A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy.

BACKGROUND: Vitamin B12 deficiency has been associated with peripheral neuropathy, loss of sensation in the peripheral nerves, and weakness in the lower extremities. Methylcobalamin is the most effective analogue of vitamin B12 used to treat or prevent the complications associated with vitamin B12 deficiency. The current study aimed to compare the serum cobalamin levels after administration of two different regimes of methylcobalamin in peripheral neuropathy patients. METHODS: The present study was a prospective, randomized, comparative study. The study consisted of two parallel groups, group A (methylcobalamin 500 µg injection intramuscularly three times a week) and group B (methylcobalamin 1500 µg injection intramuscularly once a week). A control group of healthy volunteers was also included. RESULTS: A total of 24 patients (12 in each group) were included in the study. Five healthy volunteers were also included as a control in each group. At the end of treatment, serum cobalamin levels were significantly (P = 0.028) higher in group A (1892.08 ± 234.50) as compared with group B (1438.5 ± 460.32). The serum cobalamin levels in Group A healthy volunteers were also two times higher than that of group B (P = 0.056). Both the LANSS scale and DN4 questionnaire reported similar results at end of treatment. CONCLUSIONS: The 500 µg methylcobalamin thrice weekly regime is more effective in increasing the serum cobalamin levels as compared to the 1500 µg methylcobalamin once weekly regime.

Practice Guidelines for Nutrition in Critically Ill Patients: A Relook for Indian Scenario.

BACKGROUND AND AIM: Intensive-care practices and settings may differ for India in comparison to other countries. While international guidelines are available to direct the use of enteral nutrition (EN), there are no recommendations specific to Indian settings. Advisory board meetings were arranged to develop the practice guidelines specific to Indian context, for the use of EN in critically ill patients and to overcome challenges in this field. METHODS: Various existing guidelines, meta-analyses, randomized controlled trials, controlled trials, and review articles were reviewed for their contextual relevance and strength. A systematic grading of practice guidelines by advisory board was done based on strength of the supporting evidence. Wherever Indian studies were not available, references were taken from the international guidelines. RESULTS: Based on the literature review, the recommendations for developing the practice guidelines were made as per the grading criteria agreed upon by the advisory board. The recommendations were to address challenges regarding EN versus parenteral nutrition; nutrition screening and assessment; nutrition in hemodynamically unstable; route of nutrition; tube feeding and challenges; tolerance; optimum calorie-protein requirements; selection of appropriate enteral feeding formula; micronutrients and immune-nutrients; standard nutrition in hepatic, renal, and respiratory diseases and documentation of nutrition practices. CONCLUSION: This paper summarizes the optimum nutrition practices for critically ill patients. The possible solutions to overcome the challenges in this field are presented as practice guidelines at the end of each section. These guidelines are expected to provide guidance in critical care settings regarding appropriate critical-care nutrition practices and to set up Intensive Care Unit nutrition protocols.

A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children.

Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored.

Airway Diseases Education and Expertise (ADEX ) in Pediatrics: Adaptation for Clinical Practice in India.

JUSTIFICATION: Asthma and allergic rhinitis together are part of the concept of one airway, one disease or united airway disease. The management of allergic airway diseases should address this united concept and manage the issue by educating the patients and their parents and health care providers, along with environmental control measures, pharmacotherapy and immunotherapy. Here, we present recommendations from the module of Airway Diseases Education and Expertise (ADEX) that focused on allergic rhinitis, asthma and sleep disorder breathing as a single entity or Allergic Airway Disease. PROCESS: A working committee was formed by the collaboration of Pediatric Allergy Association of India (PAAI) and Indian Academy of Pediatrics (IAP) Allergy and Applied Immunology chapter to develop a training module on united airway disease. OBJECTIVE: To increase awareness, understanding and acceptance of the concept of United Airway disease and to educate the primary health care providers for children and public health officials, in the management of united airway diseases. RECOMMENDATIONS: Recommendations for diagnosis, management and follow-up of Allergic airway disease are presented in this document. A better compliance by linking education of child, parent, grandparents and other health care providers, and scientific progress by collaboration between practitioners, academicians, researchers and pharmaceutical companies is suggested.

Potential Risks and Mitigation Strategies Before the Conduct of a Clinical Trial: An Industry Perspective.

Conduct of clinical trials has undergone substantial changes over the last two decades. Newer markets, evolving guidelines and documentation and high cost involved in conducting the trials have led pharmaceutical companies to prepare a risk mitigation plan. Extensive monitoring of potential risks is an essential element of clinical trials which helps to ensure quality and integrity of a clinical investigation. Every clinical trial has pre (before the trial), conduct and post phase. This article which has been developed as a result of extensive research at ground level by a reputed pharmaceutical company to identify the potential stages of risks that could affect the overall quality and safety of a trial and its outcome during the pre-phase of trial (the stage of the trial where the study design is being planned before initiation of the clinical trial). It includes risks associated with basic study concept, protocol design, Confidential Disclosure Agreement (CDA) and Clinical Trial Authorization (CTA) application signing, vendors of central drug laboratory, site and investigator selection, Clinical Research Coordinator (CRC) meet, Informed Consent Form (ICF), Case Report Form (CRF)/ Status Report Form (SRF) preparation, Ethics Committee (EC) submission, etc. have been highlighted. The risk based mitigation strategy (to develop an effective risk monitoring plan before staring a clinical trial) has also been suggested by authors. A well-tailored and integrated plan, recognition of potential risks and their mitigation strategy can result in the pre exclusion or end to end solution of all the risks associated with pre- phase of clinical trials.

Cross-Sectional Study for Prevalence of Non-Steroidal Anti-Inflammatory Drug-Induced Gastrointestinal, Cardiac and Renal Complications in India: Interim Report.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most common therapeutic products used for the management of inflammation and pain. However, their use is associated with gastrointestinal (GI), cardiovascular and renal complications. Although prevalence data regarding NSAID-induced complications are available worldwide, but none of the study has assessed the prevalence of GI, cardiac and renal complications in India. This study aimed to assess the point prevalence of GI, cardiac and renal complications associated with the use of NSAIDs in India. The study also aimed to evaluate the association between the risk factors and GI, renal and cardiac complications in patients using NSAIDs. METHODS: This prospective, cross-sectional, multi-centric study was conducted in eight medical colleges across India (North, East, West, South and Central India). Data related to GI complications including gastric, duodenal and gastroduodenal erosions/ulcers/gastritis, renal complications including acute and chronic renal failure or cardiac complications including acute coronary syndrome (ACS), acute myocardial infarction (AMI) and cardiac failure, were collected from patients. RESULTS: The cut-off date for interim data analysis was July 7, 2014. A total of 2,140 patients out of 3,600 were enrolled from eight centers at the time of interim analysis. The NSAID-associated point prevalence of GI complications was 30.08%; cardiac complication was 42.77%; and renal complication was 27.88%. CONCLUSIONS: Results of the present interim analysis show that the prevalence of GI, cardiac and renal complications among patients is high due to exaggerated usage; however, the final analysis would provide the overall prevalence of these complications.

Safety reporting through a comprehensive and pragmatic pharmcovigilance process for India and emerging markets: an industry perspective.

INTRODUCTION: Pharmacovigilance (PV) deals with the drug-related adverse reactions ensuring patients' safety. Emerging markets of India, South East Asia (SEA), Russia, Latin America (LA), Middle East and North Africa (MENA) have developed their own PV programs. However, under/manual reporting accompanied with lack of awareness regarding adverse drug reactions (ADRs) are major drawbacks that continue to exist due to lack of co-ordination and disparity in the regulatory approach. AREAS COVERED: Of the 118 studies identified using various databases, 60 were included for the review. The authors discuss the present PV scenario of India, SEA, Russia, LA and MENA, and explain a basic process for uniform PV data input-output across industry, which includes data collection, analysis, processing, causality assessment and data distribution systems. EXPERT OPINION: As the number of clinical trials conducted are rising in the emerging markets, there is a need to understand and implement a robust PV system, where electronically globalized, evidence based, public health oriented and regulatory compliant PV system is established. This would also improve transparency in system and ensure enhancement in safety data reporting ensuring premature and trouble-free detection of ADRs. It might result in implementing various PV boosting activities, which could yield robust patient safety data from India and emerging markets.

Long term follow-up study to evaluate immunogenicity and safety of a single dose of live attenuated hepatitis a vaccine in children.

Worldwide, viral hepatitis continues to be a cause of considerable morbidity and mortality. Mass immunization with a single dose of live attenuated HAV has been shown to significantly reduce disease burden in the community. This was a phase IV, 5-year follow up study carried out at 4 centers (Kolkata, Delhi, Mumbai and Chennai) across India. The subjects with antibody titer <20 mIU/mL at baseline were evaluated for long term immunogenicity. Of the 503 subjects enrolled, 349 subjects were baseline seronegative with an anti-HAV antibody titer <20 mIU/mL. Overall, 343 subjects could be followed up at some point of time during this 5 y post vaccination period. In the last year (60 months) of follow-up, 108 subjects (97.3%) of 111 subjects (who came for follow-up at the end of 5 y) had a protective antibody titer (anti-HAV antibody titer >20 mIU/mL). The seroconversion rates considering seroprotection levels of anti-HAV antibody titer >20 mIU/mL, following vaccination starting from 6 weeks, 6 months, 12 months, 24 months, 36 months, 48 months and 60 months were 95.1%, 97.9%, 98.3%, 96.2%, 97.8%, 92.6% and 97.3%, respectively. The geometric mean concentration (GMC) over the years increased from 64.9 mIU/mL at 6 weeks to 38.1 mIU/mL and 135.2 mIU/mL at 6 months and 12 months, respectively and was maintained at 127.1 mIU/mL at 60 months. In conclusion, the result of this 5-year follow up study showed that the single dose of live attenuated vaccine is well tolerated and provides long-term immunogenicity in healthy Indian children.

Safety and immunogenicity of single dose live attenuated varicella vaccine (VR 795 Oka strain) in healthy Indian children: a randomized controlled study.

Varicella, an acute viral systemic infection that may cause lifelong latent infection with the potential for causing clinical reactivation, may be prevented by immunization. The present study was an open label, randomized, controlled, phase III, multicentre trial, conducted to evaluate and compare the safety, tolerability and immunogenicity of a freeze dried live attenuated Oka strain Varicella Vaccine (VR 795 Oka strain) with Varilrix (Oka-RIT strain) in children. A total of 268 healthy Indian children aged 12 months to 12 y with baseline VZV IgG antibody (<100 mIU/ mL) were enrolled, and 256 children completed the study. The extent of rise of VZV IgG antibody titer assessed as 3-fold and 4-fold rise from baseline was found to be significantly higher (89.1% and 85.2%) in the test group as compared to control group (73.4% and 61.7%). The post-vaccination GMT of the test group was significantly higher (112.5 mIU/mL) as compared with the control group (67.8 mIU/mL) (P < 0.001). The seroconversion rate considering the 5 gp ELISA units/ml equivalent to 10mIU/ml were similar in the control (96.5%) and the test (98.3%) groups. The adverse events were not different in the control and test groups (P > 0.05). The test live attenuated vaccine was found to be highly immunogenic, safe and comparable to Varilrix used in control arm.

Evidence-based treatment for melasma: expert opinion and a review.

INTRODUCTION: Melasma is one of the most common pigmentary disorders seen by dermatologists and often occurs among women with darker complexion (Fitzpatrick skin type IV-VI). Even though melasma is a widely recognized cause of significant cosmetic disfigurement worldwide and in India, there is a lack of systematic and clinically usable treatment algorithms and guidelines for melasma management. The present article outlines the epidemiology of melasma, reviews the various treatment options along with their mode of action, underscores the diagnostic dilemmas and quantification of illness, and weighs the evidence of currently available therapies. METHODS: A panel of eminent dermatologists was created and their expert opinion was sought to address lacunae in information to arrive at a working algorithm for optimizing outcome in Indian patients. A thorough literature search from recognized medical databases preceded the panel discussions. The discussions and consensus from the panel discussions were drafted and refined as evidence-based treatment for melasma. The deployment of this algorithm is expected to act as a basis for guiding and refining therapy in the future. RESULTS: It is recommended that photoprotection and modified Kligman's formula can be used as a first-line therapy for up to 12 weeks. In most patients, maintenance therapy will be necessary with non-hydroquinone (HQ) products or fixed triple combination intermittently, twice a week or less often. Concomitant camouflage should be offered to the patient at any stage during therapy. Monthly follow-ups are recommended to assess the compliance, tolerance, and efficacy of therapy. CONCLUSION: The key therapy recommended is fluorinated steroid containing 2-4% HQ-based triple combination for first line, with additional selective peels if required in second line. Lasers are a last resort.

Efficacy and safety of nadifloxacin for bacterial skin infections: results from clinical and post-marketing studies.

INTRODUCTION: Skin and soft tissue infections involve microbial invasion of the skin and underlying soft tissues and are estimated to affect 7-10% of hospitalized patients worldwide. Nadifloxacin, a topical fluoroquinolone, has been shown to be effective against aerobic Gram-negative, Gram-positive (including MRSA and coagulase-negative staphylococci), and anaerobic bacteria. However, there is paucity of data comparing efficacy and safety of 1% nadifloxacin with other anti-bacterials for skin infections in Indian patients. METHODS: This article presents the results of one post-marketing surveillance (PMS) and three randomized, open, non-blinded, multi-centric clinical studies that compared nadifloxacin with mupirocin and framycetin, and nadifloxacin with fusidic acid. Patients in India, aged from 1 to 65 years old, suffering from mild to moderate bacterial skin infections including impetigo, secondarily infected wounds, folliculitis, infected atopic dermatitis, and furunculosis were randomly allocated to three treatment groups within the studies. Efficacy was assessed by the evaluation of symptoms of erythema, exudation, swelling, pruritus, crusting, pain and tenderness in all the studies. RESULTS: A total of 272 subjects were enrolled in the study and subjects were randomly assigned to one of the three treatment groups; 92 in the nadifloxacin group, 90 in the mupirocin group, and 90 in the framycetin group. A significant reduction in the mean scores for bacterial infection symptoms in the nadifloxacin groups was observed when compared to mupirocin, framycetin and fusidic acid groups. Both physician and patients rated nadifloxacin as excellent (complete remission of symptoms) on a 4-point scale in the studies. No adverse events (AEs) were reported in the clinical studies. In the PMS, only two patients (of 329, 0.6%) reported AEs including burning and itching, one in each patient that had resolved at the time of reporting. CONCLUSION: Nadifloxacin, a fluoroquinolone, is a new alternative topical agent in the treatment of bacterial skin infection with minimal AEs.

Efficacy and tolerability of topical fixed combination of nadifloxacin 1% and adapalene 0.1% in the treatment of mild to moderate acne vulgaris in Indian patients: a multicenter, open-labelled, prospective study.

BACKGROUND: A combination of topical retinoid and antibacterial therapy is often advocated for acne to enhance therapeutic efficacy. AIMS: A preliminary study to evaluate the efficacy and tolerability of a topical fixed combination of nadifloxacin (1%) and adapalene (0.1%) in the treatment of mild to moderate acne in Indian patients. MATERIALS AND METHODS: This was an open-labeled, phase 3 non-randomized, non-comparative study conducted at five centers (Ahmedabad, Nagpur, Thane, Bangalore, and Mumbai) across India. Of 119 enrolled patients with mild to moderate acne, 117 patients were evaluated at the end of the study for efficacy parameters. A fixed combination of nadifloxacin (1%) and adapalene (0.1%) topical gel was applied at the affected area once at night for a period of 8 weeks. Reduction in the total, inflammatory and non-inflammatory lesion counts from the baseline, investigator global assessment (IGA) and reduction in the severity of acne as per combined acne severity classification were the primary efficacy variables measured at 2 weeks, 4 weeks, and 8 weeks. RESULTS: Overall, 98.3% patients showed a statistically significant progressive reduction in non-inflammatory lesion counts, inflammatory lesion counts, and total lesion counts over the study duration. By the end of 8 weeks, 75% of the patients had their global assessment scores approaching to normal healthy skin score. The adverse events were mild to moderate in severity. CONCLUSION: This preliminary study shows that a fixed combination of 1% nadifloxacin and 0.1% adapalene topical gel could be an effective and well-tolerated option for the treatment of mild to moderate acne vulgaris. However, further well-controlled, randomized and comparative evaluation of this combination is necessary.

A cross-sectional, multicentric clinico-epidemiological study of melasma in India.

BACKGROUND: Melasma is one of the most common pigment disorders seen by a dermatologist and often occurs among women with darker complexion (skin type IV-VI). AIMS: The present study aimed to investigate the epidemiology of melasma in the Indian population and to focus on the regional variability in the demographics, clinical manifestations and factors that precipitate this condition. METHODS: The present multicentric study conducted across four regions in India enrolled patients (>18 years) diagnosed with melasma on Wood's light examination. Patients were examined to identify the distribution of melasma. Various precipitating and etiological factors for melasma were documented. RESULTS: The mean age of the 331 enrolled patients with melasma was 37.2 ± 9.3 years. The prevalence of melasma was higher in females with a female to male ratio of approximately 4:1. The overall population with family history was 31%, highest in the northern region (38.5%) and lowest in the eastern region (18.2%). The two prominent patterns of distribution were centrofacial (42%) and malar (39%). Only 35% of the patients were using sunscreens. Of these, 10% of the patients used sunscreen with SPF >50. The usage of sunscreens was observed to be highest in the north (69%). About 51% of women with multiple pregnancies had a history of melasma when compared with single women (25%) or with no pregnancy (24%). CONCLUSIONS: In conclusion, the result of the study showed that there was a regional variability in the demographics, clinical manifestations and factors that precipitate melasma among patients in India. There was a strong correlation between the family history and prevalence of melasma. Sun exposure is a major precipitating factor in melasma, but only 10% of the patients used sunscreen with SPF >50. Other factors such as concomitant medication, chronicity of disease, multiple pregnancies and use of oral contraceptives might precipitate melasma.

Prevalence of chronic pain, impact on daily life, and treatment practices in India.

OBJECTIVE: Chronic pain is of concern to health professionals, patients, society, and negatively impacts quality of life (QoL). The present epidemiologic study identified point prevalence of chronic pain in India, impact on individual's QoL, unveiling current pain treatment practices, and levels of satisfaction with treatment. METHODS: This epidemiological telephonic survey consisted of two questionnaires: screening questionnaire that assessed prevalence of pain, its frequency during the past week, intensity during last episode, sites of pain, and main causes, and in-depth questionnaire that evaluated demography, frequency, duration, and intensity of pain; impact of pain on QoL; respondent's perception regarding the attitude of their family, friends, and doctors toward their pain. RESULTS: A total of 5004 respondents were included from eight cities across India. The overall point prevalence of chronic pain was 13%, and the mean intensity of pain on NRS scale was 6.93. Respondents with chronic moderate and chronic severe pain were 37% and 63%, respectively. Pain in knees (32%), legs (28%), and joints (22%) was most prevalent. Respondents with chronic pain were no longer able to exercise, sleep, maintain relationships with friends and family, and maintain an independent lifestyle. About 32% of patients lost ≥4 hours of work in the past 3 months. Majority (68%) of respondents were treated for pain with over the counter (OTC) drugs, and most were taking NSAIDs (95%). CONCLUSION: A significant population of India suffers from chronic pain, and their QoL is affected leading to disability. A proportion of respondents receiving pain treatment were taking nonprescription medications with a majority of respondents on NSAIDs. A very few were consulting pain management specialists.

Efficacy and safety of an advanced formula silicone gel for prevention of post-operative scars.

INTRODUCTION: Scar formation is a natural part of the healing process that occurs when the skin repairs wounds caused by burns, trauma, surgery or disease. The appearance of scars often leads to adverse psychological effects, loss of self-esteem and the associated stigmatism and diminished quality of life. Silicones are emerging as the standard treatment for prevention of a wide range of scars. The present study evaluated the safety and efficacy of an advanced formula topical silicone gel for prevention of post-operative hypertrophic and keloid scars. METHODS: An open-label prospective trial was conducted. Patients who had undergone prior surgery (10 days-3 weeks) and having recent post-surgical scars were enrolled. Patients were asked to apply the gel twice daily to the affected areas for 3 months. Pigmentation, vascularity, pliability, height of scar and pain and pruritus in the scar were assessed. Photographs of scars were taken before commencement of treatment and at follow-up visits. RESULTS: A total of 36 patients were enrolled. At baseline, height of the scar was 2-5 mm in 57.6 % (19/33) of the subjects which was reduced in subsequent visits (P < 0.05). Hyperpigmentation (score 3) was present in 91% (30/33) of patients at baseline and was reduced to normal (score 0) after 2 months of treatment in 40% (6/14) of patients (P = 0.0313). Vascularity (54.6%, 18/33) at baseline was also reduced over the 3 months period (P = 0.0313) A significant decrease (30%, 3/10) (P = 0.0313) in pliability was seen after 3 months of treatment from the baseline (57.6%, 19/33). Only two patients reported pruritus and pain at the baseline visit; one patient reported improvement after treatment. Itching was reported as an adverse drug reaction in two patients. CONCLUSION: These preliminary findings suggest that advanced formula silicone gel is safe and effective in the prevention of hypertrophic and keloid scars; however, larger, controlled studies are warranted.