Using timeliness metrics for household contact tracing and TB preventive therapy in the private sector, India.

Although screening of household contacts (HHCs) of TB patients and provision of TB preventive therapy (TPT) is a key intervention to end the TB epidemic, their implementation globally is dismal. We assessed whether introducing a '7-1-7' timeliness metric was workable for implementing HHC screening among index patients with pulmonary TB diagnosed by private providers in Chennai, India, between November 2022 and March 2023.This was an explanatory mixed-methods study (quantitative-cohort and qualitative-descriptive).There were 263 index patients with 556 HHCs. In 90% of index patients, HHCs were line-listed within 7 days of anti-TB treatment initiation. Screening outcomes were ascertained in 48% of HHCs within 1 day of line-listing. Start of anti-TB treatment, TPT or a decision to receive neither was achieved in 57% of HHC within 7 days of screening. Overall, 24% of screened HHCs in the '7-1-7' period started TPT compared with 16% in a historical control (P < 0.01). Barriers to achieving '7-1-7' included HHC reluctance for evaluation or TPT, refusal of private providers to prescribe TPT and reliance on facility-based screening of HHCs instead of home visits by health workers for screening.Introduction of a timeliness metric is a workable intervention that adds structure to HHC screening and timely management..

An Improvised Cost-Effective Repair Technique for Management of Broken Luer Connections of Tunneled Dialysis Catheter and Salvage Existing Catheter.

Mechanical problems like break or crack in Luer connectors or hubs, clamps, and tubings are common non-infectious complications of tunneled dialysis catheters (TDC), which may lead to other TDC complications and the need to insert a new catheter. These can be tackled using TDC repair kits or spare parts, which are often not available, resulting in the insertion of a new TDC that increases morbidity, TDC-related procedures, and healthcare costs. We discuss two cases of broken Luer connections of TDC, which were managed by exchanging the broken Luer connector of TDC with the similar Luer connector of a temporary dialysis catheter. Both the repaired TDCs are thereafter functioning well. This improvised technique provides an easy, effective, long-lasting option that salvages the existing TDC and reduces the cost factor.

Implantable loop recorder in unexplained palpitations or syncope: A randomised study among young patients with structurally normal heart.

Background: The utility of an implantable loop recorder (ILR) in the evaluation of unexplained syncope or palpitations in young patients in the absence of structural heart disease or ventricular dysfunction is limited. To compare the diagnostic yield of ILR with conventional extended Holter evaluation in the detection of arrhythmias among young patients with a structurally normal heart presenting with unexplained palpitations or syncope. Methods: Open-label randomised control trial was conducted in a tertiary cardiac care centre among young patients with recurrent unexplained palpitations (≥3 episodes/year) or syncope (≥2 episodes) with normal electrocardiogram and echocardiography, after excluding non-cardiac causes. Patients were block randomised to either ILR implantation or conventional extended Holter monitoring. Results: Fourteen patients in the ILR group and 16 patients in the conventional group completed the study. The mean age of the patients was 31.9 ± 5.5 and 31.2 ± 5.4 years. Males constituted 78.5% and 75% in the two groups, respectively. Diagnosis was established in 10 (71.5%) patients in the ILR group as compared to only 3 (18.7%) in the conventional group (p = 0.01), with an RR of 0.26 (95% CI 0.089-0.76, p = 0.01). The arrhythmias diagnosed with ILR were narrow complex tachycardia (30%), atrial fibrillation (20%), VPCs (20%), severe bradycardia with asystole due to sinus arrest (10%), VPCs with bigeminy (10%), and ventricular tachycardia (10%). Conclusion: In young patients with unexplained syncope or palpitations, ILR has a higher diagnostic yield in the accurate detection of arrhythmia compared with conventional Holter strategy, resulting in better management.

Antidiabetic potential of phytochemicals isolated from the stem bark of Myristica fatua Houtt. var. magnifica (Bedd.) Sinclair.

Phytochemical investigation of the stem bark of Myristica fatua Houtt. led to the isolation of a new compound 1 (3-tridecanoylbenzoic acid), along with six known acylphenols (2-7). All the compounds displayed moderate inhibitory activity on α-amylase and significant activity on α-glucosidase; however malabaricone B (6) and C (7) were identified as potent α-glucosidase inhibitors with IC50 values of 63.70 ±â€¯0.546, and 43.61 ±â€¯0.620 µM respectively. Acylphenols (compounds 3-7) also showed significant antiglycation property. The molecular docking and dynamics simulation studies confirmed the efficient binding of malabaricone C with C-terminus of human maltase-glucoamylase (2QMJ). Malabaricone B also enhanced the 2-NBDG [2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxy glucose] uptake in L6 myotubes. These findings demonstrate that acylphenols isolated from Myristica fatua Houtt. can be considered as a lead scaffold for the treatment of type II diabetes mellitus.

Diagnostic Accuracy of Stress Myocardial Perfusion Imaging in Diagnosing Stable Ischemic Heart Disease.

OBJECTIVE: To determine the diagnostic accuracy of Stress Myocardial Perfusion Imaging (MPI) in diagnosing Stable Ischemic Heart Disease (SIHD). METHODS: To analyze the sensitivity and specificity of Stress Myocardial Perfusion Imaging (MPI) in diagnosing Stable Ischemic Heart Disease (SIHD) by comparing with "gold standard" Coronary Angiogram. RESULTS: A total of 80 patients were studied (51 male, 29 female). 52 patients had significant stenosis in coronary angiography and 49 patients had reversible perfusion defect in myocardial perfusion imaging (MPI). MPI had a sensitivity of 88.46% and a specificity of 89.29% in diagnosing stable ischemic heart disease. CONCLUSION: Coronary Angiography remains the near gold standard in diagnosing ischemic heart disease but is associated with serious complications like stroke, arrhythmias, acute renal failure, infection, etc. Though Myocardial perfusion imaging cannot replace coronary angiogram, it can be used as a reliable and sensitive non-invasive alternate investigation to diagnose stable ischemic heart disease in high risk individuals who are unwilling for angiogram.

Structural cardiac lesions in transient tachypnea of the newborn.

BACKGROUND: Transient tachypnea of the newborn (TTN) is considered a benign disorder. Given its self-limiting nature, few studies have looked for associated pathology. This study explores the association of TTN with structural cardiac lesions. METHODS: Over a six-month period, all inborn term and late preterm neonates with TTN (without predisposing factors) underwent 2D echocardiography within the first ten days of life, after tachypnea had subsided. Equal number of neonates born during the same period, matched for birth weight, gestational age, sex, and mode of delivery but without tachypnea, also underwent echocardiography before ten days of life. The cardiologist performing the echocardiography was blinded to the presence or absence of tachypnea. RESULTS: Thirty-six neonates with tachypnea and equal number of controls underwent echocardiography. Due to matching, there was no significant difference in birth weight, gestational age, sex, or mode of delivery between the two groups. Mean age at echocardiography also did not significantly differ. Neonates with TTN had significantly more structural cardiac lesions than those without (16 [44.44%] vs 5 [13.39%]; p < 0.009). CONCLUSION: Significantly more neonates with TTN have associated structural cardiac lesions. All neonates with TTN should be screened for underlying structural cardiac lesions.

How do patients access the private sector in Chennai, India? An evaluation of delays in tuberculosis diagnosis.

SETTING: The diagnosis and treatment of tuberculosis (TB) in India are characterized by heavy private-sector involvement. Delays in treatment remain poorly characterized among patients seeking care in the Indian private sector. OBJECTIVE: To assess delays in TB diagnosis and treatment initiation among patients diagnosed in the private sector, and pathways to care in an urban setting. DESIGN: Cross-sectional survey of 289 consecutive patients diagnosed with TB in the private sector and referred for anti-tuberculosis treatment through a public-private mix program in Chennai from January 2014 to February 2015. RESULTS: Among 212 patients with pulmonary TB, 90% first contacted a formal private provider, and 78% were diagnosed by the first or second provider seen after a median of three visits per provider. Median total delay was 51 days (mean 68). Consulting an informal (rather than formally trained) provider first was associated with significant increases in total delay (absolute increase 22.8 days, 95%CI 6.2-39.5) and in the risk of prolonged delay >90 days (aRR 2.4, 95%CI 1.3-4.4). CONCLUSION: Even among patients seeking care in the formal (vs. informal) private sector in Chennai, diagnostic delays are substantial. Novel strategies are required to engage private providers, who often serve as the first point of contact.

Intensified tuberculosis case finding amongst vulnerable communities in southern India.

India mainly uses passive case finding to detect tuberculosis (TB) patients through the Revised National Tuberculosis Control Programme (RNTCP). An intensified case finding (ICF) intervention was conducted among vulnerable communities in two districts of Karnataka during July-December 2013; 658 sputum smear-positive TB cases were detected. The number of smear-positive cases detected increased by 8.8% relative to the pre-intervention period (July-December 2012) in intervention communities as compared to an 8.6% decrease in communities without the ICF intervention. ICF activities brought TB services closer to vulnerable communities, moderately increasing TB case detection rates.

L'Inde recourt en majorité à la détection passive des cas de patients avec la tuberculose (TB) à travers le Programme national révisé de Lutte contre la Tuberculose. Une intervention de recherche intensifiée de cas (ICF) a été réalisée au sein de communautés vulnérables dans deux districts de Karnataka entre juillet et décembre 2013 ; 658 cas de TB à frottis positif ont été détectés. Le nombre de cas à frottis positif a augmenté de 8,8% par comparaison à la période précédant l'intervention (juillet­décembre 2012) dans les communautés bénéficiaires comparées aux 8,6% de diminution dans les communautés témoins. Des activités de recherche de cas intensifiées ont amené les services de TB plus près des communautés vulnérables, ce qui a accru modérément le taux de détection des cas de TB.

En la India se da preferencia a la estrategia de búsqueda pasiva con el fin de detectar los casos de tuberculosis (TB) en el marco del Programa Nacional Revisado. Se llevó a cabo una intervención de búsqueda intensificada de casos en las comunidades vulnerables de dos distritos de Karnataka de julio a diciembre del 2013 y se detectaron 658 casos de TB con baciloscopia positiva. El número de casos con baciloscopia positiva aumentó un 8,8% con respecto al período anterior a la intervención (de julio a diciembre del 2012) en las comunidades de la intervención, en comparación con una disminución de 8,6% en las comunidades que no recibieron la intervención. Las actividades de intensificación de la búsqueda de casos llevaron los servicios de atención de la TB a las comunidades vulnerables y aumentaron de manera moderada las tasas de detección de la enfermedad.

Retention in pre-antiretroviral treatment care in a district of Karnataka, India: how well are we doing?

SETTING: Antiretroviral treatment (ART) Centre in Tumkur district of Karnataka State, India. There is no published information about pre-ART loss to follow-up from India. OBJECTIVE: To assess the proportion lost to follow-up (defined as not visiting the ART Centre within 1 year of registration) and associated socio-demographic and immunological variables. DESIGN: Retrospective cohort study involving a review of medical records of adult HIV-infected persons (aged ⩾15 years) registered in pre-ART care during January 2010-June 2012. RESULTS: Of 3238 patients registered, 2519 (78%) were eligible for ART, while 719 (22%) were not. Four of the latter were transferred out; the remaining 715 individuals were enrolled in pre-ART care, of whom 290 (41%) were lost to follow-up. Factors associated with loss to follow-up on multivariate analysis included age group ⩾45 years, low educational level, not being married, World Health Organization Stage III or IV and rural residence. CONCLUSION: About four in 10 individuals in pre-ART care were lost to follow-up within 1 year of registration. This needs urgent attention. Routine cohort analysis in the national programme should include those in pre-ART care to enable improved review, monitoring and supervision. Further qualitative research to ascertain reasons for loss to follow-up is required to design future interventions.

Contexte : Centre de traitement antirétroviral (ART) du district de Tumkur dans l'état de Karnataka, Inde. Il n'y a pas de document publié sur les perdus de vue avant le traitement ART en Inde.Objectif : Evaluer la proportion de perdus de vue (définis comme l'absence de visite au centre d'ART dans l'année suivant l'enregistrement) et les variables sociodémographiques et immunologiques qui y sont associées.Schéma : Etude rétrospective de cohorte impliquant une revue des dossiers médicaux des patients adultes infectés par le VIH (âge ⩾15 ans) enregistrés en soins pré-ART entre janvier 2010 et juin 2012.Résultats : Sur 3238 patients enregistrés, 2519 (78%) étaient éligibles pour le traitement ART tandis que 719 (22%) ne l'étaient pas. Quatre de ces derniers ont été transférés. Parmi les 715 individus enrôlés en soin pré-ART, 290 (41%) ont été perdus de vue. Les facteurs associés avec le fait d'être perdus de vue en analyse multivariée incluaient la tranche d'âge ⩾45 ans, un niveau d'instruction faible, le célibat, le stade 3 ou 4 de l'OMS et la résidence en milieu rural.Conclusion : Près de quatre individus sur 10 en soins pre-ART ont été perdus de vue dans l'année suivant leur enregistrement. Ceci requiert une attention urgente. L'analyse de cohorte en routine du programme national devrait inclure les patients en soins pré-ART afin d'améliorer la revue des cas, leur suivi et leur supervision. Une recherche qualitative ultérieure afin de cerner les raisons des pertes de vue est nécessaire pour concevoir les interventions futures.

Marco de referencia: El centro de tratamiento antirretrovírico (ART) en el distrito de Tumkur del estado de Karnataka en la India. Hasta el momento no existen publicaciones sobre la pérdida de vista de los pacientes seropositivos durante el seguimiento antes de comenzar el ART en la India.Objetivo: Se buscó definir la proporción de pacientes perdidos de vista durante el seguimiento (definidos como los pacientes que no habían acudido al centro de ART hasta un año después de haberse registrado) y evaluar las variables socioeconómicas e inmunitarias que se asociaban con esta situación.Método: Se llevó a cabo un estudio retrospectivo de cohortes a partir del examen de las historias clínicas de los adultos (⩾15 años de edad) infectados por el virus de la inmunodeficiencia humana (VIH), que se inscribieron a la atención clínica previa al ART de enero del 2010 a junio del 2012.Resultados: De los 3238 pacientes registrados, 2519 cumplían con los requisitos para iniciar el ART (78%) y 719 de ellos no eran aptos (22%); cuatro pacientes de este último grupo se remitieron a otro centro. De las 715 personas restantes, inscritas en la atención previa al ART, 290 se perdieron de vista durante el seguimiento (41%). El análisis multifactorial puso en evidencia que los factores asociados con la pérdida de vista de los pacientes fueron el grupo de edad de ⩾45 años, una baja escolaridad, el hecho de ser solteros, el estado 3 o 4 de la enfermedad según la clasificación de la Organización Mundial de la Salud y la residencia en zona rural.Conclusión: Cerca de cuatro de cada diez pacientes inscritos en la atención clínica previa al ART se perdieron de vista durante el seguimiento en el primer año después de haberse registrado. Esta situación exige una atención urgente. Es importante que los análisis sistemáticos de cohortes del programa nacional incluyan a las personas infectadas que reciben atención antes de comenzar el ART, a fin de mejorar la evaluación, el seguimiento y la supervisión de los pacientes. Es preciso fomentar la realización de nuevas investigaciones cualitativas que determinen las razones de la pérdida de vista durante el seguimiento y contribuyan a la planificación de las intervenciones futuras.

Providing a gateway to prevention and care for the most at-risk populations in Bhutan: is this being achieved?

SETTING: Two free-standing urban human immunodeficiency virus (HIV) testing and counselling (HCT) centres in Bhutan offering services to the general population and targeting the most at-risk populations (MARPs). OBJECTIVES: To assess the trend in testing for HIV, hepatitis B and syphilis in both the general population and MARPs, and to determine if sociodemographic and risk behaviour characteristics are associated with HIV, hepatitis B and syphilis seropositivity. DESIGN: Cross-sectional study using client records, 2009 - 2012. RESULTS: Of 7894 clients, 3009 (38%) were from the general population, while 4885 (62%) were from MARPs. Over the 4-year period, testing declined progressively among the general population, while it increased or remained static for MARPs. Of 4885 MARPs, seropositivity was respectively 0.7%, 1.3% and 1.2% for HIV, hepatitis B and syphilis. Female sex workers (FSWs) (relative risk [RR] 4.4, P = 0.03) and partners of person living with HIV (RR 25.9, P < 0.001) had a higher risk of being HIV-positive. FSWs had also a greater risk of being syphilis-positive (RR 9.1, P < 0.001). CONCLUSION: The increase in uptake of HCT services by MARPs is a welcome finding; however, the relatively static trends call for the introduction of community outreach approaches. The critical gateway being provided to MARPs is an 'opportunity' for the expansion of the current service package.

Contexte : Deux centres indépendants de dépistage et conseil pour le VIH (HCT) au Bhoutan proposant leurs services à la population générale et ciblent les plus à risque (MARP).Objectifs : Evaluer la tendance des tests VIH, hépatite et syphilis dans la population générale et chez les MARP et déterminer si les caractéristiques sociodémographiques et les conduites à risque sont associées à la séropositivité pour le VIH, l'hépatite et la syphilis.Schéma : Etude transversale sur les dossiers des clients, de 2009 à 2012.Résultats :Sur 7894 clients, 3009 (38%) appartenaient à la population générale et 4885 (62%) aux MARP. Au cours des 4 années, les examens ont diminué pour la population générale tandis qu'ils augmentaient ou restaient stables pour les MARP. Sur 4885 MARP, la séropositivité était de 0,7% pour le VIH, 1,3% pour l'hépatite B et 1,2% pour la syphilis. Les professionnelles du sexe (risque relatif [RR] 4,4 ; P = 0,03) et les partenaires de personnes vivant avec le VIH (RR 25,9 ; P < 0,001) avaient davantage de risques d'être VIH positif. Les professionnelles du sexe aveint également un risque plus élevé d'être positives pour la syphilis (RR 9,1 ; P < 0,001).Conclusion : L'augmentation de l'utilisation des services de HCT par les MARP est un résultat bienvenu, mais la tendance relativement stationnaire demande l'introduction d'approches de stratégie avancées dans les communautés. La porte d'entrée critique offerte aux MARP est une « opportunité ¼ d'accroitre le paquet de services actuels.

Marco de referencia: Dos centros independientes de diagnóstico y orientación de la infección por el virus de la inmunodeficiencia humana (VIH) en Bután, que prestan servicios a la población general, con una orientación especial hacia la población de más alto riesgo (MARP).Objetivos: Evaluar la tendencia en la práctica de las pruebas diagnósticas del VIH, la hepatitis B y la sífilis en la población general y en los MARP y analizar si existen factores sociodemográficos y comportamentales que se asocien con la positividad del examen serológico de estas infecciones.Métodos: Fue este un estudio transversal a partir de los registros de los usuarios de los centros entre el 2009 y el 2012.Resultados: De los 7894 usuarios, 3009 (38%) formaban parte de la población general y 4885 (62%) pertenecían a los MARP. Durante el período de 4 años, la práctica de las pruebas diagnósticas disminuyó de manera progresiva en la población general, pero aumentó o permaneció estable en los MARP. En las 4885 personas del grupo con mayor riesgo, la seropositividad fue 0,7% frente al VIH, 1,3% a la hepatitis B y 1,2% a la sífilis. Se observó un riesgo más alto de obtener un resultado positivo al VIH en las mujeres profesionales del sexo (riesgo relativo [RR] 4,4; P = 0,03) y en las parejas de las personas resultados positivos a la serología del VIH (RR 25,9; P < 0,001). Las profesionales del sexo exhibieron un mayor riesgo de obtener una serología positiva de la sífilis (RR 9,1; P < 0,001).Conclusión: El aumento de la utilización de los servicios de diagnóstico y orientación del VIH por parte de las poblaciones con más alto riesgo constituye una observación afortunada, pero la estabilización de las tendencias invita a introducir estrategias de extensión a la comunidad. La pasarela crucial que se está ofreciendo a la población en mayor riesgo de contraer estas enfermedades representa una 'oportunidad' de difusión del conjunto de servicios que se prestan en la actualidad.

Retention and HIV seroconversion among drug users on methadone maintenance treatment in Yunnan, China.

SETTING: Thirteen methadone maintenance treatment (MMT) clinics across Yunnan, the province with the highest human immunodeficiency virus (HIV) burden in China. OBJECTIVES: To determine, among HIV-negative participants on MMT, the proportion lost to follow-up (defined as those who missed the 6-monthly follow-up examination), factors associated with loss to follow-up (LFU), HIV seroconversion rate and factors associated with seroconversion. DESIGN: Prospective cohort study from October 2008 to April 2011. All participants were administered a pre-tested structured questionnaire to capture associated factors and offered HIV testing every 6 months. χ(2) test and log-binomial regression were used for data analysis. RESULTS: Of 1146 participants, 541 (47%) were lost to follow-up in 2.5 years. Factors associated with higher LFU proportion include <6 months of previous MMT, inconvenient location of the MMT clinic and average methadone dose ⩽60 mg/day, with adjusted relative risks (RRs) of respectively 1.4 (95%CI 1.2-1.5), 1.2 (95%CI 1.0-1.4) and 1.1 (95%CI 1.0-1.3). The overall HIV seroconversion rate was 6.6 (95%CI 3.7-11.0) per 1000 person-years. Not living with a partner contributed to higher HIV rates, with an adjusted RR of 3.6 (95%CI 1.0-12.8). CONCLUSION: The retention rate of MMT participants in Yunnan was not satisfactory. Decentralising service delivery in the community and making directly observed treatment more convenient has the potential to improve retention.

Contexte : Treize centres de traitement par méthadone (MMT) dans le Yunnan, la province la plus touchée par le virus de l'immunodéficience humaine (VIH) en Chine.Objectifs : Déterminer, parmi les participants VIH négatifs, la proportion de perdus de vue (ceux qui ont manqué l'examen de suivi à 6 mois), les facteurs associés à cet abandon du suivi, le taux de séroconversion VIH et les facteurs associés.Schéma : Etude prospective de cohorte d'octobre 2008 à avril 2011. Tous les participants ont rempli un questionnaire structuré prétesté afin d'identifier ces facteurs et on leur a proposé un test VIH tous les 6 mois. L'analyse des données a été réalisée à l'aide du test χ2 et de la régression logarithmique binomiale.Résultats : Sur 1146 patients, 541 (47%) ont été perdus de vue en 2 ans et demi. Les facteurs associé à cet abandon comprenaient : <6 mois de séjour préalable dans un centre MMT, localisation peu pratique du centre et dose moyenne de méthadone ⩽60 mg/jour avec un risque relatif (RR) ajusté de 1,4 (IC95% 1,2­1,5), 1,2 (IC95% 1,0­1,4) et 1,1 (IC95% 1,0­1,3), respectivement. Le taux global de séroconversion était de 6,6% personnes-années (IC95% 3,7­11). Le fait de ne pas vivre avec un partenaire contribuait à un taux plus élevé de VIH avec un RR ajusté de 3,6 (IC95% 1,0­12,8).Conclusion : Le taux de rétention des participants à un traitement en centre MMT au Yunnan n'était pas satisfaisant. Une prestation de services décentralisée au niveau communautaire avec observation directe du traitement serait plus pratique et pourrait améliorer cette rétention.

Marco de referencia: Trece consultorios de tratamiento de mantenimiento con metadona en Yunnan, la provincia donde se observa la más alta carga de morbilidad por la infección causada por el virus de la inmunodeficiencia humana (VIH) en la China.Objetivos: Determinar la proporción de pérdidas durante el tratamiento de mantenimiento con metadona en los pacientes sin infección por el VIH (es decir, los pacientes que no acudieron al seguimiento mensual durante 6 meses), los factores que se asociaron con esta pérdida, la tasa de conversión de la serología frente al VIH y los factores relacionados con la seroconversión.Métodos: Se llevó a cabo un estudio prospectivo de cohortes entre octubre del 2008 y abril del 2011. Se administró a todos los participantes un cuestionario estructurado validado, destinado a captar los factores asociados y se les propuso la prueba diagnóstica del VIH cada 6 meses. En el análisis de los datos se aplicó la prueba de la χ2 y un análisis de regresión logarítmica binaria.Resultados: De los 1146 pacientes se perdieron durante el seguimiento 541 (47%) en 2,5 años. Los factores que se asociaron con una proporción más alta de pérdidas fueron los siguientes: una duración del tratamiento previo de mantenimiento con metadona <6 meses (riesgo relativo ajustado [RRa] 1,4; IC95% 1,2­1,5), una localización poco práctica del consultorio (RRa 1,2; IC95% 1,0­1,4) y una dosis promedio de metadona ⩽60 mg/día (RRa 1,1; IC95% 1,0­1,3). La tasa global de seroconversión frente al VIH fue 6,6 (IC95% 3,7­11,0) por 1000 años-persona. El hecho de no vivir en pareja contribuyó a una tasa más alta de serologías positivas, con un RRa de 3,6 (IC95% 1,0­12,8).Conclusión: En Yunnan, el índice de fidelización al tratamiento de mantenimiento con metadona de los participantes es deficiente. Se podría mejorar la retención de los pacientes mediante la descentralización de la prestación de los servicios hacia la comunidad y una mejor adaptación de la observación directa del tratamiento.

Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy.

BACKGROUND: Neratinib (HKI-272) is a potent irreversible pan-ErbB tyrosine kinase inhibitor with clinical activity in patients with ErbB2/HER2-positive breast cancer. PATIENTS AND METHODS: Phase I of this open-label, phase I/II study investigated the maximum tolerated dose (MTD) of oral neratinib (160 or 240 mg/day) plus vinorelbine (25 mg/m2; days 1 and 8 of each 21-day cycle) in patients with solid tumors. Phase II assessed the safety, clinical activity, and pharmacokinetics of the combination in patients with HER2-positive metastatic breast cancer; the primary efficacy end point was objective response (OR). RESULTS: In phase I (n=12), neratinib (240 mg) plus vinorelbine (25 mg/m2) was established as the MTD. In phase II, 79 patients with HER2-positive metastatic breast cancer were treated at the MTD. The most common treatment-related adverse events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients discontinued treatment due to diarrhea. No clinically important skin side-effects were observed. The OR rate in assessable phase II patients was 41% (no prior lapatinib) and 8% (prior lapatinib). There was no evidence of pharmacokinetic interaction between neratinib and vinorelbine. CONCLUSION: Neratinib plus vinorelbine showed promising antitumor activity and no unexpected toxic effects in HER2-positive metastatic breast cancer patients. Trial registration ClinicalTrials.gov #NCT00706030.

Is physical access an impediment to tuberculosis diagnosis and treatment? A study from a rural district in North India.

SETTING: All designated microscopy centres (DMCs) in Fatehgarh Sahib District, Punjab, India. OBJECTIVE: To study the association of distance (physical access) to DMCs with loss to follow-up (LTFU) of presumptive tuberculosis (TB) cases while undergoing diagnostic sputum examination and failure to initiate treatment among smear-positive TB patients after diagnosis. DESIGN: A cross-sectional, record-based study was undertaken to analyse patient records from routine laboratory registers in all DMCs from January to June 2012. RESULT: More than 50% of presumptive TB cases had to travel >7 km to reach the DMC, totalling >28 km for two sputum examinations for the evaluation of an episode. The distance (>10 km) to the diagnostic facility was found to be significantly associated (P < 0.01), both with LTFU during diagnosis and with a delay (>7 days) in initiating treatment after diagnosis. There was a significant correlation (r = 0.7) between distance to the DMC and time to initiate treatment among smear-positive TB cases. CONCLUSION: Distance from the nearest facility represents a significant risk for LTFU during diagnosis and delayed initiation of treatment after diagnosis. Further decentralisation of TB care services to the community level is required by expanding the network of DMCs or by organising sputum collection and transportation.

Pretreatment sputum smear grade and smear positivity during follow-up of TB patients in Ahmedabad, India.

In Ahmedabad, India, a retrospective record review was undertaken among 2842 sputum smear-positive tuberculosis patients registered for treatment from April to September 2011 to assess the association of pretreatment sputum smear grade with sputum positivity and the additional yield of a second sputum sample during each follow-up examination. Respectively 39%, 26%, 28% and 7% of patients had pretreatment sputum grade 3+, 2+, 1+ and scanty. The higher the pretreatment sputum grade, the higher the proportion found positive during various follow-up periods. Overall, the additional yield of the second sputum sample was <2%; it did not vary with pretreatment smear grading.

On a entrepris à Ahmedabad, en Inde, une révision rétrospective des dossiers de 2842 patients tuberculeux à frottis positif enregistrés pour traitement d'avril à septembre 2011 afin d'évaluer dans quelle mesure le degré de positivité du frottis de crachat avant traitement était en association avec la positivité des crachats et avec un rendement supplémentaire d'un deuxième échantillon de crachats au cours de chaque examen de suivi. On a observé effectivement un niveau 3+ dans près de 39% des crachats avant traitement, un niveau 2+ dans 26%, un niveau 1+ dans 28% et un niveau faiblement positif dans 7%. La proportion s'avérant positive au cours des différentes périodes de suivi est d'autant plus élevée que le degré de positivité du crachat avant traitement est plus élevé. Au total, le rendement supplémentaire d'un deuxième échantillon de crachats est <2% et ne varie pas avec le degré de positivité du frottis avant traitement.

En Ahmedabad, India, se emprendió un examen retrospectivo de las historias clínicas de 2842 pacientes con tuberculosis y baciloscopia positiva del esputo registrados en tratamiento entre abril y septiembre del 2011, con el fin de evaluar si la gradación de la baciloscopia de las muestras de esputo antes del tratamiento se asociaba con su positividad en cada examen de seguimiento y si se mejoraba el rendimiento diagnóstico con una segunda muestra de esputo durante los exámenes de control. La gradación de la baciloscopia de los pacientes antes del tratamiento fue aproximadamente como sigue: 39% de grado 3+, 26% de grado 2+, 28% de grado 1+ y 7% escasos. Se observó que entre más alto era el grado de la baciloscopia inicial de los pacientes, mayor era la proporción que presentaba una baciloscopia positiva durante los períodos de seguimiento. En general, la segunda muestra de esputo permitió una ganancia inferior al 2% en el rendimiento y no se observaron variaciones en función de la gradación de la baciloscopia inicial.

Impact of advocacy on the tuberculosis management practices of private practitioners in Chennai City, India.

BACKGROUND: Innovative schemes to ensure the participation of private practitioners (PPs) in the Revised National Tuberculosis Control Programme (RNTCP) are necessary to identify and treat all patients with tuberculosis (TB). We developed a novel public-private mix (PPM) model to encourage PPs to practise DOTS and participate in the RNTCP while retaining their patients. METHODS: The Resource Group for Education and Advocacy for Community Health (REACH) developed and implemented the programme in partnership with the Chennai local health authority and the Tuberculosis Research Centre, Chennai, India. PPs were sensitised to the RNTCP and DOTS through a one-to-one approach or group meetings, and were assisted in referring patients. Surveys were carried out at baseline and at the completion of the study to assess changes in attitudes and practices. RESULTS: Six hundred PPs underwent sensitisation about the RNTCP, after which the proportion of PPs adopting DOTS increased significantly (P < 0.001), and the majority (72.8%) used sputum testing for diagnosing TB. The proportion of PPs who used X-ray alone for diagnosis declined to 16.0% from a baseline of 45.4%. CONCLUSIONS: This PPM model, which emphasises sustained advocacy for DOTS and allows PPs to retain private patients, looks promising and needs to be tested at other sites.

Avian Flu - A Bird's Eye View.

Influenza A (H5N1) virus infects a variety of animals, birds and humans. Present ongoing epidemic of this deadly virus in poultry livestock and humans has had major economic and health repercussions. It causes a wide spectrum of clinical features in human beings ranging from mild respiratory tract infection to a fatal pneumonia leading to multi organ system failure. Diagnosis is mainly clinical, aided by lab features like lymphopaenia and non-specific chest X-ray findings. Diagnostic tests are being evolved for rapid and specific diagnosis. Management is mainly symptomatic. Newer and effective antivirals, i.e. amantadine, zanamivir etc are also being tried.

The optical stretcher: a novel laser tool to micromanipulate cells.

When a dielectric object is placed between two opposed, nonfocused laser beams, the total force acting on the object is zero but the surface forces are additive, thus leading to a stretching of the object along the axis of the beams. Using this principle, we have constructed a device, called an optical stretcher, that can be used to measure the viscoelastic properties of dielectric materials, including biologic materials such as cells, with the sensitivity necessary to distinguish even between different individual cytoskeletal phenotypes. We have successfully used the optical stretcher to deform human erythrocytes and mouse fibroblasts. In the optical stretcher, no focusing is required, thus radiation damage is minimized and the surface forces are not limited by the light power. The magnitude of the deforming forces in the optical stretcher thus bridges the gap between optical tweezers and atomic force microscopy for the study of biologic materials.

Biochemical and molecular basis for mitochondrial cardiomyopathy in neonates and children.

Defects in myocardial bioenergetics have been reported in patients with cardiomyopathy but their molecular basis and role in pathophysiology remain unclear. We sought to establish a molecular basis for cardiac mitochondrial respiratory enzyme abnormalities frequently present (75%) in a group of 16 children (including 2 neonates) with end-stage cardiomyopathy. Decreased specific activity levels were found in complexes I, III, IV and V but not in II, the only complex that is entirely nuclear encoded. Sequence analysis of cardiac mtDNA revealed 4 patients harbouring heteroplasmic mtDNA mutations in cytb, tRNAArg, and ND5 at highly conserved positions. These mutations were present neither in controls nor in patients without enzymatic defect. In addition, 4 patients exhibited marked reduction in cardiac mtDNA levels. The basis for respiratory enzyme abnormalities can be explained in a subset of our patients as a result of either pathogenic mtDNA mutation or depletion. Patients harbouring both DNA and enzymatic defects fulfil rigorous criteria defining mitochondrial cardiomyopathy.