Generational trends in the transition to womanhood in lowland rural Nepal: Changes in the meaning of early marriage.

OBJECTIVE: In South Asia, studies show secular trends toward slightly later women's marriage and first reproduction. However, data on related biological and social events, such as menarche and age of coresidence with husband, are often missing from these analyses. We assessed generational trends in key life events marking the transition to womanhood in rural lowland Nepal. METHODS: We used data on 110 co-resident mother-in-law (MIL) and daughter-in-law (DIL) dyads. We used paired t-tests and chi-squared tests to evaluate generational trends in women's education, and mean age at menarche, marriage, cohabitation with husband, and first reproduction of MIL and DIL dyads. We examined norms held by MILs and DILs on a daughter's life opportunities. RESULTS: On average, MIL was 29 years older than DIL (60 years vs. 31 years). Both groups experienced menarche at average age 13.8 years. MIL was married at average 12.4 years, before menarche, and cohabitated with husbands at average 14.8 years. DIL was simultaneously married and cohabitated with husbands after menarche, at average 15 years. DIL was marginally more educated than MIL but had their first child on average 0.8 years earlier (95% CI -1.4, -0.1). MIL and DIL held similar norms on daughters' education and marriage. CONCLUSION: While social norms remain similar, the meaning of "early marriage" and use of menarche in marriage decisions has changed in rural lowland Nepal. Compared to DIL, MIL who was married earlier transitioned to womanhood more gradually. However, DIL was still married young, and had an accelerated trajectory to childbearing.

Early efficacy and safety of Bedaquiline and Delamanid given together in a "Salvage Regimen" for treatment of drug-resistant tuberculosis.

BACKGROUND: Drug-Resistant Tuberculosis (DR-TB) patients for whom a WHO recommended regimen along with Bedaquiline (BDQ) cannot be prescribed, Delamanid (DLM) was added along with other drugs to provide a "Salvage Regimen". The experience of the Institute in respect of early efficacy and safety of both drugs given together is presented. OBJECTIVE: To ascertain the early efficacy, safety and tolerability of Bedaquline and Delamanid given together as a part of salvage regimen. METHODS: BDQ and DLM were used together to make regimens along with other drugs where four effective anti TB drugs could not be prescribed as per WHO recommendations. Patients were followed up for sputum smear and culture conversion and adverse events during the treatment. RESULTS: In this cohort study, 53 DR-TB patients (Median age-24) were initiated on regimens containing both BDQ and DLM. Sputum smear conversion was seen in 35% and 94% patients at the end of 1st week and 3rd month respectively. 84% patients had culture conversion at the end of 4th month. 29 adverse events (AE) were reported among 17 patients and there were 11 deaths. QTc prolongation more than 500 MS was seen in only 1 patient. CONCLUSION: BDQ and DLM given together in a salvage regimen is efficacious with low rate of adverse events. The combination provides hope to DR-TB patients with limited treatment options and should be provided as a life saving option.

Initial experience of bedaquiline implementation under the National TB Programme at NITRD, Delhi, India.

BACKGROUND: Bedaquiline (BDQ) was approved for treatment of drug resistant TB (DR-TB) under Conditional Access Programme (CAP) of Revised National Tuberculosis Control Programme (RNTCP) and was also implemented in the National Institute of TB and Respiratory Diseases (NITRD). We present early efficacy and safety of BDQ containing regimens for DR-TB. OBJECTIVE: To ascertain the early efficacy and safety of Bedaquline containing regimens in treatment of DR-TB. METHODS: BDQ containing regimens along with other drugs were designed as per WHO recommendations for DR-TB patients. They were followed up for sputum smear and culture conversion, adverse events during the treatment. RESULTS: A cohort of 290 DR-TB patients (Median age-29.77) were initiated on BDQ containing regimens. Of the available Sputum results, smear conversion was seen in 51% and 91% patients at the end of 1st week and 3rd month respectively. Similarly, 93% and 98% patients had culture conversion at the end of 3rd and 6th month respectively. 201 adverse events (AE) including 47 deaths were reported among 109 patients. QTc prolongation was seen in 29% patients but only 4 required discontinuation of BDQ. Lost to follow up of treatment was about 6%. CONCLUSION: Bedaquiline along with an optimized background regimen has shown early sputum conversion in larger number of difficult to treat patients having additional resistance of second line drugs along with INH and Rifampicin. The regimen is feasible in programmatic conditions and is relatively safe.

Yield of intensified tuberculosis case-finding activities using Xpert(®) MTB/RIF among risk groups in Nepal.

SETTING: Twenty-two districts of Nepal, where intensified case-finding (ICF) activities for tuberculosis (TB) were implemented among risk groups under the TB REACH initiative in collaboration with the National TB Programme from July 2013 to November 2015. OBJECTIVES: To assess the yield of TB screening using an algorithm with smear microscopy followed by Xpert(®) MTB/RIF. DESIGN: A descriptive study using routinely collected data. RESULTS: Of 145 679 individuals screened, 28 574 (19.6%) had presumptive TB; 1239 (4.3%) of these were diagnosed with TB and 1195 (96%) were initiated on anti-tuberculosis treatment. The yield of screening was highest among people living with the human immunodeficiency virus (PLHIV) (6.1%), followed by household contacts (3.5%) and urban slum dwellers (0.5%). Among other risk groups, such as prisoners, factory workers, refugees and individuals with diabetes, the yield was less than 0.5%. The number needed to screen to diagnose an active TB case was 17 for PLHIV, 29 for household contacts and 197 for urban slum dwellers. Of 11 525 patients from ICF and the routine programme, 112 (1%) were diagnosed with multidrug-resistant TB. CONCLUSION: There was a substantial yield of TB cases among risk groups such as PLHIV and household contacts. Although the yield in urban slum dwellers was found to be moderate, some intervention should nonetheless be targeted because of the large population and poor access to care in this group.

Contexte : Vingt-deux districts du Népal où des activités intensifiées de recherche des cas (ICF) de la tuberculose (TB) ont été mises en œuvre au sein de groupes à risque sous l'égide du projet TB REACH en collaboration avec le programme national TB entre juillet 2013 et novembre 2015.Objectifs : Evaluer le rendement du dépistage de la TB grâce à un algorithme basé sur la microscopie de frottis suivie d'un test Xpert® MTB/RIF.Schéma : Etude descriptive basée sur des données recueillies en routine.Résultats : Sur un total de 145 679 individus dépistés, 28 574 (19,6%) ont été présumés atteints de TB ; 1239 (4,3%) d'entre eux ont eu une confirmation du diagnostic de TB ; parmi ces derniers, 1195 (96%) ont mis en route un traitement anti-tuberculose. Le rendement a été le plus élevé parmi les personnes vivant avec le virus l'immunodéficience humaine (PVVIH) (6,1%) suivies par les contacts domiciliaires (3,5%) et les habitants des bidonvilles (0,5%). Dans d'autres groupes à risque comme les prisonniers, les travailleurs d'usine, les réfugiés et les diabétiques, le rendement a été inférieur à 0,5%. Le nombre de personnes à dépister (NNS) pour diagnostiquer un cas de TB active a été de 17 pour les PVVIH, de 29 pour les contacts domiciliaires et de 197 pour les habitants des bidonvilles urbains. Sur 11 525 patients émanant soit du programme ICF soit du dépistage de routine, 112 (1%) ont eu un diagnostic de TB multirésistante.Conclusion : Le rendement en termes de cas de TB dépistés parmi les groupes à risque comme les PVVIH et les contacts domiciliaires a été substantiel. Même si ce rendement a été modeste parmi les habitants des bidonvilles, ceux-ci justifient néanmoins une intervention en raison de leur nombre élevé et de leur médiocre accès aux soins.

Marco de referencia: Veintidós distritos de Nepal, en los cuales se ejecutaron actividades de búsqueda intensiva de casos (ICF) de tuberculosis (TB) en los grupos de riesgo, en el marco del proyecto TB REACH en colaboración con el programa nacional contra la TB de julio del 2013 a noviembre del 2015.Objetivos: Evaluar el rendimiento de la detección sistemática de la TB aplicando un algoritmo que comporta la baciloscopia, seguida de la prueba Xpert® MTB/RIF.Método: Fue este un estudio descriptivo a partir de los datos recogidos de manera sistemática.Resultados: De las 145 679 personas en quienes se practicó la detección, en 28 574 hubo una presunción diagnóstica de TB (19,6%); en 1239 de estos pacientes se estableció el diagnóstico de TB (4,3%); e iniciaron el tratamiento 1195 pacientes (96%). El rendimiento diagnóstico fue más alto en las personas viviendo con el virus de la inmunodeficiencia humana (PVVIH, 6,1%), seguidas de los contactos domiciliarios (3,5%) y los residentes en tugurios (0,5%). En otros grupos de riesgo de contraer la TB como los reclusos, los obreros de fábricas, los refugiados o los pacientes diabéticos el rendimiento diagnóstico fue inferior a 0,5%. El número de personas que se debieron examinar con el fin de detectar un caso de TB activa fue 17 en las PVVIH, 29 en los contactos domiciliarios y 197 en los habitantes de los tugurios. De las 11 525 personas examinadas en la ICF y el programa corriente, se diagnosticó TB multiresistente en 112 casos (1%).Conclusión: La detección sistemática de casos de TB exhibió un alto rendimiento en los grupos de riesgo como las PVVIH y los contactos domiciliarios. Aunque el desempeño en los tugurios urbanos fue moderado, es importante dirigir intervenciones a estos entornos, dado el tamaño de estas poblaciones y su acceso deficiente a la atención de salud.

Prader-Willi Syndrome, Management of Impulsivity, and Hyperphagia in an Adolescent.

The aim of this article is to review related literature on management of hyperphagia and impulsive behaviors in Prader-Willi syndrome (PWS) that includes either naltrexone or bupropion. In this article we also discuss a case of a 13-year-old female with PWS struggling with some behavioral and psychiatric symptoms.

Contrast-enhanced molecular ultrasound differentiates endoglin genotypes in mouse embryos.

Targeted ultrasound contrast imaging has the potential to become a reliable molecular imaging tool. A better understanding of the quantitative aspects of molecular ultrasound technology could facilitate the translation of this technique to the clinic for the purposes of assessing vascular pathology and detecting individual response to treatment. The objective of this study was to evaluate whether targeted ultrasound contrast-enhanced imaging can provide a quantitative measure of endogenous biomarkers. Endoglin, an endothelial biomarker involved in the processes of development, vascular homeostasis, and altered in diseases, including hereditary hemorrhagic telangiectasia type 1 and tumor angiogenesis, was the selected target. We used a parallel plate perfusion chamber in which endoglin-targeted (MBE), rat isotype IgG2 control and untargeted microbubbles were perfused across endoglin wild-type (Eng+/+), heterozygous (Eng+/-) and null (Eng-/-) embryonic mouse endothelial cells and their adhesion quantified. Microbubble binding was also assessed in late-gestation, isolated living transgenic Eng+/- and Eng+/+ embryos. Nonlinear contrast-specific ultrasound imaging performed at 21 MHz was used to collect contrast mean power ratios for all bubble types. Statistically significant differences in microbubble binding were found across genotypes for both in vitro (p<0.05) and embryonic studies (p<0.001); MBE binding was approximately twofold higher in Eng+/+ cells and embryos compared with their Eng+/- counterparts. These results suggest that molecular ultrasound is capable of reliably differentiating between molecular genotypes and relating receptor densities to quantifiable molecular ultrasound levels.

Arterio-venous malformations of uterus - diagnostic and management dilemmas.

Keeping in mind the life-threatening consequences of curettage in cases of undiagnosed uterine arterio-venous malformation (AVM), its possibility should be considered in patients presenting with abnormal heavy uterine bleeding and negative Human Chorionic Gonadotropin (ß-hCG) values. We collected a series of cases in which the patients presented with abnormal heavy uterine bleeding, some not responding to conservative treatment. In the presence of declining or low serum ß-hCG levels and ultrasound Doppler showing increased vascularity, patients were investigated to detect the possible presence of uterine AVM. In those patients in whom angiographic confirmation of uterine AVM was made, embolisation was done and the outcome was followed. In those patients in whom hysterectomy was done the histopathogy specimen was studied for the possible cause of increased vascularity. Arterio-venous shunting seen on ultrasound does not always imply a uterine AVM and some cases can present diagnostic and management dilemmas.

Total replacement of a lung by tuberculosis pneumatocele--an unusual post-tuberculosis sequel.

Total replacement of a lung by pneumatocele in pulmonary tuberculosis is rare. The formation of pneumatoceles in adult pulmonary tuberculosis can occur before, during or after anti-tuberculosis treatment. A case of pneumatocele formation in a 19-year young female following pulmonary tuberculosis is reported. The left lung was completely replaced by pneumatocele. Total replacement of a lung by pneumatocele inspite of successful chemotherapy of tuberculosis is rare and should be considered as one of the differential diagnosis for acquired cysts of the lung.

Evaluating the technique of using inhalation device in COPD and bronchial asthma patients.

BACKGROUND: In asthma management, poor handling of inhalation devices and wrong inhalation technique are associated with decreased medication delivery and poor disease control. The key to overcome the drawbacks in inhalation technique is to make patients familiar with issues related to correct use and performance of these medical devices. The objective of this study was to evaluate and analyse technique of use of the inhalation device used by patients of COPD and Bronchial Asthma. METHODS: A total of 300 cases of BA or COPD patients using different types of inhalation devices were included in this observational study. Data were captured using a proforma and were analysed using SPSS version 15.0. RESULT: Out of total 300 enrolled patients, 247 (82.3%) made at least one error. Maximum errors observed in subjects using MDI (94.3%), followed by DPI (82.3%), MDI with Spacer (78%) while Nebulizer users (70%) made least number of errors (p = 0.005). Illiterate patients showed 95.2% error while post-graduate and professionals showed 33.3%. This difference was statistically significant (p < 0.001). Self-educated patients committed 100% error, while those trained by a doctor made 56.3% error. CONCLUSION: Majority of patients using inhalation devices made errors while using the device. Proper education to patients on correct usage may not only improve control of the symptoms of the disease but might also allow dose reduction in long term.

Unsafe abortion after legalisation in Nepal: a cross-sectional study of women presenting to hospitals.

OBJECTIVE: To investigate abortion practices of Nepali women requiring postabortion care. DESIGN: Cross-sectional study. SETTING: Four tertiary-care hospitals in urban and rural Nepal. SAMPLE: A total of 527 women presenting with complications from induced abortion in 2010. METHODS: Women completed questionnaires on their awareness of the legal status of abortion and their abortion-seeking experiences. The method of induction and whether the abortion was obtained from an uncertified source was documented. Multivariable logistic regression was used to identify associated factors. MAIN OUTCOME MEASURES: Induction method; uncertified abortion source. RESULTS: In all, 234 (44%) women were aware that abortion was legal in Nepal. Medically induced abortion was used by 359 (68%) women and, of these, 343 (89%) took unsafe, ineffective or unknown substances. Compared with women undergoing surgical abortion, women who had medical abortion were more likely to have obtained information from pharmacists (161/359, 45% versus 11/168, 7%, adjusted odds ratio [aOR] 8.1, 95% confidence interval 4.1-16.0) and to have informed no one about the abortion (28/359, 8% versus 3/168, 2%, aOR 5.5, 95% CI 1.1-26.9). Overall, 291 (81%) medical abortions and 50 (30%) surgical abortions were obtained from uncertified sources; these women were less likely to know that abortion was legal (122/341, 36% versus 112/186, 60%, aOR 0.4, 95% CI 0.2-0.7) and more likely to choose a method because it was available nearby (209/341, 61% versus 62/186, 33%, aOR 2.5, 95% CI 1.5-4.3), compared with women accessing certified sources. CONCLUSIONS: Among women presenting to hospitals in Nepal with complications following induced abortion of pregnancy, the majority had undergone medically induced abortions using unknown substances acquired from uncertified sources. Women using medications and those accessing uncertified providers were less aware that abortion is now legal in Nepal. These findings highlight the need for continued improvements in the provision and awareness of abortion services in Nepal.

Fetomaternal outcome in pregnancy with severe thrombocytopenia.

OBJECTIVES: STo study the feto-maternal outcome in pregnancy with severe thrombocytopenia. MATERIALS AND METHODS: It was an observational study involving 1150 pregnant women with term gestation in labour, who were screened for thrombocytopenia. Ninety-four subjects (8.17%) were found to have thrombocytopenia i.e. platelet count < 1,50,/000/mm3, out of which 47 subjects (group A) had platelet count of less than 50.000/mm3 Simultaneously, 47 term pregnant women (group B) having a normal platelet count i.e. > 1.5 lac/mm3 formed the control group. All the subjects were followed during labour and postpartum period for any feto-maternal outcome. RESULTS: Significant history of bleeding tendencies like prolonged bleeding from wound site, easy bruisability and menorrhagia (p = 0.023) was evident in the study population. Abruptio placentae and early onset pregnancy induced hypertension (PIH) in previous gestations was more commonly found in the study population. Anemia and PIH were significantly more in group A. Incision site oozing during cesarean section was significantly more in group A. Moderate thrombocytopenia was more in neonates of study group (p = 0.014), but without any bleeding complications in neonates. CONCLUSIONS: Careful surveillance is required in these high risk patients for earlier detection and treatment of complications so as to decrease the fetomaternal morbidities.

Seizures with single therapeutic dose of isoniazid.

Isoniazid (INH) is an integral component of treatment of tuberculosis. An acute overdose is potentially fatal and is characterised by the clinical triad of repetitive seizures unresponsive to the usual anticonvulsants, metabolic acidosis with a high anion gap and coma. A case of isoniazid induced seizures after therapeutic dose of 600 mg. as a part of CAT I thrice weekly intermittent anti-tuberculosis regimen for pulmonary tuberculosis is reported. The frequency of the usage of Isoniazid as antituberculosis therapy requires that physicians be aware of such toxicity.

Emergence of viral hemorrhagic fevers: is recent outbreak of Crimean Congo Hemorrhagic Fever in India an indication?

The emerging and re-emerging diseases are posing a great health risk for the last few years. One such category of diseases is viral haemorrhagic fevers (VHFs), which have emerged in the new territories, worldwide. Crimean Congo Hemorrhagic Fever (CCHF) cases, for the first time in India, were reported from Gujarat, in January 2011. The emergence of diseases not reported earlier, pose great economic and social challenge, burden health system, and create panic reaction. Nonetheless, with recent experience in control of epidemic diseases, and advances in basic scientific knowledge; the public health community is better prepared for these unexpected events. This review provides information to physicians on CCHF for managing outbreak, and identifies public health measures to prevent emergence and re-emergence of VHFs (including CCHF) in future. The authors suggest that though, there are a few challenging and unanswered questions, the public health preparedness still remains the key to control emerging and re-emerging diseases. The countries where virus activities have been reported need to be prepared accordingly.

Risk factors associated with typhoid fever in children aged 2-16 years in Karachi, Pakistan.

We analysed the data from the control group in a typhoid vaccine trial in Karachi to assess the differences in individual-, household- and cluster-level characteristics for developing typhoid fever. The annual incidence of typhoid in children aged 2-16 years in the control arm of the vaccine trial was 151/100 000 population. After adjustment, the risk of typhoid was lower with increasing age [risk ratio (RR) 0·89, 95% confidence interval (CI) 0·83-0·95], was higher with an increase in population density (RR 1·13, 95% CI 1·05-1·21) and was lower in the households using a safe drinking-water source (RR 0·63, 95% CI 0·41-0·99). Typhoid fever affects younger children living in areas of high population density and lack of access to safe water in Pakistan. A combination of environmental and biological interventions is required to prevent the continued epidemiological and economic impact of typhoid fever in high-risk areas of Pakistan.

A randomized clinical trial to compare the efficacy of different doses of intravaginal misoprostol with intracervical dinoprostone for cervical ripening and labor induction.

OBJECTIVES: To compare the efficacy of 25 vs. 50 microg of intravaginal misoprostol vs. intracervical dinoprostone for cervical ripening and labor induction. MATERIALS AND METHODS: 210 women with Bishop's score <6 were randomized into 3 groups of 70 each to receive 6 hourly doses of either 25 or 50 microg of intravaginal misoprostol or 0.5 mg intracervical dinoprostone to maximum of 3 doses and outcome parameters were compared. RESULTS: Induction to vaginal delivery interval was significantly lower (p < 0.05) for 50 microg (13.8 +/- 6.62 hours) as compared to 25 microg misoprostol (16.4 +/- 7.34 hours) or dinoprostone group (16.3 +/- 7.49 hours). Maximum improvement (p < 0.05) in Bishop's score and minimum oxytocin requirement (p < 0.05) was seen with misoprostol 50 microg. No significant difference was observed for women delivering vaginally within 24 hours (93.8 vs. 89.7 vs. 85.4%), patients delivering after one dose (24.3 vs. 21.4 vs. 20%), cesarean deliveries, fetal outcome, complications like hyperstimulation and fetal heart abnormalities for the 50 vs. 25 microg misoprostol vs. dinoprostone group. CONCLUSION: Intravaginal misoprostol 50 microg administered 6 hourly appears to be most effective as it has least induction to delivery time, has maximum improvement in Bishop's score, least oxytocin requirement without any increase in complication rate.

Persistent inflammation on Pap smear: does it warrant evaluation?

OBJECTIVE: Due to the low sensitivity of Pap smear, premalignant lesions of the cervix can be missed in women with inflammatory Pap smears. However, it is not practically possible to subject all women with inflammatory Pap smear to colposcopy. This study was carried out with the aim to evaluate whether women with persistent inflammation on Pap smear need further evaluation with colposcopy. MATERIALS AND METHODS: Four hundred and twenty women were screened at a tertiary level hospital with Pap smear. Women with inflammation on Pap smear were given treatment as per WHO guidelines and Pap smear was repeated at an interval of 6-12 weeks. Women with persistent inflammation on Pap smear were then subjected to colposcopy and directed biopsy if required. RESULTS: Of the 420 women screened, 102 (24.3%) women had a Pap smear showing inflammation. Thirty six women (8.6%) had persistent inflammatory Pap smear. Thirty women were subjected to colposcopy and 16 (53.3%) had abnormal findings on colposcopy. Five out of these 30 women (16.67%) had Cervical intraepithelial neoplasia (CIN) on biopsy. CONCLUSIONS: Nearly 16.67% women with persistent inflammation on Pap smear had cervical intraepithelial neoplasia. Hence, a large number of women with CIN would be missed if persistent inflammation on Pap smear is not evaluated further.

Unilateral and painless development of isoniazid induced gynecomastia during re-treatment of pulmonary tuberculosis.

A case of isoniazid induced gynecomastia is being reported in an 18-year old male, who received a re-treatment regimen for the relapse of pulmonary tuberculosis (TB). At the end of two months of the treatment, the patient developed a painless unilateral gynecomastia, which completely disappeared after a month of the cessation of isoniazid. A review of literature on isoniazid induced gynecomastia is discussed.

Smear microscopy as surrogate for culture during follow up of pulmonary MDR-TB patients on DOTS Plus treatment.

BACKGROUND: DOTS Plus site at LRS Institute, New Delhi, covering 1.8 million population. AIMS: To ascertain if sputum smear could be used as a surrogate for culture during intensive phase of treatment of MDR-TB patients thereby enabling early shift from intensive phase to continuation phase, reducing the need for frequent cultures and saving time and cost in their management. METHODS: The study is a retrospective analysis of 138 MDR-TB patients on DOTS Plus treatment whose sputum samples were simultaneously subjected to smear microscopy and culture, monthly during Intensive Phase and once in two months during Continuation Phase. Sputum results in the treatment card were supplemented from laboratory register, if required, and analyzed. Predictive values, sensitivity and specificity of smear were compared with culture results. RESULTS: The Negative Predictive Value (NPV) of smear was high from the 3rd month onwards (above 91%), at four months 98% or more and approached 100% from eight months onwards. The specificity of smear test gradually increased during treatment and from five months onwards, it was above 90%. CONCLUSIONS: Considerable correlation was observed between sputum smear and culture during follow up of DOTS Plus treatment in the Intensive Phase. Accordingly, sputum smears can be recommended instead of culture.

Tuberculosis pneumonia as a primary cause of respiratory failure--report of two cases.

Tuberculosis (TB) is one of the treatable diseases rarely causing Acute Respiratory Failure (ARF). Hypoxic respiratory failure is often fatal in miliary tuberculosis and acute tuberculous bronchopneumonia. We describe two patients of tuberculous pneumonia with ARF who were successfully treated with early appropriate anti-tuberculosis therapy.