Adverse Drug Reactions Due to Opioid Use in Oldest-Old Patients Visiting the Emergency Unit of the Geneva Geriatric Hospital.

Opioid use has much increased in several countries during the last two decades, accompanied by a rise in associated morbidity and mortality, especially in the United States. Data on a possible opioid crisis are scarcer in Europe. We performed a study aiming to assess the frequency of adverse drug reactions (ADR) related to opioids in patients presenting to the emergency unit (EU) of a geriatric tertiary Swiss University Hospital. This particular setting is intended for patients aged 75 and older. Our retrospective, monocentric survey of opioid use and related ADR was conducted over two months in 2018. The main and secondary outcomes were the frequency of EU visits considered due to an opioid ADR and insufficient pain relief, respectively. Current opioid use was identified in 20.3% (n=99) of the 487 included EU visits (mean age 86). An ADR was the suspected cause of the EU visit in 22 opioid users, mainly fall-related injury and gastrointestinal disorders. All these patients had at least one comorbid condition. In 19/22 cases (86%) of ADR, a drug-drug interaction might have been involved. In 12 opioid users (12%), insufficient pain relief was suspected as the cause of the EU visit. In conclusion, one-third of opioid users visiting a geriatric EU consulted for a problem related to its use mainly adverse drug-related reaction (22%) followed by insufficient pain relief (12%).

Three-year efficacy and safety of certolizumab pegol for the treatment of plaque psoriasis: results from the randomized phase 3 CIMPACT trial.

BACKGROUND: Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-tumor necrosis factor biologic. OBJECTIVES: To report 3-year outcomes from the CIMPACT (NCT02346240) phase 3, CZP in moderate to severe plaque psoriasis, randomized controlled trial. METHODS: Adults were randomized 3:3:3:1 to CZP 200 mg every other week (Q2W), CZP 400 mg Q2W, etanercept biweekly or placebo. At Week 16, CZP- and etanercept-treated PASI 75 responders were re-randomized to CZP 200 mg Q2W, CZP 400 mg Q4W, CZP 400 mg Q2W or placebo for maintenance treatment; PASI 75 non-responders entered an open-label escape CZP 400 mg Q2W arm. Patients entering the open-label extension (OLE; Weeks 48-144) from blinded treatment received CZP 200 mg Q2W. RESULTS: Double-blinded results have been reported previously. 261 patients received 200 mg Q2W upon OLE entry. PASI 75 response was maintained in patients continuing 200 mg Q2W treatment through Weeks 16-144 (Week 144: 96.2%). In patients dosed down at Week 48 (double-blinded 400 mg to 200 mg Q2W), PASI 75 decreased (Week 48: 98.7%; Week 144: 85.9%). In patients who received placebo through Weeks 16-48, PASI 75 response decreased (Week 48: 60.4%), then increased following Week 48 switch to 200 mg Q2W (Week 144: 95.1%). 48 and 36 patients initially randomized to 200 and 400 mg Q2W, respectively, were Week 16 PASI 75 non-responders and entered the escape arm; at Week 144, 71.8% and 78.2% achieved PASI 75. No new safety signals were identified. CONCLUSIONS: Response to CZP was durable over three years; no new safety signals were identified.

Chronic skin disease and levels of physical activity in 17 777 Spanish adults: a cross-sectional study.

BACKGROUND: To date there is limited literature on the prevalence of chronic skin conditions and its association with levels of physical activity (PA) in Spain. AIM: To determine the prevalence of chronic skin disease and to compare levels of PA between people with and without chronic skin disease in a large representative sample of Spanish adults aged 15-69 years. METHODS: Data from the Spanish National Health Survey 2017 were analysed. Chronic skin disease was assessed using a yes/no question. PA was measured using the short form of the International Physical Activity Questionnaire. Total PA metabolic equivalent of task min/week were calculated, and PA was included in the analyses as a continuous and a five-category variable. RESULTS: This cross-sectional study included 17 777 adult participants (52.0% women; mean ± SD age 45.8 ± 14.1 years), of whom 940 (5.3%) had chronic skin disease. After adjusting for several potential confounders, there was a negative association between chronic skin disease and PA (OR = 0.87, 95% CI 0.76-1.00, P = 0.05), which was significant for men (OR = 0.76, 95% CI 0.62-0.93, P = 0.01) but not for women (OR = 0.97, 95% CI 0.81-1.16, P = 0.72). CONCLUSIONS: In this large representative sample of Spanish adults, the prevalence of chronic skin disease was low. Levels of PA were lower in men with than in men without chronic skin conditions, but this association was not seen in women.

Onychomycosis: a review.

Onychomycosis is a fungal infection of the nail, causing discoloration and thickening of the affected nail plate, and is the most common nail infection worldwide. Onychomycosis was initially thought to be predominantly caused by dermatophytes; however, new research has revealed that mixed infections and those caused by non-dermatophyte moulds (NDMs) are more prevalent than previously thought, especially in warmer climates. Microscopy and fungal culture are the gold standard techniques for onychomycosis diagnosis, but high false-negative rates have pushed for more accurate methods, such as histology and PCR. As NDMs are skin and laboratory contaminants, their presence as an infectious agent requires multiple confirmations and repeated sampling. There are several treatment options available, including oral antifungals, topicals and devices. Oral antifungals have higher cure rates and shorter treatment periods than topical treatments, but have adverse side effects such as hepatotoxicity and drug interactions. Terbinafine, itraconazole and fluconazole are most commonly used, with new oral antifungals such as fosravuconazole being evaluated. Topical treatments, such as efinaconazole, tavaborole, ciclopirox and amorolfine have less serious side effects, but also have generally lower cure rates and much longer treatment regimens. New topical formulations are being investigated as faster-acting alternatives to the currently available topical treatments. Devices such as lasers have shown promise in improving the cosmetic appearance of the nail, but due to a high variation of study methods and definitions of cure, their effectiveness for onychomycosis has yet to be sufficiently proven. Recurrence rates for onychomycosis are high; once infected, patients should seek medical treatment as soon as possible and sanitize their shoes and socks. Prophylactic application of topicals and avoiding walking barefoot in public places may help prevent recurrence.

Systematic review of the efficacies and adverse effects of treatments for pityriasis lichenoides.

BACKGROUND: Pityriasis lichenoides (PL) is a papulosquamous dermatosis affecting both children and adults, for which no standard treatment currently exists. OBJECTIVES: To characterize different treatment options and develop an evidence-based treatment algorithm for PL. METHODS: A systematic search of published literature on PL treatments was performed on 23 December 2017 via the MEDLINE, Embase, CINAHL, CENTRAL, ClinicalTrials.gov and the EU Clinical Trials Register databases. RESULTS: Of 1090 abstracts retrieved, 27 full-text articles with 502 participants were included for analysis. Seventeen of the full-text articles were retrospective cohort studies and two were randomized controlled studies. Treatment modalities included in these articles were phototherapy, antibiotics, methotrexate, pyrimethamine and trisulfapyrimidine, corticosteroids and conservative treatment. Of these treatments, phototherapy led to complete remission in the highest proportion of patients, and topical corticosteroids were found to have been trialled in the highest number of patients. CONCLUSIONS: The current literature consists almost entirely of uncontrolled studies, and none provides compelling data to support an evidence-based approach to PL treatment. Pityriasis lichenoides chronica and pityriasis lichenoides et varioliformis acuta should be distinguished in response to treatment, and definitions of response to treatment must be standardized. Additional randomized control studies with longer follow-up will help better differentiate between treatment efficacies and adverse effects.

Monotherapy for toenail onychomycosis: a systematic review and network meta-analysis.

BACKGROUND: Onychomycosis is a fungal infection of the nail caused by dermatophytes, yeasts and nondermatophyte moulds that accounts for approximately 50% of all nail-related disease. OBJECTIVES: This study aims to assess the effectiveness and safety of monotherapy and combination treatments for toenail onychomycosis using a network meta-analysis (NMA). METHODS: Quality of evidence was assessed using Cochrane-compliant rules and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Efficacy and safety outcomes were compared using a random-effects NMA to estimate pooled odds ratios (ORs) of direct and indirect comparisons among oral and topical treatments (PROSPERO 2015: CRD42018086912). There were not enough eligible combination and device-based therapy trials to include in the NMA. RESULTS: Of 77 randomized controlled trials, 26 were included in the ORs (8136 patients). There were no significant inconsistencies between the direct and indirect evidence. Relative effects show that the odds of mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg are significantly greater than topical treatments. Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure. The ORs of adverse events occurring with oral or topical treatments were not significantly different from each other. For mycological cure, evidence was of moderate or high quality while evidence ranged from very low to high quality for adverse events. CONCLUSIONS: Our review suggests that oral and topical treatments for toenail onychomycosis are safe and effective in producing mycological cure. What's already known about this topic? Topical treatments traditionally have lower success rates than oral treatments. Oral treatments have the advantage of shorter treatment durations, but also present challenges in cases of drug-drug interactions or immunosuppression. A network meta-analysis (NMA) gathers data from indirect evidence to gain confidence about all treatment comparisons and allows for estimation of comparative effects that have not been investigated in head-to-head randomized clinical trials (RCTs). What does this study add? This NMA of efficacy and safety includes all RCTs of oral, topical, combination and device-based treatments for toenail onychomycosis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for NMA. The odds of achieving mycological cure with continuous terbinafine 250 mg or continuous itraconazole 200 mg were significantly greater than topical treatments. Fluconazole, pulse regimens of terbinafine and itraconazole, and topical treatments did not differ significantly in the odds of achieving mycological cure.

The efficacy and safety of pulse vs. continuous therapy for dermatophyte toenail onychomycosis.

BACKGROUND: Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus for a significant proportion of patients. Treatment with these drugs can be continuous or intermittent, albeit the evidence on their relative efficacies remains unclear. OBJECTIVE: To determine the relative effectiveness and safety of pulse versus continuous administration, of three common oral therapies for dermatophyte onychomycosis, by conducting multiple-treatment meta-analysis. METHODS: This systematic review and network meta-analysis compared the efficacy (as per mycological cure) and adverse event rates of three oral antifungal medications in the treatment of dermatophyte toenail onychomycosis, namely terbinafine, itraconazole and fluconazole. A total of 30 studies were included in the systematic review, while 22 were included in the network meta-analysis. RESULTS: The likelihood of mycological cure was not significantly different between continuous and pulse regimens for each of terbinafine and itraconazole. Use of continuous terbinafine for 24 weeks - but not 12 weeks - was significantly more likely to result in mycological cure than continuous itraconazole for 12 weeks or weekly fluconazole for 9-12 months. Rank probabilities demonstrated that 24-week continuous treatment of terbinafine was the most effective. There were no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole and fluconazole. Drug treatments were similar to placebo in terms of their likelihood of producing adverse events. CONCLUSION: More knowledge about the fungal life cycle and drugs' pharmacokinetics in nail and plasma could further explain the relative efficacy and safety of the pulse and continuous treatment regimens. Our results indicate that in the treatment of dermatophyte toenail onychomycosis, the continuous and pulse regimens for terbinafine and itraconazole have similar efficacies and rates of adverse events.