Effect of continuous 2 MHz transcranial ultrasound as an adjunct to tenecteplase thrombolysis in acute anterior circulation ischemic stroke patients: an open labeled non-randomized clinical trial.

The treatment of acute ischemic stroke has improved in last few decades. While meta-analyses of several trials have established the safety and efficacy of Intravenous (IV) Tenecteplase thrombolysis, concomitant continuous transcranial doppler (TCD) ultrasound administration has not been assessed in any clinical trial. The aim of this study was to determine the effects of continuous 2 MHz TCD ultrasound during IV Tenecteplase thrombolysis for Middle cerebral artery (MCA) stroke. A total of 19 patients were included, 13 received TCD ultrasound and 6 sham TCD with IV Tenecteplase. TCD spectrum and difference in Pre and post TCD parameters were measured. Asymptomatic hemorrhagic transformation of infarct was seen in two patients. There was no mortality or clinical worsening in the sonothrombolysis group as against sham sonothrombolysis group. Median of peak systolic velocity was increased in both the sonothrombolysis (P = 0.0002) and sham sonothrombolysis group (P-value = 0.001). The difference in change in mean flow velocity between two groups, sonothrombolysis (11 cm/sec) and sham sonothrombolysis (3.5 cm/sec) were also significantly different (P = 0.014). This pilot work has established safety of continuous 30 min TCD application along with IV Tenecteplase thrombolysis and it concludes that concomitant 2 MHz TCD ultrasound administration significantly increased the MCA blood flow compared to chemothrombolysis alone.CTRI Registered Number: CTRI/2021/02/031418.

Skeletal muscle injury in COVID infection: Frequency and patterns.

INTRODUCTION/AIMS: Little is known about skeletal muscle injury with coronavirus disease 2019 (COVID-19). We estimate the frequency and explore the patterns of skeletal muscle injury in acute COVID-19. METHODS: A cohort of COVID patients with mild to moderate symptoms were evaluated in a COVID-designated hospital between May and December 2021 and followed for 2 weeks. Skeletal muscle injury was assessed according to creatine kinase (CK) levels, Manual Muscle Test-8 (MMT-8) score, and the Health Assessment Questionnaire (HAQ) score. Injury was defined as CK >200 IU/L with an MMT-8 score < 76. The association between such injury and severity and outcomes were evaluated using cross-tabulations. RESULTS: Two hundred fifty participants with a mean age of 50.2 years (SD: 17.2) were included. One hundred nine (43.6%) were women; 84 (34%) developed severe disease. Median CK levels were 91 IU/L (IQR 56-181). [Correction added on 17 November 2023, after first online publication: In the preceding sentence, the IQR was corrected from '56,181'.] Patients with weakness on the MMT-8 (n = 247, 98.8%) and disability on the HAQ (n = 107; 42.8%) were common. Neck flexor muscles were prominently affected. Skeletal muscle injury was seen in 22.4% (95% CI: 17.4-28.1). There was no significant association between skeletal muscle injury and maximal severity of illness or short-term outcomes. Disability increased over 14 days in most survivors (n = 172, 72.3%) and this was not seen in those with mild disease (OR: 0.4, 95% CI: 0.22-0.70). DISCUSSION: Skeletal muscle injury appears to be common in people presenting with mild to moderate COVID infection.

Cardiovascular autonomic function and baroreflex sensitivity in drug-resistant temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is often associated with autonomic manifestations. Sudden unexpected death in epilepsy (SUDEP) is a leading cause of mortality in epilepsy. Cardiac disturbances and autonomic dysfunction are the potential mechanisms behind SUDEP. Though heart rate variability (HRV) and autonomic function tests are well studied in drug-resistant temporal lobe epilepsy, there is a paucity of data on baroreflex sensitivity (BRS), a better marker of cardiac mortality in this population. We aimed to study the interictal cardiac autonomic function and BRS in people living with drug-resistant temporal lobe epilepsy compared to healthy controls. MATERIALS AND METHODS: Thirty drug-resistant temporal lobe epilepsy (TLE) individuals and thirty healthy volunteers were recruited. Heart rate variability at rest, heart rate and blood pressure (BP) at rest, during deep breathing, postural change, BP response to isometric handgrip exercise, and baroreflex sensitivity were recorded in all study participants. The results were analyzed and compared between the two groups. RESULTS: Compared to controls, the resting heart rate, HRV, parasympathetic reactivity test, and BRS significantly differed in people living with drug-resistant TLE. Time-domain indices including SDNN (p < 0.001), RMSSD (p < 0.001), NN50 (p < 0.001), and pNN50 (p < 0.001) were significantly reduced in the patients compared to controls. In frequency-domain indices, the total power was reduced (p < 0.001) in drug-resistant TLE. The parasympathetic reactivity such as changes in heart rate during deep breathing (E: I) (p < 0.02) and postural change (30:15) (p < 0.005) were significantly reduced in the patients. Baroreflex sensitivity was also significantly reduced in the drug-resistant TLE group (p < 0.001). CONCLUSION: The present study findings are suggestive of parasympathetic dysfunction in drug-resistant TLE. Reduced HRV and BRS may increase the risk of SUDEP in people living with epilepsy.

Everyday Abilities Scale for India in Screening for Poststroke Dementia Among Young Stroke Survivors.

INTRODUCTION: Cognitive dysfunction after stroke is an important concern. We explored the utility of everyday abilities scale for India (EASI) for screening for dementia among young stroke survivors. METHODS: We interviewed 150 young stroke survivors and caregivers. Vascular dementia was diagnosed according to American Heart Association-American Stroke Association (ASA-AHA) criteria. EASI was administered to all caregivers. Receiver operating characteristic curve analysis was used to determine the area under the curve and optimum cut-points for EASI for the identification of dementia. RESULTS: Median EASI scores among subjects with dementia (n=35; 23.3%) was 2 (interquartile range: 0-4) and significantly different from those without (median: 0; interquartile range: 0-1; P<0.001). The area under the curve was 0.768 (95% confidence interval: 0.674-0.863), and at the optimum cut-point of 2 on EASI, a sensitivity of 60% and specificity of 91.3% was achieved for the identification of dementia. CONCLUSION: EASI appears to be a promising tool to screen for dementia among young stroke survivors.

Video teleconsultation services for persons with epilepsy during COVID-19 pandemic: An exploratory study from public tertiary care hospital in Southern India on feasibility, satisfaction, and effectiveness.

PURPOSE: During the COVID-19 pandemic, there is a large unmet need for follow-up services, particularly for chronic diseases such as epilepsy. Alternative methods to reach these people have become necessary. We assessed the feasibility, satisfaction, and effectiveness of video teleconsultation using mobile phones for managing persons with epilepsy (PWEs) on follow-up at a tertiary care center in the southern part of India. PATIENTS AND METHODS: We included PWEs aged 18 years and over who have been evaluated in person within the past six months, with details available in electronic health records (EHRs), and advised regular follow-up after getting telephonic consent. We excluded those requiring emergency care and those seeking teleconsultation for new symptoms. Participants were sent a message in English and in the local language about the possibility of a video teleconsultation. If willing, they were informed about the date, time, and technical requirements such as smartphones, browsing facilities, etc. Feasibility and effectiveness were assessed. Satisfaction/acceptability was assessed using Telemedicine Satisfaction Questionnaire. RESULTS: From June 2020 to October 2020, we selected 336 PWEs after screening 1100 records, and we tried video teleconsultation in 141 (41.8%) PWEs. We achieved successful video connections in 95 (28.2%) and audio consultations in 46 (13.6%). The median duration for calling the participants, making successful connections, and consultation was 8 (5-14) min. The majority required two (47.4%) or three (32.6%) attempts. Sixty-five PWEs (68.4%) used caretaker's mobile phones. We gave prescriptions to all, and 18 received new drugs. Out of 95 PWEs, 90% either 'agreed' or 'strongly agreed' on 12 out of 14 telemedicine satisfaction questions. CONCLUSION: Although we need to make video teleconsultation more feasible, our synchronous mobile video teleconsultation model is an effective and acceptable method to follow up PWEs. This real-time model has the advantage that it does not require any mobile application to be downloaded and installed. Further studies are needed to evaluate methods to improve the reach of these services particularly to vulnerable groups of the population.

Interictal autonomic changes in persons with epilepsy (PWE) on carbamazepine (CBZ) versus other anti-seizure drug monotherapy: A cross-sectional study.

OBJECTIVE: Epilepsy is one of the most prevalent neurological conditions and carbamazepine is a commonly used anti-seizure drug (ASD), especially in developing nations. There are reports of carbamazepine causing atrioventricular conduction defects and autonomic dysfunctions and its implication in Sudden Unexpected Death in Epilepsy (SUDEP) is controversial. We planned this study to assess the effect of carbamazepine (CBZ) on autonomic function compared to other ASDs in persons with epilepsy. METHODS: In this cross-sectional study, we assessed the sympathetic and parasympathetic autonomic functions in persons with epilepsy (PWE) on CBZ versus other anti-seizure monotherapy using tests of heart rate variability including its time-, frequency- and non-linear domains, heart rate response to deep breathing, valsalva maneuver, and blood pressure response to isometric handgrip. RESULTS: Persons with epilepsy on CBZ monotherapy did not show a significant reduction in the time domain parameter SDRR compared to other ASDs used as monotherapy (mean ±â€¯SD, 38.04 ±â€¯18.75 ms vs 44.37 ±â€¯20.35 ms; p = 0.125). However, PWE on CBZ had significantly lower time-domain measurements including RMSSD (mean ±â€¯SD 31.95 ±â€¯17.29 ms vs 42.02 ±â€¯22.29 ms; p = 0.018), SDSD (mean ±â€¯SD 31.91 ±â€¯17.26 ms vs 41.96 ±â€¯22.27 ms; p 0.018), and pNN50 [median (IQR) 05.45(0.69-25.37) vs 16.38(2.32-36.83); p = 0.030]. Frequency domain measures of HRV, heart rate responses to deep breathing, valsalva maneuver and tilt-testing and BP responses to valsalva and tilt-testing were not significantly different between the groups. CONCLUSION: The findings of our study indicate reduced parasympathetic activity in persons on CBZ monotherapy compared to other ASDs, which may pose risk of SUDEP. Carbamazepine may thus be avoided in those at risk of autonomic dysfunction and SUDEP.

Neuropsychiatric symptoms among young stroke survivors-frequency, patterns, and associated factors.

BACKGROUND: Although neuropsychiatric symptoms are reported in stroke survivors, details of its prevalence and patterns among young stroke subjects are sparse. METHODS: In a hospital-based cross-sectional study in India, we recruited 150 young stroke subjects (aged < 45 years) and their caregivers > 3 months from ictus. Neuropsychiatric symptoms were evaluated using the Neuropsychiatric Inventory-12 (NPI-12) and self-reported depression with the Centre for Epidemiological Studies - Depression (CES-D) scale. Descriptive statistics were used. Multivariate analysis was performed to identify associated factors. All statistical analyses were carried out using STATA ver. 14.2, StataCorp, TX, USA. RESULTS: Eighty-four (56%; 95% CI: 47.7-64.1%) had ≥ 1 symptoms on the NPI-12 over median time from stroke of 2 years (IQR 2). Self-reported depression was seen in 71 (47.3%). Post-stroke epilepsy was associated with presence of at least one neuropsychiatric symptom. Dementia was associated with increased odds; and having spouse as principal caregiver with reduced odds, of self-reported depression. Multiple infarcts on imaging were associated with self-reported depression (OR: 3.29; 95%CI: 1.31-8.27) and presence of any neuropsychiatric symptom (OR: 3.55; 95% CI: 1.42-8.88). CONCLUSION: Young stroke survivors frequently have neuropsychiatric symptoms with depression being most common. Presence of multiple infarcts on imaging was associated with self-reported depression and presence of any neuropsychiatric symptom.

Positional therapy for obstructive sleep apnoea.

BACKGROUND: The modalities of therapy for obstructive sleep apnoea (OSA) include behavioural and lifestyle modifications, positional therapy, oral appliances, surgery and continuous positive airway pressure therapy (CPAP). Though CPAP has proven efficacy in treating OSA, adherence with CPAP therapy is suboptimal. Positional therapy (to keep people sleeping on their side) is less invasive and therefore expected to have better adherence. This review considered the efficacy of positional therapy compared to CPAP as well as positional therapy against no positional therapy. Devices designed for positional therapy include lumbar or abdominal binders, semi-rigid backpacks, full-length pillows, a tennis ball attached to the back of nightwear, and electrical sensors with alarms that indicate change in position. OBJECTIVES: To compare the efficacy of positional therapy versus CPAP and positional therapy versus inactive control (sham intervention or no positional therapy intervention) in people with OSA. SEARCH METHODS: We identified studies from the Cochrane Airways' Specialised Register (including CENTRAL, MEDLINE, Embase, CINAHL, AHMED and PsycINFO), ClinicalTrials.gov, and the World Health Organization trials portal (ICTRP). It also contains results derived from handsearching of respiratory journals and abstract books of major annual meetings. We searched all databases from their inception to September 2018, with no restrictions on language of publication or publication type. SELECTION CRITERIA: We included randomised controlled trials comparing positional therapy with CPAP and positional therapy with inactive control. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted the data. We used a random-effects model in the meta-analysis to estimate mean differences and confidence intervals. We assessed certainty of evidence using the GRADE approach. MAIN RESULTS: We included eight studies. The studies randomised 323 participants into two types of interventions. The comparison between positional therapy and CPAP included 72 participants, while the comparison between positional therapy and inactive control included 251 participants. Three studies used supine vibration alarm devices, while five studies used physical positioning like specially designed pillows or semirigid backpacks.Positional therapy versus CPAPThe three studies included for this comparison were randomised cross-over trials. Two studies found that there was no difference in Epworth Sleepiness Scale (ESS) scores between CPAP and positional therapy. Two studies showed that CPAP produced a greater reduction in Apnoea-Hypopnoea Index (AHI) with a mean difference (MD) of 6.4 events per hour (95% CI 3.00 to 9.79; low-certainty evidence) compared to positional therapy. Subjective adherence, evaluated in one study, was found to be significantly greater with positional therapy (MD 2.5 hours per night, 95% CI 1.41 to 3.59; moderate-certainty evidence).In terms of secondary outcomes, one study each reported quality-of-life indices and quality-of-sleep indices with no significant difference between the two groups. One study reported cognitive outcomes using multiple parameters and found no difference between the groups. There were insufficient data to comment on other secondary outcomes like respiratory disturbance index (RDI), and frequency and duration of nocturnal desaturation. None of the studies clearly reported adverse effects.Positional therapy versus inactive controlThree studies of positional therapy versus no intervention were randomised cross-over trials, while two studies were parallel-arm studies. Data from two studies showed that positional therapy significantly improved ESS scores (MD -1.58, 95% CI -2.89 to -0.29; moderate-certainty evidence). Positional therapy showed a reduction in AHI compared with control (MD -7.38 events per hour, 95% CI -10.06 to -4.7; low-certainty evidence). One study reported adherence. The number of participants who continued to use the device at two months was no different between the two groups (odds ratio (OR) 0.80, 95% CI 0.33 to 1.94; low-certainty evidence). The same study reported adverse effects, the most common being pain in the back and chest, and sleep disturbance but there was no significant difference between the two groups in terms of device discontinuation (OR 1.25, 95% CI 0.5 to 3.03; low-certainty evidence). One study each reported quality-of-life indices and quality-of-sleep indices, with no significant difference between the two groups. One study reported cognitive outcome, and found no difference between the groups. There was insufficient evidence to comment on other secondary outcomes (RDI, frequency and duration of nocturnal desaturation). AUTHORS' CONCLUSIONS: The review found that CPAP has a greater effect on improving AHI compared with positional therapy in positional OSA, while positional therapy was better than inactive control for improving ESS and AHI. Positional therapy may have better adherence than CPAP. There were no significant differences for other clinically relevant outcomes such as quality of life or cognitive function. All the studies were of short duration. We are unable to comment on the long-term effects of the therapies. This is important, as most of the quality-of-life outcomes will be evident only when the therapies are given over a longer period of time. The certainty of evidence was low to moderate.

Progressive multifocal leukoencephalopathy in idiopathic CD4+ lymphocytopenia.

Progressive multifocal leukoencephalopathy is a central nervous system demyelinating disease caused by infection with John Cunningham virus. It affects predominantly the subcortical white matter, producing progressive neurological deficits and large confluent white matter lesions on imaging. It is usually seen in immunodeficient individuals, such as those suffering from acquired immunodeficiency syndrome, those on treatment with monoclonal antibodies, and those following therapeutic bone marrow suppression. Here, we report a rare case of progressive multifocal leukoencephalopathy in an apparently immunocompetent adult, who was found to have idiopathic CD4 lymphocytopenia upon further investigation.

Cross-Sectional Study of the Relationship Between Medial Plantar Nerve Conduction Studies and Severity of Diabetic Neuropathy.

Objective: Diabetic peripheral neuropathy (DPN), a complication of diabetes, is detected only in later stages. Medial plantar nerve (MPL) can identify earlier stages of neuropathy. We evaluated the correlation of MPL sensory nerve action potentials (SNAPs) and severity of DPN measured using the Toronto Clinical Neuropathy Score (TCNS). Methods: In this hospital-based, cross-sectional study, we recruited diabetic subjects referred for suspected DPN. Neuropathy was graded with TCNS. Sural nerve conduction studies were performed using standard techniques. MPL studies were conducted using the modified Ponsford technique. All evaluations were performed on Nihon Kohden (model MEB 9200K). Averaged MPL SNAP was correlated with TCNS using Pearson's correlation coefficient. To estimate a correlation of 0.4 with 80% power (P = 0.05), we needed 46 subjects. Linear regression was conducted to adjust for age, duration, and diabetic control. Receiver operating characteristic (ROC) curve analysis was performed to obtain the cutoff for MPL SNAP values using the Youden index. Results: Fifty-one subjects with a mean age of 53.5 years (8.7) and mean duration of diabetes of 10.2 years (7.2) were included. MPL SNAPs were recordable in 12 patients, and the mean amplitude was 5.15 (2.9) µV. There was correlation between MPL SNAP and TCNS (r = -0.43, P = 0.02). No confounding was seen. Use of MPL SNAP resulted in diagnosis of DPN in an additional six (11.8%) patients. The ROC curve suggested that MPL SNAP cutoff of 1.05 µV had an accuracy of 67% in identifying neuropathy as defined by TCNS. Conclusions: MPL SNAP has a moderate correlation with clinical score and identifies more diabetic neuropathy than sural nerve.

Influence of sleep disturbance, depression, anxiety, and stress on quality of life in people with epilepsy.

OBJECTIVES: We assessed the quality of life, sleep, depression, anxiety, and stress in people with pharmacoresistant epilepsy (PRE) and newly diagnosed epilepsy (NDE). We also assessed the influence of sleep, depression, anxiety, and stress on the quality of life (QOL) and the complex association between these factors. METHODS: We recruited 80 PRE and 70 NDE people attending the epilepsy clinic. We assessed QOL, sleep quality, daytime sleepiness, and mood using the quality of life in epilepsy-31 inventory (QOLIE-31), Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), and depression anxiety stress scale (DASS-21). We compared the results between the two groups of epilepsy populations. We performed univariate and multivariate linear regression to determine the factors affecting the QOLIE-31 total score. We applied Spearman's rank correlation to find the interrelationship between variables influencing QOL. RESULTS: We found significantly lower QOLIE-31 total scores (p = .001) in PRE compared to NDE. The PSQI and ESS did not differ significantly between the PRE and NDE groups. Anxiety (p = .002) and stress (p = .003) scores were significantly higher in PRE than in NDE. QOLIE-31 total scores showed a negative correlation with PSQI as well as symptoms of depression, anxiety, and stress scores in both groups. Multiple linear regression analysis revealed depression as a major factor influencing the QOLIE-31 total score in PRE (p = .001) and NDE (p = .003). We found significant complex associations between PSQI, depression, anxiety, stress, and QOLIE total scores in both groups. SIGNIFICANCE: The QOL is poorer for people with PRE than for those with NDE. Depression is a major determinant of QOL in PWE. These factors need to be considered to improve the QOL in epilepsy.

Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B.

BACKGROUND: Chronic hepatitis B virus infection is a risk factor for development of hepatocellular carcinoma. Alpha-foetoprotein and liver ultrasonography are used to screen patients with chronic hepatitis B for hepatocellular carcinoma. It is uncertain whether screening is worthwhile. OBJECTIVES: To determine the beneficial and harmful effects of alpha-foetoprotein or ultrasound, or both, for screening of hepatocellular carcinoma in patients with chronic hepatitis B virus infection. SEARCH METHODS: Electronic searches were performed until December 2011 in the Cochrane Hepato-Biliary Group Controlled Trials Register (December 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 4) in The Cochrane Library, MEDLINE (1948 to 2011), EMBASE (1980 to 2011), Science Citation Index Expanded (1900 to 2011), Chinese Medical Literature Electronic Database (WanFang Data 1998 to 2011), and Chinese Knowledge Resource Integrated Database (1994 to 2011). SELECTION CRITERIA: All published reports of randomised trials on screening for liver cancer were eligible for inclusion, irrespective of language of publication. Studies were excluded when the hepatitis B status was uncertain, the screening tests were not sensitive or widely-used, or when the test was used for diagnosis of hepatocellular carcinoma rather than screening. DATA COLLECTION AND ANALYSIS: We independently analysed all the trials considered for inclusion. We wrote to the authors of one of the trials to obtain further information. MAIN RESULTS: Three randomised clinical trials were included in this review. All of them had a high risk of bias. One trial was conducted in Shanghai, China. There are several published reports on this trial, in which data were presented differently. According to the 2004 trial report, participants were randomised to screening every six months with alpha-foetoprotein and ultrasonography (n = 9373) versus no screening (n = 9443). We could not draw any definite conclusions from it. A second trial was conducted in Toronto, Canada. In this trial, there were 1069 participants with chronic hepatitis B. The trial compared screening every six months with alpha-foetoprotein alone (n = 532) versus alpha-foetoprotein and ultrasound (n = 538) over a period of five years. This trial was designed as a pilot trial; the small number of participants and the rare events did not allow an effective comparison between the two modes of screening that were studied. The remaining trial, conducted in Taiwan and published as an abstract, was designed as a cluster randomised trial to determine the optimal interval for screening using alpha foetoprotein and ultrasound. Screening intervals of four months and 12 months were compared in the two groups. Further details about the screening strategy were not available. The trial reported on cumulative four-year survival, cumulative three-year incidence of hepatocellular carcinoma, and mean tumour size. The cumulative four-year survival was not significantly different between the two screening intervals. The incidence of hepatocellular cancer was higher in the four-monthly screening group. The included trials did not report on adverse events. It appears that the sensitivity and specificity of the screening modes were poor, accounting for a substantial number of false-positive and false-negative screening results. AUTHORS' CONCLUSIONS: There is not enough evidence to support or refute the value of alpha-foetoprotein or ultrasound screening, or both, of hepatitis B surface antigen (HBsAg) positive patients for hepatocellular carcinoma. More and better designed randomised trials are required to compare screening against no screening.

Cost-Utility Analysis of Dabigatran and Warfarin for Stroke Prevention Among Patients With Nonvalvular Atrial Fibrillation in India.

OBJECTIVES: Dabigatran has a better safety profile and requires less monitoring, but is costlier than warfarin. This study evaluated the cost-utility of dabigatran relative to warfarin for preventing stroke in nonvalvular atrial fibrillation (NVAF) in India. METHODS: A Markov decision analysis model was developed to compare dabigatran (110 or 150 mg twice a day) to warfarin titrated to target prothrombin time in patients with NVAF at high risk of stroke. Model utilities and transition probabilities were based on literature and costs on market prices. Data on out-of-pocket expenses and income lost were taken from a nationally representative survey. We adopted a societal perspective and discounted both costs and outcomes at 3%. Ischemic stroke, intracranial bleed, other major bleeds, and death were outcomes of NVAF. The model projected the costs, life-years, and quality-adjusted life-years (QALYs) for each intervention over a lifetime. We used gross domestic product per capita of India (US dollars [US$]1889) as the cost-effectiveness threshold. Sensitivity analyses were conducted. RESULTS: Treatment with either dose of dabigatran was associated with gain in life-years and QALYs compared with warfarin. The discounted incremental cost-effectiveness ratios/QALYs for both doses of dabigatran (110 mg US$7519; 150 mg US$6634) were above the cost-effectiveness threshold, and the probability of being cost-effective at this threshold was low. Cost of dabigatran was an important factor in determining incremental cost-effectiveness ratio. Price reduction of 150 mg dose by 49% will make it cost-effective. CONCLUSIONS: Dabigatran is not cost-effective in the Indian societal context. Reducing the price of dabigatran 150 mg by half will make it cost-effective.

Prothrombotic Factors Have Significant Association with Arterial and Venous Strokes in Indian Tamilians.

BACKGROUND: Prothrombotic factors have been correlated with vascular events in young patients, with recurrent strokes, and with venous thromboembolisms. However, their prevalence in adult strokes, in healthy populations, and in specific ethnic groups is not well defined. We investigated the association of prothrombotic factors with strokes in a South Indian Tamil population. METHODS: In this hospital-based cross-sectional study, plasma homocysteine (Hcys), protein C and protein S activity levels, activated protein C resistance (APCR) as a surrogate for factor V Leiden (FVL), fibrinogen, and antithrombin III (ATIII) were determined from 75 consecutive patients with ischemic stroke (IS), 25 with cortical venous thrombosis (CVT), and 75 healthy control participants. The Student t test or Mann-Whitney U test was used for comparing prothrombotic factor levels between the stroke and control groups. The χ2 or Fisher exact test was used for comparisons of proportions of thrombophilia and estimation of odds ratios. Mid-P correction was done for multiple estimations. RESULTS: Hcys levels in patients with IS were significantly higher compared with those in healthy control participants (P = 0.02). Proportions of ATIII deficiency and hyperfibrinogenemia were significantly higher in the IS group, and no healthy control participants had hyperfibrinogenemia. Protein C deficiency was more frequent in those with IS (17%; P < 8 × 10-5) and CVT (P < 10-7) compared with healthy control participants, and protein C activity levels (P = 0.016) were also significantly lower in patients with CVT. Other parameters had no significant associations with IS and CVT. The frequency of protein S deficiency was high in healthy control participants (60%) and in both patients with IS (45%; P = 0.1) and patients with CVT (48%; P = 0.4). No patients or control participants had abnormal APCR. CONCLUSIONS: In Tamilian participants, several prothrombotic factors were associated with IS. Protein C deficiency alone was associated with CVT. Replication of the pattern in genetically linked populations around the world may affect management of stroke in those populations.

Adrenoleukodystrophy presenting as glue sniffing.

Adrenoleukodystrophy classically presents in childhood with bronze skin, spastic tetraparesis, dysphagia, behavioural abnormalities and adrenal insufficiency. However, atypical presentations are known. Here we report an adolescent with adrenoleukodystrophy who first sought medical attention for glue sniffing.

Idiopathic CD4 Lymphocytopenia: Current Insights.

Idiopathic CD4 lymphocytopenia is a condition characterized by low CD4 counts. It is rare and most of the information about this illness comes from case reports. Presentation is usually in the 4th decade of life with opportunistic infections, autoimmune disease or neoplasia. The pathophysiology of this condition is not well understood. Management revolves around treatment of the presenting condition and close follow-up of these patients. This review presents a narrative summary of the current literature on idiopathic CD4 lymphocytopenia.

Dementia Diagnosis in Seven Languages: The Addenbrooke's Cognitive Examination-III in India.

OBJECTIVE: With the rising burden of dementia globally, there is a need to harmonize dementia research across diverse populations. The Addenbrooke's Cognitive Examination-III (ACE-III) is a well-established cognitive screening tool to diagnose dementia. But there have been few efforts to standardize the use of ACE-III across cohorts speaking different languages. The present study aimed to standardize and validate ACE-III across seven Indian languages and to assess the diagnostic accuracy of the test to detect dementia and mild cognitive impairment (MCI) in the context of language heterogeneity. METHODS: The original ACE-III was adapted to Indian languages: Hindi, Telugu, Kannada, Malayalam, Urdu, Tamil, and Indian English by a multidisciplinary expert group. The ACE-III was standardized for use across all seven languages. In total, 757 controls, 242 dementia, and 204 MCI patients were recruited across five cities in India for the validation study. Psychometric properties of adapted versions were examined and their sensitivity and specificity were established. RESULTS: The sensitivity and specificity of ACE-III in identifying dementia ranged from 0.90 to 1, sensitivity for MCI ranged from 0.86 to 1, and specificity from 0.83 to 0.93. Education but not language was found to have an independent effect on ACE-III scores. Optimum cut-off scores were established separately for low education (≤10 years of education) and high education (>10 years of education) groups. CONCLUSIONS: The adapted versions of ACE-III have been standardized and validated for use across seven Indian languages, with high diagnostic accuracy in identifying dementia and MCI in a linguistically diverse context.

Myositis associated with Salmonella paratyphi A bacteremia appears to be common.

BACKGROUND: Fever and severe myalgia in a tropical country like India bring to mind leptospirosis, rickettsioses, dengue, and other viral fevers. Enteric fever is widely prevalent in Asia, but myositis has not been previously described in Salmonella paratyphi A bacteremia. MATERIALS AND METHODS: Retrospectively, we recruited patients with enteric fever admitted to our treating unit over a 6-month period. Demography, historical, clinical, and laboratory data were obtained. Data of culture-positive S. paratyphi A patients were analyzed and were compared with those patients with culture-negative enteric fever. RESULTS: Forty-three cases were found in total with 19 of S. paratyphi A bacteremia. Elevations in creatine kinase (CK) ranged from one-and-half to six times normal. Forty-seven percent had thrombocytopenia and alanine transaminase elevations, while aspartate transaminase elevations were seen in 17 patients, which corresponded to those with elevated CK levels. CONCLUSIONS: Myositis associated with S. typhi and S. paratyphi is very rare and is more often due to non-typhoidal Salmonellae. Elevated creatine kinase was seen in most of our patients with S. paratyphi A bacteremia. Such myositis has not been described previously and hence, myalgia with fever in a tropical country could be a harbinger of paratyphoid fever.