Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

Enhancing attention in children using an integrated cognitive-physical videogame: A pilot study.

Inattention can negatively impact several aspects of a child's life, including at home and school. Cognitive and physical interventions are two promising non-pharmaceutical approaches used to enhance attention abilities, with combined approaches often being marketed to teachers, therapists, and parents typically without research validation. Here, we assessed the feasibility of incorporating an integrated, cognitive-physical, closed-loop video game (body-brain trainer or 'BBT') as an after-school program, and also evaluated if there were attention benefits following its use. Twenty-two children (7-12 years of age) with a range of attention abilities were recruited to participate in this proof of concept, single-arm, longitudinal study (24 sessions over 8 weeks, ~30 min/day). We interrogated attention abilities through a parent survey of their child's behaviors, in addition to objective performance-based and neural measures of attention. Here we observed 95% compliance as well as, significant improvements on the parent-based reports of inattention and on cognitive tests and neural measures of attention that were comparable in scale to previous work. Exploratory measures of other cognitive control abilities and physical fitness also showed similar improvement, with exploratory evaluation of retained benefits on the primary attention-related outcomes being present 1-year later. Lastly, there was no correlation between the baseline parent-rated inattention score and the improvement on the primary task-based measures of attention, suggesting that intervention-based benefits were not solely attained by those who stood the most to gain. These pilot findings warrant future research to replicate and extend these findings.

An Anatomical Evaluation of Normal and Aberrant Foramen Ovale in Skull Base with Its Clinical Significance.

Introduction: Foramen ovale is one of the most significant foramina of skull base and transmits mandibular nerve. Its detailed knowledge is crucial in treatment of trigeminal neuralgia and various diagnostic practices. Aim: Aim of the study was to provide anatomical data of foramen ovale regarding number, shape, diameters and its relation to nearby bony landmarks. Material and method: The present study was ethically approved and 100 dry adult human skulls were included in the study to evaluate 200 foramina ovale. Non-metric parameters were observed and metric parameters were measured with Vernier calliper and goniometer. Results:Different kinds of shapes were found in foramen ovale. Variant features in the form of bony spine, ridge, foramen or bar were identified. The means of anteroposterior and transverse diameter of foramen ovale were found to be 8.16 and 4.97 mm on the right side, and 7.68 and 4.74 mm on the left side. The mean distance of its anterior and posterior ends from the midsagittal plane were 22.69 and 28.92 mm on the right side, and 22.18 and 22.66 mm on the left side. Distance from the lateral border of foramen ovale to the posterior end of zygoma and midpoint of infratemporal crest was found to be 30.65 and 21.05 mm on the right, and 30.30 and 20.87 mm on the left side. The mean of angle of foramen ovale with midsagittal was 45.44º on the right side and 45.78º on the left side. Conclusion:Variations found in foramen ovale are key points to keep in mind while operating in this region. Measured metric parameters were found to a higher extent on the right side than the left one. The present study will be helpful for both further research and neurosurgeons operating in this region.

Clinical standards for the dosing and management of TB drugs.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

A systematic review on SARS-CoV-2 remission: an emerging challenge for its management, treatment, immunization strategies, and post-treatment guidelines.

The COVID-19 disease caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) has posed as a major health concern for people all across the globe. Along with the increasing confirmed patients being readmitted with complaints for fever, cough, cold, the effective monitoring of 'relapse' of the SARS-CoV-2 virus in the previously discharged patients have become the next area of focus. However, availability of limited data on reactivation of SARS-CoV-2 makes the disease prognosis as well as the effective control of re-infection an immense challenge. Prompted by these challenges, we assessed the possibility of re-infection in discharged patients and the risk of the transmission, proficiency of RT-PCR results and approximate period required for the quarantine, and the real challenges for the development of vaccine. In the present review, the published literature on all the possible cases of re-infection from February to July were reported, thereby selected 142 studies from a hub of overall 669 studies after full text screening. The incomplete virus clearance, poor sensitivity of the present diagnostic testing, emergence of mutant strains, insufficient mucus collection from the throat swab etc., are some of the possible causes of re-infection. The new protocols for management of COVID-19 discharged patients should be revised in the guidelines.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Risk factors for early mortality in patients with pulmonary tuberculosis admitted to the emergency room.

BACKGROUND AND OBJECTIVES: Mortality of patients with pulmonary tuberculosis (TB) admitted to emergency departments is high. This study was aimed at analysing the risk factors associated with early mortality and designing a risk score based on simple parameters. METHODS: This prospective case-control study enrolled patients admitted to the emergency department of a referral TB hospital. Clinical, radiological, biochemical and microbiological risk factors associated with death were compared among patients dying within one week from admission (cases) and those surviving (controls). RESULTS: Forty-nine of 250 patients (19.6%) experienced early mortality. Multiple logistic regression analysis showed that oxygen saturation (SaO2) ≤90%, severe malnutrition, tachypnoea, tachycardia, hypotension, advanced disease at chest radiography, severe anaemia, hyponatremia, hypoproteinemia and hypercapnia were independently and significantly associated with early mortality. A clinical scoring system was further designed to stratify the risk of death by selecting five simple parameters (SpO2 ≤ 90%, tachypnoea, hypotension, advanced disease at chest radiography and tachycardia). This model predicted early mortality with a positive predictive value of 94.88% and a negative predictive value of 19.90%. CONCLUSIONS: The scoring system based on simple parameters may help to refer severely ill patients early to a higher level to reduce mortality, improve success rates, minimise the need for pulmonary rehabilitation and prevent post-treatment sequelae.

Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens.

BACKGROUND: Addressing TB in India is critical to meeting global targets. With the scale-up of diagnostic networks and the availability of new TB drugs, India had the opportunity to improve the detection and treatment outcomes in drug-resistant TB (DR-TB).OBJECTIVE: To document how the introduction of new drugs and regimens is helping India improve the care of DR-TB patients.DESIGN: In 2016, India´s National TB Programme (NTP) introduced bedaquiline (BDQ) under a Conditional Access Programme (BDQ-CAP) at six sites after providing extensive training and strengthening laboratory testing, pre-treatment evaluation, active drug safety monitoring and management (aDSM) and follow-up systems.RESULTS: An interim analysis reflected earlier and better culture conversion rates: 83% of the 620 patients converted within a median time of 60 days. However, 248 serious adverse events were reported, including 73 deaths (12%) and 100 cardiotoxicity events (16.3%). Encouraged by the evidence of safety and efficacy of BDQ, the NTP took steps to systematically expand its access to cover the entire population by 2018.CONCLUSION: The cautious yet focused approach used to introduce BDQ under BDQ-CAP paved the way for the rapid introduction of delamanid, as well as the shorter treatment regimen and the all-oral regimen for DR-TB.

BCG as a game-changer to prevent the infection and severity of COVID-19 pandemic?

The impact of COVID-19 is changing with country wise and depend on universal immunization policies. COVID-19 badly affects countries that did not have universal immunization policies or having them only for the selective population of countries (highly prominent population) like Italy, USA, UK, Netherland, etc. Universal immunization of BCG can provide great protection against the COVID-19 infection because the BCG vaccine gives broad protection against respiratory infections. BCG vaccine induces expressions of the gene that are involved in the antiviral innate immune response against viral infections with long-term maintenance of BCG vaccine-induced cellular immunity. COVID-19 cases are reported very much less in the countries with universal BCG vaccination policies such as India, Afghanistan, Nepal, Bhutan, Bangladesh, Israel, Japan, etc. as compared to without BCG implemented countries such as the USA, Italy, Spain, Canada, UK, etc. BCG vaccine provides protection for 50-60 years of immunization, so the elderly population needs to be revaccinated with BCG. Several countries started clinical trials of the BCG vaccine for health care workers and elderly people. BCG can be uses as a prophylactic treatment until the availability of the COVID-19 vaccine

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BCG as a game-changer to prevent the infection and severity of COVID-19 pandemic?

The impact of COVID-19 is changing with country wise and depend on universal immunization policies. COVID-19 badly affects countries that did not have universal immunization policies or having them only for the selective population of countries (highly prominent population) like Italy, USA, UK, Netherland, etc. Universal immunization of BCG can provide great protection against the COVID-19 infection because the BCG vaccine gives broad protection against respiratory infections. BCG vaccine induces expressions of the gene that are involved in the antiviral innate immune response against viral infections with long-term maintenance of BCG vaccine-induced cellular immunity. COVID-19 cases are reported very much less in the countries with universal BCG vaccination policies such as India, Afghanistan, Nepal, Bhutan, Bangladesh, Israel, Japan, etc. as compared to without BCG implemented countries such as the USA, Italy, Spain, Canada, UK, etc. BCG vaccine provides protection for 50-60 years of immunization, so the elderly population needs to be revaccinated with BCG. Several countries started clinical trials of the BCG vaccine for health care workers and elderly people. BCG can be uses as a prophylactic treatment until the availability of the COVID-19 vaccine.

An epidemiological profile of chronic obstructive pulmonary disease: A community-based study in Delhi.

BACKGROUND: Different definitions used for chronic obstructive pulmonary disease (COPD) preclude getting reliable prevalence estimates. Study objective was to find the prevalence of COPD as per standard Global Initiative for Chronic Obstructive Lung Disease definition, risk factors associated, and treatment seeking in adults >30 years. METHODOLOGY: Community-based cross-sectional study was conducted in Delhi, among 1200 adults, selected by systematic random sampling. Pretested questionnaire was used to interview all subjects and screen for symptoms of COPD. Postbronchodilator spirometry was done to confirm COPD. STATISTICAL ANALYSIS: Adjusted odds ratio (aOR) was calculated by multivariable analysis to examine the association of risk factors with COPD. Receiver operating characteristic (ROC) curve was developed to assess predictability. RESULTS: The prevalence of COPD was 10.1% (95% confidence interval [CI] 8.5, 11.9%). Tobacco smoking was the strongest risk factor associated (aOR 9.48; 95% CI 4.22, 14.13) followed by environmental tobacco smoke (ETS), occupational exposure, age, and biomass fuel. Each pack-year of smoking increased 15% risk of COPD. Ex-smokers had 63% lesser risk compared to current smokers. Clinical allergy seems to preclude COPD (aOR 0.06; 95% CI 0.02, 0.37). ROC analysis showed 94.38% of the COPD variability can be assessed by this model (sensitivity 57.4%; positive predictive value 93.3%). Only 48% patients were on treatment. Treatment continuation was impeded by its cost. CONCLUSION: COPD prevalence in the region of Delhi, India, is high, and our case-finding population study identified a high rate of patients who were not on any treatment. Our study adds to creating awareness on the importance of smoking cessation, early diagnosis of COPD, and the need for regular treatment.

THz-Frequency Modulation of the Hubbard U in an Organic Mott Insulator.

We use midinfrared pulses with stable carrier-envelope phase offset to drive molecular vibrations in the charge transfer salt ET-F_{2}TCNQ, a prototypical one-dimensional Mott insulator. We find that the Mott gap, which is probed resonantly with 10 fs laser pulses, oscillates with the pump field. This observation reveals that molecular excitations can coherently perturb the electronic on-site interactions (Hubbard U) by changing the local orbital wave function. The gap oscillates at twice the frequency of the vibrational mode, indicating that the molecular distortions couple quadratically to the local charge density.

Allergic Rhinitis: A neglected disease - A community based assessment among adults in Delhi.

BACKGROUND AND OBJECTIVES: Allergic Rhinitis is rather erroneously viewed as a trivial disease. It is important in that it can significantly affect quality of life. There is paucity of community based prevalence studies on the disease in India. This study was planned to assess the prevalence of allergic rhinitis in adults, the proportion of asthmatics among them, risk factors associated and treatment seeking behaviour among the patients. MATERIALS AND METHODS: A community based cross sectional study was conducted in Mehrauli, South Delhi among 1200 adults, aged 30 years and over selected by systematic random sampling from two randomly selected wards. A pre-tested questionnaire was used to collect information regarding symptoms, risk factors and treatment seeking behaviour. Allergic Rhinitis was diagnosed as per ARIA guidelines. Spirometry was done to diagnose asthma among them. Multivariate logistic regression analysis was done to find the association of risk factors with disease. RESULTS: The prevalence of Allergic Rhinitis was found to be 11% (132 subjects) and 33.3% (44 patients) among them also had asthma. Overcrowding (aOR = 6.4), absence of cross-ventilation (aOR = 2.5), occupational exposure to dust/ smoke (aOR = 2.1), tobacco smoking (aOR = 2.1), family history of allergic diseases (aOR = 2.7) and clinical allergy (aOR = 10.2) were found to be independent risk factors associated with Rhinitis. More patients of Rhinitis with asthma (75%) took treatment, relative to those without asthma (40%) who, mostly relied on home remedies (42%) or, did not seek any treatment (18%) (P = 0.031). Interpretations and Conclusion: The burden of Allergic Rhinitis is high with a considerable overlap with asthma. These allergic diseases and emphasize the importance of early and regular treatment.

Modified Pauwels' intertrochanteric osteotomy in the management of nonunion of a femoral neck fracture following failed osteosynthesis.

We report the outcome of 39 patients who underwent a modified Pauwels' intertrochanteric osteotomy for nonunion of a femoral neck fracture following failed osteosynthesis. There were 31 men and eight women with a mean age of 47.2 years (34 to 59). By Pauwels' classification, there were 11 Type II fractures and 28 Type III fractures. The mean follow-up was 7.9 years (2 to 19). In the 11 patients whose initial treatment had been osteotomy, union was achieved in nine (81.8%). In 28 patients whose initial treatment had been with a lag screw or a dynamic hip screw, union was achieved in 27 (96.4%). Limb lengths were equalised in 14 of 16 patients (87.5%) with pre-operative shortening. The mean neck-shaft angle improved significantly from 100.5° (80° to 120°) to 131.6° (120° to 155°) (p = 0.004). The mean modified Harris hip score was 85.6 points (70 to 97) and the mean modified Merle d'Aubigné score was 14.3 (11 to 18). Good to excellent functional outcomes were achieved in 32 patients (88.8%). A modified Pauwels' intertrochanteric osteotomy is a reliable method of treating ununited fractures of the femoral neck following failed osteosynthesis: coxa vara and shortening can also simultaneously be addressed.