Comparison of effectiveness of interventions in reducing mortality in patients of toxic epidermal necrolysis: A network meta-analysis.

BACKGROUND: Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN). AIMS: To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis. METHODS: Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN. RESULTS: Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on "surface under the cumulative ranking curves" (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs. LIMITATIONS: Evidence is mainly based on retrospective studies. CONCLUSION: The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept.

Image-based assessment in undergraduate dermatology curriculum: A step toward competency-based medical education.

BACKGROUND: Dermatology being a visual branch, there is a need to add a visual element in learning and assessment of dermatology. This study compares the utility of image-based assessment (IBA) as a new tool compared to routinely used semi-structured viva (SSV) in dermatology formative assessment at undergraduate level. METHODS: Comparison was made between batches of students in year 2018 who underwent clinical posting term ending assessment by IBA with the retrospective cohort of batch of students in year 2015 who underwent assessment by SSV. The students' marks in this assessment and their attendance were collected. Feedback was taken from batch of students who had undergone IBA assessment. Faculty feedback was also taken. RESULTS: Correlation of attendance with marks was higher in IBA batch compared to SSV. IBA is better able to assess the diagnostic skills which requires visual element and prescription writing skill. SSV can do an authentic assessment of clinical reasoning skills. IBA had higher variability in marks allotted to students suggesting that it was more objective tool whereas with narrow range of marks SSV was found to be more subjective. Both IBA and SSV had similar acceptability by students and faculty. IBA was more resource intensive at preparation stage while SSV was so in conduction stage. IBA had better educational impact, as it promoted learning through exposure to actual patients. CONCLUSION: IBA fared better in terms of validity, reliability, acceptability, and educational impact. In terms of feasibility IBA and SSV had differing challenges.

Do primary care physicians require training in core clinical dermatology? A cross sectional needs assessment study from Western India.

BACKGROUND: Primary care physicians play a crucial role in managing patients with common skin disorders who form around one-third of outpatient attendees. AIM: This study aimed to assess the need for dermatology training among primary care physicians by assessing their knowledge, self-perception of ability to diagnose and manage skin disorders, and their difficulties in managing these patients. METHODS: A descriptive, cross-sectional, needs assessment study was done among primary care physicians (n = 61) of rural (n = 34) and urban (n = 27) areas of Vadodara district. A pre-validated semi-structured questionnaire (for self-rating of the ability to diagnose/manage skin disorders and difficulties faced in managing patients) was used along with a photo-quiz (for knowledge assessment) while approaching primary care physicians during their monthly review meeting with prior permission. Data were analyzed by Epi InfoTM software and manual content analysis. RESULTS: The mean score on the photo-quiz was 4.1/10. Forty-three (70.5%) participants rated their ability to diagnose/manage skin disorders as 'average' on a five-point Likert scale. Various difficulties (n = 89) narrated by participants were related to their knowledge/skill, disease factors, patients and administrative aspects. Three-fourths of the participants managed difficulties by referring patients to dermatologists. One-third suggested conducting training in common skin disorders. LIMITATIONS: The study population included primary care physicians from the government healthcare setup only. Knowledge assessment was done using a short ten-item photo-quiz instead of actual patients. CONCLUSIONS: Primary care physicians had poor knowledge of skin disorders, and a majority overrated their own ability for clinical management of these disorders. Most common difficulties faced were related to clinical management. There is a need for training on common skin disorders.

Cutaneous Adverse Drug Reactions in a Tertiary Care Teaching Hospital in India: An Intensive Monitoring Study.

BACKGROUND: The epidemiological data based on intensive monitoring studies are limited for the cutaneous adverse drug reactions (CADRs) in terms of incidence. Most of earlier Indian studies focused only on types and causative drugs of CADRs. AIM: The aim of this study is to analyze the CADRs with reference to the incidence, its subgroup analysis, causative drugs, and other clinical characteristics in Indian population. METHODOLOGY: Intensive monitoring study was carried out over a period of 3 years in the dermatology outpatient and inpatient department. CADRs due to only systematically administered drugs were considered. The WHO definition for CADR, the WHO causality definitions, modified Schumock and Thornton's criteria for preventability, and International Conference on Harmonisation E2A guidelines for seriousness were considered. Incidence was expressed in percentage and its 95% confidence interval. The incidence was analyzed on basis of characteristics of study population and CADRs. RESULTS: A total of 171 CADRs were observed from 37,623 patients. The CADR incidence was 0.45% (95% CI: 0.39-0.53). The incidence did not significantly differ in different age groups and gender. Commonly observed CADRs were maculopapular rash (23.98%), urticaria (21.64%), and fixed drug eruptions (FDEs) (18.13%). Antimicrobials (35.18%) and nonsteroidal anti-inflammatory drugs (NSAIDs) were suspected in all common CADRs. Anti-infective and NSAIDs were most commonly suspected drugs in overall CADRs, maculopapular rash, urticaria, FDEs, and erythema multiforme. The exact nature of drugs remained inaccessible in one-fourth cases due to use of the over-the-counter self-medications. The incidence of preventable and serious and fatal CADRs was 0.08% (95% CI: 0.05-0.11), 0.04% (95% CI: 0.02-0.06), and 0.003% (95% CI: 0.000-0.001), respectively. CONCLUSION: Ethnic characteristics should be considered while interpreting incidence from the international studies. The demographic characteristics of study population do not affect the incidence of CADRs. Indian patients should be sensitized about hazards of self-medications.

Sexually transmitted infections in women: A correlation of clinical and laboratory diagnosis in cases of vaginal discharge syndrome.

AIMS: This study compares the clinical and laboratory diagnosis of vaginal discharge syndrome. SETTINGS AND DESIGN: This cross-sectional study was carried out at the gynaecology outpatient department of a tertiary care hospital in Gujarat, India. MATERIAL AND METHODS: Total of 180 females diagnosed as vaginal discharge or cervicitis based on syndromic approach and were recruited for the study. Their clinical profile was noted and they were investigated for bacterial vaginosis, trichomoniasis, candidiasis, gonorrhoea and chlamydia infection. RESULTS: Lower abdominal pain (35%) followed by burning micturition (23.9%) were the common associated complaints. Bacterial vaginosis was the most common clinical diagnosis, while trichomoniasis was least common. Upon laboratory investigation, 35.6% of cases of vaginal discharge and 12% of cases of cervicitis tested positive. Percentage of cases confirmed by laboratory investigation was 50, 27.8 and 41.7 for bacterial vaginosis, trichomoniasis and candidiasis respectively. CONCLUSION: Among all the females diagnosed as vaginal discharge syndrome, a very small percentage actually turned out to be positive upon laboratory testing.

Acute methotrexate toxicity: a fatal condition in two cases of psoriasis.

We describe two fatal cases of low dose methotrexate (MTX) toxicity in patients with psoriasis, emphasizing the factors that exacerbate MTX toxicity. The first patient was a 50-year-old male of psoriasis on intermittent treatment with MTX. After a treatment-free period of six months, he had self-medication of MTX along with analgesic for joint pain for one week which followed ulceration of the lesions, bone marrow suppression, and eventually death. The second patient was a 37-year-old male of psoriasis, who has taken MTX one week earlier without prior investigations. He had painful ulcerated skin lesions and bone marrow suppression. On investigations, he showed high creatinine level and atrophied, nonfunctioning right kidney on ultrasonography. In spite of dialysis, he succumbed to death. MTX is safe and effective if monitored properly, but inadvertent use may lead to even death also. Prior workup and proper counseling regarding the drug interactions as well as self-medication should be enforced.

Clinical profile of leprosy patients: a prospective study.

INTRODUCTION: Early diagnosis and early adequate drug treatment is very important aspect to reduce the load in cases of leprosy. So, correct labeling of paucibacillary and multibacillary cases is a prerequisite for the adequate treatment. Confirmation of diagnosis is an important indication for histopathological examination in doubtful cases. OBJECTIVES: The present study was carried out to know the clinical profile of leprosy patients, concordance between clinical and histopathological diagnosis in cases of leprosy, and to assess the therapeutic efficacy of antileprosy therapy. STUDY DESIGN: Two hundred and fifty clinically diagnosed leprosy patients attending skin outdoor patient department (OPD) were included in the study. Slit skin smear was performed in all the cases. In that case concordance between clinical and histology can be determined only in 30 cases. All the patients were treated with MDT (multidrug therapy) as per WHO guideline. RESULTS: A total of 250 patients attended the clinic with male to female ratio of 1.7:1. The highest incidence was noted in 17-40 years of age group. In the clinical disease spectrum, 40% patients were in the borderline spectrum followed by tuberculoid leprosy (TT) (29.2%), lepromatous leprosy (LL) (26.8%), and 3.9% of indeterminate leprosy (IL). A total of 18% of patients were of primary neuritic leprosy. A total of 8.3% patients had definite history of contact in the family or neighborhood. Clinicopathological correlation was noted in 60% of patients with maximum disparity (52.9%) in the borderline group of patients. A total of 52.8% were MB (Multibacillary) and 47.2% were PB (Paucibacillary) cases. Morphological index became negative after 6 months in all patients. Mean fall of bacteriological index after 6 months was 0.19, while after 1 year, it was 1.05. CONCLUSION: Timely diagnosis and adequate treatment of cases with MDT is most effective. Histopathological examination is must in doubtful cases of leprosy.

Cutaneous adverse drug reactions in Indian population: A systematic review.

BACKGROUND: Epidemiological data is limited for cutaneous adverse drug reactions (CADRs) in India. Most of the Indian studies have small sample size and are of limited duration. AIMS: The aim of this study is to analyze CADRs with reference to the causative drugs and their clinical characteristics in Indian population. MATERIALS AND METHODS: As per selection criteria, electronic databases were searched for publications describing CADRs from January-1995 to April-2013 by two independent investigators. Data of the causative drugs and clinical characteristics were extracted and summarized by absolute numbers, percentages, ranges, and means as presented by the authors. The subgroup analysis of causative drugs was performed for causality assessment, severe or nonsevere reactions and occurrence of common CADRs. Studies showing "definite" and "probable" categories of causality analysis were labeled as "definite and probable causality (DPC) studies". The other included studies were labeled as "non-DPC studies". RESULTS: Of 8337 retrieved references, 18 prospective studies were selected for analysis. The pooled incidence was 9.22/1000 total among outpatient and inpatient cases. Commonly observed reactions were maculopapular rash (32.39%), fixed drug eruptions (FDEs) (20.13%), urticaria (17.49%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (6.84%). The major causative drug groups were antimicrobials (45.46%), nonsteroidal anti-inflammatory drugs (NSAIDs) (20.87%) and anti-epileptic drugs (14.57%). Commonly implicated drugs were sulfa (13.32%), ß-lactams (8.96%) and carbamazepine (6.65%). High frequency of CADRs is observed with anti-epileptic drugs in DPC studies only. Carbamazepine, phenytoin and fluoroquinolones had higher severe to nonsevere cutaneous reaction ratio than other drugs. Antimicrobials were the main causative drugs for maculopapular rash, FDEs and SJS/TEN, and NSAIDs for the urticaria. The mortality for overall CADRs, SJS/TEN, and exfoliative dermatitis were 1.71%, 16.39%, and 3.57%, respectively. "Definitely preventable", "probably preventable" and "not preventable" categories CADRs were 15.64%, 63.14%, and 34.64%, respectively. CONCLUSION: Antimicrobials, NSAIDs and antiepileptic are common causative agents of CADRs in India. Antiepileptic agents show high rates of severe cutaneous reactions.

Skin, a mirror reflecting diabetes mellitus: A longitudinal study in a tertiary care hospital in Gujarat.

CONTEXT: Diabetes mellitus (DM) is the most common of the endocrine disorders. Mucocutaneous manifestations of diabetes mellitus are many and vary from trivial to life-threatening. Sometimes, mucocutaneous disorders may herald the onset of diabetes. AIMS: To study the pattern of mucocutaneous manifestations in diabetics and role of it in diagnosing diabetes mellitus and its complications. SETTINGS AND DESIGN: It was a longitudinal observational study of patients having diabetes with skin complaints attending skin outdoor department or admitted in wards for any reason in a tertiary care hospital. MATERIALS AND METHODS: Total 300 patients were included in the study. Detailed history, clinical examination, and relevant investigations were done to diagnose the mucocutaneous disorders, diabetes, and diabetic complications. STATISTICAL ANALYSIS USED: The data was analyzed by using Epi info software. RESULTS: Demographic profile shown majority of cases (78.66%) in more than 40 years of age with almost equal male and female preponderance. Mucocutaneous manifestations as presenting feature of diabetes were observed in 21.67% cases. Infections were most common in 119 (39.66%) cases, followed by acanthosis nigricans in 46 (15.33%) cases. Various associated complications like hypertension, retinopathy, hyperlipidemia, coronary artery disease, neuropathy, nephropathy, and diabetic ketoacidosis were observed in 160 (53.3%). CONCLUSIONS: Skin is the mirror, which reflects internal diseases; this aptly applies to skin and diabetes mellitus. Through awareness about cutaneous manifestations of DM, dermatologist can not only take credit for detecting DM but also facilitate early diagnosis of systemic complications of DM. This is immensely beneficial to patients in long run.

A case report of focal dermal hypoplasia-Goltz syndrome.

Goltz syndrome is a rare multisystem disorder with cutaneous, ocular, dental and skeletal abnormalities. Other mesoectodermal abnormalities are also present. Its hallmark is thinning of the dermis resulting subcutaneous fat herniation. The present case is a 5 year old girl having linear skin atrophy with fat herniation, skeletal abnormalities in the form of polysyndactyly, facial asymmetry, squint with coloboma iris, deformed pinna, abnormal dentition, umbilical hernia along with osteopathia striata of long bones which is consistent with Goltz syndrome. We are presenting this case due to its rarity.

Two live attenuated Shigella flexneri 2a strains WRSf2G12 and WRSf2G15: a new combination of gene deletions for 2nd generation live attenuated vaccine candidates.

Shigella infections are a major cause of inflammatory diarrhea and dysentery worldwide. First-generation virG-based live attenuated Shigella strains have been successfully tested in phase I and II clinical trials and are a leading approach for Shigella vaccine development. Additional gene deletions in senA, senB and msbB2 have been engineered into second-generation virG-based Shigella flexneri 2a strains producing WRSf2G12 and WRSf2G15. Both strains harbor a unique combination of gene deletions designed to increase the safety of live Shigella vaccines. WRSf2G12 and WRSf2G15 are genetically stable and highly attenuated in both cell culture and animal models of infection. Ocular immunization of guinea pigs with either strain induces robust systemic and mucosal immune responses that protect against homologous challenge with wild-type Shigella. The data support further evaluation of the second-generation strains in a phase I clinical trial.

Hypnosis in pregnancy with intrauterine growth restriction and oligohydramnios: an innovative approach.

The clinical application of hypnosis has been effective in obstetrics. Intrauterine growth restriction and oligohydramnios are dreaded complications of pregnancy that may result in preterm deliveries causing increased perinatal morbidity and mortality. In this longitudinal prospective study, clinical hypnosis was used in addition to the conventional medical management in such pregnancies. The perinatal outcome was compared with the control group wherein hypnosis was not used. The hypnosis group had a significantly shorter preterm delivery rate (p = .004) and fewer incidence of low birth weight babies (p = .009). Significantly reduced operative intervention in terms of lower rate of cesarean section (p = .008) was also observed in the experimental group. Hence, the use of clinical hypnosis as a viable adjunct to medical management is suggested to help to prevent neonatal morbidity and fetal loss. A multicenter randomized, controlled clinical trial is encouraged in this area.

EEC syndrome sans clefting: variable clinical presentations in a family.

Ectrodactyly, ectodermal dysplasia and cleft palate/lip syndrome (EEC) is a rare autosomal dominant syndrome with varied presentation and is actually a multiple congenital anomaly syndrome leading to intra- and interfamilial differences in severity because of its variable expression and reduced penetrance. The cardinal features include ectrodactyly, sparse, wiry, hypopigmented hair, peg-shaped teeth with defective enamel and cleft palate/lip. A family comprising father, daughter and son presented to us with split hand-split foot deformity (ectrodactyly), epiphora, hair changes and deafness with variable involvement in each family member.

Immunogenicity and characterization of WRSF2G11: a second generation live attenuated Shigella flexneri 2a vaccine strain.

Recent clinical trials involving live attenuated Shigella vaccine strains SC602 and WRSS1 have revealed that deletion of the virG(icsA) gene dramatically reduces virulence in human volunteers. These strains can be given at low oral doses and induce a strong, and in some cases, protective immune responses. However, residual vaccine associated reactogenicity suggests that further attenuation is required. A recent clinical trial indicated that the set and sen enterotoxin genes contribute to the symptoms of fever and diarrhea observed with live Shigella vaccine strains. Based on these findings, a Shigella flexneri 2a vaccine candidate, WRSf2G11, with deletions in the virG(icsA), set and sen genes has been constructed using the lambda red recombinase system. The immunogenicity and protective efficacy of WRSf2G11 compares favorably with SC602 following either intranasal (IN) or ocular (OC) immunization of guinea pigs. Taken together, these data indicate that second generation virG-based Shigella vaccine strains which lack enterotoxin genes, such as WRSf2G11, will likely show lower levels of reactogenicity without hampering the robust immune responses achieved with previous live vaccines.

Developing live Shigella vaccines using lambda Red recombineering.

Live attenuated Shigella vaccines have shown promise in inducing protective immune responses in human clinical trials and as carriers of heterologous antigens from other mucosal pathogens. In the past, construction of Shigella vaccine strains relied on classical allelic exchange systems to genetically engineer the bacterial genome. These systems require extensive in vitro engineering of long homologous sequences to create recombinant replication-defective plasmids or phage. Alternatively, the lambda red recombination system from bacteriophage facilitates recombination with as little as 40 bp of homologous DNA. The process, referred to as recombineering, typically uses an inducible lambda red operon on a temperature-sensitive plasmid and optimal transformation conditions to integrate linear antibiotic resistance cassettes flanked by homologous sequences into a bacterial genome. Recent advances in recombineering have enabled modification of genomic DNA from bacterial pathogens including Salmonella, Yersinia, enteropathogenic Escherichia coli, or enterohemorrhagic E. coli and Shigella. These advances in recombineering have been used to systematically delete virulence-associated genes from Shigella, creating a number of isogenic strains from multiple Shigella serotypes. These strains have been characterized for attenuation using both in vivo and in vitro assays. Based on this data, prototypic Shigella vaccine strains containing multiple deletions in virulence-associated genes have been generated.