Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

The impact of impulsivity on weight loss after bariatric surgery: a systematic review.

BACKGROUND: Impulsivity has been shown to be associated with obesity through links to pathological eating behavior such as binge eating. The recent literature suggests that impulsivity is linked to poorer outcomes post-bariatric surgery. Impulsivity can be measured in various ways and comprises of three broad domains: impulsive choice, impulsive action, and impulsive personality traits. The aim of this systematic review is to synthesize the current evidence on the impact of impulsivity on post-bariatric surgery weight loss. METHODS: A literature review was performed in February 2020. Original studies investigating the relationship between impulsivity and weight loss post-bariatric surgery were evaluated. RESULTS: Ten studies with a total of 1246 patients were analyzed. There were four case-control, four prospective observational and two retrospective observational studies. The postoperative follow-up ranged from 0.5 to 12 years. Eight studies measuring trait impulsivity did not show any association with weight loss post-bariatric surgery, although two studies reported an indirect effect of impulsivity on weight loss mediated via pathological eating behavior. Assessment of impulsive action by two studies showed that post-bariatric surgery weight loss is affected by impulsive action. CONCLUSION: Impulsivity may adversely affect postoperative outcomes after bariatric surgery. However, this may be specific to state impulsivity or impulsive action rather than trait impulsivity. Patients with a higher state impulsivity may benefit from closer follow-up post-bariatric surgery, as well as cognitive behavioral therapies targeting cognitive control over food. LEVEL OF EVIDENCE: Level I, systematic review.

Parkinson's Disease in Intensive Care Unit: An Observational Study of Frequencies, Causes, and Outcomes.

OBJECTIVE: To analyze the frequency, causes, and outcomes of admission to the Intensive Care Unit (ICU) among Parkinson's disease (PD) population so that preventive measures can be developed. METHODS: We prospectively observed patients with diagnosis of PD admitted to ICU from January 2014 to December 2016. Based on etiology for hospital admission, they were divided into two groups - related to PD (further divided into direct or indirect) or not associated with PD at all. Etiology for hospitalization was determined from history and investigational data. The primary outcome was death or discharge from the hospital. Factors contributing to ICU admission were analyzed by comparing these patients with a cohort of 50 PD patients admitted to the neurology ward during the same study period. All values were expressed as mean (standard deviation) and percentages using SPSS version 16.0. RESULTS: Fifty-three (36%) out of a total of 146 patients required ICU admission. Most common causes leading to admission in decreasing order of frequency were fever (34%), delirium (16%), falls (12%), encephalopathy (8%), gastrointestinal emergencies (6%); while direct disease-related severe dyskinesias were seen only in two patients (4%). 13.7% needed mechanical ventilation and mean duration of ventilation was 5.94 days with mortality rate of 20%. Significant factors predicting ICU admission, and thus, poor outcomes were age >65 years, history of previous admission within the last 12 months, delirium, and hypoalbuminemia. There was no significant association between the incidence of ICU admission and duration of disease or severity of the disease. CONCLUSIONS: Poor outcome in PD patients is due to systemic causes, hence multidisciplinary teamwork may improve outcome in these patients.

Performance, carcass characteristics and economics of broiler chickens fed dietary enzymes and probiotic.

BACKGROUND: Researchers are challenged with identification of possible feed additives with the ability to increase the efficiency of feed utilization. AIMS: The present work aimed at studying growth pattern and carcass traits in broiler fed on dietary enzymes (Enzymex) and probiotic (Yeamark) over a period of six weeks. METHODS: A completely randomized design, including 8 treatments, 3 replications and 15 birds in each experimental unit was applied. Results: The results showed that feed intake decreased significantly (P<0.05) which might be due to the birds fulfilling their nutrient requirements by taking less amount of feed with improved digestibility of energy sources and amino acids. The results of present study also demonstrate the beneficial effects on performance and dressed yield in the treated groups in broiler. CONCLUSION: Enzymes and probiotic are, therefore, suggested to be used as feed additives in broiler rations for higher profitability.

The Profile of Amyotrophic Lateral Sclerosis in Natives of Western Himalayas: Hospital-Based Cohort Study.

BACKGROUND: Despite the disabling nature of amyotrophic lateral sclerosis (ALS), there are no contemporary data on clinical characteristics available from rural hilly states from India. Thus, the present study aimed at reporting clinical profile in ALS patients from natives of Western Himalayas. MATERIALS AND METHODS: A total of 32 patients of ALS were enrolled over a period of 1 year (2013-2014) in the present study. The demographic profile, clinical characteristics, and risk factors were systematically recorded, and these patients were followed for 1 year. RESULTS: The mean age of ALS patients was 53 ± 15.88 (23-90 years). Maximum number of patients of both limb onset and bulbar onset were in the age group of 40-49 years [Figure 1]. Male to female ratio was 1.46. Limb-onset was seen in 23 (72%) and bulbar-onset in 9 (28%) of patients. Bulbar-onset was more common in females as compared to males. Mean duration of symptoms were 19.06 ± 24 months (range 4-120 months). None of the studied risk factor showed statistically significant association with outcome of the disease. No familial association was found. The most common site of weakness was upper limb distal weakness. Definite ALS was seen in 13 (40.6%) patients. Mean ALS functional rating scale (ALSFRS) at presentation is 35.7 ± 7.9. All patients were started on riluzole. Mean ALSFRS at 9-month follow-up was 32.9 ± 7.4. After 1 year of follow up, 5 out of 32 patients died and among them, 4 were of limb onset and 1 was of bulbar onset ALS. Mean age at death in males was 66 ± 16 years and in females was 56.33 ± 24.8 years; mean survival in these patients was 25 months. CONCLUSION: This present study highlights following findings: (1) Male preponderance is less common in our patients as compared to earlier reports from India. Bulbar onset is more common in elderly (age >60 years) females. (2) As per previous reports from India, when compared to Western population present study supports the fact of the younger age of onset and longer duration of symptoms and slow course of disease in Indian patients.

Access to childhood immunisation services and its determinants among recent and settled migrants in Delhi, India.

OBJECTIVES: Childhood immunisation is one of the important public health interventions, and poor migrants are vulnerable to forego these services. The objective of the study is to understand the access of childhood immunisation services to the socio-economically disadvantaged migrants and the determinants of full immunisation uptake up to the age of 1 year. METHODS: In a cross-sectional survey, 458 migrant households with a child aged up to 2 years were identified. Data on sociodemographics, migration history, receipt of various vaccines and maternal healthcare services were collected through interviewer-administered pretested questionnaires. Multiple logistic regression analysis was performed to identify the determinants of full immunisation status. RESULTS: Childhood immunisation coverage rates were low as only 31% of recent-migrant children and 53% of settled-migrant children were fully immunised against seven vaccine-preventable diseases (VPDs) by 12 months of age. Lack of awareness of the immunisation schedule and location of health facilities, mobility, illness of the child, fear of vaccines and side-effects were the main reasons for incomplete or no immunisation. Mother's educational attainment, TV viewership, hospital birth and receipt of information on childhood immunisation from the health workers during postnatal visits increased chances of getting the child fully immunised against seven VPDs by 1 year of age. CONCLUSION: The migrants, particularly the recent migrants, are at the risk of foregoing immunisation services because of livelihood insecurity, mobility and non-familiarity of services in the new urban environment. There is a need to deliver services with a focus on recent migrants. Investing in education and socio-economic development and providing secured livelihoods and equitable services are important to improve and sustain access to healthcare services in the long run.

An institutional experience with The Paris System: A paradigm shift from ambiguous terminology to more objective criteria for reporting urine cytology.

BACKGROUND: Urine cytology is a highly specific modality for diagnosing high-grade urothelial carcinoma (HGUC), but plagued by low sensitivity and wide inter-observer variability mainly ascribed to the lack of an established template of reporting. The Paris System (TPS) working group proposed such a template at the 2013 International Congress of Cytology, replete with objective criteria for categorising specimens into one of the seven categories: non-diagnostic, negative for HGUC, atypical urothelial cells, suspicious for HGUC, HGUC, low-grade urothelial neoplasm and others (including non-malignant entities). This study was undertaken to determine the impact of TPS criteria in the morphological interpretation of urine samples. METHODS: A total of 255 voided urine specimens from 97 patients who had follow-up biopsies were re-assessed according to TPS criteria and correlated with the final histological diagnosis. RESULTS: Sixty-three patients were diagnosed with HGUC, and 34 had low-grade papillary UC on biopsy. Earlier samples from 40 (41.2%) patients were categorised as merely "atypical" wheereas the "positive for malignancy" category was assigned to 33 (34%) patients. After re-evaluation of the same cases using TPS criteria, cytological features in 44 (69.8%) out of 63 HGUC patients were correctly recognised as HGUC and samples from additional seven patients were re-categorised as suspicious for HGUC (total 81%). The sensitivity of the HGUC category in predicting HGUC was 69.8% which rose to 81% when HGUC was grouped with suspicious for HGUC category. CONCLUSION: The criteria outlined by TPS facilitated the standardisation of urine cytology reporting and significantly increased the sensitivity of diagnosing HGUC.

Chronic intermittent ethanol induced axon and myelin degeneration is attenuated by calpain inhibition.

Chronic alcohol consumption causes multifaceted damage to the central nervous system (CNS), underlying mechanisms of which are gradually being unraveled. In our previous studies, activation of calpain, a calcium-activated neutral protease has been found to cause detrimental alterations in spinal motor neurons following ethanol (EtOH) exposure in vitro. However, it is not known whether calpain plays a pivotal role in chronic EtOH exposure-induced structural damage to CNS in vivo. To test the possible involvement of calpain in EtOH-associated neurodegenerative mechanisms the present investigation was conducted in a well-established mouse model of alcohol dependence - chronic intermittent EtOH (CIE) exposure and withdrawal. Our studies indicated significant loss of axonal proteins (neurofilament light and heavy, 50-60%), myelin proteins (myelin basic protein, 20-40% proteolipid protein, 25%) and enzyme (2', 3'-cyclic-nucleotide 3'-phosphodiesterase, 21-55%) following CIE in multiple regions of brain including hippocampus, corpus callosum, cerebellum, and importantly in spinal cord. These CIE-induced deleterious effects escalated after withdrawal in each CNS region tested. Increased expression and activity of calpain along with enhanced ratio of active calpain to calpastatin (sole endogenous inhibitor) was observed after withdrawal compared to EtOH exposure. Pharmacological inhibition of calpain with calpeptin (25 µg/kg) prior to each EtOH vapor inhalation significantly attenuated damage to axons and myelin as demonstrated by immuno-profiles of axonal and myelin proteins, and Luxol Fast Blue staining. Calpain inhibition significantly protected the ultrastructural integrity of axons and myelin compared to control as confirmed by electron microscopy. Together, these findings confirm CIE exposure and withdrawal induced structural alterations in axons and myelin, predominantly after withdrawal and corroborate calpain inhibition as a potential protective strategy against EtOH associated CNS degeneration.

Spinal Tuberculosis with Paraplegia in Pregnancy.

Spinal tuberculosis leading to paraplegia is uncommon in pregnancy and is a diagnostic and therapeutic challenge. We report a case of tubercular paraplegia presenting at 35 weeks of gestation. She was managed with Anti-tubercular drugs and did not require surgical intervention. Her neurological status improved and she was allowed to go in labour. She delivered a healthy term infant by cesarean. At three months follow-up, both mother and child are doing well.

Application and interpretation of genome-wide association (GWA) studies for informing pharmacogenomic research - examples from the field of age-related macular degeneration.

Genome-wide association (GWA) studies apply broad DNA scans on hundreds-of-thousands of common sequence variants in thousands of people for the purpose of mapping trait- or disease-related loci. We provide examples of ligand- and target-based studies from the field of age-related macular degeneration (AMD) to demonstrate the value of the GWA approach in confirmatory and exploratory pharmacogenomics research. Complementing this genomic analysis, we used a simple biochemical retinal pigment epithelium (RPE) oxidative, apoptotic high throughput screening (HTS) assay to identify compounds. This ligand-to-targetto DNA sequence variant-to disease approach provided guidance on rational design of preclinical studies and identified associations between: 1) valproic acid and advanced AMD-associated genes with the capacity to alter GABA-succinate signaling (ALDH5A1, CACNA1C, SUCLA2, and GABBR2) and chromatin remodeling (HDAC9); and 2) Ropinirole and a geographic atrophy-associated gene (DRD3) with the capacity to alter systems involved in cAMP-PKA signaling. In both applications of our method, the breadth of GWA findings allowed efficient expansion of results to identify enriched pathways and additional ligands capable of targeting pathway constituents. A disease associated SNP-to gene-to target-to ligand approach provided guidance to inform preventive and therapeutic preclinical studies investigating roles of targets in: 1) PPAR-RXR transcription complex constituents for neovascular AMD; and 2) the stress activated MAPK signaling cascade constituents for advanced AMD. Our conclusion is that publically available data from GWA studies can be used successfully with open-access genomics, proteomics, structural chemistry, and pharmacogenomics databases in an efficient, rational approach to streamline the processes of planning and implementation for confirmatory and exploratory pre-clinical studies of preventive or therapeutic pharmacologic treatments for complex diseases.

A multicenter study of primary graft failure after infant heart transplantation: impact of extracorporeal membrane oxygenation on outcomes.

Primary graft failure is the major cause of mortality in infant HTx. The aim of this study was to characterize the indication and outcomes of infants requiring ECMO support due to primary graft failure after HTx. We performed a retrospective review of all infants (<1 yr) who underwent Htx from three institutions. From 1999 to 2008, 92 infants (<1 yr) received Htx. Sixteen children (17%) required ECMO after Htx due to low cardiac output syndrome. Eleven (69%) infants were successfully weaned off ECMO, and 9 (56%) infants were discharged with a mean follow-up of 2.3 ± 2.5 yr. Mean duration of ECMO in survivors was 5.4 days (2-7 days) compared with eight days (2-10 days) in non-survivors (p = NS). The five-yr survival rate for all patients was 75%; however, the five-yr survival rate was 40% in the ECMO cohort vs. 80% in the non-ECMO cohort (p = 0.0001). Graft function within one month post-Htx was similar and normal between ECMO and non-ECMO groups (shortening fraction = 42 ± 3 vs. 40 ± 2, p = NS). For infants, ECMO support for primary graft failure had a lower short-term and long-term survival rate vs. non-ECMO patients. Duration of ECMO did not adversely impact graft function and is an acceptable therapy for infants after HTx for low cardiac output syndrome.

Calpain inhibition prevents ethanol-induced alterations in spinal motoneurons.

Long-term exposure of ethanol (EtOH) alters the structure and function in brain and spinal cord. The present study addresses the mechanisms of EtOH-induced damaging effects on spinal motoneurons in vitro. Altered morphology and biochemical changes of such damage were demonstrated by in situ Wright staining and DNA ladder assay. EtOH at low to moderate (25-50 mM) concentrations induced damaging effects in the motoneuronal scaffold which involved activation of proteases like µ-calpain and caspase-3. Caspase-8 was seen only at higher (100 mM) EtOH concentration. Further, pretreatment with calpeptin, a potent calpain inhibitor, confirmed the involvement of active proteases in EtOH-induced damage to motoneurons. The lysosomal enzyme cathepsin D was also elevated in the motoneurons by EtOH, and this effect was significantly attenuated by inhibitor treatment. Overall, EtOH exposure rendered spinal motoneurons vulnerable to damage, and calpeptin provided protection, suggesting a critical role of calpain activation in EtOH-induced alterations in spinal motoneurons.

An unusual cause of reversible axonal neuropathy and hypertension in a 10-year-old girl.

A 10-year-old girl, who was referred with refractory epilepsy, had 1.5 years of episodic abnormal behavior. On examination, she also had hypertension and peripheral neuropathy. Hypoglycemia with correspondingly high insulin levels was documented during a confusional episode. MRI of the abdomen revealed an islet cell tumor in the body of the pancreas. One year after tumor excision, both the neuropathy and hypertension showed remarkable improvement. A final diagnosis of insulinoma with hypoglycemic axonal neuropathy and hypertension (reversed with tumor excision) was made. Insulinoma is the commonest cause of hyperinsulinemic hypoglycemia in adults, but is rare in childhood. To our knowledge, distal symmetrical motor-sensory axonal neuropathy has been described in only 40 patients, and hypertension has not been reported with insulinoma.

Evoked response audiometry in scrub typhus: prospective, randomised, case-control study.

OBJECTIVE: To investigate the hypothesis of cochlear and retrocochlear damage in scrub typhus, using evoked response audiometry. STUDY DESIGN: Prospective, randomised, case-control study. METHODS: The study included 25 patients with scrub typhus and 25 controls with other febrile illnesses not known to cause hearing loss. Controls were age- and sex-matched. All subjects underwent pure tone audiometry and evoked response audiometry before commencing treatment. RESULTS: Six patients presented with hearing loss, although a total of 23 patients had evidence of symmetrical high frequency loss on pure tone audiometry. Evoked response audiometry found significant prolongation of absolute latencies of wave I, III, V, and wave I-III interpeak latency. Two cases with normal hearing had increased interpeak latencies. These findings constitute level 3b evidence. CONCLUSION: Findings were suggestive of retrocochlear pathology in two cases with normal hearing. In other patients, high frequency hearing loss may have led to altered evoked response results. Although scrub typhus appears to cause middle ear cochlear and retrocochlear damage, the presence of such damage could not be fully confirmed by evoked response audiometry.

Fine needle aspiration cytology of medullary carcinoma of the thyroid with a focus on rare variants: a review of 78 cases.

BACKGROUND: The cytological features of variants of medullary carcinoma of the thyroid (MCT) are sparsely documented in the literature from case reports. Detailed cytomorphological analysis of MCT variants and features helping to distinguish them from usual MCT are presented here. MATERIALS AND METHODS: A total of 78 aspirates with a diagnosis of MCT over a period of 10 years were re-evaluated. Cytomorphological details were reviewed and semiquantitatively analysed. Histology slides were reviewed in 36 cases. RESULTS: Most aspirates showed classical features of dispersed polygonal or plasmacytoid cells with areas of spindling. In 54 aspirates, a definite cytological diagnosis of medullary carcinoma was made, which in 87.1% was based on cytomorphology alone and in 12.9% was based on immunocytochemistry for calcitonin. In 30.1% of aspirates from MCT, a guarded report of tumour was given in the absence of calcitonin immunocytochemistry. Of the 78 cases, nuclear grooves were seen in 5.1%, intranuclear cytoplasmic inclusions in 28.2%, cytoplasmic granularity in 23.1% and bizarre cells with abrupt anisocytosis in 85.9%. A follicular arrangement was seen in 14.1% and was more frequent in the follicular type (one case) and mixed follicular and medullary carcinoma (one case). Melanin production was seen in aspirates from two cases. One case of the giant cell type of MCT was seen, in which background cells showed large pleomorphic nuclei and numerous bizarre tumour giant cells, prompting a differential diagnosis with anaplastic carcinoma. One example each of the small cell type, paraganglioma-like MCT and papillary MCT were seen. CONCLUSIONS: MCT has uniform cytological features in the majority of aspirates, including many of the histological variants. Searching for pigment in every aspirate of MCT may be rewarding. The giant cell type of MCT is rare and has to be differentiated from anaplastic carcinoma.