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.

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.

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.

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.

Novel approaches to detect serum biomarkers for clinical response to interferon-beta treatment in multiple sclerosis.

Interferon beta (IFNbeta) is the most common immunomodulatory treatment for relapsing-remitting multiple sclerosis (RRMS). However, some patients fail to respond to treatment. In this study, we identified putative clinical response markers in the serum and plasma of people with multiple sclerosis (MS) treated with IFNbeta. In a discovery-driven approach, we use 2D-difference gel electrophoresis (DIGE) to identify putative clinical response markers and apply power calculations to identify the sample size required to further validate those markers. In the process we have optimized a DIGE protocol for plasma to obtain cost effective and high resolution gels for effective spot comparison. APOA1, A2M, and FIBB were identified as putative clinical response markers. Power calculations showed that the current DIGE experiment requires a minimum of 10 samples from each group to be confident of 1.5 fold difference at the p<0.05 significance level. In a complementary targeted approach, Cytometric Beadarray (CBA) analysis showed no significant difference in the serum concentration of IL-6, IL-8, MIG, Eotaxin, IP-10, MCP-1, and MIP-1alpha, between clinical responders and non-responders, despite the association of these proteins with IFNbeta treatment in MS.

The multiple sclerosis whole blood mRNA transcriptome and genetic associations indicate dysregulation of specific T cell pathways in pathogenesis.

Multiple sclerosis (MS) is an autoimmune disease with a genetic component, caused at least in part by aberrant lymphocyte activity. The whole blood mRNA transcriptome was measured for 99 untreated MS patients: 43 primary progressive MS, 20 secondary progressive MS, 36 relapsing remitting MS and 45 age-matched healthy controls. The ANZgene Multiple Sclerosis Genetics Consortium genotyped more than 300 000 SNPs for 115 of these samples. Transcription from genes on translational regulation, oxidative phosphorylation, immune synapse and antigen presentation pathways was markedly increased in all forms of MS. Expression of genes tagging T cells was also upregulated (P < 10(-12)) in MS. A T cell gene signature predicts disease state with a concordance index of 0.79 with age and gender as co-variables, but the signature is not associated with clinical course or disability. The ANZgene genome wide association screen identified two novel regions with genome wide significance: one encoding the T cell co-stimulatory molecule, CD40; the other a region on chromosome 12q13-14. The CD40 haplotype associated with increased MS susceptibility has decreased gene expression in MS (P < 0.0007). The second MS susceptibility region includes 17 genes on 12q13-14 in tight linkage disequilibrium. Of these, only 13 are expressed in leukocytes, and of these the expression of one, FAM119B, is much lower in the susceptibility haplotype (P < 10(-14)). Overall, these data indicate dysregulation of T cells can be detected in the whole blood of untreated MS patients, and supports targeting of activated T cells in therapy for all forms of MS.

Study of relationship between facial index and gestational age in normal newborns.

Anthropometric dimensions are the basis of evaluation of health of newborns. Results of cephalometric studies can be used in forensic medicine, plastic surgery, pediatrics, oral surgery, dentistry, otolaryngology and syndromology. Three hundred sixty appropriate for gestational age newborns belonging to the region in and around Patiala were the subjects of the present study. The gestational age varied from 29 to 41 weeks. Face length and face width were measured and facial index was calculated. The overall mean face length and mean face width were 5.17 cm and 6.42 cm respectively. Facial index ranged from 79.3 - 81.4% with mean facial index being 80.5%. Facial index increased with increasing gestational age. Gestational age has negative correlation with face length and face width but positively significant correlation was observed between gestational age and facial index. Facial length and facial width were jointly determined. All inter-relationships improved remarkably when determined for gestational age groups. These findings have significant implication as gestational age linearly influenced facial index. In addition they provide database from 29th to 41st week of gestation and can be used as baseline for further anthropometric studies to specify the role of heredity and environment.

Anesthetic management for resection of cor triatriatum during the second trimester of pregnancy.

Hemodynamic changes during pregnancy can result in cardiovascular decompensation in women with pre-existing cardiac diseases. Despite optimized medical treatment, some patients with severe structural cardiac abnormalities may need surgical intervention during pregnancy. We describe a woman who presented at 20 weeks of gestation with acute heart failure due to cor triatriatum, a rare form of congenital heart disease. This condition is characterized by a perforated fibromuscular membrane dividing the left atrium into two chambers. The clinical presentation varies from asymptomatic to acute heart failure depending on the size of the fenestrations in the membrane and the presence of associated cardiac malformations. In our patient, two severely restrictive orifices in a membrane within the left atrium, moderate to severe pulmonary hypertension and good biventricular function were demonstrated by transthoracic echocardiography. Without surgical resection, the increased blood volume and cardiac output associated with pregnancy could have resulted in cardiovascular decompensation. She underwent urgent corrective open heart surgery with cardiopulmonary bypass. Perioperative anesthetic management included prevention of tachycardia, atrial dysrhythmias and pulmonary hypertension, close monitoring for and prompt treatment of maternal hypotension, maintaining euvolemia and good cardiac contractility and avoiding hemodilution and hypothermia. These approaches, together with minimizing bypass time, resulted in successful maternal and fetal outcome.

Short-term response of macular oedema to intravitreal bevacizumab.

BACKGROUND/AIMS: Bevacizumab has been shown to be an effective treatment of macular oedema. This study assesses the response of macular oedema to bevacizumab with specific focus on the first 24 h postinjection. METHODS: Subjects with diabetic macular oedema (DMO) or exudative age-related macular degeneration (ARMD) received intravitreal bevacizumab injections. Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity and OCT macular thickness measurements were obtained at baseline, 1, 3, 6, 24 and 48 h, 1 week and 1 month postinjection. RESULTS: The average baseline OCT was 452.91 microm (SD 182.96, range 249.00 to 784.00). After injection, there was a statistically significant decrease in OCT thickness within 2 h with a plateau phase out to 24 h, followed by a significant drop between 24 and 48 h, and a return towards baseline between 1 week and 1 month. Average changes in ETDRS visual acuity were not statistically significant, though many patients experienced a positive outcome. CONCLUSION: While there is an immediate pressure-related effect, it appears that the anti-VEGF effects of bevacizumab require approximately 24 h to become active and persist for 2-3 weeks. These results suggest that injections at 2-3-week intervals might provide improved clinical outcomes, compared with the currently typical 4-6-week interval of injections.

Comparative evaluation of 'flap on' and 'flap off' techniques of Epi-LASIK in low-to-moderate myopia.

PURPOSE: Comparative evaluation of 'flap on' and 'flap off' techniques of Epi-LASIK in low-to-moderate myopia. METHODS: Sixteen eyes of eight consecutive patients with myopia < or = 6 D were selected for this prospective, randomized, comparative, interventional case series. Epi-LASIK surgery was performed in all eyes. In one eye of each patient, the epithelial flap was retained after excimer laser ablation (flap on). In the fellow eye, the epithelial flap was discarded (flap off) after ablation. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), spherical equivalent (SEQ), postoperative pain score, time to epithelization, and corneal haze were recorded on postoperative visits. RESULTS: The mean preoperative SEQ in the two groups was -3.61+/-1.32 D (flap on) and -3.49+/-1.86 D (flap off; P=0.752). The mean follow-up period was 8.5+/-4.9 months. The mean pain score was comparable on all postoperative days except the second postoperative day when the group with flap off had a lesser mean pain score (P=0.053).Time for epithelial healing was 3.63+/-0.52 days in cases with flap off and 4.13+/-0.64 days in cases with flap on (P=0.113). Eyes with flap off had a better UCVA on the first postoperative day (0.19+/-0.11 logMAR) compared with eyes with flap on (0.41+/-0.28 logMAR; P=0.032). There was no significant difference in UCVA, BSCVA, SEQ, contrast sensitivity, corneal haze, and higher order aberrations at any other postoperative visit. CONCLUSIONS: There is no difference between flap on and flap off techniques of Epi-LASIK with regards to overall outcome of surgery.

Alkaptonuria and intramedullary calcification.

Alkaptonuria is a rare disorder of metabolism caused by deficiency of homogentisic acid oxidase enzyme and characterized by triad of homogentisic aciduria (dark urine), relentlessly progressive arthritis and ochronosis. We have documented a case with typical features of alkaptonuria along with intramedullary calcification which has not been reported in the literature before.