A Novel Large Deletion in the EVER1 Gene in a Family With Epidermodysplasia Verruciformis From India.

ABSTRACT: Epidermodysplasia verruciformis (EV) is a rare autosomal recessive genodermatosis due to mutations in EVER1 and EVER2 genes. The genetic profile of Indian patients with EV has not been previously studied. This report describes the clinical presentation and molecular analysis of a family with EV. Using genomic DNA from two affected probands and healthy controls (two other siblings), conventional polymerase chain reaction (PCR) was conducted with novel primer sets designed to amplify the coding and splice-site regions in the genes EVER1 and EVER 2. This revealed no amplification with a primer set for exons 16 to 18 in the EVER1 gene of both the probands. Subsequently, long-range PCR spanning the length of exon 15-20 and next-generation sequencing demonstrated a homozygous deletion of 2078 bp in the EVER1 gene (EVER1:c.2072_2278del). Screening the family revealed the same homozygous deletion (similar to index cases) in two other affected siblings. The parents and two asymptomatic siblings were heterozygous carriers for the deletion while one healthy sibling was negative. These results were validated with Sanger sequencing. This deletion in exons 17 and 18 of the EVER1 gene results in a frameshift, followed by a premature termination resulting in a severe phenotype. The identification and validation of this large deletion was detected using stepwise amplicon-based target enrichment and long-range PCR, respectively. In this family, this simple strategy greatly enhanced genetic counseling as well as early genetic diagnosis and screening. However, functional assays and larger studies are required to characterize and validate the genetic diversity among Indians with EV.

Diabetic foot ulcers, their characteristics, and trends in survival: Real world outcomes at a tertiary care facility in India.

AIMS: Characteristics of diabetes-related foot ulcers (DFU), association with recurrence and amputation are poorly described in the Asian Indian population. METHODS: A prospectively maintained database was reviewed to characterize DFU and its association with amputation and recurrence. RESULTS: Of 200 patients, 63.5 % were male, the median age was 62 years (Min-Max:40-86), and median BMI was 27.90 kg/m2 (Min-Max:18.5-42.7). Median duration of Diabetes mellitus was 15 years (Min-Max:2-43). Complete healing occurred at a median of three months (Min-Max:0.23-37.62). Amputation for the current ulcer was required in 43.4 % of individuals. Ulcer recurrence was documented in 42.4 % instances, 66.1 % evolving on the ipsilateral side. Previous amputation was associated with the risk of subsequent amputation (Adjusted OR-3.08,p-0.047). Median time to ulcer recurrence was 4.23 years among those with amputation, in contrast to 9.61 years in those with healing. Cardiovascular death was the commonest cause of mortality, followed by sepsis. At a median follow up of 6.08 years, mortality at 1,3,5 and 10 years was 2.5 %,2.5 %,8.2 % and 30.9 % respectively among those who underwent amputation versus 0 %,0 %,10.1 % and 24.5 % respectively for those who achieved healing. CONCLUSIONS: Patients with DFU in India incur amputations at rates higher than conventionally described. With previous amputation, subsequent amputation risk triples. Ten-year mortality is 25%-30 %. Underestimates of the burden of recurrence and mortality are consequential of limited follow-up.

Low-dose nivolumab and cabozantinib in recurrent intestinal-type papillary adenocarcinoma of the sinonasal region.

Intestinal-type sinonasal adenocarcinoma is a rare epithelial malignancy primarily treated with surgery and chemoradiation. The combination of low-dose immunotherapy and a tyrosine kinase inhibitor in recurrent disease has not been previously studied.A man in his 20s with papillary adenocarcinoma of the sinonasal region, following surgical resection, was treated with six cycles of concurrent chemoradiotherapy, followed by four cycles of docetaxel, cisplatin and capecitabine. While on treatment, he was found to have extensive residual disease and he was started on low-dose nivolumab and cabozantinib. Repeat imaging after ten months of treatment revealed a significant reduction in lesions.Non-squamous head and neck cancers are often excluded from major trials, and the effect of immunotherapy in these histologies is poorly understood. The response seen with low-dose immunotherapy underscores the need for further research in this setting.

Quality of life among those with diabetes mellitus type II attending a secondary outpatient facility in South India.

Context and Aim: Diabetes mellitus (DM) can affect one's quality of life (QoL). Literature on the association of QoL among type II diabetics with drug compliance and diet quality among rural communities is poor. This study aimed to determine the QoL among those with type II DM attending an outpatient clinic at a secondary hospital in Tamil Nadu. Settings and Design: A cross-sectional, interview-based study was carried out among those with type II DM. A questionnaire comprising the WHO-BREF tool, Diabetes Healthy Eating Index, Hill-Bone Medication Adherence Scale was administered to participants selected via systematic random sampling. Results: The prevalence of good QoL was estimated to be 51.7% (n = 45, 95% CI: 41.20-62.20). There was no association between good QoL and medication compliance. None of the patients had a good diet quality. Bivariate analysis revealed significant association (p < 0.05) between good QoL and higher education (OR-2.70), those not on medication for complications (OR-2.81) and decreased frequency of general random blood sugar (GRBS) monitoring (OR-2.44). Multivariable analysis adjusting for gender, education, treatment/medication for complications, hospitalisation for DM and GRBS frequency demonstrated significant association between good QoL, lack of medication for complications/co-morbidities and decreased GRBS monitoring frequency with likelihood ratios of 3.25 and 3.44, respectively. Conclusions: The drop in QoL observed could be due to the aftermath of the COVID pandemic. Keeping in mind the impact of healthcare interventions on the QoL of type II DM patients, primary physicians must consider dietary and treatment plans suited to their socio-economic status.

Therapeutic Interchange of Clevidipine For Sodium Nitroprusside in Cardiac Surgery.

BACKGROUND: Generic price inflation has resulted in rising acquisition costs for sodium nitroprusside (SNP), an agent historically described as the drug of choice for the treatment of perioperative hypertension in cardiac surgery. PURPOSE: To describe the implementation and cost avoidance achieved by utilizing clevidipine as an alternative to SNP in cardiac surgery patients at a 520-bed community teaching hospital that performs more than 300 cardiac surgeries each year. METHODS: A multidisciplinary team inclusive of anesthesiologists, intensivists, pharmacists, and surgeons collaborated to develop a therapeutic interchange for SNP in cardiac surgery patients. Consistent with current guidelines for therapeutic interchange, the goal was to encourage a less expensive alternative that was demonstrated to be at least therapeutically equivalent to SNP based on data derived from clinical trials published in peer-reviewed literature. A comprehensive literature review identified clevidipine as an alternative to SNP for perioperative hypertension in cardiac surgery. Nicardipine was considered as well, but was not chosen as a substitute due to lack of strong evidence and comparative data with SNP. RESULTS: Clevidipine was implemented successfully in our cardiac surgery patients and will result in a net cost avoidance of approximately $300,000 in 2016. This is thought to be driven largely by the difference in acquisition cost between clevidipine and SNP. The operating room in our institution no longer keeps SNP stocked in anesthesia trays as a result of the success of our interchange. No requests have been made to return to the SNP standard. CONCLUSION: Through effective communication and multidisciplinary collaboration, our institution was able to develop an evidence-based and effective therapeutic interchange program for SNP.

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States.

OBJECTIVE: The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the prolonged empiric antibiotic therapy rate and certain ICU characteristics. DESIGN: Multicenter, prospective, observational, 72-hour snapshot study. SETTING: Sixty-seven ICUs from 32 hospitals in the United States. PATIENTS: Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate. CONCLUSIONS: Half of all empiric antibiotics ordered in critically ill patients are continued for at least 72 hours in absence of adjudicated infection. Additional studies are needed to confirm these findings and determine the risks and benefits of prolonged empiric therapy in the critically ill.

Minimum qualifications for clinical pharmacy practice faculty.

The American College of Clinical Pharmacy 2013 Educational Affairs Committee was charged with developing recommendations for the minimum qualifications required for clinical pharmacy practice faculty in United States colleges and schools of pharmacy with respect to education, postgraduate training, board certification, and other experiences. From a review of the literature, the committee recommends that clinical pharmacy practice faculty possess the following minimum qualifications, noting that, for some positions, additional qualifications may be necessary. Clinical pharmacy practice faculty should possess the Doctor of Pharmacy degree from an Accreditation Council for Pharmacy Education­accredited institution. In addition, faculty should have completed a postgraduate year one (PGY1) residency or possess at least 3 years of direct patient care experience. Faculty who practice in identified areas of pharmacotherapy specialization, as identified by American Society of Health-System Pharmacists postgraduate year two (PGY2) residency guidelines, should have completed a PGY2 residency in that area of specialty practice. Alternatively, faculty should have completed a minimum of a PGY1 residency and 1 additional year of practice, with at least 50% of time spent in their area of specialization, which is documented in a portfolio, or 4 years of direct patient care in their area of specialization, which is documented in a portfolio. Fellowship training or a graduate degree (e.g., Ph.D.) should be required for research-intensive clinical faculty positions. All faculty should obtain structured teaching experience during or after postgraduate training, preferably through a formal teaching certificate program or through activities documented in a teaching portfolio. A baseline record of scholarship should be obtained before hire as clinical pharmacy practice faculty through exposure in postgraduate programs or previous employment. Faculty should be board certified before hire or attain board certification within 2 years of hire through the Board of Pharmacy Specialties (BPS) or, if appropriate for the practice area, through a nonBPS-certifying agency. If no certification exists in the area of specialty, the faculty member should develop a portfolio with evidence of excellence in clinical practice, teaching, and scholarship.

Drug-induced endocrine disorders in the intensive care unit.

The neuroendocrine response to critical illness is key to the maintenance of homeostasis. Many of the drugs administered routinely in the intensive care unit significantly impact the neuroendocrine system. These agents can disrupt the hypothalamic-pituitary-adrenal axis, cause thyroid abnormalities, and result in dysglycemia. Herein, we review major drug-induced endocrine disorders and highlight some of the controversies that remain in this area. We also discuss some of the more rare drug-induced syndromes that have been described in the intensive care unit. Drugs that may result in an intensive care unit admission secondary to an endocrine-related adverse event are also included. Unfortunately, very few studies have systematically addressed drug-induced endocrine disorders in the critically ill. Timely identification and appropriate management of drug-induced endocrine adverse events may potentially improve outcomes in the critically ill. However, more research is needed to fully understand the impact of medications on endocrine function in the intensive care unit.

An update on the diagnosis of adrenal insufficiency and the use of corticotherapy in critical illness.

OBJECTIVE: To examine recent literature regarding corticotherapy in critically ill patients suffering from sepsis, acute respiratory distress syndrome (ARDS), and severe community-acquired pneumonia (SCAP). DATA SOURCES: Literature was identified through MEDLINE (1966-April 2007) using combinations of the key words hydrocortisone, adrenal insufficiency, acute respiratory distress syndrome, pneumonia, sepsis, and cortisol. Bibliographies of relevant articles were reviewed for additional citations. Presentations at recent critical care meetings were also incorporated. STUDY SELECTION AND DATA EXTRACTION: Articles were chosen based upon their relevance to the topics covered. DATA SYNTHESIS: Earlier studies using high-dose corticotherapy in the intensive care unit have shown treatment to be ineffective. Recent studies using extended courses of low-to-moderate doses of steroids have found favorable results; however, these results must be interpreted with caution due to limitations in the data. One trial of steroids in septic shock found a survival benefit in patients who failed to increase their baseline cortisol by greater than 9 microg/dL in response to adrenocorticotropic hormone, but these results were not reproduced in a subsequent Phase 3 trial. Recently, inaccuracies in measuring cortisol have been identified, making interpretation of cortisol concentrations difficult. A large-scale study failed to confirm a previously reported mortality benefit of corticotherapy in late ARDS, but preliminary data suggest a role for steroid treatment in early ARDS. Finally, a pilot study has found that hydrocortisone lowers morbidity and mortality in SCAP. CONCLUSIONS: Corticotherapy may be beneficial to some patients with sepsis. The decision to administer steroids in sepsis cannot be based on biochemical markers of adrenal function; rather, treatment should be considered in septic patients with vasopressor refractory hypotension. Although preliminary evidence suggests a role for steroids in early ARDS and SCAP, there are not enough data to suggest routine administration of steroids in these conditions. Additional studies are needed to assess corticotherapy in the critically ill.

Metronidazole in Scabies.

Twenty-five patients with scabies were studied for the evaluation of metronidazole as an oral therapeutic agent. These patients were given 400 mg of metronidazole three times daily for 8 days. Good to excellent results were observed in 6 (27.27%) patients, 8 (36.36%) patients showed a fair response and no response was observed in 8 patients (36.36%). The significance of these results are discussed.