RESUMO
BACKGROUND: More than half of people who use antipsychotic medication for psychosis report having sexual dysfunction. The REMEDY trial aimed to find out if switching antipsychotic medication provides an effective way to reduce sexual dysfunction among people with psychosis. We set out to recruit 216 participants over a two-year period, but recruitment was stopped after an extended 12-month pilot phase, during which we recruited only 10 participants. As part of a nested process evaluation, we conducted qualitative interviews with front-line clinicians to examine barriers to recruitment to the trial. METHODS: We developed a semi-structured interview schedule to explore staff views on factors that influenced whether they referred potential participants to the study. We interviewed a purposive sample of 51 staff from four National Health Service (NHS) Trusts in England, ensuring a range of different backgrounds, seniority, and levels of involvement in the trial. Audio recordings of interviews were transcribed for verbatim, and data were analysed using an inductive approach to thematic analysis. RESULTS: Nine interconnected themes were generated. Six themes concerned barriers to recruitment; including; prioritising patients' mental stability, mutual discomfort and embarrassment about discussing a "taboo" subject, and concerns about unintended consequences of asking people with psychosis about their sexual functioning. Three themes, including the quality of treatment relationships and strategies for opening dialogue suggested ways to improve recognition of these "hidden" side effects. CONCLUSION: The identification and management of sexual dysfunction among people with psychosis are not priorities for mental health services in England at this time. Many staff working in front-line services feel unprepared and uncomfortable asking people with psychosis about these problems. While greater use of screening tools may improve the identification of sexual dysfunction among people with psychosis, the evaluation and implementation of interventions to manage them will continue to be challenging unless NHS leaders and senior clinicians demonstrate greater commitment to changing current clinical practice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12307891.
Assuntos
Antipsicóticos , Serviços de Saúde Mental , Transtornos Psicóticos , Antipsicóticos/uso terapêutico , Humanos , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/tratamento farmacológico , Encaminhamento e Consulta , Medicina EstatalRESUMO
BACKGROUND: Pretreatment loss to follow-up (PTLFU) is a barrier to tuberculosis (TB) control in India's Revised National TB Control Programme (RNTCP). PTLFU studies have not been conducted in India's mega-cities, where patient mobility may complicate linkage to care. METHODS: We collected data from patient registries for May 2015 from 22 RNTCP designated microscopy centers (DMCs) in Chennai and audited addresses and phone numbers for patients evaluated for suspected TB to understand how missing contact information may contribute to PTLFU. From November 2015 to June 2016, we audited one month of records from each of these 22 DMCs and tracked newly diagnosed smear-positive patients using RNTCP records, phone calls, and home visits. We defined PTLFU cases as including: (1) patients who did not start TB therapy within 14 days and (2) patients who started TB therapy but were lost to follow-up or died before official RNTCP registration. We used multivariate logistic regression to identify factors associated with PTLFU. RESULTS: In the audit of May 2015 DMC registries, out of 3696 patients evaluated for TB, 1273 (34.4%) had addresses and phone numbers that were illegible or missing. Out of 344 smear-positive patients tracked from November 2015 to June 2016, 40 (11.6%) did not start TB therapy within 14 days and 36 (10.5%) started therapy but were lost to follow-up or died before official RNTCP registration, for an overall PTLFU rate of 22.1% (95%CI: 17.8%-26.4%). Of all PTLFU patients, 55 (72.4%) were lost to follow-up and 21 (27.6%) died before starting treatment or before RNTCP registration. In the regression analysis, age > 50 years (OR 2.9, 95%CI 1.4-6.5), history of prior TB (OR 3.9, 95%CI 2.2-7.1), evaluation at a high patient volume DMC (OR 3.2, 95% CI 1.7-6.3), and absence of legible patient contact information (OR 4.5, 95%CI 1.3-15.1) were significantly associated with PTLFU. CONCLUSIONS: In an Indian mega-city, we found a high PTLFU rate, especially in patients with a prior TB history, who are at greater risk for having drug-resistance. Enhancing quality of care and health system transparency is critical for improving linkage of newly diagnosed patients to TB care in urban India.
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Tuberculose/diagnóstico , Adolescente , Adulto , Fatores Etários , Antituberculosos/uso terapêutico , Estudos de Coortes , Feminino , Seguimentos , Programas Governamentais , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde , Sistema de Registros , Análise de Regressão , Cooperação e Adesão ao Tratamento , Tuberculose/tratamento farmacológico , Adulto JovemRESUMO
Background & objectives: Large variability in anti-tuberculosis (TB) drug concentrations between patients is known to exist. However, limited information is available on intrapatient drug levels during the course of anti-TB treatment (ATT). This study was conducted to evaluate intrapatient variability in plasma rifampicin (RMP) and isoniazid (INH) concentrations during ATT at start of the treatment, at the end of intensive phase (IP) of ATT and at the end of ATT in adult TB patients being treated in the Revised National TB Control Programme (RNTCP). Methods: Adult TB patients (n=485), receiving thrice-weekly ATT in the RNTCP, were studied. Two-hour post-dosing concentrations of RMP and INH were determined at month 1, end of IP and end of ATT, after directly observed drug administration. Drug concentrations were estimated by high-performance liquid chromatography. Results: The median (inter-quartile range) RMP concentrations during the first month, at end of IP and end of ATT were 2.1 (0.4-5.0), 2.4 (0.6-5.5) and 2.2 (0.5-5.3) µg/ml, respectively. The corresponding INH concentrations were 7.1 (4.2-9.9), 7.2 (3.9-10.9) and 6.7 (3.9-9.5) µg/ml. None of the differences in drug concentrations obtained at different time points during ATT were significant. RMP and INH concentrations at different time points were significantly correlated. Age and body mass index caused significant variability in drug concentrations. Interpretation & conclusions: Plasma RMP and INH estimations in adult TB patients at two hours after drug administration remained unaltered during ATT. Clinicians can consider testing drug concentrations at any time point during ATT. These findings may assume significance in the context of therapeutic drug monitoring of anti-TB drug concentrations.
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Antituberculosos/farmacocinética , Isoniazida/farmacocinética , Rifampina/farmacocinética , Tuberculose/tratamento farmacológico , Adolescente , Adulto , Humanos , Índia , Projetos Piloto , Estudos Prospectivos , PirazinamidaRESUMO
PURPOSE: The aim of the study was to compare plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between tuberculosis (TB) patients with and without diabetes mellitus (DM). METHODS: Two-hour post-dosing concentrations of RMP, INH and PZA were determined in adult TB patients that were studied with (n = 452) and without DM (n = 1460), treated with a thrice-weekly regimen in India. Drug concentrations were estimated by HPLC. RESULTS: The median (IQR) INH [6.6 (3.9-10.0) and 7.8 (4.6-11.3)] and PZA [31.0 (22.3-38.0) and 34.1 (24.6-42.7)] microgram per milliliter concentrations were significantly lower in diabetic than non-diabetic TB patients (p < 0.001 for both drugs). Blood glucose was negatively correlated with plasma INH (r = -0.09, p < 0.001) and PZA (r = -0.092, p < 0.001). Multiple linear regression analysis showed RMP, INH and PZA concentrations were influenced by age and drug doses, INH and PZA by DM, RMP by alcohol use and PZA by gender and category of ATT. DM reduced INH and PZA concentrations by 0.8 and 3.0 µg/ml, respectively. CONCLUSIONS: TB patients with DM had lower INH and PZA concentrations. Negative correlation between blood glucose and drug concentrations suggests delayed absorption/faster elimination of INH and PZA in the presence of elevated glucose.
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Antituberculosos/sangue , Diabetes Mellitus/sangue , Isoniazida/sangue , Pirazinamida/sangue , Rifampina/sangue , Tuberculose/sangue , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/farmacocinética , Antituberculosos/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Feminino , Humanos , Isoniazida/administração & dosagem , Isoniazida/farmacocinética , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pirazinamida/administração & dosagem , Pirazinamida/farmacocinética , Pirazinamida/uso terapêutico , Rifampina/administração & dosagem , Rifampina/farmacocinética , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológicoRESUMO
BACKGROUND & OBJECTIVES: Variations in the N-acetyltransferase (NAT2) gene among different populations could affect the metabolism and disposition of isoniazid (INH). This study was performed to genotype NAT2 gene polymorphisms in tuberculosis (TB) patients from Chennai, India, and compare plasma INH concentrations among the different genotypes. METHODS: Adult patients with TB treated in the Revised National TB Control Programme (RNTCP) in Chennai, Tamil Nadu, were genotyped for NAT2 gene polymorphism, and two-hour post-dosing INH concentrations were compared between the different genotypes. Plasma INH was determined by high-performance liquid chromatography. Genotyping of the NAT2 gene polymorphism was performed by real-time polymerase chain reaction method. RESULTS: Among the 326 patients genotyped, there were 189 (58%), 114 (35%) and 23 (7%) slow, intermediate and fast acetylators, respectively. The median two-hour INH concentrations in slow, intermediate and fast acetylators were 10.2, 8.1 and 4.1 µg/ml, respectively. The differences in INH concentrations among the three genotypes were significant (P<0.001). INTERPRETATION & CONCLUSIONS: Genotyping of TB patients from south India for NAT2 gene polymorphism revealed that 58 per cent of the study population comprised slow acetylators. Two-hour INH concentrations differed significantly among the three genotypes.
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Arilamina N-Acetiltransferase/genética , Inativação Metabólica/genética , Isoniazida/sangue , Tuberculose/sangue , Adulto , Feminino , Genótipo , Humanos , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Tuberculose/tratamento farmacológico , Tuberculose/genética , Tuberculose/patologiaRESUMO
BACKGROUND & OBJECTIVES: Concomitant feeding and anti-tuberculosis (TB) drug administration are likely to reduce nausea and enhance compliance to treatment. However, food could lower plasma drug concentrations. This study was undertaken to examine the effect of food on two-hour plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA), and pharmacokinetics of these drugs in adult TB patients. METHODS: Newly diagnosed adult TB patients were recruited from the Revised National Tuberculosis Control Programme (RNTCP) treatment centres in Chennai Corporation, Chennai, India. Two-hour post-dosing plasma concentrations were determined in 25 patients, and a semi-intensive pharmacokinetic study was undertaken in six patients. RMP, INH and PZA concentrations were determined by high-performance liquid chromatography. RESULTS: The geometric mean two-hour concentrations with food and under fasting conditions were 2.2 and 5.5 µg/ml for RMP (P<0.001), 3.9 and 11.3 µg/ml for INH (P<0.001), and 18.0 and 28.2 µg/ml for PZA (P<0.001), respectively. Drug administration with food caused the plasma concentration to decrease by 50, 45 and 34 per cent for RMP, INH and PZA, respectively. Significant decreases in peak concentrations and exposures of drugs and delay in time to attain peak concentrations of drugs when taken with food were also observed. INTERPRETATION & CONCLUSIONS: Our findings showed that food lowered anti-TB drug concentrations significantly and delayed absorption. Patients may be explained the beneficial effects of taking anti-TB drugs in a fasting state and advised to do so. There is a need for more research on optimization of dosing to maximize efficacy and safety of currently used drugs.
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Antituberculosos/administração & dosagem , Alimentos/efeitos adversos , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/sangue , Antituberculosos/farmacocinética , Jejum , Feminino , Humanos , Índia/epidemiologia , Isoniazida/administração & dosagem , Isoniazida/sangue , Isoniazida/farmacocinética , Masculino , Pessoa de Meia-Idade , Pirazinamida/administração & dosagem , Pirazinamida/sangue , Pirazinamida/farmacocinética , Rifampina/administração & dosagem , Rifampina/sangue , Rifampina/farmacocinética , Tuberculose/sangue , Tuberculose/patologiaRESUMO
Tuberculosis (TB) constitutes the major cause of death due to infectious diseases. Cytokines play a major role in defence against Mycobacterium tuberculosis infection. Polymorphisms in the genes encoding various cytokines have been associated with tuberculosis susceptibility. Household contacts (HHC) are at increased risk of developing the disease. In this study, we examined the association of IL-1ß and IL-10 cytokine gene polymorphisms with risk of developing tuberculosis in TB patients, their HHC and healthy controls (HC) using JavaStat and SPSS. Multifactor dimensionality reduction (MDR) analyses were performed to explore the potential gene-gene interactions. The genotype and allele frequencies of IL-1ß +3954C/T polymorphism did not vary significantly between TB patients and HC. GG (P < 0.005, OR = 0.219 and 95% CI = 0.059-0.735) and GA (P < 0.0001, OR = 2.938 and 95% CI = 1.526-5.696) genotypes of IL-10-1082 G/A polymorphism were found to be significantly associated with patients versus HC. HHC with CC (P < 0.03, OR = 1.833 and 95% CI = 1.1-3.35) genotype in IL-1ß and GA (P < 0.0001, OR = 4.612 and 95% CI = 2.225-9.702) genotype in IL-10 were at increased risk of developing tuberculosis. MDR tests revealed high-risk genotypes in IL-1ß and IL-10 based on the association model. Our results demonstrate that the polymorphisms of IL-1ß and IL-10 genes may be valuable markers to predict the risk for the development of TB in household contacts.
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Predisposição Genética para Doença , Interleucina-10/genética , Interleucina-1beta/genética , Polimorfismo Genético , Adulto , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/genéticaRESUMO
BACKGROUND: Patients with concurrent diabetes mellitus (DM) and tuberculosis (TB) pose an increased risk of treatment failure in TB and management of DM is complicated. Anti-diabetic and anti-TB drugs may interact with on another other when co-administered. The role of anti-TB drugs on the excretion of metformin in urine has not been studied. Therefore, we carried out a study in DM patients with and without TB to compare the percentage of metformin excreted in urine. METHODS: A total of 52 DMTB and 17 DM patients were recruited in this study from the Chennai Corporation Centres. DM and DM - TB patients were administered the prescribed anti-TB and anti-diabetic drugs (metformin (MET), glipizide (GLP),glimepiride (GLM),glibenclamide (GLB),rifampicin (RMP),isoniazid (INH), pyrazinamide (PZA) and ethambutol (EMB). DM and DMTB patients received metformin (MET) alone and in combination with sulphonylureas as diabetic drugs. The urine samples were collected from 0 to 8 hours after drug administration. Urine MET excreted in DM and DMTB patients were estimated by high performance liquid chromatography (HPLC) and percent dose was calculated. RESULTS: The percent dose of MET excreted in urine in DMTB patients was significantly higher when compared to DM patients. There is significant difference in the percent dose of MET excreted among DM patients with and without sulphonylureas, values being 23.3 and 17.7% respectively (p = 0.044). CONCLUSION: This is the first study to report on the percent dose of MET excretion in urine in patients with DM and DMTB receiving MET along with anti-TB drugs.
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Diabetes Mellitus , Metformina , Tuberculose , Humanos , Metformina/uso terapêutico , Índia , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Antituberculosos/uso terapêutico , Isoniazida/uso terapêutico , Pirazinamida/uso terapêutico , Diabetes Mellitus/tratamento farmacológicoRESUMO
BACKGROUND: Early diagnosis of drug-resistant TB (DR-TB) is crucial in preventing the spread of the disease in the community. Introduction of upfront decentralised drug susceptibility testing to district-level as part of universal drug susceptibility testing (UDST) policy increased the feasibility of rapid and early testing for drug resistance closer to the patient and has resulted in reduced circumstances for transmission. The introduction of the first-line line-probe assay (FL-LPA), GenoType® MTBDRplus v2, has had an extensive impact on the management of multidrug-resistant TB (MDR-TB) in India.MATERIALS and METHODS: Sputum samples of patients with presumptive TB and DR-TB from selected districts of Tamil Nadu received through National TB Elimination Programme (NTEP) were subjected to FL-LPA as per programme guidelines. In this study, we present trends in genotypic resistance to isoniazid (INH) and rifampicin (RIF) during the 4 years (2016-2019) among these patients. Band patterns were analysed as per the updated GLI (Global Laboratory Initiative) LPA interpretation and reporting guidelines.RESULTS: A total of 26,349 samples were received during the study period. Smear-positive samples (n = 20231) were directly subjected to FL-LPA; smear-negative samples were cultured in liquid media and M. tuberculosis-positive cultures were tested using FL-LPA. A total of 18,441 were MTB-positive on FL-LPA. INH monoresistance, RIF monoresistance and MDR-TB was observed in respectively 8.7%, 1.1% and 3.3% of the samples. There was a decreasing trend in all types of resistance observed particularly after 2017 (P < 0.001). MDR-TB showed a steady decrease from 5.6% to 1.8%. S531L (19.5%) and S315T (61.1%) were the most common mutations identified in the rpoB and katG genes, respectively. The percentage of inhA-c-15t promoter mutation, indicating low-level INH resistance, showed a consistent increase (P < 0.001).CONCLUSION: The impact of the UDST policy on the NTEP may have led to this decreasing trend in RIF and INH resistance observed in the study period. The increase in low-level INH resistance mutation inhA-c-15t may be associated with ethionamide/prothionamide resistance, and this should be taken into account when designing DR-TB regimen.
Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Humanos , Índia/epidemiologia , Isoniazida/farmacologia , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Rifampina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
Introduction: Pretreatment loss to follow-up (PTLFU)-dropout of patients after diagnosis but before treatment registration-is a major gap in tuberculosis (TB) care in India and globally. Patient and healthcare worker (HCW) perspectives are critical for developing interventions to reduce PTLFU. Methods: We tracked smear-positive TB patients diagnosed via sputum microscopy from 22 diagnostic centres in Chennai, one of India's largest cities. Patients who did not start therapy within 14 days, or who died or were lost to follow-up before official treatment registration, were classified as PTLFU cases. We conducted qualitative interviews with trackable patients, or family members of patients who had died. We conducted focus group discussions (FGDs) with HCWs involved in TB care. Interview and FGD transcripts were coded and analysed with Dedoose software to identify key themes. We created categories into which themes clustered and identified relationships among thematic categories to develop an explanatory model for PTLFU. Results: We conducted six FGDs comprising 53 HCWs and 33 individual patient or family member interviews. Themes clustered into five categories. Examining relationships among categories revealed two pathways leading to PTLFU as part of an explanatory model. In the first pathway, administrative and organisational health system barriers-including the complexity of navigating the system, healthcare worker absenteeism and infrastructure failures-resulted in patients feeling frustration or resignation, leading to disengagement from care. In turn, HCWs faced work constraints that contributed to many of these health system barriers for patients. In the second pathway, negative HCW attitudes and behaviours contributed to patients distrusting the health system, resulting in refusal of care. Conclusion: Health system barriers contribute to PTLFU directly and by amplifying patient-related challenges to engaging in care. Interventions should focus on removing administrative hurdles patients face in the health system, improving quality of the HCW-patient interaction and alleviating constraints preventing HCWs from providing patient-centred care.
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Tuberculose , Seguimentos , Pessoal de Saúde , Humanos , Índia , Pesquisa Qualitativa , Tuberculose/diagnóstico , Tuberculose/terapiaRESUMO
INTRODUCTION: With the introduction of newer molecular diagnostic tools, an increasing number of Non-tuberculous Mycobacteria (NTM) affecting the respiratory system and mimicking symptoms of pulmonary tuberculosis (PTB) are being identified. They may be misdiagnosed and treated as PTB, often categorized as treatment failures if they do not respond to treatment. This manuscript aims to characterize patients with pulmonary NTM disease. METHODS: Patient characteristics of bacteriologically confirmed pulmonary NTM disease, attending the ICMR-National Institute for Research in Tuberculosis, Chennai were prospectively compiled over a two-year period (2017-2018). RESULTS: A total of 122 patients with recurrent chest symptoms and not responding to anti-tuberculosis treatment were screened for NTM. Thirty-nine cases (26 males and 13 females) of symptomatic pulmonary NTM were diagnosed. The mean (SD) patient age and body mass index were 48.6 ± 11 years and 16.3 ± 3. All male participants were smokers, had at least one episode of previous ATT. Mycobacterium kansasii (48.7%) was the most frequently isolated species followed by Mycobacterium intracellulare (20.5%), Mycobacterium abscessus (7.6%) followed by Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium kyorinense, and Mycobacterium simiae. Infection with multiple NTMs was seen in four patients. Isoniazid resistance was identified in 20 patients. Based on species identified, treatment was initiated as per American Thoracic Society guidelines and continued up to 12 months of culture negativity. CONCLUSIONS: M. kansasii is the commonest pulmonary NTM isolated in Tamilnadu with a higher prevalence in males and elderly. Sensitization of both patients and providers is essential to avoid misdiagnosis and delay in diagnosis of pulmonary NTM disease as pulmonary TB.
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Infecções por Mycobacterium não Tuberculosas/epidemiologia , Micobactérias não Tuberculosas/isolamento & purificação , Adulto , Idoso , Antituberculosos/farmacologia , Estudos de Coortes , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/efeitos dos fármacos , Prevalência , Estudos Prospectivos , Escarro/microbiologia , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/microbiologia , Adulto JovemAssuntos
Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Humanos , Seguimentos , Índia/epidemiologia , Tuberculose/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Atenção à Saúde , Antituberculosos/uso terapêuticoRESUMO
BACKGROUND: Worldwide, there's concern over high pre-diagnosis and pre-treatment attritions or delays in Multidrug resistant tuberculosis (MDR-TB) diagnosis and treatment pathway (DTP). We conducted this operational research among patients with presumptive MDR-TB in north and central Chennai, India to determine attrition and turnaround times (TAT) at various steps of DTP and factors associated with attrition. METHODS: Study was conducted in Revised National Tuberculosis Control Programme setting. It was a retrospective cohort study involving record review of all patients with presumptive MDR-TB (eligible for DST) in 2014. RESULTS: Of 628 eligible for DST, 557 (88%) underwent DST and 74 (13%) patients were diagnosed as having MDR-TB. Pre-diagnosis and pre-treatment attrition was 11% (71/628) and 38% (28/74) respectively. TAT [median (IQR)] to test from eligibility for DST and initiate DR-TB treatment from diagnosis were 14 (9,27) and 18 (13,36) days respectively. Patients with smear negative TB and detected in first quarter of 2014 were less likely to undergo DST. Patients in first quarter of 2014 had significantly lower risk of pre-treatment attrition. CONCLUSION: There was high uptake of DST. However, urgent attention is required to reduce pre-treatment attrition, improve TAT to test from eligibility for DST and improve DST among patients with smear-negative TB.
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Antituberculosos/uso terapêutico , Diagnóstico Tardio/estatística & dados numéricos , Diagnóstico Precoce , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Estudos de Coortes , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Adulto JovemRESUMO
OBJECTIVE: To determine the effect of SLCO1B1 gene polymorphisms (rs11045819, rs4149032 and rs4149033) on rifampicin (RMP) concentrations in adult tuberculosis (TB) patients from south India. METHODS: We genotyped adult TB patients for three SLCO1B1 gene polymorphisms-rs11045819, rs4149032 and rs4149033-and compared 2-h post-dosing RMP concentrations of the different genotypes for each of the polymorphisms. Plasma RMP was determined using high-performance liquid chromatography. Genotyping was performed using direct sequencing. RESULTS: Among the 256 study patients, minor allele frequencies were respectively 0.01 (A), 0.46 (C) and 0.07 (A) for rs11045819, rs4149032 and rs4149033 polymorphisms; genotype distributions followed Hardy-Weinberg equilibrium. RMP concentrations did not significantly differ between the different genotypes of the three polymorphisms. CONCLUSION: This is the first study to show that rs11045819, rs4149032 and rs4149033 polymorphisms in the SLCO1B1 gene did not influence RMP concentrations in Indian patients.
Assuntos
Antibióticos Antituberculose/sangue , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Polimorfismo de Nucleotídeo Único , Rifampina/sangue , População Branca/genética , Adulto , Antibióticos Antituberculose/uso terapêutico , Feminino , Frequência do Gene , Genótipo , Técnicas de Genotipagem , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Rifampina/uso terapêutico , Tuberculose/sangue , Tuberculose/tratamento farmacológico , Tuberculose/genéticaRESUMO
OBJECTIVE: To study the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in adult tuberculosis (TB) patients and examine factors that influence drug pharmacokinetics. METHODS: Adult TB patients (n = 101) receiving thrice-weekly anti-tuberculosis treatment in the Revised National TB Control Programme (RNTCP) were studied. The study was conducted at steady state after directly observed drug administration. RMP, INH and PZA concentrations were estimated using high-performance liquid chromatography and NAT2 genotyping by real-time polymerase chain reaction. RESULTS: RMP peak concentration (Cmax) was sub-therapeutic (<8 µg/ml) in 88% of the patients. The Cmax of RMP, INH and PZA at 2 h was observed in respectively 83.2%, 97.0% and 92.1% of the patients. The Cmax and area under the curve from 0 to 8 h (AUC0-8) of PZA was lower in TB patients with diabetes mellitus than in non-diabetics. Significant associations were observed between the Cmax and the AUC0-8 of RMP, INH and PZA with drug doses; RMP with category of treatment; INH with smoking, body mass index and N-acetyl transferase 2 genotype; and PZA with sex and smoking. CONCLUSIONS: Several risk factors for drug concentration variations were identified. Two-hour post-dosing drug concentrations mimicked Cmax. A high proportion of TB patients had RMP Cmax below the expected range, which is a matter of concern.
Assuntos
Antituberculosos/farmacocinética , Isoniazida/farmacocinética , Pirazinamida/farmacocinética , Rifampina/farmacocinética , Tuberculose/tratamento farmacológico , Adulto , Antituberculosos/uso terapêutico , Arilamina N-Acetiltransferase/genética , Feminino , Técnicas de Genotipagem , Humanos , Índia , Isoniazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Pirazinamida/uso terapêutico , Rifampina/uso terapêutico , Tamanho da Amostra , Adulto JovemRESUMO
A novel electrode material of graphene sheet/graphene nanoribbon (GS/GNR) hybrid material was developed by incorporating graphene nanoribbons into graphene nanosheets through simultaneous chemical reduction of graphene oxide sheets and graphene oxide ribbons. The structure and properties of synthesized GS/GNR were characterized by transmission electron microscope, scanning electron microscope, X-ray diffraction, Brunauer Emmett Teller measurements and Fourier transform infrared spectroscopy. This work compares the electro catalytic performance of the GS/GNR, chemically reduced graphene oxide sheets (CRGOS) and GS/carbon nanotube (CNT) by modifying the glassy carbon electrode (GCE) using ascorbic acid (AA) as analyte. The electrochemical impedance spectroscopy revealed that the charge transfer resistance of GS/GNR modified electrode was less than that of CRGOS modified electrode and bare GCE. The cyclic voltammetric sensing of GS/GNR modified electrode towards AA was negatively shifted (0.08 V) compared to CRGOS, GS/CNT modified electrode and bare GCE (0.222, 0.150 and 0.666 V). This catalytic oxidation allows an amperometric detection of AA with a detection limit of 230 nM and sensitivity of 22 nA µM(-1) cm(-2). GS/GNR modified GCE exhibited a high selectivity for ascorbic acid in the presence of other interferents like dopamine, uric acid and citric acid.
RESUMO
Advances in sensor technology, personal mobile devices, and wireless broadband communications are enabling the development of an integrated personal mobile health monitoring system that can provide patients with a useful tool to assess their own health and manage their personal health information anytime and anywhere. Personal mobile devices, such as PDAs and mobile phones, are becoming more powerful integrated information management tools and play a major role in many people's lives. We focus on designing a health-monitoring system for people who suffer from cardiac arrhythmias. We have developed computer simulation models to evaluate the performance of appropriate electrocardiogram (ECG) analysis techniques that can be implemented on personal mobile devices. This paper describes an ECG analyzer to perform ECG beat and episode detection and classification. We have obtained promising preliminary results from our study. Also, we discuss several key considerations when implementing a mobile health monitoring solution. The mobile ECG analyzer would become a front-end patient health data acquisition module, which is connected to the Personal Health Information Management System (PHIMS) for data repository.
Assuntos
Eletrocardiografia Ambulatorial/instrumentação , Eletrocardiografia/instrumentação , Monitorização Ambulatorial/instrumentação , Monitorização Fisiológica/métodos , Telemedicina/métodos , Arritmias Cardíacas/diagnóstico , Artefatos , Redes de Comunicação de Computadores , Simulação por Computador , Computadores de Mão , Diagnóstico por Computador/métodos , Eletrocardiografia/métodos , Eletrocardiografia Ambulatorial/métodos , Desenho de Equipamento , Humanos , Monitorização Ambulatorial/métodos , Movimento , SoftwareRESUMO
A distributed personal health information management system (D-PHIMS) has been tested at a nursing home for the senior citizens (NHSC) in Singapore. The personal health information management system (PHIMS) from the University of Washington was customized to Singapore's context for teledermatology. A clinical trial commenced in October 2005 is ongoing and the survey results obtained indicate that the participants are satisfied with the D-PHIMS system. The diagnosis and treatment recommendations made by the dermatologists using the D-PHIMS diagnosis module were effective in most cases based on feedback from the nursing staff at the elderly nursing home. The results suggest that a teledermatology system could become a useful tool for the nursing homes and to control increasing healthcare costs for elderly care.
Assuntos
Dermatologia/instrumentação , Sistemas de Informação Administrativa , Idoso , Bases de Dados Factuais , Diagnóstico por Computador , Serviços de Saúde para Idosos , Instituição de Longa Permanência para Idosos , Humanos , Sistemas de Informação , Internet , Assistência de Longa Duração , Sistemas Computadorizados de Registros Médicos , Enfermeiras e Enfermeiros , Casas de Saúde , Singapura , Software , TelemedicinaRESUMO
This paper presents an adaptive PI control of mean blood pressure using vasoactive drugs like SNP. A new algorithm updating variations in time delay and sensitivity of the system is proposed and its effectiveness is discussed. For demonstration, simulations under clinical conditions are carried out and the results show that the adaptive control system can effectively handle the changes in patient's dynamics and provide satisfactory performance in regulation of blood pressure of hypertension patients.
RESUMO
Recent rapid growth in mobile computing technologies enables telemedicine applications to operate on mobile devices. Our focus is on the design of an integrated electrocardiogram (ECG) beat detector on a Personal Digital Assistant (PDA) platform for the health screening process. The ECG beat detector module will be supported by the PDA version of Personal Health Information Management System (PHIMS) and Facilitated Accurate Referral Management System (FARMS) through wireless network infrastructure as a home-based mobile cardiac monitoring solution.