Practical Recommendations for the Use of Angiotensin Receptor-Neprilysin Inhibitors (ARNI) in Heart Failure: Insights from Indian Cardiologists.

Heart failure is a significant public health concern characterized by notable rates of morbidity and mortality. Despite the presence of guideline-directed medical therapy (GDMT), its utilization remains inadequate. This practical recommendation paper focuses on the utilization of angiotensin receptor-neprilysin inhibitor (ARNI) as a pivotal treatment for heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), and heart failure with improved ejection fraction (HFimpEF). The recommendations presented in this paper have been developed by a group of cardiologists in India who convened six advisory board meetings to discuss the utilization of ARNI in the management of heart failure. The paper emphasizes the importance of accurate biomarkers for diagnosing heart failure, particularly N-terminal pro-B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP), which are commonly used. Additionally, the paper advocates the use of imaging, specifically echocardiography, in diagnosing and monitoring heart failure patients. Moreover, the paper highlights the role of ARNI in heart failure management, with numerous clinical trials that have demonstrated its effectiveness in reducing cardiovascular death or heart failure hospitalization, enhancing quality of life, and diminishing the risk of ventricular arrhythmias. This practical recommendation paper offers valuable insights into the utilization of ARNI in the management of heart failure, aiming to enhance the implementation of GDMT and ultimately alleviate the burden of heart failure on society.

Bempedoic Acid for Lipid Management in the Indian Population: An Expert Opinion.

Lipid-lowering is a central theme in the management of patients with atherosclerotic cardiovascular disease (ASCVD) and heterozygous familial hypercholesterolemia (HeFH), with statins being currently used as the first-line lipid-lowering agent (LLAs). Bempedoic acid (BA) has been recently approved for lipid management in ASCVD/HeFH patients. This expert opinion paper brings out the essential concept to assess the current place of BA in the Indian population. Here we highlight that the majority of the patients with clinical ASCVD may not be receiving the optimal dose of statin, thereby failing to achieve their lipid targets. The addition of BA to statin results in a significant reduction in low-density lipoprotein cholesterol (LDL-C) along with substantial reductions in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) levels. For patients who do not achieve LDL-C targets, BA can be an effective add-on alternative to choose among non-statin LLAs. BA is a good choice for statin-intolerant cases, especially in combination with ezetimibe. Given the lack of effect of worsening hyperglycemia or any increase in the occurrence of new-onset diabetes, BA can be used without hesitation in patients with diabetes. The small risk of hyperuricemia could be mitigated with appropriate patient selection and monitoring of serum uric acid levels in patients at high risk of hyperuricemia. We believe BA is an excellent non-statin therapy that is efficacious, well-tolerated, and cost-effective for lipid management in ASCVD, HeFH, and statin-intolerant patients in India.

Correlation between Stroke Risk and Systolic Blood Pressure in Patients over 50 Years with Uncontrolled Hypertension: Results from the SYSTUP-India Study.

OBJECTIVES: To assess mean systolic and diastolic blood pressure (SBP and DBP) levels in patients ≥50 years with uncontrolled hypertension (HTN) and evaluate the correlation between BP and stroke risk. It also assessed therapeutic drug classes prescribed in these patients. METHODS: A cross-sectional, observational study was conducted at 176 outpatient centers across India, including patients aged ≥50 years with elevated SBP (≥140 mmHg). The relationship between stroke risk, calculated using Stroke Riskometer™, and mean SBP, mean DBP, and other risk factors was evaluated using Pearson correlation coefficient and logistic regression analysis. RESULTS: The study included 3791 patients (men, 60.0%; mean age: 62.1 ± 8.3 years; mean BMI: 27 kg/m2) with mean SBP 157.3 ± 12.8 mmHg and mean DBP 89.8 ± 9.7 mmHg. Five-year stroke risk in 33.9% and 10-year stroke risk in 70% patients were moderate to severe. A ~4% increase in both 5- and 10-year stroke risk with each 1 mmHg increase in mean SBP (p < 0.0001) was seen. However, mean DBP did not exhibit any significant correlation with 5-year (p = 0.242) or 10-year (p = 0.8038) stroke risk. There was a positive correlation between mean SBP and patient age, comorbid diabetes, and smoking and alcohol habits (p < 0.0001). Comorbid diabetes and smoking increased 5- and 10-year stroke risk by 2- to 5-fold. Irrespective of the risk category, most patients received antihypertensive therapy with an angiotensin receptor blocker. CONCLUSION: Findings corroborate an association between stroke risk and mean SBP. These real-world clinical findings indicate that efforts are required to improve primary prevention of stroke and reduce the prevalence of recurrent stroke in India.

An assessment of the reported impact of the COVID-19 pandemic on leprosy services using an online survey of practitioners in leprosy referral centres.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to governments implementing a variety of public health measures to control transmission and has affected health services. Leprosy is a communicable neglected tropical disease caused by Mycobacterium leprae and is an important health problem in low- and middle-income countries. The natural history of leprosy means that affected individuals need long-term follow-up. The measures recommended to reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can create barriers to health services. We evaluated the impact of the COVID-19 epidemic response on leprosy services and disease management. METHODS: We conducted a cross-sectional online survey with healthcare professionals in leprosy referral centres. RESULTS: Eighty percent of leprosy diagnostic services were reduced. All respondents reported that multidrug therapy (MDT) was available but two reported a reduced stock. Clinicians used alternative strategies such as telephone consultations to maintain contact with patients. However, patients were not able to travel to the referral centres. DISCUSSION: This study highlights the effects of the initial phase of the SARS-CoV-2 pandemic on leprosy services in a range of leprosy-endemic countries. Many services remained open, providing leprosy diagnosis, MDT and leprosy reaction medications. Centres developed innovative measures to counter the negative impacts of the COVID-19 pandemic.

Prognostic usefulness of planar 123I-MIBG scintigraphic images of myocardial sympathetic innervation in congestive heart failure: Follow-Up data from ADMIRE-HF.

BACKGROUND: To evaluate whether planar 123I-MIBG myocardial scintigraphy predicts risk of death in heart failure (HF) patients up to 5 years after imaging. METHODS AND RESULTS: Subjects from ADMIRE-HF were followed for approximately 5 years after imaging (964 subjects, median follow-up 62.7 months). Subjects were stratified according to the heart/mediastinum (H/M) ratio (< 1.60 vs ≥ 1.60) on planar 123I-MIBG scintigraphic images obtained at baseline in ADMIRE-HF. Cox proportional hazards models and Kaplan-Meier analyses were used to evaluate time to death, cardiac death, or arrhythmic events for subjects stratified by H/M ratio, baseline left ventricular ejection fraction (LVEF: < 25% and 25 to ≤ 35%), and by H/M strata within LVEF strata. All-cause mortality was 38.4% vs 20.9% and cardiac mortality was 16.8% vs 4.5%, in subjects with H/M < 1.60 vs ≥ 1.60, respectively (P < 0.05 for both comparisons). Subjects with preserved sympathetic innervation of the myocardium (H/M ≥ 1.60) were at significantly lower risk of all-cause and cardiac death, arrhythmic events, sudden cardiac death, or potentially life-threatening arrhythmias. Within LVEF strata, a trend toward a higher mortality for subjects with H/M < 1.60 was observed reaching significance for LVEF 25 to ≤ 35% only. CONCLUSIONS: During a median follow-up of 62.7 months, patients with H/M ≥ 1.60 were at significantly lower risk of death and arrhythmic events independently of LVEF values.

Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial.

INTRODUCTION: Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the 'MTX and prednisolone study in ENL' (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL. METHODS AND ANALYSIS: MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients' reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events. ETHICS AND DISSEMINATION: Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.

Reliability of the 123I-mIBG heart/mediastinum ratio: Results of a multicenter test-retest reproducibility study.

A quantitative measurement, the Heart-to-Mediastinum (H/M) ratio of counts derived from a planar acquisition approximately 4 hours after injection of 123I-mIBG, is a strong predictor of outcomes in patients with stable class II-III heart failure and LVEF ≤ 35%. This study assessed the test-retest reproducibility of the H/M ratio in such patients. 47 subjects with class II-III systolic heart failure and LVEF ≤ 35% were tested at two time intervals separated by 5 to 14 days. Subjects were imaged twice on the same camera using the same radionuclide dose. Images were sent to a core analysis lab, where three nuclear technologists independently determined the H/M ratios. The primary endpoint was test-retest H/M ratio reproducibility calculated as the absolute difference in mean value determined by the three readers. Mean subject age was 65 ± 12 years, 85% were male, and mean BMI was 29 ± 6 kg/m2. Mean injected activity was 10.18 ± 0.43 mCi for first dose and 10.09 ± 0.52 mCi for the second dose. The mean and SD values for first and repeat studies were almost identical: the 95% confidence interval of the mean test-retest difference was 0.055 to 0.076. Bland-Altman plots showed no systematic effect of the H/M ratio on the magnitude of the difference between replicate measurements. Inter-reader measurements were nearly identical. There were no serious adverse events despite exposure to 123I-mIBG on 2 occasions in a short time period. The Heart-to-Mediastinum ratio of 123I-mIBG is a consistent and highly reproducible measurement in stable Class II to III heart failure patients.

Diagnosis and impact of neuropathic pain in leprosy patients in Nepal after completion of multidrug therapy.

OBJECTIVES: Neuropathic pain (NP) can occur as a chronic complication of leprosy neuropathy. NP epidemiology and its impact on patients have not been well documented. This study investigates NP prevalence and impact in the years after patients are declared "released from treatment" (RFT) following multidrug therapy (MDT) completion. METHODS: In this cross-sectional study, 85 RFT patients were recruited within leprosy referral services in Nepal. The Douleur Neuropathique 4 Questionnaire (DN4) was used to screen for NP. Pain severity, impacts on patients' daily activities and mental health were measured by using the Brief Pain Inventory (BPI), Screening of Activity Limitation and Safety Awareness (SALSA), and General Health Questionnaire-12 (GHQ-12) respectively. RESULTS: 96% surveyed had been treated for multibacillary leprosy. 44 (52%) complained of pain of which 30 (68%) were diagnosed with NP. NP was not associated with age, gender, or presence of skin lesions or nerve symptoms at leprosy diagnosis. 70% of patients with NP had either history of or ongoing reactions and 47% had grade 2 disability. Nerve tenderness (p = 0.023) and current reactions (p = 0.018) were significant risk factors for NP. Patients with NP suffered significantly higher intensity pain (p = 0.023) and daily life interference (p = 0.003) and were more likely to have moderate to extreme daily activity limitations (p = 0.005). 13 (43%) exhibited psychological distress, and medications only reduced moderate degree (50-60%) of pain. CONCLUSIONS: In our study, 35% of RFT patients had ongoing NP. Risk factors include nerve tenderness and reaction. They suffer from more daily life interference and psychological distress. Leprosy patient care should include recognition and management of NP.

Effectiveness of 32 versus 20 weeks of prednisolone in leprosy patients with recent nerve function impairment: A randomized controlled trial.

BACKGROUND: While prednisolone is commonly used to treat recent nerve function impairment (NFI) in leprosy patients, the optimal treatment duration has not yet been established. In this "Treatment of Early Neuropathy in Leprosy" (TENLEP) trial, we evaluated whether a 32-week prednisolone course is more effective than a 20-week course in restoring and improving nerve function. METHODS: In this multi-centre, triple-blind, randomized controlled trial, leprosy patients who had recently developed clinical NFI (<6 months) were allocated to a prednisolone treatment regimen of either 20 weeks or 32 weeks. Prednisolone was started at either 45 or 60 mg/day, depending on the patient's body weight, and was then tapered. Throughout follow up, NFI was assessed by voluntary muscle testing and monofilament testing. The primary outcome was the proportion of patients with improved or restored nerve function at week 78. As secondary outcomes, we analysed improvements between baseline and week 78 on the Reaction Severity Scale, the SALSA Scale and the Participation Scale. Serious Adverse Events and the need for additional prednisolone treatment were monitored and reported. RESULTS: We included 868 patients in the study, 429 in the 20-week arm and 439 in the 32-week arm. At 78 weeks, the proportion of patients with improved or restored nerve function did not differ significantly between the groups: 78.1% in the 20-week arm and 77.5% in the 32-week arm (p = 0.821). Nor were there any differences in secondary outcomes, except for a significant higher proportion of Serious Adverse Events in the longer treatment arm. CONCLUSION: In our study, a 20-week course of prednisolone was as effective as a 32-week course in improving and restoring recent clinical NFI in leprosy patients. Twenty weeks is therefore the preferred initial treatment duration for leprosy neuropathy, after which likely only a minority of patients require further individualized treatment.

Opening a Can of Worms: Leprosy Reactions and Complicit Soil-Transmitted Helminths.

BACKGROUND: >94% of new annual leprosy cases are diagnosed in populations co-endemic for soil-transmitted helminths (STH). STH can profoundly dysregulate host immune responses towards Th2 bias, which can be restored over time after deworming. We hypothesize that STH co-infection is associated with leprosy reaction (denoted as simply "reaction" herein) occurrence within a co-endemic population. METHODS: A cohort study was performed on a cohort of Nepalese leprosy patients across treatment and diagnostic classifications who were screened by routine fecal smear microscopy and multiplex quantitative PCR (qPCR) for Ascaris lumbricoides (Al), Strongyloides stercoralis (Ss), Ancyclostoma duodenale (Ad) and Necator americanus (Na). RESULTS: Among 145 patients, 55% were positive for ≥1 STH (STH+): 34% Al+, 18% Ss+, 17% Ad+and 5% Na+. Significant inverse STH and reaction relationships were evidenced by the bulk of cases: 63% reaction-negative were STH+ of total cases (p=0.030) while 65% reaction-positive were STH- in new cases (96; p=0.023). Strikingly, the majority of STH+ were reaction-negative, even when considering each species: 59% Al+, 60% Ss+, 62% Ad+and 67% Na+of new leprosy cases. CONCLUSIONS: Absence of STH co-infection is associated with leprosy reaction at diagnosis within a co-endemic population. This is likely due to immune reconstitution effects after deworming or interruption of chronic STH-mediated immune dysregulation.

A leprosy clinical severity scale for erythema nodosum leprosum: An international, multicentre validation study of the ENLIST ENL Severity Scale.

OBJECTIVES: We wished to validate our recently devised 16-item ENLIST ENL Severity Scale, a clinical tool for measuring the severity of the serious leprosy associated complication of erythema nodosum leprosum (ENL). We also wished to assess the responsiveness of the ENLIST ENL Severity Scale in detecting clinical change in patients with ENL. METHODS: Participants, recruited from seven centres in six leprosy endemic countries, were assessed using the ENLIST ENL Severity Scale by two researchers, one of whom categorised the severity of ENL. At a subsequent visit a further assessment using the scale was made and both participant and physician rated the change in ENL using the subjective categories of "Much better", "somewhat better", "somewhat worse" and "much worse" compared with "No change" or "about the same". RESULTS: 447 participants were assessed with the ENLIST ENL Severity Scale. The Cronbach alpha of the scale and each item was calculated to determine the internal consistency of the scale. The ENLIST ENL Severity Scale had good internal consistency and this improved following removal of six items to give a Cronbach's alpha of 0.77. The cut off between mild ENL and more severe disease was 9 determined using ROC curves. The minimal important difference of the scale was determined to be 5 using both participant and physician ratings of change. CONCLUSIONS: The 10-item ENLIST ENL Severity Scale is the first valid, reliable and responsive measure of ENL severity and improves our ability to assess and compare patients and their treatments in this severe and difficult to manage complication of leprosy. The ENLIST ENL Severity Scale will assist physicians in the monitoring and treatment of patients with ENL. The ENLIST ENL Severity Scale is easy to apply and will be useful as an outcome measure in treatment studies and enable the standardisation of other clinical and laboratory ENL research.

A Study of salt and fat Consumption pattern in Regional Indian diet among hypertensive and dyslipidemic PaTients - SCRIPT study.

BACKGROUND: Cardiovascular diseases are leading cause of mortality and morbidity. There is an increasing prevalence of hypertension and dyslipidemia due to globalization and adoption of westernized dietary habits in India. These transitions are manifest in dietary patterns and health outcomes. OBJECTIVE: To study the dietary salt and fat intake among patients diagnosed with hypertension and dyslipidemia in India. METHODS: SCRIPT study was a pilot exploratory, cross-sectional, observational, descriptive, multi-center study. It was conducted across hospitals and clinics in five metro cities of India, represented into four regional zones. In each region (North, n = 113; East, n = 98; West, n = 83; South, n = 152), patients diagnosed with hypertension and dyslipidemia were enrolled in the study. Socio-demographic and treatment details were recorded. Participants were interviewed by a dietician and their dietary intake was assessed by a three-day recall of food item questionnaire/ food diary. RESULTS: Overall the mean total daily salt consumption was 10.9 grams. Region-wise, the mean daily salt consumption in North, East, West and South were 14.13, 9.81, 10.12 and 9.38 grams respectively. The daily salt consumption in the North was significantly higher than other regions (P=0.012). The daily consumption of saturated fats (total saturated fat, ghee and butter) in the North was higher and statistically significantly in comparison to West, South and East (P <0.05). Overall, fats contributed to 24.1%, proteins contributed to 12.7% and carbohydrate contributed to 63.2% of total energy per day. The percentage of fat and protein contributing to total energy per day was within the acceptable range. CONCLUSIONS: Our study documented higher dietary salt intake than that recommended in India. There is an urgent need to address the issue of high salt and saturated fat consumption. Nutritional strategies for reducing salt intake, saturated fat and balancing energy nutrients should be urgently applied in Indian hypertensive and dyslipidemia patients.

ENLIST 1: An International Multi-centre Cross-sectional Study of the Clinical Features of Erythema Nodosum Leprosum.

Erythema nodosum leprosum (ENL) is a severe multisystem immune mediated complication of borderline lepromatous leprosy and lepromatous leprosy. ENL is associated with skin lesions, neuritis, arthritis, dactylitis, eye inflammation, osteitis, orchitis, lymphadenitis and nephritis. The treatment of ENL requires immunosuppression, which is often required for prolonged periods of time and may lead to serious adverse effects. ENL and its treatment is associated with increased mortality and economic hardship. Improved, evidence-based treatments for ENL are needed; however, defining the severity of ENL and outcome measures for treatment studies is difficult because of the multiple organ systems involved. A cross-sectional study was performed, by the members of the Erythema Nodosum Leprosum International STudy (ENLIST) Group, of patients with ENL attending seven leprosy referral centres in Brazil, Ethiopia, India, Nepal, the Philippines and the United Kingdom. We systematically documented the clinical features and type of ENL, its severity and the drugs used to treat it. Patients with chronic ENL were more likely to be assessed as having severe ENL. Pain, the most frequent symptom, assessed using a semi-quantitative scale was significantly worse in individuals with "severe" ENL. Our findings will determine the items to be included in a severity scale of ENL which we are developing and validating. The study also provides data on the clinical features of ENL, which can be incorporated into a definition of ENL and used for outcome measures in treatment studies.

Helicobacter pylori eradication: A randomised comparative trial of 7-day versus 14-day triple therapy.

Background. Helicobacter pylori is associated with several upper gastrointestinal conditions including chronic gastritis, peptic ulcer disease, and gastric malignancy. Proton pump inhibitor-based triple therapies are considered the standard regimens for H. pylori eradication, but the optimal duration of therapy is controversial. To prevent infection and complications, local studies should be undertaken to evaluate H. pylori eradication rates in a country. Objectives. We compared 7-day and 14-day regimens to determine the optimum duration of triple therapy for H. pylori eradication. Methods. We undertook a prospective randomised comparative trial of 7-day and 14-day triple therapy regimen for H. pylori eradication at the Aga Khan University Hospital, Nairobi; 120 patients with dyspepsia and H. pylori infection were randomised to receive esomeprazole, amoxicillin and clarithromycin for either 7 days (EAC 7) or 14 days (EAC 14). Compliance and side-effects were assessed 2 weeks after the start of therapy and H. pylori eradication was assessed by stool antigen tests 4 weeks after treatment. Results. Both the intention-to-treat (ITT; N=120) and per protocol (PP; N=97) analyses showed no significant differences between the eradication rates of EAC 7 (ITT 76.7%; PP 92%) and EAC 14 (ITT 73.3%; PP 93.6%) (ITT p=0.67; PP p=0.76). Poor compliance was reported in one patient in the EAC 14 group. The incidence of adverse events was comparable in the two groups. Conclusion. One-week and 2-week triple treatments for H. pylori eradication are similar in terms of efficacy, safety and patient compliance.

Leprosy blindness in Nepal.

Leprosy is a systemic disease with highest incidence of ocular complications and one of the important causes of blindness in the world. A comparative cross-sectional study was carried out to see the ocular involvement in leprosy leading to blindness in two groups of patients, one with the active disease and second already cured and thus released from treatment (RFT). Active cases attending Anandaban leprosy clinic, Patan hospital and RFT cases from Khokana leprosarium were included in the study consecutively. Total of 70 active cases and 101 RFT cases were evaluated during the study period. Active group of patients showed more of multibacillary type of disease than in RFT group. The prevalence of ocular manifestations was seen much higher among RFT cases accounting for 66.3% in contrast to active group where only 14.3% had ocular problems. Blindness was frequently seen in multibacillary (MB) leprosy patients in compare to paucibacillary (PB) disease in both the groups. However blindness frequency was seen more often among RFT cases accounting for 24% in compare to only 2.9% among active group. Causes of blindness were mainly corneal and cataract related disorders. Risk of blindness also increased with the increase in duration of illness. RFT group of leprosy patients are at higher risk of developing blindness than the active group thus eye care services should be more focused for this group. Having multibacillary type of disease could also be a risk for development of blindness.

Gamma irradiation of municipal sludge for safe disposal and agricultural use.

Gamma radiation was found to be an effective tool for hygienization of municipal wastewater sludge. The sludge received from the primary settling tank of a municipal wastewater treatment plant was gamma irradiated using a cobalt-60 source in a sludge hygienization research irradiator. The process parameters were adjusted to effectively eliminate coliform bacteria in the sludge and to prevent their regrowth. Irradiated sludge was found to be free of fecal coliform and could be directly disposed after drying in a landfill or used as manure. It could also be used as a medium for growth of Rhizobium sp for obtaining a bio-fertilizer.

Effective treatment of erythema nodosum leprosum with thalidomide is associated with immune stimulation.

The immunomodulatory drug thalidomide is the treatment of choice for erythema nodosum leprosum (ENL), an inflammatory cutaneous and systemic complication of multibacillary leprosy. To elucidate the mechanism of action of thalidomide in this syndrome, we prospectively investigated 20 patients with ENL who were treated with thalidomide for 21 days. All patients responded to treatment, with the majority of them having complete resolution of cutaneous lesions within 7 days. This response was associated with a marked but transient increase in ex vivo mitogen-induced expression of interleukin (IL)-2 and interferon- gamma by CD4(+) and CD8(+) T cells that was observed on treatment day 7, but these returned to pretreatment levels by day 21. Plasma tumor necrosis factor- alpha levels were not high at baseline, and they increased modestly during treatment. Plasma levels of IL-12 increased steadily during thalidomide treatment. Hence, the therapeutic effect of thalidomide in ENL appears to be associated with transient immune stimulation, which suggests that the drug may promote an active immunoregulatory response.

Cotinine, thioether, and glucuronide excretion among active and passive bidi smokers in India.

The authors examined biomarkers for environmental tobacco smoke exposure (ETS) from bidis (Indian cigarettes) among male smokers, their nonsmoking female family members (passive smokers), and an unexposed control group (N = 66). The 3 parameters used to determine the magnitude of exposure were cotinine (a tobacco-specific alkaloid indicating nicotine exposure) and thioethers and glucuronides (indicators of electrophilic burden). Urinary excretion of cotinine was significantly higher among active smokers (4.30 +/- 1.18), compared with passive smokers (wives = 1.76 +/- 0.50; daughters = 0.50 +/- 0.26). Similar trends were noted for thioethers and glucuronides. The authors found that cotinine and glucuronide levels were correlated significantly with exposure to ETS among both active and passive bidi smokers.