Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

Pulmonary drug delivery and retention: A computational study to identify plausible parameters based on a coupled airway-mucus flow model.

Pulmonary drug delivery systems rely on inhalation of drug-laden aerosols produced from aerosol generators such as inhalers, nebulizers etc. On deposition, the drug molecules diffuse in the mucus layer and are also subjected to mucociliary advection which transports the drugs away from the initial deposition site. The availability of the drug at a particular region of the lung is, thus, determined by a balance between these two phenomena. A mathematical analysis of drug deposition and retention in the lungs is developed through a coupled mathematical model of aerosol transport in air as well as drug molecule transport in the mucus layer. The mathematical model is solved computationally to identify suitable conditions for the transport of drug-laden aerosols to the deep lungs. This study identifies the conditions conducive for delivering drugs to the deep lungs which is crucial for achieving systemic drug delivery. The effect of different parameters on drug retention is also characterized for various regions of the lungs, which is important in determining the availability of the inhaled drugs at a target location. Our analysis confirms that drug delivery efficacy remains highest for aerosols in the size range of 1-5 µm. Moreover, it is observed that amount of drugs deposited in the deep lung increases by a factor of 2 when the breathing time period is doubled, with respect to normal breathing, suggesting breath control as a means to increase the efficacy of drug delivery to the deep lung. A higher efficacy also reduces the drug load required to be inhaled to produce the same health effects and hence, can help in minimizing the side effects of a drug.

A study on the effect of mobile phone use on sleep.

Background & objectives: Several studies have been conducted globally to assess the impact of usage of mobile phones on quality and duration of sleep as also on day time sleepiness. The objective of the present study was to assess the effect of mobile phone usage on the quality and composition of sleep in a sample from Indian population. Methods: The study was conducted at two tertiary care hospitals in north India from July 2014 to September 2019. A total of 566 participants were recruited in this study from both the centres. Sleep quality was assessed with the help of the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Subsequently, actigraphy was done in 96 participants and polysomnography in 95 participants. Results: Of the 566 participants, 128 (22.61%) had PSQI ≥5, reflecting poor sleep quality. A higher use of mobile phone was significantly associated with a poor sleep quality as a component of PSQI questionnaire (P=0.01) and higher overall PSQI score (P=0.01). The latency from sleep onset to N2 and N3 sleep stages was significantly shorter in participants having a higher mobile phone usage as compared to those with a lower usage [Median (range): 13.5 min (1.5-109) vs. 6.5 min (0-89); P=0.02] and [Median (range): 49 min (8.5-220.5) vs. 28.75 min (0-141); P=0.03], respectively. Interpretation & conclusions: This study focused on the maladaptive changes brought on by mobile phone usage on sleep. More studies with larger sample sizes need to be done that may serve to confirm the hypothesis generating findings of our study.

Arterial and venous thrombosis in a patient with Covid-19: A unique presentation.

Severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection not only affects the respiratory system but also induces coagulation abnormalities and thrombosis. We report a middle-aged woman who presented during the Covid-19 pandemic with sudden-onset acute left upper limb ischaemia of short duration, with no history of dry cough, breathlessness or fever, and tested positive on TrueNAT for SARS-CoV-2. Later, she developed deep venous thrombosis of the right lower limb during isolation in the hospital.

Serum procalcitonin as a biomarker of bloodstream infection & focal bacterial infection in febrile patients.

Background & objectives: Bacteraemia is a serious form of infection in patients presenting with fever, thus, there is a necessity for a biomarker for rapid diagnosis of bacteraemia in such patients to make better therapeutic decisions. This study was conducted to measure the serum procalcitonin (PCT) levels at the time of initial presentation as a biomarker for identifying bacteraemia and as a predictor of mortality in patients admitted with acute fever. Methods: Four hundred and eighty patients, who presented with acute fever requiring admission to a tertiary care teaching hospital in south India, were prospectively studied. All patients were evaluated with a detailed history, physical examination, laboratory and imaging studies. Baseline serum PCT was measured for each patient within six hours of admission. Results: Among patients with single infectious cause (n=275), significantly higher median serum PCT levels were evident in bacteraemia compared to leptospirosis (P=0.002), dengue (P <0.001), scrub typhus (P <0.001) and evident focus of infection without bacteraemia (P=0.036). By receiver-operator characteristic curve analysis, at a cut-off value of >3.2 ng/ml, the sensitivity and specificity of serum PCT levels in predicting bacteraemia were 81.1 and 63.3 per cent, respectively. As per the worst-case scenario analysis, 91 (18.9%) patients had a poor outcome and these had significantly higher median serum PCT levels compared to survivors (n=389) [9.46 (2.03-44.4) vs. 1.23 (0.34-7.645); P <0.001]. At a cut-off value of >3.74 ng/ml, serum PCT levels at initial presentation predicted in-hospital mortality with a sensitivity and specificity of 67 and 67.5 per cent, respectively. Interpretation & conclusions: Our observations suggest that serum PCT level may be a useful biomarker for identifying bacteraemia as well as predicting mortality in patients with acute fever requiring admission to hospital.

Cleistanthus collinus Poisoning.

How to cite this article: Mohan A, Harikrishna J. Cleistanthus collinus Poisoning. Indian J Crit Care Med 2019;23(Suppl 4):S256-S259.

Novel mutations in the exon 5, intron 2 and 3' UTR regions of IL-12B gene were observed in clinically proven tuberculosis patients of south India.

Interleukin-12 (IL-12) is formed by the interaction of IL-12p35 and IL-12p40 expressed independently from IL-12A and IL-12B genes. This interleukin plays prominent role in the T-helper type-1 (Th1) response against intracellular pathogens. Variations in IL-12B gene causes disruption of various activities one of them is suppression of Th1 response and is one of the characteristic features observed in patients with active tuberculosis. Hence, in the present study IL-12B gene status was evaluated in 50 new sputum smear-positive pulmonary tuberculosis patients (NSP-PTB) as identified by Ziehl-Nielsen (ZN) staining and 50 apparently healthy control subjects (HCS) who were sputum smear-negative. The sequence analysis showed novel missense mutations p.Ser205Ile, p.Leu206Glu, p.Pro207Ser, p.Glu209Lys, p.Val210Ser, p.(Ser205_Cys327delinsIleGlu) and p.(Lys217_Leu218delinsIle) were found in exon 5 of the IL-12B gene in nine patients resulting formation of inactive IL-12 and three patients showed novel frame shift mutations p.(Asn222Leufs∗23) in exon 5 of causing the formation of truncated protein. Several mutations were noted in intron 2 of the IL-12B gene in 5 patients and in 13 patients mutations were observed in 3' UTR region. All together 30/50 patients (60%) showed mutations in IL-12B gene. Decreased levels of interferon-gamma (IFN-γ) and IL-12 as determined by ELISA and flow cytometry were observed in the peripheral blood mononuclear cell culture supernatants in TB patients having mutations compared with control subjects. Further, in silico analysis revealed due to frame shift mutations in exon 5 at Asn222 resulted in deletion of functional fibronectin type-III (FN3) domain which leads to formation of inactive IL-12 in these patients.

Comparison of Disease Activity Score in 28 joints with ESR (DAS28), Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) & Routine Assessment of Patient Index Data with 3 measures (RAPID3) for assessing disease activity in patients with rheumatoid arthritis at initial presentation.

BACKGROUND & OBJECTIVES: In patients with rheumatoid arthritis (RA), disease severity assessment is done using Disease Activity Score in 28 joints with ESR (DAS28). Computing DAS28 is time-consuming, requires laboratory testing and an online calculator. There is a need to validate rapid methods of disease severity assessment for routine daily use. This study was conducted to compare DAS28, Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire Disability Index (HAQ-DI) and Routine Assessment of Patient Index Data with 3 measures (RAPID3) to assess the disease activity in patients with RA. METHODS: We prospectively studied the utility of CDAI, HAQ-DI and RAPID3 scoring in 100 consecutive newly diagnosed, disease modifying antirheumatic drugs (DMARDs) naïve adult patients with RA seen during January 2013 and June 2014 at a tertiary care teaching hospital in south India. RESULTS: The mean age of the patients was 42.1±11.6 yr, there were 82 females. The median [interquartile range (IQR)] symptom duration was 6 (range 4-12) months. The median (IQR) DAS28, CDAI, HAQ-DI and RAPID3 scores at presentation were 7 (6-7), 36 (28-43), 2 (1-2) and 17 (13-19), respectively. A significant positive correlation was observed between DAS28 and CDAI (r=0.568; P<0.001); DAS28 and HAQ-DI (r=0.304; P=0.002) and DAS28 and RAPID3 (r=0.404; P<0.001). A 'slight-to-fair' agreement was observed in between DAS28 and CDAI (kappa-statistic=0.296). The agreement between DAS28 and HAQ-DI (kappa-statistic=0.007) and RAPID3 (kappa-statistic=0.072) was less robust. INTERPRETATION & CONCLUSIONS: In adult patients with RA, in the setting where illiteracy is high, CDAI emerged as the preferred choice for rapid assessment of severity of disease at the time of initial presentation.

Provider-initiated HIV testing & counselling in incident tuberculosis cases under National TB Programme conditions at a tertiary care teaching hospital in Tirupati, south India.

BACKGROUND & OBJECTIVES: : As sparse published data are available regarding burden of human immunodeficiency virus (HIV) infection in incident tuberculosis (TB) cases at tertiary care teaching hospitals under National TB Programme conditions from India, the present study was designed to assess the proportion of referred registered TB patients who had actually undergone HIV testing and HIV-seropositivity in these. METHODS: : This was a study of provider-initiated HIV testing and counselling in patients registered for the treatment under Revised National TB Control Programme (RNTCP) of Government of India at a tertiary care teaching hospital in Tirupati, south India, during 2012-2013. RESULTS: : Between January 2012 and June 2013, 610 adult patients registered under RNTCP who were referred to Integrated Counselling and Testing Centre for HIV testing, were prospectively studied. Of these, 458 patients (75%) [mean age: 38.6±16.3 yr; 295 (64.4%) males] underwent HIV testing; HIV-co-infection was present in 21 (4.6%) patients. A significantly higher proportion of HIV co-infection was evident in PTB compared with EPTB [13/179 (7.2%) vs 8/279 (2.8%); respectively, P=0.038] and in previously treated patients compared to new patients [6/51 (11.8%) vs 15/407 (3.7%); respectively, P=0.009]. INTERPRETATION & CONCLUSIONS: : The findings of this study showed that a higher proportion of TB patients underwent HIV testing (75%) compared to the national figure of 63 per cent in 2013-2014. HIV seropositivity (4.6%) in TB patients who underwent HIV testing was similar to the five per cent figure observed at national level during 2013-2014. The HIV status of 25 per cent of patients with incident TB still remained unknown, suggesting a need for better integration and co-ordination for effective management of HIV-TB co-infection.

Index-TB guidelines: Guidelines on extrapulmonary tuberculosis for India.

Extrapulmonary tuberculosis (EPTB) is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB. Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i) use of Xpert MTB/RIF in diagnosis, (ii) use of adjunct corticosteroids in treatment, and (iii) duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research.

Cleistanthus collinus poisoning: experience at a medical intensive care unit in a tertiary care hospital in south India.

BACKGROUND & OBJECTIVES: Ingestion of Cleistanthus collinus causes hypokalemia and cardiac arrhythmias leading to mortality in most cases. We undertook this retrospective study to evaluate the clinical presentation and predictors of outcome in critically ill patients admitted with C. collinus poisoning. METHODS: The case records of 56 patients admitted to the medical intensive care unit (MICU) of a tertiary care teaching hospital in south India (2000-2014) with C. collinus poisoning were retrospectively analysed. RESULTS: The mean age of patients was 36.7±13.3 yr; there were 30 males. Salient clinical manifestations included hypokalemia (58%), neutrophilic leucocytosis (48.2%), acute kidney injury (AKI) (42.9%), acute respiratory failure requiring mechanical ventilation (AcRFMv) (32.1%), shock (21.4%); cardiac arrhythmias and neuromuscular weakness (19.6% each); 21 patients (37.5%) had adverse outcome. Longer time-lapsed from consumption to reaching emergency room [median (interquartile range)] (hours) [49 (22-97) vs. 28 (7-56), p =0.0380 ]; higher acute physiology and chronic health evaluation II (APACHE II) score at presentation [14 (8.25-14.75) vs. 2 (0-6) P<0.001]; and presence of the following [odds ratio (95% confidence intervals)] at initial presentation: shock [37.40 (4.29-325.98), P=0.001]; AcRFMv [26.67 (5.86-121.39), P<0.001]; elevated alanine aminotransferase [5.71 (1.30-25.03), p0 =0.021]; metabolic acidosis [5.48 (1.68-17.89), P=0.005]; acute kidney injury (AKI) [5 (1.55-16.06), P=0.007]; hyponatremia [4.67 (1.25-17.44), P=0.022]; and neutrophilic leucocytosis [3.80 (1.02-14.21), P=0.047] predicted death. A significant (P<0.001) increasing trend in mortality was observed with increasing International Program on Chemical Safety Poisoning Severity Score (IPCS-CSS) grade. INTERPRETATION & CONCLUSIONS: C. collinus is a lethal poison associated with high mortality for which there is no specific antidote. Careful search and meticulous monitoring of the predictors of death and initiating appropriate corrective measures can be life saving.

Evaluation of activity of hypothalamo-pituitary-gonadal axis in postmenopausal women suffering from severe acute illness.

BACKGROUND & OBJECTIVES: Postmenopausal women constitute an ideal model for studying the extent of hypothalamo-pituitary gonadal (HPG) axis suppression in critical illness as the gonadotropins are normally high and non-cyclical in them. The objective was to assess the impact of acute severe illness in postmenopausal women on the HPG axis and the activities of the hypothalamo-pituitary-adrenal (HPA), the hypothalamo- pituitary-thyroid (HPT) axes; and levels of serum prolactin, by comparison between critically ill postmenopausal women and otherwise healthy postmenopausal women. METHODS: Thirty five consecutive postmenopausal women older than 60 yr admitted to medical intensive care with a s0 implified a0 cute p0 hysiology s0 core II (SAPS II) more than 30 were included. On day five of their in-hospital stay, blood samples were collected for oestradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol, androstenedione, prolactin and thyroid profile. Thirty five apparently healthy postmenopausal women were selected as controls. RESULTS: Levels of LH, FSH, thyrotropin, free thyroxin (fT 4 ) and free tri-iodothyronine (fT 3 ) were lower while oestradiol, cortisol and dehydroepiandrosterone were higher among patients in comparison to healthy controls. Prolactin levels were similar in patients and controls. Among sick patients both FSH and fT 4 showed a negative correlation ( P<0.05) with the SAPS II score. INTERPRETATION & CONCLUSIONS: In critically ill postmenopausal women, paradoxically elevated oestrogen levels despite gonadotropin suppression suggests a non-ovarian origin. Prolactin remained unaltered in patients despite their illness, possibly reflecting atrophy of lactotrophs in menopause.

Derivation & validation of glycosylated haemoglobin (HbA 1c ) cut-off value as a diagnostic test for type 2 diabetes in south Indian population.

BACKGROUND & OBJECTIVES: Glycosylated haemoglobin (HbA 1c ) has been in use for more than a decade, as a diagnostic test for type 2 diabetes. Validity of HbA 1c needs to be established in the ethnic population in which it is intended to be used. The objective of this study was to derive and validate a HbA 1c cut-off value for the diagnosis of type 2 diabetes in the ethnic population of Rayalaseema area of south India. METHODS: In this cross-sectional study, consecutive patients suspected to have type 2 diabetes underwent fasting plasma glucose (FPG) and 2 h post-load plasma glucose (2 h-PG) measurements after a 75 g glucose load and HbA 1c estimation. They were classified as having diabetes as per the American Diabetes Association criteria [(FPG ≥7 mmol/l (≥126 mg/dl) and/or 2 h-PG ≥11.1 mmol/l (≥200 mg/dl)]. In the training data set (n = 342), optimum cut-off value of HbA 1c for defining type 2 diabetes was derived by receiver-operator characteristic (ROC) curve method using oral glucose tolerance test results as gold standard. This cut-off was validated in a validation data set (n = 341). RESULTS: On applying HbA 1c cut-off value of >6.3 per cent (45 mmol/mol) to the training data set,sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for diagnosing type 2 diabetes were calculated to be 90.6, 85.2, 80.8 and 93.0 per cent, respectively. When the same cut-off value was applied to the validation data set, sensitivity, specificity, PPV and NPV were 88.8 , 81.9, 74.0 and 92.7 per cent, respectively, although the latter were consistently smaller than the proportions for the training data set, the differences being not significant. INTERPRETATION & CONCLUSIONS: HbA 1c >6.3 per cent (45 mmol/mol) appears to be the optimal cut-off value for the diagnosis of type 2 diabetes applicable to the ethnic population of Rayalaseema area of Andhra Pradesh state in south India.

Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus & occurrence of osteoporosis.

BACKGROUND & OBJECTIVES: Type 2 diabetes mellitus (T2DM) is considered to be a protective factor against development of osteoporosis. But oral hypoglycaemic agents (OHA) are likely to increase the risk of osteoporosis. This study was carried out to evaluate the effect of various OHA on bone mineral density (BMD) in patients with T2DM. METHODS: Forty one patients (study group) with T2DM (mean age 51.9±5.5 yr; 31 females) receiving treatment with oral hypoglycaemic agents (OHA) [thiazolidinediones alone (n=14) or in combination with other OHA (n=27)] for a period of at least three consecutive years and 41 age- and gender-matched healthy controls (mean age 51.4±5.1 yr) were included in the study. A detailed clinical history was taken and all were subjected to physical examination and recording of anthropometric data. BMD was assessed for both patients and controls. RESULTS: The mean body mass index (kg/m [2] ) (26.5±4.90 vs 27.3 ±5.33) and median [inter-quartile range (IQR)] duration of menopause (yr) among women [6(2-12) vs 6(1-13)] were comparable between both groups. The bone mineral density (BMD; g/cm [2] ) at the level of neck of femur (NOF) (0.761±0.112 vs 0.762±0.110), lumbar spine antero-posterior view (LSAP) (0.849±0.127 vs 0.854±0.135); median Z-score NOF {0.100[(-0.850)-(0.550)] vs -0.200[(-0.800)-(0.600)]}, LSAP {-1.200[(-1.700)-(-0.200)] vs -1.300 [(-1.85)-(-0.400)]} were also similar in study and control groups. Presence of normal BMD (9/41 vs 8/41), osteopenia (16/41 vs 18/41) and osteoporosis (16/41 vs 15/41) were comparable between the study and control groups. No significant difference was observed in the BMD, T-scores and Z-scores at NOF and LSAP among T2DM patients treated with thiazolidinediones; those treated with other OHA and controls. INTERPRETATION & CONCLUSIONS: The present findings show that the use of OHA for a period of three years or more does not significantly affect the BMD in patients with T2DM.

Consensus & Evidence-based INOSA Guidelines 2014 (First edition).

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive Sleep Apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or comorbidities or ≥ 15 such episodes without any sleep related symptoms or comorbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.

Subclinical atherosclerosis in patients with rheumatoid arthritis by utilizing carotid intima-media thickness as a surrogate marker.

BACKGROUND & OBJECTIVES: Patients with rheumatoid arthritis (RA) are more prone for accelerated atherosclerosis and Asian Indians as an ethnic group are predisposed to a high risk of premature atherosclerosis. However, sparse data are available regarding the burden of atherosclerosis among asymptomatic adult patients with RA in south India. We studied the burden of asymptomatic atherosclerosis in adult south Indian patients with RA at Tirupati, Andhra Pradesh, India, utilizing carotid intima-media thickness (CIMT) as a surrogate marker. METHODS: Ultrasound examination of the carotids and CIMT measurement (mm) were carried out in 32 patients with RA, 32 age- and gender-matched normal controls, and 32 patients with atherosclerosis and angiographically proven coronary artery disease. The CIMT values in patients with CAD and normal controls were used to derive the appropriate cut-off value of CIMT for defining atherosclerosis that would be applicable for the ethnic population studied. RESULTS: Patients with RA had a higher mean CIMT (mm) compared with normal control subjects (0.598 ± 0.131 vs 0.501 ± 0.081; p0 = 0.001). Carotid plaque was found more frequently among the cases compared with normal controls [5/32 (15.6%) vs 0/32 (0%), p0 =0.020]. Using this cut-off value derived by the receiver operator characteristic curve method (≥ 0.57 mm; sensitivity 84.4; specificity 90.6%) and the 75 th percentile value among normal controls (≥ 0.55 mm) as surrogate markers, the presence of subclinical atherosclerosis was significantly more among asymptomatic patients with RA compared with normal controls [(59.3 vs 12.5%; p0 <0.001) and (62.5 vs 25%; P<0.001) respectively]. INTERPRETATION & CONCLUSIONS: Based on the present findings CIMT appears to be a useful surrogate marker for detecting subclinical atherosclerosis in adult Indian patients with RA.

Consensus & evidence-based INOSA Guidelines 2014 (first edition).

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive sleep apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or co-morbidities or ≥ 15 such episodes without any sleep related symptoms or co-morbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the "gold standard" for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.

Tuberculosis: From an incurable scourge to a curable disease - journey over a millennium.

Globally, tuberculosis (TB) still remains a major public health problem. India is a high TB burden country contributing to 26 per cent of global TB burden. During 1944-1980, TB became treatable and short-course chemotherapy emerged as the standard of care. When TB elimination seemed possible in the early 1980s, global human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) pandemic resulted in a resurgence of TB. Widespread occurrence of multidrug-resistant and extensively drug-resistant TB (M/XDR-TB) is threatening to destabilize TB control globally. Atypical clinical presentation still poses a challenge. Disseminated, miliary and cryptic TB are being increasingly recognized. Availability of newer imaging modalities has allowed more efficient localization of lesions and use of image guided procedures has facilitated definitive diagnosis of extrapulmonary TB. Introduction of liquid culture, rapid drug-susceptibility testing (DST), molecular diagnostic methods has helped in rapid detection, speciation and DST profiling of Mycobacterium tuberculosis isolates. While treatment of TB and HIV-TB co-infection has become simpler, efforts are on to shorten the treatment duration. However, drug toxicities and drug-drug interactions still constitute a significant challenge. Recently, there has been better understanding of anti-TB drug-induced hepatotoxicity and its frequent confounding by viral hepatitis, especially, in resource-constrained settings; and immune reconstitution inflammatory syndrome (IRIS) in HIV-TB. Quest for newer biomarkers for predicting a durable cure, relapse, discovery/repurposing of newer anti-TB drugs, development of newer vaccines continues to achieve the goal of eliminating TB altogether by 2050.