Strengthening midwives' competencies for addressing maternal and newborn mortality in Tanzania: Lessons from Midwifery Emergency Skills Training (MEST) project.

INTRODUCTION: In Low- and Middle-Income Countries (LMICs), maternal and infant mortality remains a significant problem. Inadequate healthcare provider competencies, including those of midwives, are cited as one of the major contributors to the high maternal and newborn mortality rates. Thus, enhancing the skills of midwives is a prerequisite for enhancing positive maternal and newborn health outcomes. This study describes the lessons learned from a Midwifery Emergencies Skills Training (MEST) project implemented in Tanzania between 2013 and 2018. METHODS: An exploratory qualitative study was used to purposefully recruit and interview twelve health facility in-charges and eighteen midwives from twelve selected health facilities in six districts of Tanzania mainland to discover their perceptions about the midwifery practice after MEST training. The data were transcribed verbatim and analysed with qualitative content analysis. RESULTS: Four categories were generated from the analysis (i) enhanced knowledge and skills in the provision of midwifery care and management of obstetric emergencies, (ii) improved midwives' communication skills, (iii) increased trust and support between midwives and community and (iv) transformed attitudes of midwives toward continued professional development (CPD). CONCLUSION: MEST enhanced the knowledge and skills of midwives in the management of obstetric emergencies and referral protocol practice. However, notable gaps remain in the capacity of midwives to provide human rights-based respectful maternity care. Continued professional development for nurses and midwives through training, mentorship and supervision programs is recommended for improving maternal and newborn health.

Tailoring a sexual health curriculum to the sexual health challenges seen by midwifery, nursing and medical providers and students in Tanzania.

BACKGROUND:  Tanzania is a country experiencing multiple sexual health challenges, but providers receive no formal training in sexual health. AIM:  This study aimed to assess (1) what sexual health challenges are commonly seen in clinics in Tanzania, (2) which are raised by patients, (3) which are not addressed and (4) which topics to prioritise for a sexual health curriculum. SETTING:  Healthcare settings in Tanzania. METHODS:  Participants were 60 experienced and 61 student doctors, nurses and midwives working in Dar es Salaam. The authors conducted 18 focus groups stratified by profession (midwifery, nursing or medicine) and experience (practitioners vs. students). RESULTS:  Providers identified six common sexual health concerns: (1) Human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) and sexually transmissible infection (STI) (especially syphilis and gonorrhoea), (2) sexual violence (including intimate partner violence and female genital mutilation), (3) early and unwanted pregnancy (including early sexual debut and complications from abortion), (4) sexual dysfunctions, (5) key population concerns (e.g. lesbian, gay, bisexual, transgender (LGBT); sex work) and (6) non-procreative sexual behaviour (including pornography and masturbation in males and oral and anal sex practices in heterosexual couples). Across professions, few differences were observed. Homosexuality, sex work, masturbation and pornography were identified as taboo topics rarely discussed. Most participants (81%) wanted one comprehensive sexual health curriculum delivered across disciplines. CONCLUSION:  A sexual health curriculum for health students in Tanzania needs to address the most common sexual health concerns of patients. In addition to teaching sexual science and clinical care, skills training in how to address taboo topics is recommended. Students endorsed almost all sexual health topics, which suggests that a comprehensive curriculum is appropriate.

The management of childhood sexual abuse by midwifery, nursing and medical providers in Tanzania.

BACKGROUND: Child sexual abuse (CSA) is a significant public health problem affecting one billion children aged 2 to 17 globally. The prevalence of CSA in Tanzania is one of the highest; however, how health care providers manage CSA cases has not been studied. OBJECTIVES: This study investigated how medical, nursing, and midwifery professionals in Tanzania handle cases of CSA and identified the factors that facilitate or impede the provision of quality care to CSA victims. METHODS: Participants were 60 experienced healthcare professionals and 61 health students working in Dar es Salaam, Tanzania. We conducted 18 focus groups stratified by profession (midwifery, nursing, or medicine) and experience (practitioners versus students). RESULTS: Three main themes emerged. First, child abuse management involved using a multi-disciplinary approach, including proper history taking, physical assessment, treatment, and referral. Second, factors that enhanced disclosure of CSA included building rapport, privacy, and confidentiality. Third, factors that impeded care included fear of harm to the child if the abuse was reported, abuse reporting being perceived as a "waste of time" for providers, loss of evidence from the victim, family resistance, poverty, corruption and cultural dynamics. CONCLUSIONS: Midwives, nurses and doctors were all experienced in and reported similar challenges in addressing CSA. At a structural level, the ratio of providers to patients in health facilities inhibits quality care. These findings have implications for strengthening CSA policy/guidelines and clinical practice in Tanzania. Mandated CSA training is necessary for midwifery, nursing, and medical students as well as in continuing education courses for more experienced providers.

Assessing the effect of a mind-body exercise, qigong Baduanjin, on sleep disturbance among women experiencing intimate partner violence and possible mediating factors: a randomized-controlled trial.

STUDY OBJECTIVES: To evaluate the effects of a mind-body exercise, qigong Baduanjin, on sleep disturbances in women experiencing intimate partner violence and explore the mediating role of depressive symptoms, perceived stress, and inflammation in producing the effects. METHODS: A subgroup of a parent randomized controlled trial was randomized for a 22-week Baduanjin intervention (n = 94) or wait-list control (n = 92). Questionnaires, including the General Sleep Disturbance Scale, Perceived Stress Scale, and Beck Depression Inventory version II, were administered at baseline, posttraining (6 weeks), and postintervention (22 weeks), and blood samples were collected to assess tumor necrosis factor and interleukin 6 levels at baseline and postintervention only. RESULTS: Of the 186 participants, 170 completed the study. Results indicate that the total sleep disturbance scores for the intervention group were significantly lower than those for the wait-list control group at week 6 (difference = -7.96; 95% confidence interval [CI], -13.63 to -2.30; P = .006) and week 22 (difference = -7.17; 95% CI, -12.58 to -1.76; P = .01). Mediation analysis showed a statistically significant indirect effect of the intervention on sleep improvement through reducing depressive symptoms (ß = 2.58, 95% CI, 0.69 to 5.09), while the mediating effects of perceived stress and inflammation were not significant. CONCLUSIONS: Qigong Baduanjin can be recommended for women who experience intimate partner violence and report sleep disturbances. More research is needed to understand the clinical significance of the observed sleep improvements. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Qigong Intervention Program for Abused Chinese Women; URL: https://clinicaltrials.gov/ct2/show/NCT02060123; Identifier: NCT02060123.

Effect of a Qigong Intervention on Telomerase Activity and Mental Health in Chinese Women Survivors of Intimate Partner Violence: A Randomized Clinical Trial.

Importance: Qigong is a mind-body exercise that may be an effective self-care intervention for improving the well-being of women survivors of intimate partner violence. Objective: To test whether a qigong intervention would increase telomerase activity and improve mental health in Chinese women who survived intimate partner violence. Design, Setting, and Participants: A single-blind randomized clinical trial among Chinese women (N = 271) who survived intimate partner violence in the past 2 years recruited from a community center in Hong Kong, China. The trial was conducted from March 12, 2014, to May 26, 2016. Data analysis was by intention to treat and performed from June 7 to August 24, 2018. Interventions: Randomization (1:1) to a 22-week qigong intervention (n = 136) that included 22 weeks of Baduanjin qigong group training (1-6 weeks: 2-hour sessions biweekly; 7-22 weeks: 1-hour follow-up sessions weekly) and self-practice (30 minutes per day for 22 weeks) or to a wait-list control group (n = 135) that received optional monthly health education sessions unrelated to qigong after 6 weeks (posttraining period) and qigong training after 22 weeks (postintervention period). Main Outcomes and Measures: The primary outcome was telomerase activity in peripheral blood mononuclear cells. The secondary outcomes included levels of proinflammatory cytokines (tumor necrosis factor and interleukin 6) in peripheral blood plasma, depressive symptoms (Beck Depression Inventory II score; score range, 0-63; higher scores represent more severe depressive symptoms), perceived stress (Perceived Stress Scale; score range, 0-40; higher scores represent higher stress), and perceived coping (Perceived Coping Scale; score range, 0-13; higher scores represent use of more coping strategies). Results: From 1611 Chinese women screened (mean [SD] age, 42.0 [8.8] years), 247 of 271 randomized participants completed the study (intervention group, 120; wait-list control group, 127). Telomerase activity of the intervention group participants after 22 weeks was not significantly different from that of the wait-list control group participants (5.18 U [95% CI, 5.05-5.31 U] in the intervention group vs 5.14 U [95% CI, 5.01-5.27 U] in the wait-list control group; P = .66). The mean change in telomerase activity from baseline was marginally significant in the intervention group (effect size [d], 0.13; 95% CI, 0.001-0.27) but not in the wait-list control group (d, -0.03; 95% CI, -0.16 to 0.10). Perceived stress and depressive symptoms were significantly lower in the intervention group than in the wait-list control group after 6 weeks (between-group differences: perceived stress: d, -1.81; 95% CI, -3.27 to -0.34; depressive symptoms: d, -3.57; 95% CI, -6.25 to -0.90), but not after 22 weeks (between-group differences: perceived stress: d, -1.03; 95% CI, -2.50 to 0.43; depressive symptoms: d, -1.78; 95% CI, -4.26 to 0.70). Conclusions and Relevance: The findings of this study do not support a significant benefit of Baduanjin qigong on telomerase activity in women who have survived intimate partner violence. However, outcomes related to mental health seem to be improved, which should be confirmed by additional studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02060123.

Insights into Local Tumor Microenvironment Immune Factors Associated with Regression of Cutaneous Melanoma Metastases by Mycobacterium bovis Bacille Calmette-Guérin.

Mycobacterium bovis bacille Calmette-Guérin (BCG) is listed as an intralesional (IL) therapeutic option for inoperable stage III in-transit melanoma in the National Comprehensive Cancer Network Guidelines. Although the mechanism is unknown, others have reported up to 50% regression of injected lesions, and 17% regression of uninjected lesions in immunocompetent patients after direct injection of BCG into metastatic melanoma lesions in the skin. BCG and other mycobacteria express ligands capable of stimulating the γ9δ2 T cells. Therefore, we hypothesized that γ9δ2 T cells play a role in promoting BCG-mediated antitumor immunity in patients treated with IL-BCG for in-transit cutaneous melanoma metastases. Indeed, we found γ9δ2 T cell infiltration in melanoma skin lesions during the course of IL-BCG treatment. Gene expression analysis revealed that BCG injection elicits the expression of a vast array of chemokines in tumor lesions, including strong expression of CXCL9, 10, and 11, a set of chemokines that attract T cells expressing the CXCR3 chemokine receptor. In corroboration with our hypothesis, approximately 85% of γδ T cells express high levels of CXCR3 on their surface. Importantly, the injected tumor lesions also express genes whose protein products are the antigenic ligands for γδ T cells (BTN3A1 and MICB), and the cytokines that are the typical products of activated γδ T cells. Interestingly, we also found that γδ T cells infiltrate the regressed lesions that did not receive BCG injections. Our study suggests that γ9δ2 T cells may contribute to melanoma regression induced by IL-BCG treatment.

Associations of novel genetic variations in the folate-related and ARID5B genes with the pharmacokinetics and toxicity of high-dose methotrexate in paediatric acute lymphoblastic leukaemia.

High-dose methotrexate (HD-MTX) plays an important role in the consolidation therapy of acute lymphoblastic leukaemia (ALL) in many treatment regimens worldwide. However, there is a large interpatient variability in the pharmacokinetics and toxicity of the drug. We investigated the influence of single nucleotide polymorphisms (SNPs) in genes of the folate metabolic pathway, transporter molecules and transcription proteins on the pharmacokinetics and toxicity of MTX and 7-hydroxy-methotrexate (7-OH-MTX). 63 SNPs of 14 genes were genotyped and a total of 463 HD-MTX courses (administered according to the ALL-BFM 95 and ALL IC-BFM 2002 protocols) were analysed. Haematological, hepatic and renal toxicities, estimated by routine laboratory parameters were evaluated. Random forest and regression trees were used for variable selection and model building. Linear mixed models were established to prove the significance of the selected variables. SNPs (rs4948502, rs4948496, rs4948487) of the ARID5B gene were associated with the serum levels of MTX (P < 0·02), serum levels and area under the curve of 7-OH-MTX (P < 0·02) and with hypoproteinaemia (P = 0·004). SLCO1B1 rs4149056 also showed a significant association with serum MTX levels (P < 0·001). Our findings confirm the association of novel genetic variations in folate-related and ARID5B genes with the serum MTX levels and acute toxicity.

Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by Bayesian relevance and effect size analysis.

In this study we investigated whether polymorphisms in the folate pathway influenced the risk of childhood acute lymphoblastic leukemia (ALL) or the survival rate of the patients. For this we selected and genotyped 67 SNPs in 15 genes in the folate pathway in 543 children with ALL and 529 controls. The results were evaluated by gender adjusted logistic regression and by the Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) methods. Bayesian structure based odds ratios for the relevant variables and interactions were also calculated. Altogether 9 SNPs in 8 genes were associated with altered susceptibility to ALL. After correction for multiple testing, two associations remained significant. The genotype distribution of the MTHFD1 rs1076991 differed significantly between the ALL and control population. Analyzing the subtypes of the disease the GG genotype increased only the risk of B-cell ALL (p = 3.52×10(-4); OR = 2.00). The GG genotype of the rs3776455 SNP in the MTRR gene was associated with a significantly reduced risk to ALL (p = 1.21×10(-3); OR = 0.55), which resulted mainly from the reduced risk to B-cell and hyperdiploid-ALL. The TC genotype of the rs9909104 SNP in the SHMT1 gene was associated with a lower survival rate comparing it to the TT genotype (80.2% vs. 88.8%; p = 0.01). The BN-BMLA confirmed the main findings of the frequentist-based analysis and showed structural interactional maps and the probabilities of the different structural association types of the relevant SNPs especially in the hyperdiploid-ALL, involving additional SNPs in genes like TYMS, DHFR and GGH. We also investigated the statistical interactions and redundancies using structural model properties. These results gave further evidence that polymorphisms in the folate pathway could influence the ALL risk and the effectiveness of the therapy. It was also shown that in gene association studies the BN-BMLA could be a useful supplementary to the traditional frequentist-based statistical method.

The Drosophila p38 MAPK pathway is required during oogenesis for egg asymmetric development.

In mammalian cells, the p38 mitogen-activated protein kinase (MAPK) pathway is activated in response to a variety of environmental stresses and inflammatory stimuli. However, the role of p38 MAPK signaling in unchallenged conditions remains largely unknown. We have isolated mutations in a Drosophila p38 MAPKK gene homolog, licorne (lic), and show that during oogenesis, lic is required in the germ line for correct asymmetric development of the egg. In lic mutant egg chambers, oskar mRNA posterior localization is not properly maintained, resulting in anteroposterior patterning defects in the embryo. Furthermore, lic loss-of-function in the germ line leads to reduced EGF receptor activity in dorsal follicle cells and ventralization of the egg shell. Both these defects are associated with a diminution of gurken protein levels in the oocyte. Our phenotypic data argue for a role of lic in a post-transcriptional regulation of the grk gene. Furthermore, they show that in addition to the well-characterized Ras/Raf/ERK MAPK pathway acting in the follicle cells, another related signaling cascade, the p38 MAPK pathway, is required in the germ line for correct axes determination. These results provide the first genetic demonstration of an essential function for a p38 pathway during development.