The impact of pneumonia in human immunodeficiency virus (HIV-1) infected pregnant women on perinatal and early infant mortality.

Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2007.Background: Although the prevalence of pneumonia in pregnancy is reported to be less than 1%, the pregnant state and risk factors associated with the development of pneumonia adversely influence the outcome of pregnancy. KwaZulu-Natal is at the epicenter of the dual epidemics of tuberculosis and HIV-1 and the impact of these diseases occurring concurrently in pregnant women at King Edward VIII hospital (KEH), South Africa have been described previously. The impact of antenatal pneumonia in HIV-1 infected and uninfected women however has not been described in the study population and was investigated. Methods: Pregnant women with clinical and radiological evidence of pneumonia were recruited from the antenatal clinic and labour ward at KEH. The study was conducted prospectively between January and December 2000. The clinical profile of these women and the causative organisms were determined. In addition the impact of HIV-1 infection, maternal immunosuppression and maternal pneumonia on obstetric and perinatal outcomes were evaluated. Mothers diagnosed with tuberculosis and multi drug resistant tuberculosis were hospitalised at King George V hospital until delivery. Results: Twenty nine women were diagnosed with antenatal pneumonia (study arm) with Mycobacterium tuberculosis the only causative organism isolated. A control arm of 112 pregnant women was also studied. Maternal and perinatal mortality was restricted to the study arm with a maternal mortality ratio of 99 per 100 000 live births and a perinatal mortality rate of 240 per 1000 births. Pneumonia was significantly associated with a negative overall obstetric outcome in the presence of HIV- l infection, antenatal care, anaemia and second trimester booking status. In addition, the presence of pneumonia was significantly associated with maternal mortality. There was a highly significant association between exposure to pneumonia and poor neonatal outcome. Maternal pneumonia, maternal HIV infection and the presence of medical and obstetric conditions were significantly associated with low birth weight and neonatal pneumonia. Further, maternal pneumonia (p <0.001) and concurrent HIV infection (p=0.002) was significantly associated with neonatal death. Conclusion: The presence of pneumonia in the antenatal period impacts negatively on maternal and neonatal morbidity and mortality. Health care providers must maintain a high degree of suspicion when managing a pregnant woman with unresolving upper respiratory tract symptoms and refer timeously for further investigation. Pneumonia and in particular pulmonary tuberculosis associated with HIV co- infection in pregnancy is a threat to mother and baby. Therefore in areas endemic for TB and HIV infection, it may be prudent to screen HIV positive pregnant women for symptoms suggestive of pneumonia and thereby identify women requiring further investigations such as sputummicroscopy and cultures, and a screening chest radiograph

A situation analysis of the PMTCT programme between 2013 and 2014 in the eThekwini Municipality.

Master of Medical Science in Public Health Medicine. University of KwaZulu-Natal, Howard College 2015.Background The contribution of the human immunodeficiency virus (HIV) epidemic to morbidity and mortality in pregnancy has been well documented. Effective antiretroviral treatment (ART) improves maternal and newborn health as well as preventing mother-to-child transmission (PMTCT); yet access to ART for PMTCT in low and middle income countries only reached 62% (66-85%) in 2012. Of the pregnant women who required ART for their own health, 58% accessed treatment. Provider initiated HIV counseling and testing in a number of health care facilities including antenatal clinics, was recommended in an attempt to improve health outcomes within the expanding HIV epidemic. Further, screening for tuberculosis and initiation of isoniazid prophylaxis is advised in high risk groups. The main aim of the study was to explore the implementation of guidelines for the management of both seropositive and seronegative pregnant women as limited information is available in three key areas in the continuum of care for pregnant women: firstly, time to initiation of ART in women living with HIV; secondly, the implementation of the TB screening processes during pregnancy; and thirdly, follow-up (HIV) testing in uninfected pregnant women. Methods An exploratory, observational, cross sectional study design presenting both descriptive and analytic statistics was used. A two stage cluster sampling using a 30X7 strategy was applied in the selection of antenatal clinics within the metropolitan district. Data from records of eligible women between 32 and 36 weeks gestation was captured onto a data collection sheet. Demographic data and details of ART initiation, TB screening and repeat HIV testing practices were collected. All data was then entered onto a Microsoft Excel spreadsheet for importing into SPSS for processing and analysis. Measures of central tendency were used and chi squared tests and the Mann Whitney tests were applied for the analytic component of the study. Results Data was collected from records of 420 women, 210 were recorded seropositive and 210 were recorded seronegative at initial presentation. Overall, records show 202 women (48%) presented before 20 weeks gestation. Nurse initiation of ART occurred upon diagnosis of HIV infection was documented in 97% of women; TB screening practices however did not appear to be consistent and differed statistically according to administrative authority. The offer of a repeat HIV test to those women who initially tested uninfected was recorded to be offered at a standard rather than an individualised time point. Acute seroconversion was recorded in eight women. Statistically significant associations between HIV status and both median gestational age at first antenatal contact and age (in years) as well as between administrative authority and TB screening practices were found. Discussion, conclusion and recommendations Implementation of national guidelines for the management of pregnant women does not appear to be consistent within or across sampled clinics. Successful integration of HIV services was documented; however TB screening processes and feedback mechanisms following referral require strengthening. Deferment and delays in repeat testing in women who initially test seronegative are particularly concerning. Training and support of health care workers on the value of complete medical records for the overall management and continuity of care of a pregnant female is essential. Further, the benefit in implementation of national guidelines in relation to PMTCT must be highlighted

Evaluation of Medication Adherence and its Predictors Among Psychiatric Outpatients at a Mental Healthcare Hospital in Lahore, Pakistan: A Cross-Sectional Study

The study aimed to assess the level of medication adherence among psychiatric outpatients and to determine the main predictors associated with medication non-adherence. A cross sectional study was conducted among 298 psychiatric outpatients at Punjab Institute of Mental Health (PIMH), Lahore, Pakistan. A designed questionnaire was used as data collection tool and adherence was evaluated using MARS (Medication Adherence Rating Scale). Data was analyzed using SPSS version 21.0. Logistic regression was applied to determine the predictors of non-adherence. Medication adherence rate varied from low (39.3%) to high (60.7%) adherence. The impact of demographic factors such as age, gender, diagnosis, employment status and comorbidity on medication adherence were insignificant. Results of chi-square found that marital status, duration of illness from last visit, patient factors, medication factors, disease factors were significantly associated with adherence (p&lt;0.05). Multivariate binary logistic regression indicated that qualification, marital status, number of tablets per day, duration of illness from last visit, patient factors, disease factors were the main predictors of medication non-adherence.&nbsp

Study of Influence of Formulation Variables on Drug Release: Optimization of Sustained Release Matrix Tablets of Metoclopramide HCl Using Central Composite Experimental Design

Metoclopramide Hydrochloride (MCP), has a short half-life. In order to maintain therapeutic levels in blood, it administered in dose of 10-15 mg four times a day. Fluctuation in plasma concentration of drug is commonly observed for drugs that are rapidly absorbed and eliminated when used in long term therapy. This attribute makes metoclopramide a suitable candidate for controlled release delivery. In this work HPMC K4M was used as release rate controlling polymer for the development of controlled release tablet formulation. Experimental Design using CCRD was utilized to determine the influence of varying the concentration of different variables such as polymer and diluents on the release behavior of the drug from matrix tablets and optimization of formulation. Different SR formulation prepared were designed and optimized with the help of software Design Expert® version 10. Using Central Composite Rotatable Design (CCRD), fifteen formulations were selected and prepared using HPMC K4M, Avicel PH-102 and Lactose DC as variables. All the trial formulations were evaluated using different pharmacotechnical tests including hardness, friability, disintegration, dissolution. Online Dissolution apparatus type II and 900 ml different dissolution media in the pH range 1-6.8 and distilled water for dissolution. The drug release was studied by applying the dissolution models by DDSolver® software. Hixson-Crowell model was best fit to the F13 SR formulation. The CCRD experimental design was successfully used in optimization of sustained release Metoclopramide HCl formulation

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS ESTIMATION OF CURCUMIN AND CYCLOSPORINE BY RP-HPLC

Objective: The present work was undertaken with an aim to develop and validate a rapid reverse-phase high-performance liquid chromatography (RP-HPLC) method for the estimation of curcumin and cyclosporine in the capsule dosage form. Methods: The RP-HPLC method for the simultaneous estimation of curcumin and cyclosporine was developed using Agilent (Infinity 1260) HPLC system and Eclipse XDB-C18 (4.6 x 150 mm i.d., 5µ) stationary phase. The optimized mobile phase comprised of acetonitrile: water: methanol (50: 10: 40 v/v/v) pumped at a flow rate of 0.5 ml/min. Separation of drugs was achieved in an isocratic mode and elution was monitored using PDA detector at 214 nm. The method was validated as per ICH-Q2R1 guidelines. Results: Retention time of the curcumin and cyclosporine were found to be 3.073 min and 6.373 min with the correlation coefficient (R2) of 0.9993 and 0.998 respectively. The response of curcumin and cyclosporine was found linear in the concentration range of 8-48 μg/ml and 4-24 μg/ml respectively. The percent recovery values were found in the range of 97-103% indicating satisfactory accuracy of the method. The percent relative standard deviation (% RSD) values for the precision study was less than 2 which suggest that the method is precise. Conclusion: The proposed method was found accurate, precise and specific for the determination of curcumin and cyclosporine in bulk as well as in capsule dosage form. Thus, the present method can be used for routine analysis and quality control of curcumin and cyclosporine in bulk and capsule dosage form

Prevalence of needle stick injury and its associated factors among nursing staff working at a tertiary care hospital of North India

Background: Needle stick injury is a serious concern for healthcare workers as it poses a major risk for HIV, Hepatitis and other diseases transmission. The study aimed to determine the prevalence of NSI and its associated factors among nursing staff working at SKIMS, a tertiary care hospital of Kashmir, India. Methods: A descriptive cross-sectional study was conducted among 200 nurses working in different departments of SKIMS. Data regarding socio-demographic, various organizational and behavioral factors that may contribute to NSI, was collected using self-structured questionnaire and analysed using IBM statistical package for social sciences (SPSS), version 23. Results: The overall prevalence of NSI among nurses of SKIMS was 61% and it was 43.5% in the last 1 year. The nurses working for &gt;40 hrs per week were found more at risk of NSI and it was more prevalent in young nurses with ≤5 years of experience. The nurses working in emergency unit were found more prone to NSI than the other units and recapping was found as the most common practice responsible for NSI. Post exposure to NSI, only 21.5% were found to wash the injury site with soap, water and applied antiseptics and most of them (75%) had not reported NSI to the concerned body. Conclusions: The magnitude of needlestick injury among nurses was high. Awareness generation regarding occupational health hazards of NSI, protective measures, the importance of reporting of incident and sharp management is the need of hour

Relationship between machining variables and process characteristics during wire EDM

Abstract. Wire EDM is in use for a long time for cutting punches and dies, shaped pockets and other machine parts. Surface finish of the machined surface mainly depends on current and voltage used during machining. In the present work experimental investigations have been conducted to establish relationships job surface finish with current and voltage. Brass wires of diameters 0.3 mm, 0.25 mm, 0.20 mm and 0.15 mm were used. Work materials tested were mild steel, aluminium, cemented carbide, copper and stainless steel. After machining each material with specific current and voltage the hardness and the job surface roughness were measured and their surfaces were observed under a scanning- electron microscope. Results of the experiments show that in general the machined surface becomes rougher with increase in current and voltage. Microstructures of the specimens also show that craters on the finished surface become larger as a result of using higher current and voltage. It was also found that wires of smaller diameters give smoother surface than those cut with larger diameters. It has been established that machining of carbides should be limited to wires with diameter equal to or less than 0.15 mm. Use of wires of greater diameters causes frequent wire breakage

Micro-RNA and Proteomic Profiles of Plasma-Derived Exosomes from Irradiated Mice Reveal Molecular Changes Preventing Apoptosis in Neonatal Cerebellum

Cell communication via exosomes is capable of influencing cell fate in stress situations such as exposure to ionizing radiation. In vitro and in vivo studies have shown that exosomes might play a role in out-of-target radiation effects by carrying molecular signaling mediators of radiation damage, as well as opposite protective functions resulting in resistance to radiotherapy. However, a global understanding of exosomes and their radiation-induced regulation, especially within the context of an intact mammalian organism, has been lacking. In this in vivo study, we demonstrate that, compared to sham-irradiated (SI) mice, a distinct pattern of proteins and miRNAs is found packaged into circulating plasma exosomes after whole-body and partial-body irradiation (WBI and PBI) with 2 Gy X-rays. A high number of deregulated proteins (59% of WBI and 67% of PBI) was found in the exosomes of irradiated mice. In total, 57 and 13 miRNAs were deregulated in WBI and PBI groups, respectively, suggesting that the miRNA cargo is influenced by the tissue volume exposed to radiation. In addition, five miRNAs (miR-99b-3p, miR-200a-3p, miR-200a, miR-182-5p, miR-182) were commonly overexpressed in the exosomes from the WBI and PBI groups. In this study, particular emphasis was also given to the determination of the in vivo effect of exosome transfer by intracranial injection in the highly radiosensitive neonatal cerebellum at postnatal day 3. In accordance with a major overall anti-apoptotic function of the commonly deregulated miRNAs, here, we report that exosomes from the plasma of irradiated mice, especially in the case of WBI, prevent radiation-induced apoptosis, thus holding promise for exosome-based future therapeutic applications against radiation injury

Diagnosed hematological malignancies in Bangladesh - a retrospective analysis of over 5000 cases from 10 specialized hospitals

Background The global burden from cancer is rising, especially as low-income countries like Bangladesh observe rapid aging. So far, there are no comprehensive descriptions reporting diagnosed cancer group that include hematological malignancies in Bangladesh. Methods This was a multi-center hospital-based retrospective descriptive study of over 5000 confirmed hematological cancer cases in between January 2008 to December 2012. Morphological typing was carried out using the “French American British” classification system. Results A total of 5013 patients aged between 2 to 90 years had been diagnosed with malignant hematological disorders. A 69.2% were males (n = 3468) and 30.8% females (n = 1545), with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42 years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35 years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non-Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years), myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin’s lymphoma (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%). Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older patients, aged 50-over. Conclusions For the first time, our study presents the pattern and distribution of diagnosed hematological cancers in Bangladesh. It shows differences in population distributions as compared to other settings with possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting of affected women. Further studies are necessary on the epidemiology, genetics and potential environmental risk factors within this rapidly aging country

Health system determinants of tuberculosis mortality in South Africa: a causal loop model

Background: Tuberculosis (TB) is a major public health concern in South Africa and TB-related mortality remains unacceptably high. Numerous clinical studies have examined the direct causes of TB related mortality, but its wider, systemic drivers are less well understood. Applying systems thinking, we aimed to identify factors underlying TB mortality in South Africa and describe their relationships. At a meeting organised by the ‘Optimising TB Treatment Outcomes’ task team of the National TB Think Tank, we drew on the wide expertise of attendees to identify factors underlying TB mortality in South Africa. We generated a causal loop diagram to illustrate how these factors relate to each other. Results: Meeting attendees identified nine key variables: three ‘drivers’ (adequacy & availability of tools, implementation of guidelines, and the burden of bureaucracy); three ‘links’ (integration of health services, integration of data systems, and utilisation of prevention strategies); and three ‘outcomes’ (accessibility of services, patient empowerment, and socioeconomic status). Through the development and refinement of the causal loop diagram, additional explanatory and linking variables were added and three important reinforcing loops identified. Loop 1, ‘Leadership and management for outcomes’ illustrated that poor leadership led to increased bureaucracy and reduced the accessibility of TB services, which increased TBrelated mortality and reinforced poor leadership through patient empowerment. Loop 2, ‘Prevention and structural determinants’ describes the complex reinforcing loop between socio-economic status, patient empowerment, the poor uptake of TB and HIV prevention strategies and increasing TB mortality. Loop 3, ‘System capacity’ describes how fragmented leadership and limited resources compromise the workforce and the performance and accessibility of TB services, and how this negatively affects the demand for higher levels of stewardship. Conclusions: Strengthening leadership, reducing bureaucracy, improving integration across all levels of the system, increasing health care worker support, and using windows of opportunity to target points of leverage within the South African health system are needed to both strengthen the system and reduce TB mortality. Further refinement of this model may allow for the identification of additional areas of intervention