Showing papers by "David J. Margolis published in 2016"

Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011

Abstract: Importance The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient antibiotic use is unknown. Objective To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States. Design, Setting, and Participants Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated. Exposures Ambulatory care visits. Main Outcomes and Measures Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population. Results Of the 184 032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions [95% CI, 48-64]), followed by suppurative otitis media (47 antibiotic prescriptions [95% CI, 41-54]), and pharyngitis (43 antibiotic prescriptions [95% CI, 38-49]). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions. Conclusions and Relevance In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.

Prevalence of Inappropriate Antibiotic Prescriptions among US Ambulatory Care Visits, 2010-2011

Abstract: Importance The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient antibiotic use is unknown. Objective To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States. Design, Setting, and Participants Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated. Exposures Ambulatory care visits. Main Outcomes and Measures Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population. Results Of the 184 032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions [95% CI, 48-64]), followed by suppurative otitis media (47 antibiotic prescriptions [95% CI, 41-54]), and pharyngitis (43 antibiotic prescriptions [95% CI, 38-49]). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions. Conclusions and Relevance In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.

Global, regional, and national levels of maternal mortality, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Abstract: Background In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015. Methods We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10–54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Findings Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68% in 1990 to more than 80% in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91% coverage of one antenatal care visit, 78% of four antenatal care visits, 81% of in-facility delivery, and 87% of skilled birth attendance. Interpretation Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care—including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population. Funding Bill & Melinda Gates Foundation.

Association of diabetic foot ulcer and death in a population-based cohort from the United Kingdom.

Abstract: Aims The presence of diabetic foot ulcers is strongly associated with an increased risk of death. In this study, we investigate whether the effects of diabetes-associated complications can explain the apparent relationship between diabetic foot ulcers and death. Methods We analysed data from 414 523 people with diabetes enrolled in practices associated with The Health Improvement Network in the United Kingdom. Our methods were designed to control for potential confounders in order to isolate the relationship between diabetic foot ulcers and death. Using proportional hazards models and the area under the receiver operator curve, we evaluated the effects of diabetic foot ulcers and the covariates on death. Results Among the patients, 20 737 developed diabetic foot ulcers; 5.0% of people with new ulcers died within 12 months of their first foot ulcer visit and 42.2% of people with foot ulcers died within 5 years. After controlling for major known complications of diabetes that might influence mortality, the correlation between diabetic foot ulcers and death remained strong with a fully adjusted hazard ratio of 2.48 (95% confidence interval: 2.43, 2.54). Geographic variance existed but was not spatially associated. Conclusions Diabetic foot ulcers are linked to an increased risk of death. This cannot be explained by other common risk factors. These results suggest that either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow-up.

WHS guidelines update: Diabetic foot ulcer treatment guidelines.

Abstract: 1. Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, 2. Cardinal Health Wound Management, Pompano Beach, Florida, 3. Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, 4. Department of Orthopaedics, Sanford Health, Sioux Falls, South Dakota, 5. Department of Plastic Surgery, Georgetown University, School of Medicine, Washington, DC, 6. Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, 7. Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands

Risk of Nonmelanoma Skin Cancer Associated With the Use of Immunosuppressant and Biologic Agents in Patients With a History of Autoimmune Disease and Nonmelanoma Skin Cancer

Abstract: Importance Immune dysfunction underlies the pathogenesis of rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Immunosuppressive therapy is the standard of care for these diseases. Both immune dysfunction and therapy-related immunosuppression can inhibit cancer-related immune surveillance in this population. Drug-induced immunosuppression is a risk factor for nonmelanoma skin cancer (NMSC), particularly squamous cell tumors. For patients with a history of NMSC, data are limited on the effect of these drugs on the risk of additional NMSCs. Objective To determine the relative hazard of a second NMSC in patients with RA or IBD who use methotrexate, anti–tumor necrosis factor (anti-TNF) therapy, or thiopurines after an initial NMSC. Design, Setting, and Participants In this retrospective cohort study, we studied 9460 individuals with RA or IBD enrolled in Medicare from January 1, 2006, through December 31, 2012. Exposures Exposure to methotrexate, thiopurines, anti-TNFs, sulfasalazine, hydroxychloroquine, abatacept, or rituximab after the incident NMSC surgery. Main Outcomes and Measures A second NMSC occurring 1 year or more after the incident NMSC using Cox proportional hazards regression models. Results Among 9460 individuals (6841 with RA and 2788 with IBD), the incidence rate of a second NMSC per 1000 person-years was 58.2 (95% CI, 54.5-62.1) and 58.9 (95% CI, 53.2-65.2) in patients with RA and IBD, respectively. Among patients with RA, methotrexate used in conjunction with other medications was associated with an increased risk of a second NMSC (hazard ratio [HR], 1.60; 95% CI, 1.08-2.37). Adjusted for other medications, the risk of NMSC increased with 1 year or more of methotrexate use (HR, 1.24; 95% CI, 1.04-1.48). Compared with methotrexate alone, the addition of anti-TNF drugs was significantly associated with risk of NMSC (HR, 1.49; 95% CI, 1.03-2.16). Abatacept and rituximab were not associated with increased NMSC risk. The nonsignificant HRs for 1 year or more of thiopurine and anti-TNF use for IBD were 1.49 (95% CI, 0.98-2.27) and 1.36 (95% CI, 0.76-2.44), respectively. Conclusions and Relevance Methotrexate use is associated with an increased risk of a second NMSC. Anti-TNF use may increase the risk of a second NMSC when used with methotrexate for RA. Further long-term studies are required before one can conclude that thiopurine and/or anti-TNF do not increase the risk of a second NMSC in patients with IBD.

What's new: Management of venous leg ulcers: Treating venous leg ulcers

Abstract: Venous leg ulcers account for approximately 70% of all leg ulcers and affect 2.2 million Americans annually. After a comprehensive patient and wound assessment, compression therapy remains the cornerstone of standard care. Adjuvant care with topical or systemic agents is used for wounds that do not heal within 4 weeks. Once healed, long-term compression therapy with stockings or surgical intervention will reduce the incidence of recurrence. This continuing medical education article aims to outline optimal management for patients with venous leg ulcers, highlighting the role of a multidisciplinary team in delivering high quality care.

What's new: Management of venous leg ulcers: Approach to venous leg ulcers

Abstract: Leg ulcerations are a common problem, with an estimated prevalence of 1% to 2% in the adult population. Venous leg ulcers are primarily treated in outpatient settings and often are managed by dermatologists. Recent advances in the diagnosis and treatment of leg ulcers combined with available evidence-based data will provide an update on this topic. A systematized approach and the judicious use of expensive advanced therapeutics are critical. Specialized arterial and venous studies are most commonly noninvasive. The ankle brachial pressure index can be performed with a handheld Doppler unit at the bedside by most clinicians. The vascular laboratory results and duplex Doppler findings are used to identify segmental defects and potential operative candidates. Studies of the venous system can also predict a subset of patients who may benefit from surgery. Successful leg ulcer management requires an interdisciplinary team to make the correct diagnosis, assess the vascular supply, and identify other modifiable factors to optimize healing. The aim of this continuing medical education article is to provide an update on the management of venous leg ulcers. Part I is focused on the approach to venous ulcer diagnostic testing.

Regulation of Physical Microglia-Neuron Interactions by Fractalkine Signaling after Status Epilepticus.

Abstract: Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia-neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid- or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice. Interestingly, a deficiency of the fractalkine receptor (CX3CR1) decreased MPCs, whereas fractalkine (CX3CL1) treatment increased MPCs, suggesting that fractalkine signaling is a critical regulator of these microglia-neuron interactions. Furthermore, we found that interleukin-1β was necessary and sufficient to trigger CX3CR1-dependent MPCs. Finally, we show that a deficiency in fractalkine signaling corresponds with increased seizure phenotypes. Together, our results identify the neuroglial CX3CL1-CX3CR1 communication axis as a modulator of potentially neuroprotective microglia-neuron physical interactions during conditions of neuronal hyperactivity.

In vivo analysis of the effect of panobinostat on cell-associated HIV RNA and DNA levels and latent HIV infection

Abstract: The latent reservoir in resting CD4+ T cells presents a major barrier to HIV cure. Latency-reversing agents are therefore being developed with the ultimate goal of disrupting the latent state, resulting in induction of HIV expression and clearance of infected cells. Histone deacetylase inhibitors (HDACi) have received a significant amount of attention for their potential as latency-reversing agents. Here, we have investigated the in vitro and systemic in vivo effect of panobinostat, a clinically relevant HDACi, on HIV latency. We showed that panobinostat induces histone acetylation in human PBMCs. Further, we showed that panobinostat induced HIV RNA expression and allowed the outgrowth of replication-competent virus ex vivo from resting CD4+ T cells of HIV-infected patients on suppressive antiretroviral therapy (ART). Next, we demonstrated that panobinostat induced systemic histone acetylation in vivo in the tissues of BLT humanized mice. Finally, in HIV-infected, ART-suppressed BLT mice, we evaluated the effect of panobinostat on systemic cell-associated HIV RNA and DNA levels and the total frequency of latently infected resting CD4+ T cells. Our data indicate that panobinostat treatment resulted in systemic increases in cellular levels of histone acetylation, a key biomarker for in vivo activity. However, panobinostat did not affect the levels of cell-associated HIV RNA, HIV DNA, or latently infected resting CD4+ T cells. We have demonstrated robust levels of systemic histone acetylation after panobinostat treatment of BLT humanized mice; and we did not observe a detectable change in the levels of cell-associated HIV RNA, HIV DNA, or latently infected resting CD4+ T cells in HIV-infected, ART-suppressed BLT mice. These results are consistent with the modest effects noted in vitro and suggest that combination therapies may be necessary to reverse latency and enable clearance. Animal models will contribute to the progress towards an HIV cure.

Pupil Dynamics Reflect Behavioral Choice and Learning in a Go/NoGo Tactile Decision-Making Task in Mice.

Abstract: The eye’s pupil undergoes dynamic changes in diameter associated with cognitive effort, motor activity, and emotional state, and can be used to index brain state across mammalian species. Recent studies in head-fixed mice have linked arousal-related pupil dynamics with global neural activity as well as the activity of specific neuronal populations. However, it has remained unclear how pupil dynamics in mice report trial-by-trial performance of behavioral tasks, and change on a longer time scale with learning. We measured pupil dynamics longitudinally as mice learned to perform a Go/NoGo tactile decision-making task. Mice learned to discriminate between two textures presented to the whiskers by licking in response to the Go texture (Hit trial) or withholding licking in response to the NoGo texture (correct reject trial, CR). Characteristic pupil dynamics were associated with behavioral choices: large-amplitude pupil dilation prior to and during licking accompanied Hit and False Alarm (FA) responses, while smaller amplitude dilation followed by constriction accompanied CR responses. With learning, the choice-dependent pupil dynamics became more pronounced, including larger amplitude dilations in both Hit and FA trials and earlier onset dilations in Hit and CR trials. A more pronounced constriction was also present in CR trials. Furthermore, pupil dynamics predicted behavioral choice increasingly with learning to greater than 80% accuracy. Our results indicate that pupil dynamics reflect behavioral choice and learning in head-fixed mice, and have implications for understanding decision- and learning-related neuronal activity in pupil-linked neural circuits.

Optimizing Technology Use for Chronic Lower-Extremity Wound Healing: A Consensus Document.

Abstract: Innovations in technology are used in managing chronic wounds. Despite the wide range of technologies available, healing of chronic wounds remains variable. In this paper, the authors offer an evidence based approach to the use of technology for diagnosis and management based on the concept of standardised care.

Duration of oral tetracycline-class antibiotic therapy and use of topical retinoids for the treatment of acne among general practitioners (GP): A retrospective cohort study

Abstract: Background Guidelines recommend limiting the duration of oral antibiotic therapy in acne to 3 to 6 months and prescribing concomitant topical retinoids for all patients. Objective We sought to evaluate the duration of therapy with oral tetracyclines and the use of topical retinoids among patients with acne treated primarily by general practitioners in the United Kingdom. Methods We conducted a retrospective cohort study using the Health Improvement Network database. Results The mean duration of therapy was 175.1 days. Of antibiotic courses, 62% were not associated with a topical retinoid; 29% exceeded 6 months in duration. If all regions were to achieve uses similar to the region with the shortest mean duration of therapy, approximately 3.3 million antibiotic days per year could be avoided in the United Kingdom. Limitations The Health Improvement Network does not include information on acne severity and clinical outcomes. Conclusions Prescribing behavior for oral antibiotics in the treatment of acne among general practitioners is not aligned with current guideline recommendations. Increasing the use of topical retinoids and considering alternative agents to oral antibiotics when appropriate represent opportunities to reduce antibiotic exposure and associated complications such as antibiotic resistance and to improve outcomes in patients treated for acne.

Strategies used for measuring long-term control in atopic dermatitis trials: A systematic review

Abstract: Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. There are no standardised methods for capturing long-term control of AD. Objective: To identify how long-term control has been captured in published randomised controlled trials (RCTs). Resultswill initiate consensus discussions on how best to measure long-term control in the core outcome set for AD. Methods: Systematic review of RCTs of AD treatments published between 2000 and 2013, with a follow-up period of ≥3 months, at least one outcome measure recorded at ≥3 time-points, full paper available, and published in English. Results: 101/ 353 RCTs were eligible. Methods to capture long-term control included: repeated measurement of AD outcomes (92 RCTs; 91%), use of AD medication (29 RCTs; 28.7%); and AD flares/remissions (26 RCTs; 25.7%). Repeated measurements of AD outcomes were typically collected 3 to 5 times during a trial, but analysis methods often failed to make best use of the data. Time to first flare was most commonly for trials including flare data (21/52). Medication-use was recorded based on quantity, potency and frequency of application. Limitations: Included RCT data only Conclusion: This review illustrates the difficulties in measuring long-term control, and points to the need for improved harmonization of outcomes.

Measurements of CD34+/CD45-dim Stem Cells Predict Healing of Diabetic Neuropathic Wounds

Abstract: Management of neuropathic foot ulcers in patients with diabetes (DFUs) has changed little over the past decade, and there is currently no objective method to gauge probability of successful healing. We hypothesized that studies of stem/progenitor cells (SPCs) in the early weeks of standard wound management could predict who will heal within 16 weeks. Blood and debrided wound margins were collected for 8 weeks from 100 patients undergoing weekly evaluations and treatment. SPC number and intracellular content of hypoxia-inducible factors (HIFs) were evaluated by flow cytometry and immunohistochemistry. More SPCs entered the bloodstream in the first 2 weeks of care in patients who healed (n = 37) than in those who did not (n = 63). Logistic regression demonstrated that the number of blood-borne SPCs and the cellular content of HIFs at study entry and the first-week follow-up visit predicted healing. Strong correlations were found among week-to-week assessments of blood-borne SPC HIF factors. We conclude that assays of SPCs during the first weeks of care in patients with DFUs can provide insight into how well wounds will respond and may aid with decisions on the use of adjunctive measures.

Correlation Between Appropriate Use Criteria and the Frequency of Subclinical Spread or Reconstruction With a Flap or Graft for Melanomas Treated With Mohs Surgery With Melanoma Antigen Recognized by T Cells 1 Immunostaining.

Abstract: Background Published appropriate use criteria (AUC) for Mohs micrographic surgery (MMS) for melanoma are based on consensus opinion. Objective To evaluate whether published AUC identify melanomas for which MMS may benefit patients by detecting subclinical spread or confirming clear microscopic margins before flap or graft reconstruction. Materials and methods Retrospective cohort study of 591 melanomas in 556 patients evaluating the correlation between current AUC (anatomic location, recurrent status, and tumor stage) and subclinical spread or reconstruction with a flap or graft. Results Anatomic location on the head, neck, genitalia, hands, feet, or pretibial leg was associated with a significantly higher frequency of subclinical spread (odds ratio (OR) 1.89, p = .0280) and flap or graft reconstruction (OR 10.3, p = .0001). Compared with primary lesions, recurrent melanomas had a higher frequency of subclinical spread (OR 1.78, p = .0104) and reconstruction with a flap or graft (OR 1.67, p = .0217). The frequencies of subclinical spread and flap or graft reconstruction did not differ between in situ and invasive melanomas. Conclusion Anatomic location and recurrent status are useful criteria to identify melanomas that may benefit from MMS. Tumor stage is not a useful criterion, as MMS has similar benefits for subsets of both invasive and in situ melanomas.

Ten Years of Screening and Testing for Acute HIV Infection in North Carolina.

Abstract: OBJECTIVE To describe demographic and behavioral characteristics of persons with acute HIV infection (AHI) over time. METHODS We conducted a retrospective assessment of AHI identified through the Screening and Tracing Active Transmission (STAT) program from 2003 to 2012 in North Carolina (NC). AHI was identified using pooled nucleic acid amplification for antibody negative samples and individual HIV-1 RNA for antibody indeterminate samples. The STAT program provides rapid notification and evaluation. We compared STAT-collected demographic and risk characteristics with all persons requesting tests and all non-AHI diagnoses from the NC State Laboratory of Public Health. RESULTS The STAT Program identified 236 AHI cases representing 3.4% (95% confidence interval: 3.0% to 3.9%) of all HIV diagnoses. AHI cases were similar to those diagnosed during established HIV. On pretest risk-assessments, AHI cases were predominately black (69.1%), male (80.1%), young (46.8% < 25 years), and men who have sex with men (MSM) (51.7%). Per postdiagnosis interviews, the median age decreased from 35 (interquartile range 25-42) to 27 (interquartile range 22-37) years, and the proportion <25 years increased from 23.8% to 45.2% (trend P = 0.04) between 2003 and 2012. AHI men were more likely to report MSM risk post-diagnosis than on pretest risk-assessments (64%-82.9%; P < 0.0001). Post-diagnosis report of MSM risk in men with AHI increased from 71.4% to 96.2%. CONCLUSIONS In NC, 3.4% of individuals diagnosed with HIV infection have AHI. AHI screening provides a real-time source of incidence trends, improves the diagnostic yield of HIV testing, and offers an opportunity to limit onward transmission.

Zoster vaccination is associated with a reduction of zoster in elderly patients with chronic kidney disease.

Abstract: Background Growing epidemiological evidence demonstrates increased zoster risks in people with chronic kidney disease (CKD). Study objectives were to determine zoster vaccine effectiveness in individuals with CKD in pragmatic use. Methods A population-based cohort study was undertaken in a 5% random sample of US Medicare from 2007 to 2009 involving 766 330 eligible individuals aged ≥65 years who were (29 785) and were not (736 545) exposed to the zoster vaccine. Incidence rates for zoster in vaccinated and unvaccinated individuals and hazard ratios for zoster comparing vaccinated with unvaccinated were determined for individuals with CKD. Time-updated Cox proportional hazards models were used, adjusting for relevant confounders. Results CKD was present in 183 762 (24%) of individuals (15% of vaccinees). Adjusted vaccine effectiveness [95% confidence intervals (CIs)] in individuals with CKD was 0.49 (0.36-0.65). The adjusted vaccine effectiveness in participants with both CKD and diabetes mellitus was 0.46 (95% CI 0.09-0.68). Vaccine effectiveness estimates were similar to those previously reported for the general population [vaccine effectiveness 0.48 (95% CI 0.39-0.56)]. Conclusions Zoster vaccine is effective against incident zoster in older individuals with CKD. Extra efforts are warranted to increase vaccine uptake in individuals with CKD given the known low uptake in these higher risk individuals.

The Effect of Total Household Decolonization on Clearance of Colonization With Methicillin-Resistant Staphylococcus aureus

Abstract: OBJECTIVE To determine the impact of total household decolonization with intranasal mupirocin and chlorhexidine gluconate body wash on recurrent methicillin-resistant Staphylococcus aureus (MRSA) infection among subjects with MRSA skin and soft-tissue infection. DESIGN Three-arm nonmasked randomized controlled trial. SETTING Five academic medical centers in Southeastern Pennsylvania. PARTICIPANTS Adults and children presenting to ambulatory care settings with community-onset MRSA skin and soft-tissue infection (ie, index cases) and their household members. INTERVENTION Enrolled households were randomized to 1 of 3 intervention groups: (1) education on routine hygiene measures, (2) education plus decolonization without reminders (intranasal mupirocin ointment twice daily for 7 days and chlorhexidine gluconate on the first and last day), or (3) education plus decolonization with reminders, where subjects received daily telephone call or text message reminders. MAIN OUTCOME MEASURES Owing to small numbers of recurrent infections, this analysis focused on time to clearance of colonization in the index case. RESULTS Of 223 households, 73 were randomized to education-only, 76 to decolonization without reminders, 74 to decolonization with reminders. There was no significant difference in time to clearance of colonization between the education-only and decolonization groups (log-rank P=.768). In secondary analyses, compliance with decolonization was associated with decreased time to clearance (P=.018). CONCLUSIONS Total household decolonization did not result in decreased time to clearance of MRSA colonization among adults and children with MRSA skin and soft-tissue infection. However, subjects who were compliant with the protocol had more rapid clearance Trial registration. ClinicalTrials.gov identifier: NCT00966446 Infect Control Hosp Epidemiol 2016;1-8.

Peripheral optogenetic stimulation induces whisker movement and sensory perception in head-fixed mice.

Abstract: We discovered that optical stimulation of the mystacial pad in Emx1-Cre;Ai27D transgenic mice induces whisker movements due to activation of ChR2 expressed in muscles controlling retraction and protraction. Using high-speed videography in anesthetized mice, we characterize the amplitude of whisker protractions evoked by varying the intensity, duration, and frequency of optogenetic stimulation. Recordings from primary somatosensory cortex (S1) in anesthetized mice indicated that optogenetic whisker pad stimulation evokes robust yet longer latency responses than mechanical whisker stimulation. In head-fixed mice trained to report optogenetic whisker pad stimulation, psychometric curves showed similar dependence on stimulus duration as evoked whisker movements and S1 activity. Furthermore, optogenetic stimulation of S1 in expert mice was sufficient to substitute for peripheral stimulation. We conclude that whisker protractions evoked by optogenetic activation of whisker pad muscles results in cortical activity and sensory perception, consistent with the coding of evoked whisker movements by reafferent sensory input.

Antibiotics and acne: an emerging iceberg of antibiotic resistance?

Abstract: In the entire history of medicine, few therapeutic options have been as successful in curing disease as antibiotics. However, the future effectiveness of antibiotics is now in jeopardy, with the World Health Organization declaring the threat of antibiotic resistance (AR) a most urgent crisis. Similarly, in the U.K., the Chief Medical Officer (CMO) has warned of the apocalyptic nature of AR and more recently has suggested that gains achieved in mortality reductions during the last century could be offset by increases in AR-related mortality. Acne vulgaris is an important disease to focus on in relation to AR as more than 80% of adolescents and young adults have acne, and prolonged broad-spectrum oral antibiotic treatment is the standard of care for moderate-to-severe acne. While clinical experience strongly favours the use of oral antibiotics to treat acne, there is a dearth of data exploring the association between AR and long-term antibiotic use in acne. Whitehouse et al. highlight the issue of inappropriate antibiotic prescribing for acne in the U.K., demonstrating that among recent referrals to secondary care, the mean duration of antibiotic use was 305 days. In primary care, antibiotic usage extends to 6 months on average, with a third of patients with acne continuing to use antibiotics for longer than this duration. The consequences of unrestrained antibiotic use to treat acne are twofold. Firstly, Propionibacterium acnes is increasingly resistant to standard antibiotics for acne. In approximately 1000 patients attending specialist clinics in Harrogate, 80% had resistance to erythromycin or clindamycin or both, while 25% were resistant to tetracyclines. These results are in concordance with a wider European pattern. The second consequence extends beyond acne treatment. Adverse outcomes including higher rates of upper respiratory tract infections have been reported in people treated with oral antibiotics for acne. Such outcomes may result from changing the microbial milieu leading to selective pressure for resistant bacteria, such as Streptococcus pyogenes. The emergence of erythromycinresistant S. aureus strains after the use of topical erythromycin in acne is equally concerning. The U.K. CMO has launched a multi-pronged approach to tackling AR, concentrating on improving antibiotic stewardship and enhancing global leadership on maintaining the effectiveness of currently used antibiotics. What can those who treat acne, namely dermatologists and general practitioners (GPs), do to play their part in this battle? Firstly, the most important step is antibiotic stewardship; ensuring judicious use of both oral and topical antibiotics. There are now several guidelines for the management of acne that are in unison in their recommendations for the prudent use of antibiotics. All recommendations advise against using an oral and topical antibiotic together, and all recommend using a topical retinoid or benzoyl peroxide in combination with oral antibiotics to reduce the potential for resistance. However, there are slight disparities on the advised timelines for use of oral antibiotics. For example, the NICE Clinical Knowledge Summaries advise that a review of antibiotic therapy is conducted at 6–8 weeks, and if there is evidence of some response, treatment can be continued for up to 6 months. In contrast, the American Academy of Dermatology suggests review of antibiotic treatment at 3–4 months. Meanwhile, the most recent European guidelines state that oral antibiotic treatment be limited to 3 months. To mount an effective group response to this potential global health crisis, those treating acne with antibiotics must agree on unified guidelines and then enforce those guidelines. At that point, stewardship will be a powerful tool, as previously demonstrated in the U.K. in relation to methicillin-resistant S. aureus infections. Secondly, the role of diagnostics and drug development may be an area for exploration to inform the safe use of antibiotics or to find alternatives to antibiotic treatment in acne. Given that one in four patients with acne is colonized by a tetracycline-resistant P. acnes strain, swabbing, culturing and testing for resistant strains may be one way to help avoid chronic use of ineffective antibiotics. Admittedly, these investigations would introduce a financial and time cost to prescribers and patients, although future point-of-care testing may reduce the burden. While we cannot be certain that tetracyclines mediate their whole effect via antibacterial action, at the very least this approach would create cohorts of patients who are most likely to benefit, assuming tetracyclines have some antibiotic effect on P. acnes. Many dermatologists use antibiotics for their anti-inflammatory effect in acne. Much work on the molecular processes underpinning acne has revealed that Toll-like receptors and protease-activated receptors are key mediators in the inflammatory process. These molecular substrates hold promise for drug development in this clinical area, offering potential advantages in limiting the extent to which antibiotics are used. Other innovative therapeutic approaches with potential utility include retinoic acid metabolism-blocking agents; ectopeptidase inhibitors; new formulations of benzyl and hydrogen peroxide topical preparations; dapsone gel; metformin; and 5-lipoxygenase inhibitors.

Patient-reported quality of life and psychosocial health prior to skin cancer treatment – A cross-sectional study

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Statins may be associated with six-week diabetic foot ulcer healing.

Abstract: Diabetic foot ulcers (DFUs) affect 1.5 million Americans annually, of which only a minority heal with standard care, and they commonly lead to amputation. To improve care, investigations are underway to better understand DFU pathogenesis and develop more effective therapies. Some currently used medications may improve healing. One small, randomized clinical trial found statins improve DFU healing. In this secondary analysis of a large multisite prospective observational cohort of 139 patients with DFUs receiving standard care, we investigated whether there was an association between 6-week DFU wound size reduction and use of a variety of medications including alpha-blockers, beta-blockers, angiotensin converting enzyme inhibitors (ACEi) and statins. We found no significant (p < 0.05) association between six-week wound reduction and use of any of the evaluated drugs; however, statins did trend toward an association (p = 0.057). This suggests a potential benefit of statins on DFU healing, and larger, targeted studies are warranted.

Clinical interventions for venous leg ulcers: Proposals to improve the quality of clinical leg ulcer research.

Abstract: The present status of clinical leg ulcer healing research was reviewed by 25 experts over 2 days on September 28 and 29, 2015. Multiple clinical effectiveness reviews were presented suggesting that published clinical wound healing research often does not meet present (2015) evidence based standards. Specific areas requiring remediation were highlighted and approaches to overcoming existing challenges were proposed. Participants using anonymous voting technology developed an action plan to resolve perceived deficiencies. Statements were accepted if 75% of participants agreed. Older patients with a high frequency of comorbid conditions posed particular difficulties in designing clinical research protocols and better diagnostic categorization is necessary A standardized model template for collecting information about diagnosis and evaluation of the effect of interventions on healing of all types of leg ulcers was considered a high priority. Such a model template could be modified depending on the specific etiology of the leg ulcers. Generally agreed on quantifiable standards to establish degree of morbidity was considered a high priority. There was universal agreement that sources of funding and conflicts of interest needed to be disclosed in presentations and all publications. All clinical research studies should be registered with appropriate authorities. There was substantial enthusiasm for a clinical research network with quality standards for membership and an advisory research core available to investigators. Such a network should be funded and actively managed to insure long-term viability. The governance of such an entity needs to be established by the wound care community. The present trend to integrate patients into the clinical research process was endorsed and there was enthusiasm to develop patient advocacy for wound healing research.