopharmacology and Bioactivity Data.

Several studies have been conducted and published on medicinal plants used to manage Diabetes Mellitus worldwide. It is of great interest to review available studies from a country or a region to resort to similarities/discrepancies and data quality. Here, we examined data related to ethnopharmacology and bioactivity of antidiabetic plants used in the Democratic Republic of Congo. Data were extracted from Google Scholar, Medline/PubMed, Scopus, ScienceDirect, the Wiley Online Library, Web of Science, and other documents focusing on ethnopharmacology, pharmacology, and phytochemistry antidiabetic plants used in the Democratic Republic of Congo from 2005 to September 2021. The Kew Botanic Royal Garden and Plants of the World Online web databases were consulted to verify the taxonomic information. CAMARADES checklist was used to assess the quality of animal studies and Jadad scores for clinical trials. In total, 213 plant species belonging to 72 botanical families were reported. Only one plant, Droogmansia munamensis, is typically native to the DRC flora; 117 species are growing in the DRC and neighboring countries; 31 species are either introduced from other regions, and 64 are not specified. Alongside the treatment of Diabetes, about 78.13% of plants have multiple therapeutic uses, depending on the study sites. Experimental studies explored the antidiabetic activity of 133 plants, mainly in mice, rats, guinea pigs, and rabbits. Several chemical classes of antidiabetic compounds isolated from 67 plant species have been documented. Rare phase II clinical trials have been conducted. Critical issues included poor quality methodological protocols, author name incorrectly written (16.16%) or absent (14.25%) or confused with a synonym (4.69%), family name revised (17.26%) or missing (1.10%), voucher number not available 336(92.05%), ecological information not reported (49.59%). Most plant species have been identified and authenticated (89.32%). Hundreds of plants are used to treat Diabetes by traditional healers in DRC. However, most plants are not exclusively native to the local flora and have multiple therapeutic uses. The analysis showed the scarcity or absence of high-quality, in-depth pharmacological studies. There is a need to conduct further studies of locally specific species to fill the gap before their introduction into the national pharmacopeia.

Antibacterial prescription and the associated factors among outpatients diagnosed with respiratory tract infections in Mbarara Municipality, Uganda.

BACKGROUND: Respiratory tract infections (RTI) are the second most frequent diagnosis after Malaria amongst Outpatients in Uganda. Majority are Non pneumonia cough and flu which are self-limiting and often do not require antibacterials. However, antibiotics are continuously prescribed for these conditions and are a major contributor to antimicrobial resistance and wastage of health resources. Little is known about this problem in Uganda hence the impetus for the study. OBJECTIVES: To determine the antibacterial prescribing rate and associated factors among RTI outpatients in Mbarara municipality METHODOLOGY: This was a retrospective cross-sectional study on records of RTI outpatients from 1st April 2019 to 31st March 2020 (prior to the novel corona virus disease pandemic) in four selected public health facilities within Mbarara municipality. A pretested data caption tool was used to capture prescribing patterns using WHO/INRUD prescribing indicators. We used logistic regression to determine factors associated to antibacterial prescribing. RESULTS: A total of 780 encounters were studied with adults (18-59 years) forming the largest proportion of age categories at (337, 43.15%) and more females (444, 56.85%) than men (337, 43.15%). The antibacterial prescribing rate was 77.6% (606) with Amoxicillin the most prescribed 80.4% (503). The prescribing pattern showed an average of 2.47 (sd 0.72) drugs per encounter and the percentage of encounters with injection at 1.5% (24). Drugs prescribed by generic (1557, 79%) and drugs prescribed from essential medicine list (1650, 84%) both not conforming to WHO/INRUD standard; an indicator of possible irrational prescribing. Female gender (adjusted odds ratio [aOR] = 1.51, 95% confidence interval [CI]: (1.06-2.16); 18-59 years age group (aOR = 1.66, 95% CI: 1.09-2.33) and Individuals prescribed at least three drugs were significantly more likely to have an antibacterial prescribed (aOR= 2.72, 95% CI: 1.86-3.98). CONCLUSION: The study found a high antibacterial prescribing rate especially among patients with URTI, polypharmacy and non-conformity to both essential medicine list and generic name prescribing. This prescribing pattern does not comply with rational drug use policy and needs to be addressed through antimicrobial stewardship interventions, prescriber education on rational drug use and carrying out more research to determine the appropriateness of antibacterial prescribed.

Ethnotherapeutic Uses and Phytochemical Composition of Physalis peruviana L.: An Overview.

BACKGROUND: Plant-derived medicines are widespread and continue to increase in traditional and modern medicine, especially in developing countries. Physalis peruviana L. is among the most used plants in conventional medication worldwide. This review aimed to highlight the ethnotherapeutic uses and phytochemical status of identified compounds in P. peruviana. METHODS: Data were collected from Google Scholar, PubMed/Medline, SciFinder, Science Direct, Scopus, the Wiley Online Library, Web of Science, and any other helpful search engine using Physalis peruviana as the primary keyword. RESULTS: Some countries, worldwide, use P. peruviana in their traditional medicine system to manage diverse ailments, mainly diseases and gastrointestinal tract disorders (25.33%). Leaf was the mostly used part (49.28%), prepared by decoction (31.58%) and overall administrated orally (53.57%) as the main route of admission. Around 502 phytoconstituents were identified in different plant parts, especially fruit (38.19%) ethanol/ethyl acetate extract. In most cases (36.17%), the solvent of the extract was not specified. Several phytochemical classes were found in the plant, especially terpenes (26.09%) and phenolic compounds (14.94%). Esters were also abundant (11.55%). In the terpenes category, carotenoids were the most abundant (11.15% followed by monoterpenes (8.76%) and diterpenes (3.18%). However, flavonoids (5.17%) followed by cinnamic acid derivatives (3.99%), monophenolic compounds (1.79%), and phenolic acids (1.33 M) are the most reported phenolic compounds. Hexadecanoic acid (palmitic acid) was the most cited (five times). CONCLUSION: P. peruviana plays an essential role in managing diseases in some countries and is rich in chemical compounds, which need to be isolated and investigated pharmacologically before clinical trials.

Structured and sustained family planning support facilitates effective use of postpartum contraception amongst women living with HIV in South Western Uganda: A randomized controlled trial.

BACKGROUND: Despite low pregnancy intentions, many women accessing contraception discontinue use, increasing the risk of unwanted pregnancies among women living with HIV (WLWH). We evaluate whether a family planning support intervention, inclusive of structured immediate one-on-one postpartum counseling, and a follow-up mechanism through additional health information and SMS reminders affects continuous contraceptive use and pregnancy incidence among recently postpartum WLWH. METHODS: We performed a randomized controlled trial between October 2016 and June 2018 at a referral hospital in southwestern Uganda. We included adult WLWH randomized and enrolled in a 1:1 ratio to receive family planning support or standard of care (control) and completed an interviewer-administered questionnaire at enrolment, 6 and 12 months postpartum. Our two primary outcomes of interest were; continuous use of contraception, and incidence of pregnancy. Secondary outcomes included contraception uptake, method change, discontinuation and pregnancy intentions. The trial was registered with clinicaltrials.gov (NCT02964169). RESULTS: A total of 317(99%) completed all study procedures. Mean age was 29.6 (SD = 6.0) vs 30.0 (SD = 5.9) years for the intervention vs control groups respectively. All women were enrolled on ART. Total women using contraception continuously were 126 (79.8%) in the intervention compared to 110 (69.2%) in control group (odds ratio (OR) = 1.75; confidence interval (CI) = 1.24-2.75, P = 0.003). Pregnancy rates were 2% (N = 3) in the intervention vs 9% (N = 14) in the control group (OR = 0.20, 95% CI = 0.05-0.62, P = 0.006). Pregnancy intention was lower in the intervention vs control group (OR = 0.23, 95% CI = 0.08-0.64, P = 0.002). Women actively enrolled on contraception reduced more in the control compared to the intervention group (OR = 3.92, 95% CI = 1.66-9.77, P = 0.001). Women enrolled on each contraceptive method did not differ by group except for implants. More women initiating contraception use within three months postpartum had better continued use for either intervention (N = 123, 97.6% vs N = 3,2.4%) or control group (N = 86,78.2% vs N = 24,21.8%). Method-related side effects were less reported in the intervention group (OR = 0.25, 95% CI = 0.10-0.60, P = 0.001). CONCLUSION: We found that sustained and structured family planning support facilitates continuous use of contraception and lowers rates of pregnancy amongst postpartum WLWH in rural southwestern Uganda. Women who initiated contraception within three months postpartum were more likely to maintain continuous use of contraception than those initiating later. Further evaluation of actual and perceived facilitators to the continuous contraception use by this support intervention will help replication in similar settings. TRIAL REGISTRATION: NCT02964169.

Registration and local production of essential medicines in Uganda.

BACKGROUND: Universal access to high quality essential medicines is critical to sustainable development (SDG 3.8). However low- and middle-income countries struggle to ensure access to all medicines on their national essential medicines lists (EML). Market registration is the first step in determining both access and availability yet the extent to which essential medicines are registered for use at country level is not known. Companies apply for a marketing authorisation, however low price or lack of a market is a disincentive. Local production has been promoted to ensure availability of essential medicines but research in this area is also limited. METHODS: The study took place between 2011 and 2015. We systematically examined the registration status of medicines and vaccines listed in the Ugandan 2012 EML and conducted 20 interviews with regulators, ministry of health representatives, donors, and pharmaceutical producers and analysed quality assurance issues affecting registration, procurement, and local production of medicines in Uganda. In 2017 we conducted a further three interviews to clarify issues around non-registration of essential medicines highlighted by our analysis. RESULTS: Of the 566 essential medicines and vaccines nearly half (49%; 275/566) had no registered product in 2012. Of the 3130 registered products, just over a quarter (28%; 880/3130) were listed on the EML. Six local producers had registered 138 products of which 40 corresponded to 32 unique essential medicines. Interviews highlighted alternative routes to availability other than registration. Local producers faced considerable barriers to achieving international quality standards required for international procurement of medicines for the domestic market. CONCLUSIONS: Monitoring and audit of the registration of essential and non-essential medicines should be a priority nationally and, regionally through harmonisation of registration requirements in the East African Community. National and regional manufacturing plans should consider local production of unregistered essential medicines.

Provision of family planning vouchers and early initiation of postpartum contraceptive use among women living with HIV in southwestern Uganda: A randomized controlled trial.

BACKGROUND: Unwanted pregnancies remain a burden for women living with HIV (WLWH). Family planning prevents unplanned pregnancies while promoting longer birth intervals, key strategies to eliminate perinatal transmission of HIV and promote maternal and child health. We evaluated the effect of a family planning voucher, inclusive of immediate postpartum counseling, on uptake, early initiation, and continuation of modern contraceptive methods among recently postpartum WLWH delivering at a publicly funded regional referral hospital in rural, southwestern Uganda. METHODS AND FINDINGS: We performed a randomized controlled trial between October, 2016 and June, 2018 at a referral hospital in southwestern Uganda. This interim analysis includes adult WLWH randomized and enrolled equally to receive a family planning voucher or standard of care (control). Enrolled postpartum WLWH completed an interviewer-administered questionnaire at enrollment and 6 months postpartum. Our primary outcome of interest for this analysis is initiation of a modern family planning method within 8 weeks postpartum. Secondary outcomes included family planning initiation at 12, 14, 16, and 20 weeks postpartum, family planning discontinuation and/or change, pregnancy incidence, and mean time without contraception. The trial was registered with clinicaltrials.gov (NCT02964169). At enrollment, half of the women in both the voucher (N = 87, 55%) and control (N = 86, 54%) groups wanted to have a child in 2 years postpartum. Over 80% of referent pregnancies in the voucher (N = 136, 86%) and control (N = 128, 81%) groups were planned. All women were accessing ART. The mean CD4 count was 396 cells/mm3 (SD = 61) for those enrolled in the control group versus 393 cells/mm3 (SD = 64) in the family planning voucher group. By 8 weeks postpartum, family planning was initiated in 144 (91%) participants in the voucher group and 83 (52%) participants in the control group (odds ratio [OR] 9.42; CI 4.67-13.97, P < 0.001). We also found high family planning uptake rates for both groups, with higher rates among the intervention group at 12 weeks (OR 5.66; CI 2.65-12.12, P < 0.001), 14 weeks (OR 2.51; CI 1.31-4.79, P < 0.001), 16 weeks (OR 4.02; CI 1.66-9.77, P = 0.001), and 20 weeks (OR 3.65; CI 1.40-9.47, P = 0.004) postpartum. The average time to family planning initiation was reduced to 5.9 weeks (SD = 2.4) for those in the voucher group compared to 9.3 weeks (SD = 5) in the control (P < 0.001). One pregnancy was recorded in the group receiving standard of care; none were reported in the voucher group. Method mix did not differ by group: injectables were selected by most women (N = 150, 50%), and 52% of this proportion were in the experimental arm, with <10% in each arm selecting condoms, oral contraception, or intrauterine devices (IUDs). Similar proportions of women changed contraceptive methods over the 6-month follow-up in the voucher and control groups (N = 8, 5% versus N = 5, 4%; P = 0.467). More women in the control group discontinued contraception for 1 to 2 weeks (N = 19, 13% versus N = 7, 5%; P = 0.008) or more than 4 weeks (N = 15, 10% versus N = 3, 2%; P = 0.002) compared to those given a family planning voucher. The main limitation of this study is that its findings may not be generalized to settings without improved availability of contraceptives in publicly funded facilities. CONCLUSION: These findings indicate that a well-structured, time-bound family planning voucher program appeared to increase early postpartum contraceptive uptake and continuation in a setting in which users are faced with financial, knowledge, and structural barriers to contraceptive services. Further work should clarify the role of vouchers in empowering WLWH to avoid unintended pregnancies over time. TRIAL REGISTRATION: ClinicalTrials.gov NCT02964169.

Factors Associated with Pregnancy Intentions Amongst Postpartum Women Living with HIV in Rural Southwestern Uganda.

Comprehensive HIV treatment and care makes it safer for women living with HIV (WLWH) to have the children they desire, partly through provision and appropriate use of effective contraception. However, nearly one third of WLWH in-care in a large Ugandan cohort became pregnant within 3 years of initiating ART and half of these incident pregnancies (45%) were unplanned. We therefore describe future pregnancy plans and associated factors among postpartum WLWH in rural southwestern Uganda in order to inform interventions promoting postpartum contraceptive uptake. This analysis includes baseline data collected from adult WLWH enrolled into a randomized controlled trial to evaluate the effect of family planning support versus standard of care at 12 months postpartum in southwestern Uganda. Enrolled postpartum WLWH completed an interviewer-administered questionnaire at enrolment. Among 320 enrolled women, mean age, CD4 count, and duration on ART was 28.9 (standard deviation [SD] 5.8) years, 395 cells/mm3 (SD = 62) and 4.6 years (SD = 3.9), respectively. One-hundred and eighty nine (59%) of women reported either personal (175, 55%) or partner (186, 58%) desire for more children in the next 2 years. Intentions to have more children was strongly associated with partner's desire for more children (AOR = 31.36; P < 0.000), referent pregnancy planned (AOR = 2.69; P = 0.050) and higher household income > 150,000 Shs per month (AOR = 1.37; P = 0.010). Previous use of modern contraception (AOR = 0.07; P = 0.001), increasing age (AOR = 0.34; P = 0.012), having > 2 own children living in a household (AOR = 0.42; P = 0.021) and parity > 2 (AOR = 0.59; P = 0.015) were associated with reduced odds of pregnancy intention. Our findings highlight the role male partners play in influencing pregnancy intentions postpartum and the importance of engaging men in sexual and reproductive health counselling about child spacing for the health of women, children, and families. This should be addressed alongside key individual-level social, demographic, economic and structural factors within which couples can understand risks of unplanned pregnancies and access effective contraceptive methods when they need or want them.

Measuring Post-Partum Haemorrhage in Low-Resource Settings: The Diagnostic Validity of Weighed Blood Loss versus Quantitative Changes in Hemoglobin.

BACKGROUND: Accurate estimation of blood loss is central to prompt diagnosis and management of post-partum hemorrhage (PPH), which remains a leading cause of maternal mortality in low-resource countries. In such settings, blood loss is often estimated visually and subjectively by attending health workers, due to inconsistent availability of laboratory infrastructure. We evaluated the diagnostic accuracy of weighed blood loss (WBL) versus changes in peri-partum hemoglobin to detect PPH. METHODS: Data from this analysis were collected as part of a randomized controlled trial comparing oxytocin with misoprostol for PPH (NCT01866241). Blood samples for complete blood count were drawn on admission and again prior to hospital discharge or before blood transfusion. During delivery, women were placed on drapes and had pre-weighed sanitary towels placed around their perineum. Blood was then drained into a calibrated container and the sanitary towels were added to estimate WBL, where each gram of blood was estimated as a milliliter. Sensitivity, specificity, negative and positive predictive values (PPVs) were calculated at various blood volume loss and time combinations, and we fit receiver-operator curves using blood loss at 1, 2, and 24 hours compared to a reference standard of haemoglobin decrease of >10%. RESULTS: A total of 1,140 women were enrolled in the study, of whom 258 (22.6%) developed PPH, defined as a haemoglobin drop >10%, and 262 (23.0%) had WBL ≥500mL. WBL generally had a poor sensitivity for detection of PPH (<75% for most volume-time combinations). In contrast, the specificity of WBL was high with blood loss ≥ 500mL at 1h and ≥750mL at any time points excluding PPH in over 97% of women. As such, WBL has a high PPV (>85%) in high prevalence settings when WBL exceeds 750mL. CONCLUSION: WBL has poor sensitivity but high specificity compared to laboratory-based methods of PPH diagnosis. These characteristics correspond to a high PPV in areas with high PPH prevalence. Although WBL is not useful for excluding PPH, this low-cost, simple and reproducible method is promising as a reasonable method to identify significant PPH in such settings where quantifiable red cell indices are unavailable.

Civil Society Organizations and medicines policy change: a case study of registration, procurement, distribution and use of misoprostol in Uganda.

Misoprostol use for postpartum haemorrhage (PPH) has been promoted by Civil Society Organizations (CSOs) since the early 2000s. Yet, CSOs' role in improving access to misoprostol and shaping health policy at global and national levels is not well understood. We document the introduction of misoprostol in Uganda in 2008 from its registration, addition to treatment guidelines and national Essential Medicines List (EML), to its distribution and use. We then analyse the contribution of CSOs to this health policy change and service provision. Policy documents, procurement data and 82 key informant interviews with government officials, healthcare providers, and CSOs in four Ugandan districts of Kampala, Mbarara, Apac, Bundibugyo were collected between 2010 and 2013. Five key CSOs promoted and accelerated the rollout of misoprostol in Uganda. They supported the registration of misoprostol with the National Drug Authority, the development of clinical guidelines, and the piloting and training of health care providers. CSOs and National Medical Stores were procuring and distributing misoprostol country-wide to health centres two years before it was added to the clinical guidelines and EML of Uganda and in the absence of good evidence. The evidence suggests an increasing trend of misoprostol procurement and availability over the medicine of choice, oxytocin. This shift in national priorities has serious ramifications for maternal health care that need urgent evaluation. The absence of clinical guidelines in health centres and the lack of training preclude rational use of misoprostol. CSOs shifted their focus from the public to the private sector, where some of them continue to promote its use for off-label indications including induction of labour and abortion. There is an urgent need to build capacity to improve the robustness of the national and local institutions in assessing the safety and effectiveness of all medicines and their indications in Uganda.

Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in Uganda: a double-blind randomized non-inferiority trial.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal death in sub-Saharan Africa. Although the World Health Organization recommends use of oxytocin for prevention of PPH, misoprostol use is increasingly common owing to advantages in shelf life and potential for sublingual administration. There is a lack of data about the comparative efficacy of oxytocin and sublingual misoprostol, particularly at the recommended dose of 600 µg, for prevention of PPH during active management of labor. METHODS AND FINDINGS: We performed a double-blind, double-dummy randomized controlled non-inferiority trial between 23 September 2012 and 9 September 2013 at Mbarara Regional Referral Hospital in Uganda. We randomized 1,140 women to receive 600 µg of misoprostol sublingually or 10 IU of oxytocin intramuscularly, along with matching placebos for the treatment they did not receive. Our primary outcome of interest was PPH, defined as measured blood loss ≥ 500 ml within 24 h of delivery. Secondary outcomes included measured blood loss ≥ 1,000 ml; mean measured blood loss at 1, 2, and 24 h after delivery; death; requirement for blood transfusion; hemoglobin changes; and use of additional uterotonics. At 24 h postpartum, primary PPH occurred in 163 (28.6%) participants in the misoprostol group and 99 (17.4%) participants in the oxytocin group (relative risk [RR] 1.64, 95% CI 1.32 to 2.05, p<0.001; absolute risk difference 11.2%, 95% CI 6.44 to 16.1). Severe PPH occurred in 20 (3.6%) and 15 (2.7%) participants in the misoprostol and oxytocin groups, respectively (RR 1.33, 95% CI 0.69 to 2.58, p = 0.391; absolute risk difference 0.9%, 95% CI -1.12 to 2.88). Mean measured blood loss was 341.5 ml (standard deviation [SD] 206.2) and 304.2 ml (SD 190.8, p = 0.002) at 2 h and 484.7 ml (SD 213.3) and 432.8 ml (SD 203.5, p<0.001) at 24 h in the misoprostol and oxytocin groups, respectively. There were no significant differences between the two groups in any other secondary outcomes. Women in the misoprostol group more commonly experienced shivering (RR 1.91, 95% CI 1.65 to 2.21, p<0.001) and fevers (RR 5.20, 95% CI 3.15 to 7.21, p = 0.005). This study was conducted at a regional referral hospital with capacity for emergency surgery and blood transfusion. High-risk women were excluded from participation. CONCLUSIONS: Misoprostol 600 µg is inferior to oxytocin 10 IU for prevention of primary PPH in active management of labor. These data support use of oxytocin in settings where it is available. While not powered to do so, the study found no significant differences in rate of severe PPH, need for blood transfusion, postpartum hemoglobin, change in hemoglobin, or use of additional uterotonics between study groups. Further research should focus on clarifying whether and in which sub-populations use of oxytocin would be preferred over sublingual misoprostol. TRIAL REGISTRATION: ClinicalTrials.gov NCT01866241 Please see later in the article for the Editors' Summary.

The availability of six tracer medicines in private medicine outlets in Uganda.

OBJECTIVES: Many low income countries struggle to provide safe and effective medicines due to poor public health care infrastructure, budgetary constraints, and lack of human resource capacity. Private sector pharmacies and drug shops are used by a majority of the population as an alternative to public pharmacies. This study looks at the availability of six essential medicines in private drug outlets across Uganda. METHODS: A standardised medicines availability survey developed by the World Health Organization and Health Action International was adapted for use in this project to collect availability data for six tracer medicines in 126 private medicine outlets across four districts in Uganda from September 2011 to October 2012. RESULTS: Artemisinin-based combination treatments and metformin were the most commonly found medicines in the private medicine outlets surveyed. Ninty-nine percent of all outlets carried artemisinin-based combinations while 93% of pharmacies and 53% of drug shops stocked metformin. Oxytocin was found in one third of outlets surveyed. Fluoxetine was in 70% of pharmacies yet was not found in any drug shops. Rifampicin and lamivudine were found infrequently in outlets across all districts; 10% and 2%, respectively. Not all brands found in surveyed outlets were listed on the Ugandan National Drug Register. In particular, five unlisted brands of rifampicin were found in private medicine outlets. CONCLUSIONS: The regulatory process should be improved through the enforcement of outlet licensing and medicine registration. Additional studies to elucidate the reasons behind the use of private medicine outlets over the public sector would assist the government in implementing interventions to increase use of public sector medicine outlets.

The analgesic and antiplasmodial activities and toxicology of Vernonia amygdalina.

Vernonia amygdalina possesses several bioactive compounds and is used in traditional medicines of southwestern Uganda, along with other regions. Its analgesic potential has not been investigated thus far. The present study examines the antinociceptive potential of the aqueous leaf extract (50-200 mg/kg) using three models of nociception (acetic acid-induced writhing, formalin test, and tail-flick test), antiplasmodial activity, and toxicology of the extract. The results show the extract significantly inhibits acetic acid-induced writhing and the formalin test in mice but did not give a potent effect in the tail-flick test, suggesting that the extract may have peripheral and central analgesic properties. The extract also exhibited significant antiplasmodial activity in mice against Plasmodium berghei with 73% inhibition in the group that received a dose of 200 mg/kg i.p. daily for 4 days. Toxicology results show no clinical signs of toxicity or adverse toxicological effects in the treated groups, except for a significant decrease in red blood cell count and a dose-dependent increase in serum bilirubin. These changes were within control values based on historical reference ranges at doses of 500-2,000 mg/kg/day for 14 consecutive days as compared to the control. This study supports the traditional use of V. amygdalina as an alternative therapy for malaria and the symptomatic relief of pain usually associated with malaria.