Obstetric fistulae in southern Mozambique: incidence, obstetric characteristics and treatment.

BACKGROUND: Obstetric fistula is one of the most devastating consequences of unmet needs in obstetric services. Systematic reviews suggest that the pooled incidence of fistulae in community-based studies is 0.09 per 1000 recently pregnant women; however, as facility delivery is increasing, for the most part, in Africa, incidence of fistula should decrease. Few population-based studies on fistulae have been undertaken in Sub-Saharan Africa, including Mozambique. This study aimed to estimate the incidence of obstetric fistulae in recently delivered mothers, and to describe the clinical characteristics and care, as well as the outcome, after surgical repair. METHODS: We selected women who had delivered up to 12 months before the start of the study (June, 1st 2016). They were part of a cohort of women of reproductive age (12-49 years), recruited from selected clusters in rural areas of Maputo and Gaza provinces, Southern Mozambique, who were participating in an intervention trial (the Community Level Interventions for Pre-eclampsia trial or CLIP trial). Case identification was completed by self-reported constant urine leakage and was confirmed by clinical assessment. Women who had confirmed obstetric fistulae were referred for surgical repair. Data were entered into a REDCap database and analysed using R software. RESULTS: Five women with obstetric fistulae were detected among 4358 interviewed, giving an incidence of 1.1 per 1000 recently pregnant women (95% CI 2.16-0.14). All but one had Caesarean section and all of the babies died. Four were stillborn, and one died very soon after birth. All of the patients identified and reached the primary health facility in reasonable time. Delays occurred in the care: in diagnosis of obstructed labour, and in the decision to refer to the secondary or third-level hospital. All but one of the women were referred to surgical repair and the fistulae successfully closed. CONCLUSION: This population-based study reports a high incidence of obstetric fistulae in an area with high numbers of facility births. Few first and second delays in reaching care, but many third delays in receiving care, were identified. This raises concerns for quality of care

Potential for task-sharing to Lady Health Workers for identification and emergency management of pre-eclampsia at community level in Pakistan.

BACKGROUND: An estimated 276 Pakistani women die for every 100,000 live births; with eclampsia accounting for about 10 % of these deaths. Community health workers contribute to the existing health system in Pakistan under the banner of the Lady Health Worker (LHW) Programme and are responsible to provide a comprehensive package of antenatal services. However, there is a need to increase focus on early identification and prompt diagnosis of pre-eclampsia in community settings, since women with mild pre-eclampsia often present without symptoms. This study aims to explore the potential for task-sharing to LHWs for the community-level management of pre-eclampsia and eclampsia in Pakistan. METHODS: A qualitative exploratory study was undertaken February-July 2012 in two districts, Hyderabad and Matiari, in the southern province of Sindh, Pakistan. Altogether 33 focus group discussions (FGDs) were conducted and the LHW curriculum and training materials were also reviewed. The data was audio-recorded, then transcribed verbatim for thematic analysis using QSR NVivo-version10. RESULTS: Findings from the review of the LHW curriculum and training program describe that in the existing community delivery system, LHWs are responsible for identification of pregnant women, screening women for danger signs and referrals for antenatal care. They are the first point of contact for women in pregnancy and provide nutritional counselling along with distribution of iron and folic acid supplements. Findings from FGDs suggest that LHWs do not carry a blood pressure device or antihypertensive medications; they refer to the nearest public facility in the event of a pregnancy complication. Currently, they provide tetanus toxoid in pregnancy. The health advice provided by lady health workers is highly valued and accepted by pregnant women and their families. Many Supervisors of LHWs recognized the need for increased training regarding pre-eclampsia and eclampsia, with a focus on identifying women at high risk. The entire budget of the existing lady health worker Programme is provided by the Government of Pakistan, indicating a strong support by policy makers and the government for the tasks undertaken by these providers. CONCLUSION: There is a potential for training and task-sharing to LHWs for providing comprehensive antenatal care; specifically for the identification and management of pre-eclampsia in Pakistan. However, the implementation needs to be combined with appropriate training, equipment availability and supervision. TRIAL REGISTRATION: ClinicalTrial.gov, NCT01911494

Tamoxifen is not effective in good prognosis patients with hepatocellular carcinoma

BACKGROUND: Large randomised clinical trials and systematic reviews substantiate that tamoxifen is ineffective in improving survival of patients with hepatocellular carcinoma (HCC). However, a recent report suggested that the drug might prolong survival among patients with well preserved liver function. The aim of this paper is to validate this hypothesis. METHODS: We used the updated database of the phase 3 randomised CLIP-1 trial that compared tamoxifen with supportive therapy. Primary endpoint was overall survival. Treatment arms were compared within strata defined according to the Okuda stage and the CLIP-score. Survival differences were tested by the Log-rank test. RESULTS: Tamoxifen was not effective in prolonging survival in Okuda I-II subgroup (p = 0.501). Median survival times were equal to 16.8 (95%CI 12.7–18.5) months for tamoxifen and 16.8 (95%CI 13.5–22.4) months for the control arms; 1-year survival probabilities were equal to 58.8% (95%CI 51.7–65.8) and 59.4 (95%CI 52.5–66.2), respectively. Similar results were observed in the better CLIP subgroup (score 0/1), without evidence of difference between the two treatment arms (p = 0.734). Median survival times were equal to 29.2 (95%CI 20.1–36.4) months with tamoxifen and 29.0 (95%CI 23.3–35.2) months without; 1-year survival probabilities were equal to 80.9% (95%CI 72.5–89.3) with tamoxifen and 77.1% (95%CI 68.6–85.7) for the control arm. CONCLUSION: The recent suggestion that tamoxifen might be effective in the subgroup of patients with better prognosis is not supported by a reanalysis of the CLIP-1 trial. Tamoxifen should no longer be considered for the treatment of HCC patients and future trials of medical treatment should concentrate on different drugs

The community-level interventions for pre-eclampsia (CLIP) cluster randomised trials in Mozambique, Pakistan, and India: An individual participant-level meta-analysis

Background: To overcome the three delays in triage, transport and treatment that underlie adverse pregnancy outcomes, we aimed to reduce all-cause adverse outcomes with community-level interventions targeting women with pregnancy hypertension in three low-income countries.Methods: In this individual participant-level meta-analysis, we de-identified and pooled data from the Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomised controlled trials in Mozambique, Pakistan, and India, which were run in 2014-17. Consenting pregnant women, aged 12-49 years, were recruited in their homes. Clusters, defined by local administrative units, were randomly assigned (1:1) to intervention or control groups. The control groups continued local standard of care. The intervention comprised community engagement and existing community health worker-led mobile health-supported early detection, initial treatment, and hospital referral of women with hypertension. For this meta-analysis, as for the original studies, the primary outcome was a composite of maternal or perinatal outcome (either maternal, fetal, or neonatal death, or severe morbidity for the mother or baby), assessed by unmasked trial surveillance personnel. For this analysis, we included all consenting participants who were followed up with completed pregnancies at trial end. We analysed the outcome data with multilevel modelling and present data with the summary statistic of adjusted odds ratios (ORs) with 95% CIs (fixed effects for maternal age, parity, maternal education, and random effects for country and cluster). This meta-analysis is registered with PROSPERO, CRD42018102564.Findings: Overall, 44 clusters (69 330 pregnant women) were randomly assigned to intervention (22 clusters [36 008 pregnancies]) or control (22 clusters [33 322 pregnancies]) groups. 32 290 (89·7%) pregnancies in the intervention group and 29 698 (89·1%) in the control group were followed up successfully. Median maternal age of included women was 26 years (IQR 22-30). In the intervention clusters, 6990 group and 16 691 home-based community engagement sessions and 138 347 community health worker-led visits to 20 819 (57·8%) of 36 008 women (of whom 11 095 [53·3%] had a visit every 4 weeks) occurred. Blood pressure and dipstick proteinuria were assessed per protocol. Few women were eligible for methyldopa for severe hypertension (181 [1%] of 20 819) or intramuscular magnesium sulfate for pre-eclampsia (198 [1%]), of whom most accepted treatment (162 [89·5%] of 181 for severe hypertension and 133 [67·2%] of 198 for pre-eclampsia). 1255 (6%) were referred to a comprehensive emergency obstetric care facility, of whom 864 (82%) accepted the referral. The primary outcome was similar in the intervention (7871 [24%] of 32 290 pregnancies) and control clusters (6516 [22%] of 29 698; adjusted OR 1·17, 95% CI 0·90-1·51; p=0·24). No intervention-related serious adverse events occurred, and few adverse effects occurred after in-community treatment with methyldopa (one [2%] of 51; India only) and none occurred after in-community treatment with magnesium sulfate or during transport to facility.Interpretation: The CLIP intervention did not reduce adverse pregnancy outcomes. Future community-level interventions should expand the community health worker workforce, assess general (rather than condition-specific) messaging, and include health system strengthening.Funding: University of British Columbia, a grantee of the Bill & Melinda Gates Foundation

Transitioning from the “Three Delays” to a focus on continuity of care: a qualitative analysis of maternal deaths in rural Pakistan and Mozambique

Background: The Three Delays Framework was instrumental in the reduction of maternal mortality leading up to, and during the Millennium Development Goals. However, this paper suggests the original framework might be reconsidered, now that most mothers give birth in facilities, the quality and continuity of the clinical care is of growing importance. Methods: The paper explores the factors that contributed to maternal deaths in rural Pakistan and Mozambique, using 76 verbal autopsy narratives from the Community Level Interventions for Pre-eclampsia (CLIP) Trial. Results: Qualitative analysis of these maternal death narratives in both countries reveals an interplay of various influences, such as, underlying risks and comorbidities, temporary improvements after seeking care, gaps in quality care in emergencies, convoluted referral systems, and arrival at the final facility in critical condition. Evaluation of these narratives helps to reframe the pathways of maternal mortality beyond a single journey of care-seeking, to update the categories of seeking, reaching and receiving care. Conclusions: There is a need to supplement the pioneering “Three Delays Framework” to include focusing on continuity of care and the “Four Critical Connection Points”: (1) between the stages of pregnancy, (2) between families and health care workers, (3) between health care facilities and (4) between multiple care-seeking journeys. Trial registration: NCT01911494, Date Registered 30/07/2013

Mothers' satisfaction with care during facility-based childbirth: a cross-sectional survey in southern Mozambique.

BACKGROUND: Client satisfaction is an essential component of quality of care. Health system factors, processes of care as well as mothers' characteristics influence the extent to which care meets the expectations of mothers and families. In our study, we specifically aimed to address the mothers' experiences of, and satisfaction with, care during childbirth. METHODS: A population-based cross-sectional study, using structured interviews with published sequences of questions assessing satisfaction, including 4358 mothers who gave birth during the 12 months before June 2016 to estimate satisfaction with childbirth care. Regression analysis was used to determine the predictors of client satisfaction. RESULTS: Most mothers (92.5%) reported being satisfied with care during childbirth and would recommend that a family member to deliver at the same facility. Specifically, 94.7% were satisfied with the cleanliness of the facility, 92.0% reported being satisfied with the interaction with the healthcare providers, but only 49.8% felt satisfied with the assistance to feed their baby. Mothers who had negative experiences during the process of care, such as being abandoned when needing help, disrespect, humiliation, or physical abuse, reported low levels of satisfaction when compared to those who had not had such experiences (68.5% vs 93.5%). Additionally, they reported higher levels of dissatisfaction (20.1% vs 2.1%). Regression analysis revealed that mothers who gave birth in primary level facilities tended to be more satisfied than those who gave birth in hospitals, and having a companion increased, on average, the overall satisfaction score, with 0.06 in type II health centres (CI 0.03-0.10) and with 0.05 in type I health centres (CI - 0.02 - 0.13), compared to - 0.01(CI -0.08 - 0.07) in the hospitals, irrespective of age, education and socio-economic background. CONCLUSION: Childbirth at the primary level facilities contributes to the level of satisfaction. The provision of childbirth care should consider women's preferences and needs, including having a companion of choice. We highlight the challenge in balancing safety of care versus satisfaction with care and in developing policies on the optimum configuration of childbirth care. Interventions to improve the interaction with providers and the provision of respectful care are recommended

Community Engagement for Birth Preparedness and Complication Readiness in the Community Level Interventions for Pre-eclampsia (CLIP) Trial in India: A Mixed-Method Evaluation

Objective: To describe the process of community engagement (CE) in northern Karnataka, India and its impact on pre-eclampsia knowledge, birth preparedness and complication readiness, pregnancy-related care seeking and maternal morbidity. Design: This study was a secondary analysis of a cluster randomised trial of Community Level Interventions for Pre-eclampsia (CLIP). A total of 12 clusters based on primary health centre catchment areas were randomised to intervention or control. CE was conducted in intervention clusters. CE attendance was summarised according to participant group using both quantitative and qualitative assessment. Pre-eclampsia knowledge, birth preparedness, health services engagement and perinatal outcomes was evaluated within trial surveillance. Outcomes were compared between trial arms using a mixed effects logistic regression model on RStudio (RStudio, Boston, USA). Community feedback notes were thematically analysed on NVivo V.12 (QSR International, Melbourne, Australia). Setting: Belagavi and Bagalkote districts in rural Karnataka, India. Participants: Pregnant women and women of reproductive age, mothers and mothers-in-law, community stakeholders and male household decision-makers and health workers. Results: A total of 1379 CE meetings were conducted with 39 362 participants between November 2014 and October 2016. CE activities may have had an effect on modifying community attitudes towards hypertension in pregnancy and its complications. However, rates of pre-eclampsia knowledge, birth preparedness, health services engagement and maternal morbidities among individual pregnant women were not significantly impacted by CE activities in their area. Conclusion: Evaluation of our CE programme in India demonstrates the feasibility of reaching pregnant women alongside household decision-makers, community stakeholders and health workers. More research is needed to explore the pathways of impact between broad community mobilisation to strengthen support for maternal care seeking and clinical outcomes of individual pregnant women. Trial registration number: NCT01911494

Efficacy of the combination of long-acting release octreotide and tamoxifen in patients with advanced hepatocellular carcinoma: a randomised multicentre phase III study

To assess the efficacy of the combination of long-acting release (LAR) octreotide and tamoxifen (TMX) for the treatment of advanced hepatocellular carcinoma (HCC). A total of 109 patients with advanced HCC were randomised to receive octreotide LAR combined with TMX (n=56) (experimental treatment group) or TMX alone (n=53; control group). The clinical, biological and tumoural parameters were recorded every 3 months until death. Primary end point was patient survival; secondary end points were the impact of therapy on tumour response, quality of life and variceal bleeding episodes. Univariate and multivariate analyses were performed for assessment of specific prognostic factors. The median survival was 3 months (95% CI 1.4–4.6) for the experimental treatment group and 6 months (CI 95% 2–10) for the control group (P=0.609). There was no difference in terms of α-foetoprotein (α-FP) decrease, tumour regression, improvement of quality of life and prevention of variceal bleeding between the two groups. Variables associated with a better survival in the multivariate analysis were: presence of cirrhosis, α-FP level <400 ng ml−1 and Okuda stage I. The combination of octreotide LAR and TMX does not influence survival, tumour progression or quality of life in patients with advanced HCC

Prospective validation of CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma.

The Cancer of the Liver Italian Program(CLIP) investigator