Each novel vaccine candidate needs to be evaluated for safety, immunogenicity, and protective efficacy in humans before it is licensed for use. After initial safety evaluation in healthy adults, each vaccine candidate follows a unique development path. This article on clinical development gives an overview on the development path based on the expectations of various guidelines issued by the World Health Organization (WHO), the European Medicines Agency (EMA), and the United States Food and Drug Administration (USFDA). The manuscript describes the objectives, study populations, study designs, study site, and outcome(s) of each phase (Phase I-III) of a clinical trial. Examples from the clinical development of a malaria vaccine candidate, a rotavirus vaccine, and two vaccines approved for human papillomavirus (HPV) have also been discussed. The article also tabulates relevant guidelines, which can be referred to while drafting the development path of a novel vaccine candidate.

Background and Objectives: School students with specific learning disabilities (SpLDs) experience chronic academic underachievement and resultant stress. The present study aimed to determine if school students with newly diagnosed SpLD were more likely to have anxiety than their regular peers. Materials and Methods: The study cases (aged 8-15 years) were recruited from our institute's learning disability clinic. The matched controls were recruited from four schools in Mumbai, Maharashtra, India. Anxiety was measured using the Spence Children's Anxiety Scale (SCAS)-child self-report version questionnaire. Median SCAS scores and the proportion of students with an SCAS score in the "clinical anxiety" range were compared between the groups. Results: SCAS scores were significantly higher in 8-11-year-old learning-disabled male and female students (P < 0.0001 for both groups) and 12-15-year-old female students (P = 0.004), as compared with matched controls. A significantly higher number of learning-disabled students were found to have "clinical anxiety" [24.64% vs 4.35%, crude odds ratio (OR) = 7.19, 95% confidence interval (CI) 2.91-17.78, P = 0.0001], as compared with the controls regardless of gender, age group, presence of comorbid attention-deficit/hyperactivity disorder (ADHD), or associated medical conditions. A significantly higher proportion of 8-11-year-old learning-disabled students, especially males, were found to have "clinical anxiety" as compared with 12-15-year-old learning-disabled students (crude OR = 4.38, 95% CI 1.94-9.92, P = 0.0004). Gender, presence of comorbid ADHD or associated medical conditions, and type of school attended or curriculum did not impact the prevalence of "clinical anxiety" in learning-disabled students. Interpretation and Conclusions: Students with newly diagnosed SpLD have greater odds of being "clinically anxious" relative to their regular peers. We recommend screening for anxiety in children with SpLD immediately after diagnosis so that their optimum rehabilitation can be facilitated.

Background and Rationale: Most patients with chronic hepatitis C show virological response to telaprevir-based triple therapy, and achieve an end-of-treatment response (ETR). However, some patients showing ETR develop virological relapse. This study was carried out to evaluate factors associated with relapse after triple therapy. Materials and Methods: A prospective, multicentric study was conducted in chronic hepatitis C patients who received telaprevir-based triple therapy. We evaluated independent variables such as age, with or without cirrhosis, prior treatment response to interferon (IFN) therapy, IL28B genotype, core amino acid (aa) 70 mutation, drug adherence, white blood cell counts, hemoglobin level, and serum low-density lipoprotein (LDL) cholesterol level. The characteristics of the patients who relapsed after achieving ETR were compared with those who did not. Results: Among 168 patients, 157 patients achieved ETR (93.5%) and 11 discontinued. Of these 157 patients, relapse occurred in 21 patients (13.4%). Nineteen patients (90.5%) of 21 relapsed patients had the IL28B non-TT genotype (P = 1.79 × 10 ^-9 ). Multivariate analysis identified core amino acid 70 [P = 0.018, crude odds ratio (OR): 6.927] and the IL28B genotype (P = 3.758 × 10 ^-5 , crude OR: 39.311) as significantly independent factors that influenced the relapse-related variables. Among the 49 patients with the IL28B non-TT, 18 patients had core aa70 mutation and 31 patients had core aa70 wild-type. In addition, 66.7% (12/18) of those with core aa70 mutation and 22.6% (7/31) of those with core aa70 wild-type developed relapse (P = 0.005). Discussion: Core aa70 mutation and the IL28B non-TT genotype were identified as independent factors that influenced relapse after achievement of ETR for telaprevir-based triple therapy.

Background and Objective: In the analysis of dichotomous type response variable, logistic regression is usually used. However, the performance of logistic regression in the presence of sparse data is questionable. In such a situation, a common problem is the presence of high odds ratios (ORs) with very wide 95% confidence interval (CI) (OR: >999.999, 95% CI: <0.001, >999.999). In this paper, we addressed this issue by using penalized logistic regression (PLR) method. Materials and Methods: Data from case-control study on hyponatremia and hiccups conducted in Christian Medical College, Vellore, Tamil Nadu, India was used. The outcome variable was the presence/absence of hiccups and the main exposure variable was the status of hyponatremia. Simulation dataset was created with different sample sizes and with a different number of covariates. Results: A total of 23 cases and 50 controls were used for the analysis of ordinary and PLR methods. The main exposure variable hyponatremia was present in nine (39.13%) of the cases and in four (8.0%) of the controls. Of the 23 hiccup cases, all were males and among the controls, 46 (92.0%) were males. Thus, the complete separation between gender and the disease group led into an infinite OR with 95% CI (OR: >999.999, 95% CI: <0.001, >999.999) whereas there was a finite and consistent regression coefficient for gender (OR: 5.35; 95% CI: 0.42, 816.48) using PLR. After adjusting for all the confounding variables, hyponatremia entailed 7.9 (95% CI: 2.06, 38.86) times higher risk for the development of hiccups as was found using PLR whereas there was an overestimation of risk OR: 10.76 (95% CI: 2.17, 53.41) using the conventional method. Simulation experiment shows that the estimated coverage probability of this method is near the nominal level of 95% even for small sample sizes and for a large number of covariates. Conclusions: PLR is almost equal to the ordinary logistic regression when the sample size is large and is superior in small cell values.

Journal Impact Factor (JIF) has been used in assessing scientific journals. Other indices, h- and g-indices and Article Influence Score (AIS), have been developed to overcome some limitations of JIF. The aims of this study were, first, to critically assess the use of JIF and other parameters related to medical education research, and second, to discuss the capacity of these indices in assessing research productivity as well as their utility in academic promotion. The JIF of 16 medical education journals from 2000 to 2011 was examined together with the research evidence about JIF in assessing research outcomes of medical educators. The findings were discussed in light of the nonnumerical criteria often used in academic promotion. In conclusion, JIF was not designed for assessing individual or group research performance, and it seems unsuitable for such purposes. Although the g- and h-indices have demonstrated promising outcomes, further developments are needed for their use as academic promotion criteria. For top academic positions, additional criteria could include leadership, evidence of international impact, and contributions to the advancement of knowledge with regard to medical education.

The disorders of large granular lymphocytes include reactive proliferation as well as indolent or aggressive neoplasms of cytotoxic T cells, γδ T cells, and natural killer (NK) cells. They are associated with autoimmune and infectious disorders and have varied immunophenotypic features. We report a case, which highlights this complex association of autoimmune and infectious diseases with large granular lymphocytosis, the overlapping spectrum of large granular lymphocyte leukemias, and γδ T cell lymphomas as well as the difficulties in the diagnosis and management of these indolent T cell lymphomas in the usual clinical settings.

The well-recognized erosion of pathoanatomic correlations in basic medical training, combined with the increasing everyday pressures of time-efficacy in patient examination, continue to place strain on junior clinicians. Over the years, many refinements to tried-and-true basic physical examination techniques have been described, allowing improvement in diagnostic yield. A multitude of "screening" techniques are available for physical assessment; however, such approaches are often nonstandardized and inconsistently taught and applied in the clinical realm. Great interexaminer inconsistency in the documentation of many forms of screening techniques also substantively undermines their respective clinical value. The current work presents a novel refinement/combination of previously described examination approaches for the assessment of peripheral upper limb (UL) motor function - the "K" sign. Having been successfully applied in both the acute and ambulatory clinical settings for several years, we feel that the technique has a useful role as a rapid and specific screening technique that is easily taught, learnt, and applied. Arguably, its employment serves to improve time efficacy in the screening examination, and may even improve diagnostic yield through its reliable reproducibility and provision of direct bilateral comparison. Its inherent simplicity also lends itself well to high levels of uptake (and retention) by medical students and junior clinicians alike. On top of presenting the simple screening test itself, we offer a simple means of subsequent notation for the patient's case note record, again in the hope of standardization and endurance of clinical value beyond the time of patient examination.