Assessing adherence to dermatology treatments: a review of self-report and electronic measures

Nonadherence to prescribed medications is a common problem in dermatology, and assessing adherence can be difficult. Electronic monitors are not always practical, but self-report measures may be less reliable.To review the literature for self-report instruments and electronic monitors used to measure medication adherence in patients with chronic disease.A PubMed literature search was conducted using the terms ‘scale,’‘measure,’‘self-report,’‘electronic,’ and ‘medication adherence.’ Relevant articles were reviewed and selected if they addressed self-report or electronic measures of adherence in chronic disease.Eleven self-report instruments for the measurement of adherence were identified. Four were validated using electronic monitors. All produced an estimate of adherence that correlated with actual behavior, although this correlation was not strong for any of the measures. None of the scales was tested in patients who had dermatologic disease and/or used topical medications. Several electronic monitoring systems were identified, including pill counts, pharmacy refill logs, and the Medication Event Monitoring System (MEMS ® ). Validity was higher among electronic monitoring systems compared with self-report measures.While several self-report measures of adherence have been validated in chronic disease populations, their relevance in dermatology patients has not been studied. A dermatology-specific instrument for the measurement of adherence would contribute to improved outcomes; until such a tool exists, researchers and clinicians should consider nonadherence as a possible factor in skin disease that is not responsive to treatment. Electronic monitoring provides the most reliable means of measuring adherence, and may provide additional clues to identify barriers to adherence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79087/1/j.1600-0846.2010.00431.x.pd

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Are topical keratolytic agents needed in the treatment of scalp psoriasis?

Background: Topical corticosteroids are the primary treatment for scalp psoriasis. Keratolytic agents are promoted as adjunctive treatments.  However, complex treatment regimens may result in poor adherence and outcomes.Objective: To evaluate the evidence for the need for use of topical keratolytic agents as opposed to topical corticosteroid monotherapy in the treatment of scalp psoriasis.Methods: A review of the literature was performed seeking clinical trials using topical keratolytics, topical corticosteroids or the combination for treatment of scalp psoriasis.Results: Complete clearance of scalp psoriasis can be achieved in 10-78% of patients using topical corticosteroids alone, in 3% of patients using topical keratolytics alone, and in up to 84% using a combination of topical keratolytics and topical steroids. Clinical trials comparing the combination of keratolytics and topical corticosteroids versus topical corticosteroids alone found marginally more efficacy using combination regimens.Limitations: We could not find any long term study evaluating the efficacy of combination therapy in scalp psoriasis and its effect on the patients’ adherence.Conclusion: High potency topical corticosteroids are usually effective in treating scalp psoriasis in clinical trials.  Poor efficacy in clinical practice may be owing to poor adherence to the treatment regimen. Using a keratolytic agent in conjunction with a topical corticosteroid may provide marginal additional benefit in clinical trials, but that benefit is likely outweighed by the downside of complicating treatment and reducing adherence in the clinical setting, unless a single product containing both medications were used

Are topical keratolytic agents needed in the treatment of scalp psoriasis?

Background: Topical corticosteroids are the primary treatment for scalp psoriasis. Keratolytic agents are promoted as adjunctive treatments.  However, complex treatment regimens may result in poor adherence and outcomes.Objective: To evaluate the evidence for the need for use of topical keratolytic agents as opposed to topical corticosteroid monotherapy in the treatment of scalp psoriasis.Methods: A review of the literature was performed seeking clinical trials using topical keratolytics, topical corticosteroids or the combination for treatment of scalp psoriasis.Results: Complete clearance of scalp psoriasis can be achieved in 10-78% of patients using topical corticosteroids alone, in 3% of patients using topical keratolytics alone, and in up to 84% using a combination of topical keratolytics and topical steroids. Clinical trials comparing the combination of keratolytics and topical corticosteroids versus topical corticosteroids alone found marginally more efficacy using combination regimens.Limitations: We could not find any long term study evaluating the efficacy of combination therapy in scalp psoriasis and its effect on the patients’ adherence.Conclusion: High potency topical corticosteroids are usually effective in treating scalp psoriasis in clinical trials.  Poor efficacy in clinical practice may be owing to poor adherence to the treatment regimen. Using a keratolytic agent in conjunction with a topical corticosteroid may provide marginal additional benefit in clinical trials, but that benefit is likely outweighed by the downside of complicating treatment and reducing adherence in the clinical setting, unless a single product containing both medications were used

Subcutaneous sarcoidosis without systemic involvement

Subcutaneous sarcoidosis is a rare variant of cutaneous sarcoidosis, which typically presents as single or multiple, indurated, ill-defined plaques, typically on the upper extremities. Granulomas consisting of macrophages with multinucleated giant cells and sparse lymphocytic inflammation are confined to the subcutaneous tissue, rather than to their usual location within the dermis in typical lesions of cutaneous sarcoidosis. An association between subcutaneous sarcoidosis and systemic involvement has been reported, although response to treatment and prognosis remain good. We report a case of a middle-aged woman with subcutaneous sarcoidosis, with negative work-up for systemic involvement of sarcoidosis. Interestingly, family history was significant for a son who died from complications of pulmonary sarcoidosis. The patient was successfully treated with a tapering course of oral prednisone in combination with hydroxychloroquine

Cardiac manifestations of cutaneous disorders

A number of cutaneous disorders encountered by the dermatologist have overlapping cardiac pathology. In recent years, many genetic linkages common to pathological processes in the cutaneous and cardiovascular systems have been identified. This review will describe primary cutaneous disorders with potential cardiac manifestations, including congenital syndromes, inherited cutaneous disorders associated with later cardiovascular disease, and syndromes associated with early cardiovascular pathology. The dermatologist may be the first to diagnose cutaneous findings associated with underlying cardiovascular disease; therefore, it is of prime importance for the dermatologist to be aware of these associations and to direct the appropriate workup

Subcutaneous sarcoidosis without systemic involvement

Subcutaneous sarcoidosis is a rare variant of cutaneous sarcoidosis, which typically presents as single or multiple, indurated, ill-defined plaques, typically on the upper extremities. Granulomas consisting of macrophages with multinucleated giant cells and sparse lymphocytic inflammation are confined to the subcutaneous tissue, rather than to their usual location within the dermis in typical lesions of cutaneous sarcoidosis. An association between subcutaneous sarcoidosis and systemic involvement has been reported, although response to treatment and prognosis remain good. We report a case of a middle-aged woman with subcutaneous sarcoidosis, with negative work-up for systemic involvement of sarcoidosis. Interestingly, family history was significant for a son who died from complications of pulmonary sarcoidosis. The patient was successfully treated with a tapering course of oral prednisone in combination with hydroxychloroquine