BabyGel Pilot: a pilot cluster randomised trial of the provision of alcohol handgel to postpartum mothers to prevent neonatal and young infant Infection-related morbidity in the community

Background Alcohol-based hand rub (ABHR) is widely used in both health and social facilities to prevent infection, but it is not known whether supplying it for regular perinatal use can prevent newborn sepsis in African rural homes. Our study piloted a cluster randomised trial of providing ABHR to postpartum mothers to prevent neonatal infection-related morbidity in the communities. Methods We conducted a pilot parallel cluster randomised controlled trial across ten villages (clusters) in rural Eastern Uganda. Pregnant women of over 34 weeks’ gestation were recruited over a period of 3 months. Both clusters received the standard of care of antenatal health education, Maama Kit, and clinic appointments. In addition, women in the intervention villages received ABHR, instructions on ABHR use, a poster on the ‘three moments of hand hygiene’, and training. We followed up each mother-baby pair for 3 months after birth and measured rates of consent, recruitment, and follow-up (our target rate was more than 80%). Other measures included ABHR use (the acceptable use was more than four times a day) and its mode of distribution (village health workers (VHWs) or pharmacy), acceptability of study protocol and electronic data capture, and the use of WHO Integrated Management of Childhood Illness (IMCI) tool to screen for newborn infection. Results We selected 36% (10/28) of villages for randomisation to either intervention or control. Over 12 weeks, 176 pregnant women were screened and 58.5% (103/176) were eligible. All, 100% (103/103), eligible women gave consent and were enrolled into the trial (55 intervention and 48 control). After birth, 94.5% (52/55) of mothers in the intervention and 100% (48/48) of mothers in the control villages were followed up within 72 h. Most, 90.9% (50/55), of the mothers in the intervention villages (96.2% of live births) and 95.8% (46/48) of mothers in the control villages (95.9% of live births) were followed up at 3 months. In intervention villages, the average hand rub use was 6.6 times per day. VHWs accounted for all ABHR stock, compared to the pharmacy that could not account for 5 l of ABHR. The screening tool was positive for infection among a third of babies, i.e. 29.2% (14/48) in the intervention villages versus 31.4% (16/51) in the control villages. VHWs completed the first four questions of IMCI screening tool with ease and accuracy. There were no adverse reactions with the ABHR. Conclusion It is feasible to conduct a cluster-randomised controlled trial (cRCT) of the provision of ABHR to postpartum mothers to prevent neonatal infection-related morbidity in the community in resource-poor settings. Our results indicate that home recruitment promotes excellent follow-up and retention of participants in community trials. The intervention was safe. This pilot study informed the substantial changes necessary in the larger cRCT, including a change in the primary outcome to a composite outcome considering multiple methods of infection detection. A large BabyGel cluster randomised controlled trial is now required

The MamaMiso study of self-administered misoprostol to prevent bleeding after childbirth in rural Uganda: a community-based, placebo-controlled randomised trial

BACKGROUND: 600 mcg of oral misoprostol reduces the incidence of postpartum haemorrhage (PPH), but in previous research this medication has been administered by health workers. It is unclear whether it is also safe and effective when self-administered by women. METHODS: This placebo-controlled, double-blind randomised trial enrolled consenting women of at least 34 weeks gestation, recruited over a 2-month period in Mbale District, Eastern Uganda. Participants had their haemoglobin measured antenatally and were given either 600 mcg misoprostol or placebo to take home and use immediately after birth in the event of delivery at home. The primary clinical outcome was the incidence of fall in haemoglobin of over 20% in home births followed-up within 5 days. RESULTS: 748 women were randomised to either misoprostol (374) or placebo (374). Of those enrolled, 57% delivered at a health facility and 43% delivered at home. 82% of all medicine packs were retrieved at postnatal follow-up and 97% of women delivering at home reported self-administration of the medicine. Two women in the misoprostol group took the study medication antenatally without adverse effects. There was no significant difference between the study groups in the drop of maternal haemoglobin by >20% (misoprostol 9.4% vs placebo 7.5%, risk ratio 1.11, 95% confidence interval 0.717 to 1.719). There was significantly more fever and shivering in the misoprostol group, but women found the medication highly acceptable. CONCLUSIONS: This study has shown that antenatally distributed, self-administered misoprostol can be appropriately taken by study participants. The rarity of the primary outcome means that a very large sample size would be required to demonstrate clinical effectiveness. TRIAL REGISTRATION: This study was registered with the ISRCTN Register (ISRCTN70408620)

Achieving community-based postpartum follow up in eastern Uganda: the field experience from the MamaMiso Study on antenatal distribution of misoprostol.

BackgroundAdvance provision of misoprostol to women during antenatal care aims to achieve broader access to uterotonics for the prevention of postpartum hemorrhage. Studies of this community-based approach usually involve antenatal education as well as timely postpartum follow-up visits to confirm maternal and neonatal outcomes. The MamaMiso study in Mbale, Uganda sought to assess the feasibility of conducting follow-up visits in the postpartum period following advance provision of misoprostol for postpartum hemorrhage prevention. MamaMiso recruited women during antenatal care visits. Participants were asked to contact the research team within 48 h of giving birth so that postpartum follow-up visits could be carried out at their homes. Women's baseline and delivery characteristics were collected and analyzed with respect to follow-up time ('on time' ≤ 7 days, 'late' > 7 days, and 'lost to follow up'). Every woman who was followed up late due to a failure to report the delivery was asked for the underlying reasons for the delay. When attempts at following up participants were unsuccessful, a file note was generated explaining the details of the failure. We abstracted data and identified themes from these notes.ResultsOf 748 recruited women, 700 (94%) were successfully followed up during the study period, 465 (62%) within the first week postpartum. The median time to follow up was 4 days and was similar for women who delivered at home or in facilities and for women who had attended or unattended births. Women recruited at the urban hospital site (as opposed to rural health clinics) were more likely to be lost to follow up or followed up late. Of the women followed up late, 202 provided a reason. File notes explaining failed attempts at follow up were generated for 164 participants. Several themes emerged from qualitative analysis of these notes including phone difficulties, inaccurate baseline information, misperceptions, postpartum travel, and the condition of the mother and neonate.ConclusionsKeeping women connected to the health system in the postpartum period is feasible, though reaching them within the first week of their delivery is challenging. Understanding characteristics of women who are harder to reach can help tailor follow-up efforts and elucidate possible biases in postpartum study data. Trial Registration Number ISRCTN70408620 December 28, 2011

Identifying women giving birth preterm and care at the time of birth: a prospective audit of births at six hospitals in India, Kenya, Pakistan and Uganda

Background: Globally, 15 million infants are born preterm each year, and one million die due to complications of prematurity. Over 60% of preterm births occur in Sub-Saharan Africa and south Asia. Care at birth for premature infants may be critical for survival and long term outcome. We conducted a prospective audit to assess whether women giving birth preterm could be identified, and to describe cord clamping and neonatal care at hospitals in Africa and south Asia.Methods: This prospective audit of livebirths was conducted at six hospitals in Uganda, Kenya, India and Pakistan. Births were considered preterm if between 28+0 and 33+6 weeks gestation and/or the birthweight was 1.00 to 1.99 kg. A pre-specified audit plan was agreed with each hospital. Livebirths before 28 weeks gestation with birthweight less than 1.0 kg were excluded. Data were collected on estimated and actual gestation and birthweight, cord clamping, and neonatal care. Results: Of 4149 women who gave birth during the audit, data were available for 3687 (90%). As 107 were multiple births, 3781 livebirths were included, of which 257 (7%) were preterm. Antenatal assessment correctly identified 148 infants as ‘preterm’ and 3429 as ‘term’, giving a positive predictive value of 72% and negative predictive value of 97%. For term births, cord clamping was usually later at the two Ugandan hospitals, median time to clamping 50 and 76 seconds, compared with 23 at Kenyatta (Kenya), 7 at CMC (India) and 12 at FBH/LNH (Pakistan). At the latter two, timing was similar between term and preterm births, and between vaginal and Caesarean births. For all the hospitals, the cord was clamped quickly at Caesarean births, with Mbale (Uganda) having the highest median time to clamping (15 seconds ‘term’, 19 ‘preterm’). For preterm infants temperature on admission to the neonatal unit was below 35.5°C for 50%, and 59 (23%) died before hospital discharge. Conclusions: Antenatal identification of preterm birth was good. Timing of cord clamping varied between hospitals, although at each there was no difference between ‘term’ and ‘preterm’ births. For premature infants hypothermia was common, and mortality before hospital discharge was high

Preventing neonatal sepsis in rural Uganda: a cross-over study comparing the tolerance and acceptability of three alcohol-based hand rub formulations

BACKGROUND Neonatal sepsis causes 0.5 million deaths annually, mostly in low resource settings. Babies born in African rural homes without running water or toilet facilities are especially vulnerable. Alcohol-based hand rub (ABHR) may be used by mothers and carers as an alternative to hand washing with soap to prevent neonatal infection. However, no definite study has established the preferred formulation of hand rub for the mothers. This study aimed to assess the effects of addition of bitterants and perfume towards the acceptability of the alcohol-based hand rubs by the mothers in their homes after childbirth. METHODS This was a 3-way blinded cross-over study design. Mothers with children aged ≤3 months were recruited from immunisation clinics at 3 local health facilities in rural eastern Uganda and received 3-different ABHR formulations (in the order plain, bitterant and perfumed) packed in 100 ml bottles. Each ABHR was used for 5 consecutive days followed by a 2-day 'washout' period (evaluation period). Overall satisfaction with each hand rub was evaluated at the end of each week using a 7-point Likert scale. RESULTS A total of 43 women were recruited, whose ages ranged from 16 to 45 years (mean 26.2 years old). None of the participants normally used a hand protective lotion/cream. The three formulations were used for a mean of 5 (range 3-7) days. A significantly greater volume of the "bitterant" and "perfumed" formulations (mean 91 and 83 ml respectively) were used in comparison to the "plain" formulation (mean 64 ml). Overall satisfaction was high with all the hand rubs, but the perfumed formulation had a significantly higher overall satisfaction score [mean 6.7, range 4-7] compared with the plain [6.4, 3-7] and bitterant [6.2, 2-7] formulations. CONCLUSIONS All the 3 ABHR formulations were well accepted with little to choose between them. The ABHR with added perfume scored highest on overall satisfaction and was used significantly more often than plain ABHR. ABHR with bitterant additive did, however, score highly and may be a preferable choice to those with concern over alcohol misuse. TRIAL REGISTRATION ISRCTN67852437 , prospectively registered on 18/03/2018

Barriers to Initiation of Pediatric HIV Treatment in Uganda: A Mixed-Method Study

Although the advantages of early infant HIV diagnosis and treatment initiation are well established, children often present late to HIV programs in resource-limited settings. We aimed to assess factors related to the timing of treatment initiation among HIV-infected children attending three clinical sites in Uganda. Clinical and demographic determinants associated with early disease (WHO clinical stages 1-2) or late disease (stages 3-4) stage at presentation were assessed using multilevel logistic regression. Additionally, semistructured interviews with caregivers and health workers were conducted to qualitatively explore determinants of late disease stage at presentation. Of 306 children initiating first-line regimens, 72% presented late. Risk factors for late presentation were age below 2 years old (OR 2.83, P = 0.014), living without parents (OR 3.93, P = 0.002), unemployment of the caregiver (OR 4.26, P = 0.001), lack of perinatal HIV prophylaxis (OR 5.66, P = 0.028), and high transportation costs to the clinic (OR 2.51, P = 0.072). Forty-nine interviews were conducted, confirming the identified risk factors and additionally pointing to inconsistent referral from perinatal care, caregivers' unawareness of HIV symptoms, fear, and stigma as important barriers. The problem of late disease at presentation requires a multifactorial approach, addressing both health system and individual-level factors

Optimising informed consent for participants in a randomised controlled trial in rural Uganda: a comparative prospective cohort mixed-methods study

Background Poor participant understanding of research information can be a problem in community interventional studies with rural African women, whose levels of illiteracy are high. This study aimed to improve the informed consent process for women living in rural eastern Uganda. We assessed the impact of alternative consent models on participants’ understanding of clinical trial information and their contribution to the informed consent process in rural Uganda. Methods The study applied a parallel mixed-methods design for a prospective comparative cohort, nested within a pilot study on the community distribution of an alcohol-based hand rub to prevent neonatal sepsis (BabyGel pilot trial). Women of at least 34 weeks’ pregnancy, suitable for inclusion in the BabyGel pilot trial, were recruited into this study from their homes in 13 villages in Mbale District. As part of the informed consent process, information about the trial was presented using one of three consent methods: standard researcher-read information, a slide show using illustrated text on a flip chart or a video showing the patient information being read as if by a newsreader in either English or the local language. In addition, all women received the patient information sheet in their preferred language. Each information-giving method was used in recruitment for 1 week. Two days after recruitment, women’s understanding of the clinical trial was evaluated using the modified Quality of Informed Consent (QuIC) tool. They were also shown the other two methods and their preference assessed using a 5-point Likert scale. Semi-structured interviews were administered to each participant. The interviews were audio-recorded, transcribed and translated verbatim, and thematically analysed. Results A total of 30 pregnant women in their homes participated in this study. Their recall of the trial information within the planned 48 h was assessed for the majority (90%, 27/30). For all three consent models, women demonstrated a high understanding of the study. There was no statistically significant difference between the slide-show message (mean 4.7; standard deviation, SD 0.47; range 4–5), video message (mean 4.9; SD 0.33; range 4–5) and standard method (mean 4.5; SD 0.53; range 4–5; all one-way ANOVA, p = 0.190). The slide-show message resulted in the most objective understanding of question items with the highest average QuIC score of 100 points. For women who had been recruited using any of the three models, the slide show was the most popular method, with a mean score for all items of not less than 4.2 (mean 4.8; SD 0.6; range 4–5). Most women (63%, 19/30) preferred the slide-show message, compared with 17% (5/30) and 20% (6/30) for the standard and video messages, respectively. The reasons given included the benefits of having pictures to aid understanding and the logical progression of the information. Conclusion Our results from this small study suggest that slide-show messages may be an effective and popular alternative way of presenting trial information to women in rural Uganda, many of whom have little or no literacy

A Randomized Trial of Prophylactic Antibiotics for Miscarriage Surgery.

BACKGROUND: Surgical intervention is needed in some cases of spontaneous abortion to remove retained products of conception. Antibiotic prophylaxis may reduce the risk of pelvic infection, which is an important complication of this surgery, particularly in low-resource countries. METHODS: We conducted a double-blind, placebo-controlled, randomized trial investigating whether antibiotic prophylaxis before surgery to complete a spontaneous abortion would reduce pelvic infection among women and adolescents in low-resource countries. We randomly assigned patients to a single preoperative dose of 400 mg of oral doxycycline and 400 mg of oral metronidazole or identical placebos. The primary outcome was pelvic infection within 14 days after surgery. Pelvic infection was defined by the presence of two or more of four clinical features (purulent vaginal discharge, pyrexia, uterine tenderness, and leukocytosis) or by the presence of one of these features and the clinically identified need to administer antibiotics. The definition of pelvic infection was changed before the unblinding of the data; the original strict definition was two or more of the clinical features, without reference to the administration of antibiotics. RESULTS: We enrolled 3412 patients in Malawi, Pakistan, Tanzania, and Uganda. A total of 1705 patients were assigned to receive antibiotics and 1707 to receive placebo. The risk of pelvic infection was 4.1% (68 of 1676 pregnancies) in the antibiotics group and 5.3% (90 of 1684 pregnancies) in the placebo group (risk ratio, 0.77; 95% confidence interval [CI], 0.56 to 1.04; P = 0.09). Pelvic infection according to original strict criteria was diagnosed in 1.5% (26 of 1700 pregnancies) and 2.6% (44 of 1704 pregnancies), respectively (risk ratio, 0.60; 95% CI, 0.37 to 0.96). There were no significant between-group differences in adverse events. CONCLUSIONS: Antibiotic prophylaxis before miscarriage surgery did not result in a significantly lower risk of pelvic infection, as defined by pragmatic broad criteria, than placebo. (Funded by the Medical Research Council and others; AIMS Current Controlled Trials number, ISRCTN97143849.)

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3L) utility index

10.1186/s12955-019-1135-8Health and Quality of Life Outcomes1718