Safety of Systemic Medications Among Older Adults With Psoriasis and Atopic Dermatitis: A Systematic Review of Observational Studies.

BACKGROUND: Psoriasis and atopic dermatitis are common among older adults (≥65 years old), but clinical trials often exclude that population. OBJECTIVE: To synthesize evidence from observational studies on the safety of systemic therapies (conventional or biologic) for psoriasis and atopic dermatitis among older adults in a systematic review. METHODS: We searched MEDLINE and EMBASE (inception to October 31, 2019) and included observational studies reporting adverse events among older people treated with systemic therapy for psoriasis or atopic dermatitis. Outcomes were death, hospitalization, emergency department visits, infections, major cardiovascular events, renal toxicity, hepatotoxicity, and cytopenias. We assessed study quality using the Newcastle-Ottawa Scale. RESULTS: We included 22 studies on treatment for psoriasis and 2 for atopic dermatitis. Most studies were small and non-comparative and 20 of 24 were low quality. Studies comparing safety between medications or medication classes or between older and younger adults did not show apparent differences but had wide confidence intervals around relative effect estimates. Heterogeneity of study design and reporting precluded quantitative synthesis. CONCLUSIONS: There is scant evidence on the safety of conventional systemic and biologic medications for older adults with psoriasis or atopic dermatitis; older adults and their clinicians should be aware of this evidence gap.

Inclusion of Older Adults in Randomized Clinical Trials for Systemic Medications for Atopic Dermatitis: A Systematic Review.

Importance: Despite increasing evidence that atopic dermatitis is common in older adults, it is unclear whether the evidence base for treating atopic dermatitis with systemic therapy is generalizable to that population. Older adults are most at risk for adverse events from medications, given age-related alterations in drug metabolism, increased comorbidity, and polypharmacy. Objective: This systematic review examines the representation of older adults in randomized clinical trials (RCTs) of systemic immunomodulatory treatments for atopic dermatitis and whether safety and efficacy data are reported specifically for older individuals. Evidence Review: The Cochrane Central Register of Controlled Trials, Embase, MEDLINE databases, and the ClinicalTrials.gov trial register were searched from inception (MEDLINE via Ovid, 1946; Embase via Ovid, 1974) to November 7, 2019. RCTs investigating systemic immunomodulatory treatments for adults with atopic dermatitis were included. Titles, abstracts, and full-text papers were screened, and data were extracted in duplicate. Findings: A total of 32 trials with 4547 participants were reviewed. The mean (SD) age of trial participants was 34.4 (5.4) years. The median number of participants per trial was 44 (range, 10-740). Eleven trials (34%) reported explicit upper age limits ranging from 42 to 70 years of age. Most of these trials (n = 9) examined safety and effectiveness of cyclosporine. Twenty-two trials (69%) had other exclusion criteria that might disproportionately exclude older adults. In total, 10 trials (31%) included adults aged 65 years or older. Within 7 trials that reported the proportion of participants aged 65 and older (all evaluating dupilumab), 112 of 2964 participants (4%) were 65 years or older. None of the included trials reported stratified safety or effectiveness data for older adults. Conclusions and Relevance: Study results suggest that older adults are underrepresented in RCTs of systemic treatment for atopic dermatitis, resulting in a lack of evidence supporting safe clinical use for older adults. Clinicians and patients should be aware of this evidence gap when prescribing systemic therapy for atopic dermatitis. Randomized trials and observational studies that include older patients with atopic dermatitis are needed.

Establishment of an erythroid progenitor cell line capable of enucleation achieved with an inducible c-Myc vector.

BACKGROUND: A robust scalable method for producing enucleated red blood cells (RBCs) is not only a process to produce packed RBC units for transfusion but a potential platform to produce modified RBCs with applications in advanced cellular therapy. Current strategies for producing RBCs have shortcomings in the limited self-renewal capacity of progenitor cells, or difficulties in effectively enucleating erythroid cell lines. We explored a new method to produce RBCs by inducibly expressing c-Myc in primary erythroid progenitor cells and evaluated the proliferative and maturation potential of these modified cells. RESULTS: Primary erythroid progenitor cells were genetically modified with an inducible gene transfer vector expressing a single transcription factor, c-Myc, and all the gene elements required to achieve dox-inducible expression. Genetically modified cells had enhanced proliferative potential compared to control cells, resulting in exponential growth for at least 6 weeks. Inducibly proliferating erythroid (IPE) cells were isolated with surface receptors similar to colony forming unit-erythroid (CFU-Es), and after removal of ectopic c-Myc expression cells hemoglobinized, decreased in cell size to that of native RBCs, and enucleated achieving cultures with 17% enucleated cells. Experiments with IPE cells at various levels of ectopic c-Myc expression provided insight into differentiation dynamics of the modified cells, and an optimized two-stage differentiation strategy was shown to promote greater expansion and maturation. CONCLUSIONS: Genetic engineering of adult erythroid progenitor cells with an inducible c-Myc vector established an erythroid progenitor cell line that could produce RBCs, demonstrating the potential of this approach to produce large quantities of RBCs and modified RBC products.

Thirty-Day Outcomes Following Surgical Decompression of Thoracic Outlet Syndrome.

BACKGROUND: Surgical thoracic outlet syndrome (TOS) management involves decompression of the neurovascular structures by releasing the anterior and/or middle scalene muscles, resection of the first and/or cervical ribs, or a combination. Various surgical approaches (transaxillary, supraclavicular, infraclavicular, and transthoracic) have been used with varying rates of complications. The purpose of this study was to evaluate early postoperative outcomes following surgical decompression for TOS. We hypothesized that first and/or cervical rib resection would be associated with increased 30-day complications and health care utilization. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed for all TOS cases of brachial plexus surgical decompression in the region of the thoracic inlet from 2005 to 2013. RESULTS: There were 225 patients (68% females; mean age: 36.4 years ± 12.1; 26% body mass index [BMI] ⩾ 30). There were 205 (91%) patients who underwent first and/or cervical rib resection (±scalenectomy), and 20 (9%) underwent rib-sparing scalenectomy. Compared with rib-sparing scalenectomy, rib resection was associated with longer operative time and hospital stays ( P < .001). In the 30 days postoperatively, 8 patients developed complications (rib-scalenectomy, n = 7). Only patients with rib resection returned to the operating room (n = 10) or were readmitted (n = 9). CONCLUSIONS: Early postoperative complications are infrequent after TOS decompression. Rib resection is associated with longer surgical times and hospital stays. Future studies are needed to assess the association between early and long-term outcomes, surgical procedure, and health care utilization to determine the cost-effectiveness of the various surgical interventions for TOS.

Risk Factors for Titanium Mesh Implant Exposure Following Cranioplasty.

PURPOSE: Titanium mesh is used to reconstruct the neurocranium in cranioplasties. Though it is generally well-tolerated, erosion of the overlying soft tissue with exposure of the implant is a complication that adversely affects patient outcomes. The purpose of this study is to investigate potential risk factors for titanium mesh exposure. METHODS: This study comprises all consecutive patients who underwent titanium mesh cranioplasty between January 2000 and July 2016. A retrospective chart review was conducted to extract demographics, details of management, and outcome. Latest postoperative computed tomography scans were reviewed to document the thickness of soft tissue coverage over the implant and the presence of significant extradural dead space deep to it. RESULTS: Fifty patients were included. Implant exposure occurred in 7 (14%), while threatened exposure was observed in 1 additional patient, for a total complication count of 8 (16%).Four (50%) exposure and 3 (7.1%) nonexposure patients underwent preoperative radiotherapy (odds ratio [OR] = 19.67, P = 0.018). Similarly, 4 (50%) exposure and 5 (11.9%) nonexposure patients had a free flap tissue transfer for implant coverage (OR = 6.50, P = 0.046). Postoperative computed tomography scans revealed significant thinning of soft tissues over titanium mesh in 7 (87.5%) exposure and 15 (35.7%) nonexposure patients (OR = 10.71 P = 0.040). No significant association was found between transposition/rotation flap, postoperative radiotherapy, or the presence of significant extradural dead space, and exposure (P = 0.595, P = 0.999, P = 0.44). CONCLUSION: Preoperative radiotherapy, free flap coverage, and soft tissue atrophy resulted in greater odds of titanium mesh exposure. The findings of this study provide important considerations for reconstructive surgeons using titanium mesh for cranioplasty.

Informational and Supportive Care Needs of Brain Metastases Patients and Caregivers: a Systematic Review.

While brain metastases (BM) are associated with significant morbidity and mortality, the needs of BM patients and their caregivers (CGs) remain largely unknown. The purpose of this systematic review was to summarize (a) the informational needs of BM patients and CGs, (b) their supportive care needs, and (c) studies evaluating existing programs and resources addressing one or more of informational needs. A systematic search was conducted in four databases to identify studies, published from 2000 to April 2015, discussing informational or supportive care needs of BM patients and/or their CGs. Duplicate screening, data abstraction, and risk of bias assessments were conducted. Results were qualitatively summarized. From 973 references, seven studies fulfilled inclusion criteria. While physical and medical informational needs concerning prognosis, symptom management, treatment options, and side effects were reported, no studies exploring patient or CG social, emotional, or spiritual informational needs were identified. Discordance was observed between patient, CG, and health care professional perspectives on patient supportive care needs. One study evaluated an intervention addressing informational needs. Patients required information on prognosis, managing symptoms, and available treatment options and associated side effects. They needed support managing housework, pain, and fatigue. The findings of this study suggest an ongoing need to elicit psychosocial informational needs, supportive care needs, and a need for patient- and CG-centered resource development. Since ascertaining these needs is vital to the delivery of patient-centered care, efforts must be undertaken to explore these in the context of BM patients and CGs.

Neurofibromatosis Clinic: A Report on Patient Demographics and Evaluation of the Clinic.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a common single-gene disorder. A multidisciplinary approach to the management of NF1 patients is necessitated by the heterogeneity of clinical manifestations. Although multidisciplinary paediatric clinics have been well established, there is a dearth of such resources for adults with NF1. Herein we report our one-year institutional experience with a multidisciplinary adult NF1 clinic. METHODS: A multidisciplinary team was assembled, and an NF Patient Registry Initiative questionnaire was adapted to collect patient-reported data during clinics. Multiple databases were searched to identify publications pertaining to the experience of other multidisciplinary NF1 clinics focusing on adult patients. Data on patient epidemiology and clinical staff were compared to our data. RESULTS: A total of 77 patients were scheduled, and 68 attended the clinic, of whom 66 completed the intake questionnaire. The demographic and clinical data from this Canadian population are mostly consistent with previous reports, with some exceptions. Clinical data related to immune system involvement such as asthma, airway/breathing-related difficulties or allergies were striking in our NF1 population. Six relevant published reports of other NF1 clinics were identified. Reports from these studies pertained to periods ranging from 10 to 38 months, and the number of adults assessed ranged from 19 to 177 patients. CONCLUSIONS: The structure of our clinic and the patient volume are comparable to those of other established centres found in the literature. Our data offer valuable cross-sectional prevalence statistics in the Canadian population. The patient-reported data concerning involvement of the immune system contribute to an emerging recognized medical concern within the NF1 population and warrant further clinical and basic investigation.

Importance of patient-centred signage and navigation guide in an orthopaedic and plastics clinic.

Gulshan & Nanji Orthopaedic and Plastics Center at the North York General Hospital is the second busiest site after the emergency department serving more than 26,000 patients annually. Increase in patient flow, overworked staff, and recent renovations to the hospital have resulted in patients experiencing long wait times, and thusly patient dissatisfaction and stress. Several factors contribute to patient dissatisfaction and stress: i) poor and unfriendly signage; ii) inconsistent utilization of the numbering system; and iii) difficulty navigating to and from the imaging center. A multidisciplinary QI team was assembled to improve the patient experience. We developed a questionnaire to assess patient stress levels at the baseline. Overall, more than half of the patients (54.8%) strongly agreed or agreed to having a stressful waiting experience. Subsequently, based on patient feedback and staff perspectives, we implemented two PDSA cycles. For PDSA 1, we placed a floor graphic (i.e. black tape) to assist patients in navigating from the clinic to the imaging centre and back. For PDSA 2, we involved creating a single 21"×32" patient-friendly sign at the entrance to welcome patients, with clear instructions outlining registration procedures. Surveys were re-administered to assess patient stress levels. A combination of both interventions caused a statistically significant reduction in patient stress levels based on the Kruskal-Wallis and Mann-Whitney U Tests. The present project highlighted the importance of involving stakeholders as well as frontline staff when undertaking quality improvement projects as a way to identify bottlenecks as well as establish sustainable solutions. Additionally, the team recognized the importance of incorporating empirical based solutions and involving experts in the field to optimize results. The present project successfully implemented strategies to improve patient satisfaction and reduce stress in a high flow community clinic. These endpoints were achieved by incorporating patient friendly signage, as well as improving patient flow directors.