Factors for change in maternal and perinatal audit systems in Dar es Salaam hospitals, Tanzania

<p>Abstract</p> <p>Background</p> <p>Effective maternal and perinatal audits are associated with improved quality of care and reduction of severe adverse outcome. Although audits at the level of care were formally introduced in Tanzania around 25 years ago, little information is available about their existence, performance, and practical barriers to their implementation. This study assessed the structure, process and impacts of maternal and perinatal death audit systems in clinical practice and presents a detailed account on how they could be improved.</p> <p>Methods</p> <p>A cross sectional descriptive study was conducted in eight major hospitals in Dar es Salaam in January 2009. An in-depth interview guide was used for 29 health managers and members of the audit committees to investigate the existence, structure, process and outcome of such audits in clinical practice. A semi-structured questionnaire was used to interview 30 health care providers in the maternity wards to assess their awareness, attitude and practice towards audit systems. The 2007 institutional pregnancy outcome records were reviewed.</p> <p>Results</p> <p>Overall hospital based maternal mortality ratio was 218/100,000 live births (range: 0 - 385) and perinatal mortality rate was 44/1000 births (range: 17 - 147). Maternal and perinatal audit systems existed only in 4 and 3 hospitals respectively, and key decision makers did not take part in audit committees. Sixty percent of care providers were not aware of even a single action which had ever been implemented in their hospitals because of audit recommendations. There were neither records of the key decision points, action plan, nor regular analysis of the audit reports in any of the facilities where such audit systems existed.</p> <p>Conclusions</p> <p>Maternal and perinatal audit systems in these institutions are poorly established in structure and process; and are less effective to improve the quality of care. Fundamental changes are urgently needed for successful audit systems in these institutions.</p

Factors associated with child sexual abuse in Tanzania: a qualitative study

Background: Child sexual abuse (CSA) is one of the most pervasive occurrences which are reported all over the world. It often goes unnoticed and undocumented due to surrounding taboos; its sensitivity in nature and affects the less powerful population. Anecdote information is available on the nature and extent of sexual abuse among children in Tanzania. The aim of this study was to explore factors, forms, context of abuse and perpetrators of child sex abuse in selected regions of Tanzania.Methods: Key informant interviews were conducted among adults including parents of the victims to explore factors associated with sexual abuse of children under 10 years old in Tanzania. The interview guide centred on factors for child sexual abuse, the type of perpetrators and the context into which these abuses take place.Results: There were incidences of child sexual abuse in Tanzania and the major forms were anal and vaginal penetration, and the most affected were girls. The abuses were rarely reported due to shame and embarrassment faced by the affected children and parents. The causes of child sexual abuse were poverty, ambitions and moral degradation, myths and beliefs, urbanization, foreign culture and poor parental care. Incidents of CSA were reported to occur in perpetrators’ homes and in semi-finished housing structures, madrassa and recreational venues where children can freely access entertainment by watching movies. These acts were committed by people in position of power, close relationship and trusted by the children. Contexts where child sexual abuses occur included overcrowded living spaces and social activities that go on late into the night.Conclusion: We recommend for strengthened interventions at different levels within the society to address the root causes and different contexts in which child sex abuse occurs. Increased awareness of the root causes should go hand in hand with measures to encourage parents and survivors to report incidents to relevant authorities timely as they occur

Associations between tamoxifen, estrogens, and FSH serum levels during steady state tamoxifen treatment of postmenopausal women with breast cancer

<p>Abstract</p> <p>Background</p> <p>The cytochrome P450 (CYP) enzymes 2C19, 2D6, and 3A5 are responsible for converting the selective estrogen receptor modulator (SERM), tamoxifen to its active metabolites 4-hydroxy-tamoxifen (4OHtam) and 4-hydroxy-<it>N</it>-demethyltamoxifen (4OHNDtam, endoxifen). Inter-individual variations of the activity of these enzymes due to polymorphisms may be predictors of outcome of breast cancer patients during tamoxifen treatment. Since tamoxifen and estrogens are both partly metabolized by these enzymes we hypothesize that a correlation between serum tamoxifen and estrogen levels exists, which in turn may interact with tamoxifen on treatment outcome. Here we examined relationships between the serum levels of tamoxifen, estrogens, follicle-stimulating hormone (FSH), and also determined the genotypes of CYP2C19, 2D6, 3A5, and SULT1A1 in 90 postmenopausal breast cancer patients.</p> <p>Methods</p> <p>Tamoxifen and its metabolites were measured by liquid chromatography-tandem mass spectrometry. Estrogen and FSH levels were determined using a sensitive radio- and chemiluminescent immunoassay, respectively.</p> <p>Results</p> <p>We observed significant correlations between the serum concentrations of tamoxifen, <it>N</it>-dedimethyltamoxifen, and tamoxifen-<it>N</it>-oxide and estrogens (p < 0.05). The genotype predicted CYP2C19 activity influenced the levels of both tamoxifen metabolites and E1.</p> <p>Conclusions</p> <p>We have shown an association between tamoxifen and its metabolites and estrogen serum levels. An impact of CYP2C19 predicted activity on tamoxifen, as well as estrogen kinetics may partly explain the observed association between tamoxifen and its metabolites and estrogen serum levels. Since the role of estrogen levels during tamoxifen therapy is still a matter of debate further prospective studies to examine the effect of tamoxifen and estrogen kinetics on treatment outcome are warranted.</p

Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer

INTRODUCTION: Tamoxifen therapy reduces the risk of recurrence and prolongs the survival of oestrogen-receptor-positive patients with breast cancer. Even if most patients benefit from tamoxifen, many breast tumours either fail to respond or become resistant. Because tamoxifen is extensively metabolised by polymorphic enzymes, one proposed mechanism underlying the resistance is altered metabolism. In the present study we investigated the prognostic and/or predictive value of functional polymorphisms in cytochrome P450 3A5 CYP3A5 (*3), CYP2D6 (*4), sulphotransferase 1A1 (SULT1A1; *2) and UDP-glucuronosyltransferase 2B15 (UGT2B15; *2) in tamoxifen-treated patients with breast cancer. METHODS: In all, 677 tamoxifen-treated postmenopausal patients with breast cancer, of whom 238 were randomised to either 2 or 5 years of tamoxifen, were genotyped by using PCR with restriction fragment length polymorphism or PCR with denaturing high-performance liquid chromatography. RESULTS: The prognostic evaluation performed in the total population revealed a significantly better disease-free survival in patients homozygous for CYP2D6*4. For CYP3A5, SULT1A1 and UGT2B15 no prognostic significance was observed. In the randomised group we found that for CYP3A5, homozygous carriers of the *3 allele tended to have an increased risk of recurrence when treated for 2 years with tamoxifen, although this was not statistically significant (hazard ratio (HR) = 2.84, 95% confidence interval (CI) = 0.68 to 11.99, P = 0.15). In the group randomised to 5 years' tamoxifen the survival pattern shifted towards a significantly improved recurrence-free survival (RFS) among CYP3A5*3-homozygous patients (HR = 0.20, 95% CI = 0.07 to 0.55, P = 0.002). No reliable differences could be seen between treatment duration and the genotypes of CYP2D6, SULT1A1 or UGT2B15. The significantly improved RFS with prolonged tamoxifen treatment in CYP3A5*3 homozygotes was also seen in a multivariate Cox model (HR = 0.13, CI = 0.02 to 0.86, P = 0.03), whereas no differences could be seen for CYP2D6, SULT1A1 and UGT2B15. CONCLUSION: The metabolism of tamoxifen is complex and the mechanisms responsible for the resistance are unlikely to be explained by a single polymorphism; instead it is a combination of several mechanisms. However, the present data suggest that genetic variation in CYP3A5 may predict response to tamoxifen therapy

Results of a randomized, double blind, placebo controlled, crossover trial of melatonin for treatment of Nocturia in adults with multiple sclerosis (MeNiMS)

© 2018 The Author(s). Background: Nocturia is a common urinary symptom of multiple sclerosis (MS) which can affect quality of life (QoL) adversely. Melatonin is a hormone known to regulate circadian rhythm and reduce smooth muscle activity such as in the bladder. There is limited evidence supporting use of melatonin to alleviate urinary frequency at night in the treatment of nocturia. The aim of this study was to evaluate the effect of melatonin on the mean number of nocturia episodes per night in patients with MS. Methods: A randomized, double blind, placebo controlled crossover trial was conducted. 34 patients with nocturia secondary to multiple sclerosis underwent a 4-day pre-treatment monitoring phase. The patients were randomized to receive either 2 mg per night (taken at bedtime) of capsulated sustained-release melatonin (Circadin®) or 1 placebo capsule for 6 weeks followed by a crossover to the other regimen for an additional 6 weeks after a 1-month washout period. Results: From the 26 patients who completed the study, there was no significant difference observed in the signs or symptoms of nocturia when taking 2 mg melatonin compared to placebo. The primary outcome measure, mean number of nocturia episodes on bladder diaries, was 1.8/night at baseline, and 1.4/night on melatonin, compared with 1.6 for placebo (Medians 1.70, 1.50, and 1.30 respectively, p = 0.85). There was also no significant difference seen in LUTS, QoL and sleep quality when taking melatonin. No significant safety concerns arose. Conclusions: This small study suggests that a low dose of melatonin taken at bedtime may be ineffective therapy for nocturia in MS. Trial registration: (EudraCT reference) 2012-00418321 registered: 25/01/13. ISRCTN Registry: ISRCTN38687869