Evaluation of a traditional birth attendant training programme in Bangladesh

Background and context

the 1997 Safe Motherhood Initiative effectively eliminated support for training traditional birth attendants (TBAs) in safe childbirth. Despite this, TBAs are still active in many countries such as Bangladesh, where 88% of deliveries occur at home. Renewed interest in community-based approaches and the urgent need to improve birth care has necessitated a re-examination of how provider training should be conducted and evaluated.

Objective

to demonstrate how a simple evaluation tool can provide a quantitative measure of knowledge acquisition and intended behaviour following a TBA training program.

Design

background data were collected from 45 TBAs attending two separate training sessions conducted by Bangladeshi non-governmental organization (NGO) Gonoshasthaya Kendra (GK). A semi-structured survey was conducted before and after each training session to assess the TBAs’ knowledge and reported practices related to home-based management of childbirth.

Setting

two training sessions conducted in Vatshala and Sreepur in rural Bangladesh.

Participants

45 active TBAs were recruited for this training evaluation.

Findings

there were significant improvements following the training sessions regarding how TBAs reported they would: (a) measure blood loss, (b) handle an apneic newborn, (c) refer women with convulsions and (d) refer women who are bleeding heavily. A greater degree of improvement, and higher scores overall, were observed among TBAs with no prior training and with less birth experience.

Key conclusions and recommendations for practice

as the Safe Motherhood community strives to improve safe childbirth care, the quality of care in pregnancy and childbirth for women who rely on less-skilled providers should not be ignored. These communities need assistance from governments and NGOs to help improve the knowledge and skill levels of the providers upon which they depend. Gonoshasthaya Kendra's extensive efforts to train and involve TBAs, with the aim of improving the quality of care provided to Bangladeshi women, is a good example of how to effectively integrate TBAs into safe motherhood efforts in resource-poor settings. The evaluation methodology described in this paper demonstrates how trainees’ prior experiences and beliefs may affect knowledge acquisition, and highlights the need for more attention to course content and pedagogic style.     

A murine model of bone marrow micrometastasis in breast cancer

Bone marrow (BM) is one of the most common sites and often the first clinical indication of metastatic progression of breast cancer. Multivariate analyses have shown that the presence of cytokeratin positive tumor cells in the marrow of women with newly diagnosed stage I, II or III breast cancer is an independent predictor of survival. The objective of this study was to develop an orthotopic model of spontaneous BM metastasis to facilitate studies of this process. A murine mammary adenocarcinoma cell line, Clone 66, was transduced with the neomycin resistance gene (Cl66^neo) and injected orthotopically into female Balb/c mice. Polymerase chain reaction (PCR) for the neo gene performed on BM cells harvested from tumor bearing mice demonstrated as few as 10² injected tumor cells produced BM micrometastases at 4 weeks post-injection. Small foci of tumor cells were identified in the mammary fatpad (mfp) without gross evidence of primary tumors. Higher doses of tumor cells produced BM micrometastases, detectable by PCR, at one week post-injection. Constructs containing green fluorescent protein (GFP) and the neomycin resistance gene (neo) were also transduced into Clone 66 cells (Cl66-GFP^neo) and injected into the mfp. GFP transduced tumor cells were identified in multiple tissues in addition to BM by flow cytometric analysis (FACS) but less 13% of the animals developed gross metastases. This model is a clinically relevant tool for the analysis of organ specificity of metastasis. This revised version was published online in July 2006 with corrections to the Cover Date.     

Sodium channel blocking actions of the kappa-opioid receptor agonist U50,488 contribute to its visceral antinociceptive effects

The goal of the present study was to determine whether the kappa-opioid receptor agonist (ORA) U50,488 attenuates behavioral and primary afferent nerve responses to noxious colorectal distension (CRD) by sodium channel blockade. We tested the analgesic kappa-ORA (+/-)-trans U50,488, its enantiomers (-)-trans (1S,2S)-U50,488 and non kappa-ORA (+)-trans (1R,2R)-U50,488, and/or its diastereomer (-)-cis (1S,2R)-U50,488 for their ability to attenuate visceromotor and pelvic nerve afferent fiber responses to noxious CRD in vivo and voltage-activated sodium current in colon sensory neurons in vitro. In unanesthetized rats, subcutaneous administration of U50,488, (1S,2S)-U50,488, and (1R,2R)-U50,488 attenuated the behavioral visceromotor response to noxious CRD; the rank order of potency was: (1S,2S)-U50,488 > U50,488 angle quotation mark, right (1R,2R)-U50,488. U50,488 and its stereoisomers also inhibited responses of decentralized pelvic nerve afferent fibers to noxious CRD in a dose-dependent manner. Cumulative doses of 16 mg/kg of (1S,2S)-U50,488, (1S,2R)-U50,488, and (1R,2R)-U50,488 reduced responses to a mean 29, 30, and 47% of control, respectively. The mean inhibitory doses of these drugs were not different (range: 6.6-10.8 mg/kg). Sodium channel blockers mexiletine and carbamazepine mimicked the effect of U50,488. In contrast, the kappa-ORAs dynorphin (1-13) and ICI 204,488 were ineffective in attenuating pelvic nerve activity. Perfusion of (1S,2S)-U50,488, (1S,2R)-U50,488, or (1R,2R)-U50,488 on colon sensory neurons in vitro decreased voltage-activated sodium currents. This inhibition by U50,488 and its stereoisomers was not opioid receptor-mediated because it could not be reversed by the opioid receptor antagonist naloxone and was also not a G protein-mediated effect. The results reported here suggest that the visceral antinociceptive effects of U50,488 and its stereoisomers are contributed to by their peripheral sodium channel blocking actions.     

Murine macrophage chemokine receptor CCR2 plays a crucial role in macrophage recruitment and regulated inflammation in wound healing

Macrophages play a critical role in the establishment of a regulated inflammatory response following tissue injury. Following injury, CCR2⁺ monocytes are recruited from peripheral blood to wound tissue, and direct the initiation and resolution of inflammation that is essential for tissue repair. In pathologic states where chronic inflammation prevents healing, macrophages fail to transition to a reparative phenotype. Using a murine model of cutaneous wound healing, we found that CCR2‐deficient mice (CCR2^?/?) demonstrate significantly impaired wound healing at all time points postinjury. Flow cytometry analysis of wounds from CCR2^?/? and WT mice revealed a significant decrease in inflammatory, Ly6C^Hi recruited monocyte/macrophages in CCR2^?/? wounds. We further show that wound macrophage inflammatory cytokine production is decreased in CCR2^?/? wounds. Adoptive transfer of mT/mG monocyte/macrophages into CCR2^+/+ and CCR2^?/? mice demonstrated that labeled cells on days 2 and 4 traveled to wounds in both CCR2^+/+ and CCR2^?/? mice. Further, adoptive transfer of monocyte/macrophages from WT mice restored normal healing, likely through a restored inflammatory response in the CCR2‐deficient mice. Taken together, these data suggest that CCR2 plays a critical role in the recruitment and inflammatory response following injury, and that wound repair may be therapeutically manipulated through modulation of CCR2.     

Influenza in patients with hematological malignancies: Experience at two comprehensive cancer centers

The burden of influenza infections in patients with hematological malignancies (HMs) is not well defined. We describe the clinical presentation and associated outcomes of influenza at two comprehensive cancer centers (center 1 in the United States and center 2 in Mexico). Clinical and laboratory data on patients with HMs and influenza infection diagnosed from April 2009 to May 2014 at the two centers were reviewed retrospectively. A total of 190 patients were included, the majority were male (63%) with a median age of 49 years (range, 1‐88 years), and had active or refractory HMs (76%). Compared to center 1, patients in center 2 were significantly sicker (active cancer, decreased albumin levels, elevated creatinine levels, or hypoxia at influenza diagnosis) and experienced higher lower respiratory tract infection (LRI) rate (42% vs 7%; P < 0.001). In multivariable logistic regression analysis (odds ratio, 95% confidence interval), leukemia, (3.09, 1.23‐7.70), decreased albumin level (3.78, 1.55‐9.20), hypoxia at diagnosis (14.98, 3.30‐67.90), respiratory co‐infection (5.87, 1.65‐20.86), and corticosteroid use (2.71, 1.03‐7.15) were significantly associated with LRI; and elevated creatinine level (3.33, 1.05‐10.56), hypoxia at diagnosis (5.87, 1.12‐30.77), and respiratory co‐infection (6.30, 1.55‐25.67) were significantly associated with 60 day mortality in both centers. HM patients with influenza are at high risk for serious complications such as LRI and death, especially if they are immunosuppressed. Patients with respiratory symptoms should seek prompt medical care during influenza season.     

Opposing effects of pro‐ and anti‐inflammatory cytokine gene polymorphisms on the risk for breast cancer in western Indian women: a pilot study

In an earlier study, the genotypes associated with higher level of transforming growth factor‐β1 (TGF‐β1) were found to reduce the risk for breast cancer in western Indian women. This observation implied that gene polymorphisms affecting the levels of pro‐ and anti‐inflammatory cytokines may influence the risk for breast cancer in this population. Hence, we performed genotyping for three more functional single‐nucleotide polymorphisms (SNPs) responsible for variations in the levels of cytokines associated with inflammation. To that effect, polymorphisms in genes coding for IL‐4 (IL‐4 C‐590T; rs2243250), IFN‐γ (IFN‐G A + 874T; rs2430561) and MCP‐1 (MCP‐1 A‐2578G; rs1024611) were examined in premenopausal, healthy women (N = 239) and patients with breast cancer (N = 182) from western India. In carriers of the IL‐4*590T allele, a reduced risk for the disease (dominant model; OR = 0.61, 95% CI 0.37–0.98) was seen similar to that seen in TGF‐B1*10C carriers. An opposite trend was observed with respect to the alleles associated with higher expression of MCP‐1 or IFN‐γ. In individuals positive for three or more alleles associated with higher levels of either pro‐ or anti‐inflammatory cytokines, an additive effect on the modulation of risk for the disease was evident (for TGF‐B1 & IL‐4, OR = 0.33, 95% CI 0.12–0.87; for IFN‐G & MCP‐1, OR = 2.29, 95% CI 0.95–5.51). In the context of contrasting observations in other populations, these results indicate a significant contribution of anti‐inflammatory genotypes in the modulation of risk for breast cancer in western Indian women.     

Interleukin 6 −174G>C polymorphism and cancer risk: Meta-analysis reveals a site dependent differential influence in Ancestral North Indians

In our earlier studies, single nucleotide polymorphisms (SNPs) associated with anti-inflammatory cytokines were found to influence risk for breast cancer in western Indian women. Analysis of Interleukin 6 (IL-6) −174G>C polymorphism in this cohort (patients = 182; controls = 236) suggested a protective role for IL-6 −174C allele associated with the lower expression of the cytokine (OR = 0.54; 95% CI 0.32–0.89, dominant model). Together these observations suggested that in comparison to Caucasians, inflammation associated-cytokine gene polymorphisms may have higher influence on risk for cancer in this population. To examine this possibility we analyzed data assessing influence of Interleukin 6 (IL-6) −174G>C polymorphism on risk for various cancers. Overall, there was a marginally higher risk for rare allele homozygotes compared to wild type homozygotes (OR = 1.07; 95% CI 1.00–1.15). Increased risks for genitourinary cancers and for skin cancer were also indicated. The ethnicity based analysis indicated a protective effect of the minor allele in Ancestral North Indians (OR = 0.73; 95% CI 0.55–0.97). Site by ethnicity analysis once again revealed a significant protection against breast cancer (OR = 0.51; 95% CI = 0.37–0.70; dominant model) but an opposite influence on the risk of genitourinary malignancies (OR = 2.51; 95% CI 1.59–3.96; recessive model) in this population alone. The observations imply that contribution of IL-6 to inflammation or effector immunity may depend on the site of malignancy. Assessment of available data in relation to prognosis in breast cancer patients also revealed trends that are compatible with the observations of the meta-analysis. Thus, IL-6 −174G>C polymorphism clearly represents a potential modulator of risk for malignant disorders with ethnicity and site dependent trends. The results also support the possibility of higher influence of inflammation related cytokine gene polymorphisms on the risk for cancers in Ancestral North Indians.