Identification of Risk Factors for Gliptin-associated Bullous Pemphigoid among Diabetic Patients.

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer's disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p < 0.0001 for both). While compared with sitagliptin, exposure to linagliptin and vildagliptin were associated with bullous pemphigoid with an odds ratio of 5.68 and 6.61 (p < 0.0001 for both), respectively. These results suggest gliptins should be prescribed with caution to patients with type 2 diabetes with coexisting Alzheimer's and other dementias, or patients receiving long-term use of thiazides and loop diuretics. The use of sitagliptin over linagliptin and vildagliptin should be preferred in these patients.

Minimally invasive micro sclerostomy (MIMS) procedure in the treatment of open-angle glaucoma.

BACKGROUND: To evaluate the safety and efficacy of the Minimally Invasive Micro Sclerotomy (MIMS) procedure in the management of uncontrolled open-angle glaucoma. METHODS: A prospective, open-label, single-arm clinical evaluation with intra-subject comparisons performed at the Ophthalmologic Center after S.V. Malayan, Yerevan, Armenia. Included were adults with primary open-angle glaucoma (OAG) (N = 114) or exfoliative glaucoma (N = 6) who were uncontrolled (IOP > 21) on tolerated topical medication. Mild (N = 7), moderate (N = 66) and severe (n = 47) cases were prospectively included without preselection. Following subconjunctival Mitomycin C, an ab-interno MIMS procedure was performed alone (N = 100) or combined with phacoemulsification (N = 20). Patients were followed for 52 weeks. Procedure-related complications and adverse events were recorded. Success criteria were defined as -5 < IOP ≤ 21mmHg OR a reduction in IOP of ≥ 20% from baseline with (qualified success) or without (complete success) hypotensive medications. RESULTS: Mean patient age was 69 ± 10.1 years. The mean duration of the procedure was 2:01 ± 0:41 min:sec. Scleral drainage channels were achieved in all cases. No device malfunctions, intraoperative complications, or serious adverse events were reported. Iris plugging of the sclerostomy site and early spikes in IOP were the most common adverse events. The only reason for failure was final IOP > 21 mmHg on tolerated medication. At 52 weeks (n = 93), mean IOP decreased by 38% from baseline (P < 0.001), from 27.9 ± 3.7 to 17.5 ± 5.3 mmHg, a difference of 10.5 mmHg (95% CI: -11.7, -9.3). One-year qualified success was documented in 82.1% (95% CI: 72.9%,89.2%) of the patients and complete success, in 70.5% (60.3-79.4%). 60% (95 CI:49.4%,69.9%) of the patients achieved maximum IOP level of 14 mmHg or at least 30% reduction in IOP. CONCLUSIONS: MIMS procedure is a relatively simple, short and safe minimally invasive bleb-forming procedure. Its efficacy, as found in this short-term evaluation, lends it suitable for mild and moderate uncontrolled open-angle glaucoma patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04503590 2019-05-29.

Virucidal effect of mouthwash on acyclovir-resistant herpes simplex virus.

OBJECTIVES: The symptoms of herpes simplex viruses type 1 (HSV-1) infections might be severe and persistent in immunocompromised patients in whom they reactivate at a high frequency. The development of Acyclovir (ACV) resistant strains due to long-term treatment with antiviral agents in those patients is not uncommon. The aim of the present study was to assess the virucidal effect of commercially available mouthwashes against ACV-resistant HSV-1 strains. MATERIALS AND METHODS: Two acyclovir-resistant HSV-1 strains were exposed for 30 s to essential oil-based (Listerine Fresh Burst® and Listerine Zero®), chlorhexidine gluconate 0.2% (Hexidyl®) and povidone-iodine 7.5% (Betadine Gargle®) mouthwashes. Loss of virus infectivity was determined by means of plaque reduction assays in a cell culture system. RESULTS: All 4 of the tested solutions significantly reduced virus infectivity, with the essential oil-based and povidone-iodine mouthwashes being slightly more efficacious, compared to chlorhexidine. CONCLUSION: The findings of this analysis revealed that the tested oral rinses demonstrated in-vitro antiviral activity against ACV-resistant HSV. Comparative clinical trials are required to establish the clinical effectiveness of daily use of oral rinses in reducing the appearance of oral HSV lesions in immunocompromised patients.

Coping with emotional dysregulation among young adults with ADHD: A mixed-method study of self-awareness and strategies in daily life.

BACKGROUND: Emotional dysregulation (ED) impacts functional outcomes among individuals with attention-deficit hyperactivity disorder (ADHD). Self-awareness and strategies may enhance coping with ED yet are rarely studied in ADHD. OBJECTIVES: To explore ED-related self-awareness and strategies in daily life of adults with ADHD, and to examine the interrelations between them and their association with symptoms. METHODS: Sixty young adults with ADHD participated in a mixed-method study. At baseline, self-awareness and strategies were assessed using the Self-Regulation Skills Interview (SRSI); ADHD symptoms were self-rated using the ASRS symptom checklist. Then, symptoms were rated over 5-days using ecological momentary assessment (EMA). RESULTS: Significant challenges in self-awareness and strategies were demonstrated quantitatively and qualitatively. Awareness of ED was associated with variability of ADHD symptoms on EMA yet not with symptom severity. Qualitative content analysis revealed a range of self-awareness levels, which were related to noticing ED-related cues and understanding contextual factors predictive of ED. Self-awareness and strategies were significantly associated. Strategies varied regarding effort, individual preference and temporality. CONCLUSIONS: Variability of ADHD symptoms was negatively associated with self-awareness of ED. Strategy selection in daily-life among adults with ADHD may be affected by self-awareness and by a possible trade-off between short-term effort and long-term effectiveness.

Who should be screened for carbapenemase-producing Enterobacterales and when? A systematic review.

Carbapenemase-producing Enterobacterales (CPE) cases increases every year in Denmark and the proportion of CPE-positive cases with a travel history decreases. Several epidemiological links show transmission in Danish healthcare setting indicating infection prevention and control challenges and raising questions about the Danish CPE screening protocol. The aim of this review was to identify additional risk factors to those described in the Danish CPE-screening protocol in order to detect the Danish CPE-positive patients and thereby reduce the risk of transmission and outbreaks. A systematic literature search was conducted in PubMed, Embase and Cochrane Library during March 2022. A total of 1487 articles were screened, and 19 studies were included. Retrieved studies dealt with patients with laboratory-confirmed CPE (colonization and/or infection) and associated risk factors. Antimicrobial therapy, especially broad-spectrum antimicrobial agents, prior or current hospitalization of approximately one week in ICU and 20-28 days in other wards and travel history with or without hospitalization abroad were significant risk factors associated with CPE acquisition. Comorbidities and invasive procedures were identified as risk factors, but without identifying specific comorbidities or invasive procedures associated with risk for CPE-acquisition. This study suggests the need to develop an additional algorithm for CPE-screening in Denmark. In addition to risk-based screening on admission, screening of inpatients should be considered. The screening protocol might include screening of inpatients with comorbidities who are hospitalized >1 week in ICU or >3 weeks in other wards and who have previously received or currently are receiving antibiotic treatment. Further research is needed to develop a new CPE-screening algorithm.

Intralesional human papillomavirus vaccine for the treatment of recalcitrant cutaneous warts.

Human papillomavirus (HPV) is ubiquitously distributed in the population worldwide and its most frequent clinical presentation is cutaneous warts. Despite various treatment options currently available, many patients experience persistent and refractory disease. We sought to evaluate the clinical effectiveness and safety profile of intralesional HPV 9-valent vaccine for the treatment of recalcitrant warts. A retrospective study was performed for all cases of cutaneous warts treated with intralesional 9-valent HPV vaccine between January 2017 and March 2021. Epidemiologic, clinical, and treatment data, including safety and effectiveness scores, were reviewed. Our cohort was composed of 20 patients: 13 adults and seven children. Twelve patients (60%) displayed a complete response whereas 8 patients (40%) showed a partial response. Older age was associated with a better response to treatment, while a history of laser therapy was associated with a worse prognosis. Adverse events were local, transient, and negligible. No systemic adverse effects were reported. Intralesional 9-valent HPV vaccine may be considered for the treatment of recalcitrant cutaneous warts. Controlled studies are required to confirm these results.

The Pictorial Interview of Children's Metacognition and Executive Functions (PIC-ME): Cultural Adaptation for Ultra-Orthodox Jewish Populations.

Introduction: Executive functions (EFs) are strongly linked to attention deficit hyperactivity disorder (ADHD). The pictorial interview of children's metacognition and executive functions (PIC-ME) assesses children's self-perceptions regarding their EF. This study is aimed at describing the cultural adaptation of the PIC-ME to the ultra-Orthodox (UO) Jewish population in Israel. Method: In the first of three stages, 30 occupational therapists, who were experienced in working with children with ADHD from the UO population, completed a questionnaire about the suitability of PIC-ME for the UO community. In the second stage, six therapists participated in a focus group to discuss the recommendations and the adaptations made following the first stage. In the third stage, 20 UO children aged 5-10 participated in the tool validation process. Results: First stage: most of the items of the original tool were found to be appropriate in representing the EFs of UO children and did not need to be adapted. No significant differences were found between the boys' and girls' versions regarding the tool's adaptability. However, most of the therapists suggested that the pictures in both versions needed adaptations. Second stage: additional recommendations led to the development of a final adapted version. Third stage: over 70 percent agreement was found among UO children regarding the clarity of the adapted pictures. No significant differences were found between boys and girls or between age groups. Conclusions: This study presented wide agreement on the necessity for cultural adaptation of the PIC-ME to the UO population and described the adaptation process. Based on its face validity, the UO version may be a useful tool to assess the self-perception of EF among UO children. Further studies are needed to assess its psychometric properties and its usefulness as an outcome measure. The study findings may contribute to the cultural adaptation of other tools for culturally distinct populations.

Pediatric Psoriasis with or without Arthritis: Does It Make a Difference?

BACKGROUND: Psoriasis and psoriatic arthritis can present simultaneously or separately in children and may pose a diagnostic challenge. OBJECTIVE: To compare the dermatological manifestations in pediatric psoriatic patients with and without arthritis. METHODS: A retrospective case-control study of psoriatic patients ≤ 18 years old at Sheba Medical Center was conducted between 2011 and 2021. Patients with psoriatic arthritis versus psoriasis-only were compared according to body surface area (BSA) involvement, cutaneous distribution, severity of skin disease, response to treatment and related side effects. RESULTS: The study cohort included 29 psoriatic arthritis and 64 psoriasis-only patients matched by age and sex. The psoriasis-only group had a significantly higher mean BSA (19.7%, SD ± 18.7) than the psoriatic arthritis group (6.1%, SD ± 11.4), (p = 0.029). The skin distribution differed with the psoriasis group showing more involvement of the extremities, scalp, trunk, and genitals. Both groups primarily experienced partial responses to methotrexate, whereas the psoriasis group mainly saw complete responses to biologics. Adverse events were rare, with a higher incidence in the psoriasis group. CONCLUSION: This retrospective study highlights the differences in cutaneous disease characteristics, severity, and treatment response in pediatric patients with psoriasis and psoriatic arthritis, providing valuable insights for diagnosis and disease course in the pediatric population.

Monitoring oral propranolol for infantile hemangiomata.

Treating infantile hemangiomas with oral propranolol may be initiated in accordance with various protocols some require hospitalization. However, different adverse events have been reported during treatment, thus it is of special importance to find a protocol which is both safe and feasible. We performed a retrospective cohort study of all cases of infantile hemangiomas treated with oral propranolol at our institute between January 2010 and February 2020. Pretreatment evaluation consisted of pediatric cardiologist evaluation including electrocardiography and echocardiography. The propranolol starting dosage was 0.5 mg/kg bid; 2 weeks later the dosage was escalated to 1 mg/kg bid. During the initiation and escalation visits, heart rate and blood pressure were measured before and every hour for a total of 3 h, and blood glucose level was measured within the first hour of treatment. A total of 131 children were treated during the study period. Scalp, facial and genital region infantile hemangiomas were more prevalent in regard to their relative body surface area. No symptomatic bradycardia, hypotension, hypoglycemia, or any other adverse events were documented; few patients had asymptomatic bradycardia and hypotension, which were more common in infants below 6-months of age. Only one patient had asymptomatic hypoglycemia, not requiring any intervention. Initiation and escalation of propranolol treatment for infantile hemangiomas proved to be safe, and without symptomatic adverse effects. However, considering the young age of the patients and the possible asymptomatic adverse reactions, we recommend the following simple protocol as presented, for pretreatment evaluation and short monitoring during treatment initiation and dose escalation.

Superimposed type 2 segmental atopic dermatitis: case series and review of the literature.

Generalized acquired dermatoses can seldom manifest more prominently or exclusively along the lines of Blaschko. Six individuals with segmental atopic dermatitis (AD) have been reported to date. We present three additional cases of segmental cutaneous manifestations superimposed on generalized AD, and review the relevant literature.

Specific Detection of SARS-CoV-2 Variants B.1.1.7 (Alpha) and B.1.617.2 (Delta) Using a One-Step Quantitative PCR Assay.

In this report, we describe the development of a reverse transcription-quantitative PCR (RT-qPCR) assay, termed Alpha-Delta assay, which can detect all severe acute respiratory syndrome coronavirus 2 (SC-2) variants and distinguish between the Alpha (B.1.1.7) and Delta (B.1.617.2) variants. The Alpha- and Delta-specific reactions in the assay target mutations that are strongly linked to the target variant. The Alpha reaction targets the D3L substitution in the N gene, and the Delta reaction targets the spike gene 156 to 158 mutations. Additionally, we describe a second Delta-specific assay that we use as a confirmatory test for the Alpha-Delta assay that targets the 119 to 120 deletion in the Orf8 gene. Both reactions have similar sensitivities of 15 to 25 copies per reaction, similar to the sensitivity of commercial SC-2 detection tests. The Alpha-Delta assay and the Orf8119del assay were successfully used to classify clinical samples that were subsequently analyzed by whole-genome sequencing. Lastly, the capability of the Alpha-Delta assay and Orf8119del assay to identify correctly the presence of Delta RNA in wastewater samples was demonstrated. This study provides a rapid, sensitive, and cost-effective tool for detecting and classifying two worldwide dominant SC-2 variants. It also highlights the importance of a timely diagnostic response to the emergence of new SC-2 variants with significant consequences on global health. IMPORTANCE The new assays described herein enable rapid, straightforward, and cost-effective detection of severe acute respiratory syndrome coronavirus 2 (SC-2) with immediate classification of the examined sample as Alpha, Delta, non-Alpha, or non-Delta variant. This is highly important for two main reasons: (i) it provides the scientific and medical community with a novel diagnostic tool to rapidly detect and classify any SC-2 sample of interest as Alpha, Delta, or none and can be applied to both clinical and environmental samples, and (ii) it demonstrates how to respond to the emergence of new variants of concern by developing a variant-specific assay. Such assays should improve our preparedness and adjust the diagnostic capacity to serve clinical, epidemiological, and research needs.

Pilot Study of the Cognitive-Functional Intervention for Adults (Cog-Fun A): A Metacognitive-Functional Tool for Adults With Attention Deficit Hyperactivity Disorder.

IMPORTANCE: Adults with attention deficit hyperactivity disorder (ADHD) often experience chronic challenges in their life roles. There is a need for evidence-based occupational therapy interventions to help enhance their functioning. OBJECTIVE: To determine the preliminary effectiveness of the Cognitive-Functional Intervention for Adults (Cog-Fun A), a metacognitive-functional occupational therapy tool for the improvement of occupational performance (OP) and quality of life (QoL) in adults with ADHD. DESIGN: One-group pretest-posttest design with a 3-mo follow-up. SETTING: Community setting in Jerusalem, Israel. PARTICIPANTS: Fourteen adults, ages 18-60 yr, with a valid diagnosis of ADHD and an indication of executive function (EF) impairment. INTERVENTION: Participants received 15 1-hr weekly sessions that addressed self-awareness of strengths and challenges through education and guided discovery as well as strategy acquisition and implementation within a context of occupational goal attainment. OUTCOMES AND MEASURES: The Behavioral Rating Inventory of Executive Function-Adult version, an adult ADHD QoL measure, the Canadian Occupational Performance Measure, and the Self-Regulation Skills Interview were administered. RESULTS: Twelve participants completed the intervention. Posttreatment scores revealed statistically significant improvements in EF, awareness, OP, and QoL. Gains in QoL showed a modest reduction at the 3-mo follow-up. CONCLUSIONS AND RELEVANCE: The Cog-Fun A is a promising intervention for improving OP and QoL among adults with ADHD and should be investigated further. What This Article Adds: The Cog-Fun A offers an effective nonpharmacological, metacognitive-functional, occupation-centered treatment option for adults with ADHD.

Ex vivo organotypic cultures for synergistic therapy prioritization identify patient-specific responses to combined MEK and Src inhibition in colorectal cancer.

Translating preclinical studies to effective treatment protocols and identifying specific therapeutic responses in individuals with cancer is challenging. This may arise due to the complex genetic makeup of tumor cells and the impact of their multifaceted tumor microenvironment on drug response. To find new clinically relevant drug combinations for colorectal cancer (CRC), we prioritized the top five synergistic combinations from a large in vitro screen for ex vivo testing on 29 freshly resected human CRC tumors and found that only the combination of mitogen-activated protein kinase kinase (MEK) and proto-oncogene tyrosine-protein kinase Src (Src) inhibition was effective when tested ex vivo. Pretreatment phosphorylated Src (pSrc) was identified as a predictive biomarker for MEK and Src inhibition only in the absence of KRASG12 mutations. Overall, we demonstrate the potential of using ex vivo platforms to identify drug combinations and discover MEK and Src dual inhibition as an effective drug combination in a predefined subset of individuals with CRC.

A review of combined treatments for melasma involving energy-based devices and proposed pathogenesis-oriented combinations.

BACKGROUND: Melasma is an acquired disorder of hyperpigmentation, affecting a million individuals worldwide. Energy-based devices (EBDs) employed to treat melasma include various types of lasers, intense pulsed light (IPL), and radiofrequency (RF). Recent studies have attempted to address recalcitrant and recurring melasma by combining energy-based devices with topical or oral medications. OBJECTIVE: This article reviews EBDs-based augmented treatment for melasma and suggests practical pathogenesis-oriented treatment regimens. Treatment algorithms are proposed to address various components of melasma. METHODS: A systematic PubMed search was conducted acquiring information from various studies on combination treatments of melasma involving EBDs. RESULTS: The 286 retrieved articles were filtered by title to contain at least one type of energy-based modality such as laser, IPL, or RF along with at least one other treatment method. Based on their subject matter, combinations were further categorized into the subheadings: laser plus medication, laser plus laser, and IPL- and RF-containing treatment methods. CONCLUSION: There are many energy-based combination treatments that have been explored for mitigation of melasma including laser therapy with medication, multi-laser therapies, IPL, RF, and microneedling devices. Melasma is an exceedingly difficult condition to treat, however, choosing the appropriate tailor-made treatment combination can improve the final outcome.

Feasibility of hybrid Ivor-Lewis oesophagectomy after sleeve gastrectomy.

Oesophageal resection is a challenging procedure, and it is more so in patients who have undergone bariatric procedures, especially after laparoscopic sleeve gastrectomy. We present the case of a patient with a history of an laparoscopic sleeve gastrectomy who underwent a hybrid Ivor-Lewis oesophagectomy in which the sleeve was successfully used to reconstruct the upper gastrointestinal tract.

The SARS-CoV-2 Lambda variant and its neutralisation efficiency following vaccination with Comirnaty, Israel, April to June 2021.

The SARS-CoV-2 Lambda (Pango lineage designation C.37) variant of interest, initially identified in Peru, has spread to additional countries. First detected in Israel in April 2021 following importations from Argentina and several European countries, the Lambda variant infected 18 individuals belonging to two main transmission chains without further spread. Micro-neutralisation assays following Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer) vaccination demonstrated a significant 1.6-fold reduction in neutralising titres compared with the wild type virus, suggesting increased susceptibility of vaccinated individuals to infection.