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To investigate perioperative outcomes of esophagectomies by age groups. Retrospective analysis of esophageal cancer patients undergoing esophagectomy from 2005 to 2020 at a single academic institution. Baseline characteristics and outcomes were analyzed by 3 age groups:70, 70-79, and ≥80 years-old. Sub-analysis was done for 2 time periods: 2005-2012 and 2013-2020. Of 1135 patients, 789 patients were70, 294 were 70-79, and 52 were ≥80 years-old. Tumor characteristics, and operative technique were similar, except positive longitudinal margins rates (all3%) (P = 0.008). Older adults experienced increased complications (53.6% vs 69.7% vs 65.4% respectively; P0.001) attributable to grade II complications (41.4% vs 62.2% vs 63.5% respectively; P0.001). Hospital length of stay (LOS) and rehabilitation requirements were higher in older adults (both P0.05). 30-day readmissions, reoperation, and 30-day mortality rates (all2%) showed no association with age group. Overall complications, LOS, discharge disposition and re-operative rates improved from 2005 to 2012 to 2013-2020 for all (P0.05). Increasing age was an independent risk factor for cardiovascular complications (OR 1.7, 95% CI 1.23-2.46 for ages 70-79 and OR 2.7, 95% CI 1.37-5.10 for ages ≥80 ), inpatient rehabilitation (OR 3.3, 95% CI 2.26-5.05 for ages 70-79 and OR 12.1 95% CI 5.83-25.04 for ages ≥80), and prolonged LOS (OR 1.64 95% CI 1.16-2.31 for ages 70-79 and OR 3.6 95% CI 1.71-7.67 for ≥80. After adjusting for time period, older age remained associated with complications (P0.05). Highly selected older adults at a large volume esophagectomy center can undergoesophagectomy with increased minor complication and rehabilitation needs.

BACKGROUND: Patterns of overall and disease-free survival after esophagectomy for esophageal cancer in older adults have not been carefully studied. METHODS: Retrospective analysis of all patients with esophageal cancer undergoing esophagectomy from 2005 to 2020 at our institution was performed. Differences in outcomes were stratified by age groups, < 75 and ≥ 75 years old, and two time periods, 2005–2012 and 2013–2020. RESULTS: A total of 1135 patients were included: 979 (86.3%) patients were < 75 (86.3%), and 156 (13.7%) were ≥ 75 years old. Younger patients had fewer comorbidities, better nutritional status, and were more likely to receive neoadjuvant and adjuvant therapy (all p < 0.05). However, tumor stage and operative approach were similar, except for increased performance of the McKeown technique in younger patients (p = 0.02). Perioperatively, younger patients experienced fewer overall and grade II complications (both p < 0.05). They had better overall survival (log-rank p-value < 0.001) and median survival, 62.2 vs. 21.5 months (p < 0.05). When stratified by pathologic stage, survival was similar for yp0 and pathologic stage II disease (both log-rank p-value > 0.05). Multivariable Cox models showed older age (≥ 75 years old) had increased hazard for reduced overall survival (HR 2.04 95% CI 1.5–2.8; p < 0.001) but not disease-free survival (HR 1.1 95% CI 0.78–1.6; p = 0.54). Over time, baseline characteristics remained largely similar, while stage became more advanced with a rise in neoadjuvant use and increased performance of minimally invasive esophagectomy (all p < 0.05). While overall complication rates improved (p < 0.05), overall and recurrence-free survival did not. Overall survival was better in younger patients during both time periods (both log-rank p < 0.05). CONCLUSIONS: Despite similar disease-free survival rates, long-term survival was decreased in older adults as compared to younger patients. This may be related to unmeasured factors including frailty, long-term complications after surgery, and competing causes of death. However, our results suggest that survival is similar in those with complete pathologic responses.

Background/Aims: The novel coronavirus SARS-CoV-2 has caused a pandemic threatening millions of people worldwide. This study aimed to describe clinical characteristics, outcomes, and risk factors of SARS-CoV-2-positive, asymptomatic, frail older adults. Methods: A retrospective cohort study was conducted in 6 designated COVID-19 units, in skilled nursing homes. Subjects were severely frail older adults, positive for SARS-CoV-2, and asymptomatic at the time of their admission in these units. Residents’ characteristics and symptoms were obtained via electronic medical records. The primary outcome was a composite of death or hospitalization by day 40. We looked at time to the primary outcome and used Cox regression for a multivariate analysis. Results: During March–November 2020, 849 residents met inclusion criteria. Median age was 84 years. Most were completely dependent for basic activities of daily living and showed cognitive impairment. Six hundred forty-one (75.5%) residents were discharged after considered cured from COVID-19, 125 (14.7%) were hospitalized, and 82 (9.7%) died in the facilities. In survival analysis, 35% reached the primary outcome of death or hospitalization by day 40. Age (hazard ratio [HR] 1.23; 95% confidence interval [CI] 1.1–1.4), male gender (HR 1.41; 95% CI: 1.1–1.88), and COPD (HR 1.8; 95% CI: 1.23–2.67) were significant risk factors. Conclusions: In this large cohort, we report care and prognosis of asymptomatic older adults with major functional or cognitive impairments during the COVID-19 pandemic. Most presymptomatic patients do not develop severe infection, and age stays a predominant risk factor, even in the frailest older adults.

Background Accurate quality of life (QoL) data and functional results after cancer surgery are lacking for older patients. The international, multicenter Geriatric Oncology Surgical Assessment and Functional rEcovery after Surgery (GOSAFE) Study compares QoL before and after surgery and identifies predictors of decline in QoL. Methods GOSAFE prospectively collected data before and after major elective cancer surgery on older adults (≥70 years). Frailty assessment was performed and postoperative outcomes recorded (30, 90, and 180 days postoperatively) together with QoL data by means of the three-level version of the EuroQol five-dimensional questionnaire (EQ-5D-3L), including 2 components: an index (range = 0-1) generated by 5 domains (mobility, self-care, ability to perform the usual activities, pain or discomfort, anxiety or depression) and a visual analog scale. Results Data from 26 centers were collected (February 2017-March 2019). Complete data were available for 942/1005 consecutive patients (94.0%): 492 male (52.2%), median age 78 years (range = 70-95 years), and primary tumor was colorectal in 67.8%. A total 61.2% of all surgeries were via a minimally invasive approach. The 30-, 90-, and 180-day mortality was 3.7%, 6.3%, and 9%, respectively. At 30 and 180 days, postoperative morbidity was 39.2% and 52.4%, respectively, and Clavien-Dindo III-IV complications were 13.5% and 18.7%, respectively. The mean EQ-5D-3L index was similar before vs 3 months but improved at 6 months (0.79 vs 0.82; P Conclusions GOSAFE shows that older adults’ preoperative QoL is preserved 3 months after cancer surgery, independent of their age. Frailty screening tools, patient-reported outcomes, and goals-of-care discussions can guide decisions to pursue surgery and direct patients’ expectations.

Population divergence and gene flow are key processes in evolution and ecology. Model-based analysis of genome-wide datasets allows discrimination between alternative scenarios for these processes even in non-model taxa. We used two complementary approaches (one based on the blockwise site frequency spectrum (bSFS), the second on the Pairwise Sequentially Markovian Coalescent (PSMC)) to infer the divergence history of a fig wasp,Pleistodontes nigriventris. Pleistodontes nigriventrisand its fig tree mutualistFicus watkinsianaare restricted to rain forest patches along the eastern coast of Australia, and are separated into northern and southern populations by two dry forest corridors (the Burdekin and St. Lawrence Gaps). We generated whole genome sequence data for two haploid males per population and used the bSFS approach to infer the timing of divergence between northern and southern populations ofP. nigriventris,and to discriminate between alternative isolation with migration (IM) and instantaneous admixture (ADM) models of post divergence gene flow.Pleistodontes nigriventrishas low genetic diversity (π = 0.0008), to our knowledge one of the lowest estimates reported for a sexually reproducing arthropod. We find strongest support for an ADM model in which the two populations divergedca. 196kya in the late Pleistocene, with almost 25% of northern lineages introduced from the south during an admixture eventca.57kya. This divergence history is highly concordant with individual population demographies inferred from each pair of haploid males using PSMC. Our analysis illustrates the inferences possible with genome-level data for small population samples of tiny, non-model organisms and adds to a growing body of knowledge on the population structure of Australian rain forest taxa.

Manufacturing has been the key factor limiting rollout of vaccination during the COVID‐19 pandemic, requiring rapid development and large‐scale implementation of novel manufacturing technologies. ChAdOx1 nCoV‐19 (AZD1222, Vaxzevria) is an efficacious vaccine against SARS‐CoV‐2, based upon an adenovirus vector. We describe the development of a process for the production of this vaccine and others based upon the same platform, including novel features to facilitate very large‐scale production. We discuss the process economics and the “distributed manufacturing” approach we have taken to provide the vaccine at globally‐relevant scale and with international security of supply. Together, these approaches have enabled the largest viral vector manufacturing campaign to date, providing a substantial proportion of global COVID‐19 vaccine supply at low cost., Well over a billion doses of the ChAdOx1 nCoV‐19 vaccine developed by The University of Oxford and AstraZeneca have been produced and distributed at low cost. This represents a substantial proportion of global COVID‐19 vaccine supply to date, especially in low‐ and middle‐income countries. The authors report on the development of the manufacturing process for the vaccine, and the process economics and distributed manufacturing approach involving bulk vaccine (drug substance) production on five continents.

Advanced understanding of the molecular pathways of oncologic diseases has shifted therapeutic treatment development to focus on mechanism of actions targeting specific genomic alterations. These precision medicines are indicated for patient subsets defined by these specific mutations as determined by diagnostic devices approved by the Food and Drug Administration (FDA). The Intended Use section within the companion diagnostic (CDx) labeling has historically specified the therapeutic products for which they have been clinically validated. In April 2020, the FDA reiterated their position that therapeutic class labeling may be used, if appropriate, instead of named products. Labels for FDA approved in vitro CDxs were reviewed to evaluate the implementation of therapeutic class labeling. A total of 47 devices have been approved as of 2 January 2022, of which 3 labels were found to contain therapeutic class labeling: two devices targeting EGFR mutations for the treatment of non-small cell lung cancer (NSCLC), and one targeting BRAF V600E and BRAF/MEK inhibitor combinations for melanoma. Two devices received therapeutic class labeling upon initial approval, while the third implemented the language though a label revision. A total of 25 different indications were identified across the 47 CDx devices, of which 9 (34.6%) were associated with more than 1 CDx device. Implementation of therapeutic class labeling has been slow following the release of the FDA’s April 2020 guidance; however, the potential to incorporate such language into existing and newly approved CDx labels exists. Precedence and manufacturer experience are expected to drive an increase in therapeutic class labeling.

Poor food environments and disproportionate food insecurity among African Americans (AAs) represent determinants of chronic disease disparities by race/ethnicity. We used PhotoVoice to explore the food environment in Baltimore, MD, through the perspectives of Black residents with hypertension. Findings illuminated structural racism and classism as root causes of “food desert” conditions. Respondents provided critical analysis of existing food access barriers, including problematic policies, and offered asset-based solutions. Using an exhibition of participants’ photographs to set the tone of the discussion, we will convene a stakeholder meeting including study participants, community advisory board members, local and state government agencies, civic organizations, community farmers, agricultural organizations, non-profit food providers, churches, local restauranteurs, convenience store owners, insurance payers, and transportation providers. Discussion will center on three areas of action informed by findings: systems level issues; individual activation, agency, and advocacy; and community-based solutions. Meeting proceedings will be disseminated through academic and lay publications.

Introduction: The COVID-19 pandemic has impacted millions of lives globally. To learn more about this disease and find potential diagnostic, therapeutic, and preventative products, the healthcare community has initiated a staggering number of clinical trials. Methods: ClinicalTrials.gov was reviewed to determine if trial sponsor type had a relationship to time to COVID-19 response, which was defined as the date from disease discovery in Wuhan, China to ClinicalTrials.gov study “First Posted” date. Results: A total of 673 United States (US) sponsored, interventional study listings were retrieved, of which 293 (43.5%) were Industry-sponsored, 349 (51.9%) were Academic sponsored, and 31 (4.6%) were Other sponsor types. Of the Academic studies, 181 (51.9%) were Clinical and Translational Science Award (CTSA) hubs. The average response time for all sponsor types was 189 days, with Academic sponsors having the shortest average response time of 172.6 days (P < 0.001). CTSA hubs had a significantly (P < 0.001) shorter average response time (168.1 days) compared to all other sponsor types (197.4 days). However, while shorter in duration by 9.4 days, response time was not significantly different from non-CTSA sponsors (177.5 days; P = 0.238). Additionally, ANOVA indicated significant relationships (P < 0.001) between funding type, study phase, number of sites, and enrollment size on response time. Conclusions: Studies posted with the shortest response time were Academic-sponsored trials and included smaller sized investigations of repurposed approved or investigational drugs for the treatment of COVID-19 symptoms. A small second wave of study postings occurred approximately 4 months later, and included small, unique therapies targeting prevention or treatment of COVID-19.

The COVID-19 pandemic poses a barrier to equal and evidence-based management of cancer in older adults. The International Society of Geriatric Oncology (SIOG) formed a panel of experts to develop consensus recommendations on the implications of the pandemic on several aspects of cancer care in this age group including geriatric assessment (GA), surgery, radiotherapy, systemic treatment, palliative care and research. Age and cancer diagnosis are significant predictors of adverse outcomes of the COVID-19 infection. In this setting, GA is particularly valuable to drive decision-making. GA may aid estimating physiologic reserve and adaptive capability, assessing risk-benefits of either providing or temporarily withholding treatments, and determining patient preferences to help inform treatment decisions. In a resource-constrained setting, geriatric screening tools may be administered remotely to identify patients requiring comprehensive GA. Tele-health is also crucial to ensure adequate continuity of care and minimize the risk of infection exposure. In general, therapeutic decisions should favor the most effective and least invasive approach with the lowest risk of adverse outcomes. In selected cases, this might require deferring or omitting surgery, radiotherapy or systemic treatments especially where benefits are marginal and alternative safe therapeutic options are available. Ongoing research is necessary to expand knowledge of the management of cancer in older adults. However, the pandemic presents a significant barrier and efforts should be made to ensure equitable access to clinical trials and prospective data collection to elucidate the outcomes of COVID-19 in this population. ispartof: JOURNAL OF GERIATRIC ONCOLOGY vol:11 issue:8 pages:1190-1198 ispartof: location:Netherlands status: published

International audience; GJA8 encodes connexin 50 (Cx50), a transmembrane protein involved in the formation of lens gap junctions. GJA8 mutations have been linked to early onset cataracts in humans and animal models. In mice, missense mutations and homozygous Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract, suggesting that Gja8 may play a role in both lens development and ocular growth. Following screening of GJA8 in a cohort of 426 individuals with severe congenital eye anomalies, primarily anophthalmia, microphthalmia and coloboma, we identified four known [p.(Thr39Arg), p.(Trp45Leu), p.(Asp51Asn), and p.(Gly94Arg)] and two novel [p.(Phe70Leu) and p.(Val97Gly)] likely pathogenic variants in seven families. Five of these co-segregated with cataracts and microphthalmia, whereas the variant p.(Gly94Arg) was identified in an individual with congenital aphakia, sclerocornea, microphthalmia and coloboma. Four missense variants of unknown or unlikely clinical significance were also identified. Furthermore, the screening of GJA8 structural variants in a subgroup of 188 individuals identified heterozygous 1q21 microdeletions in five families with coloboma and other ocular and/or extraocular findings. However, the exact genotype-phenotype correlation of these structural variants remains to be established. Our data expand the spectrum of GJA8 variants and associated phenotypes, confirming the importance of this gene in early eye development.

Objective: Older patients with cancer value functional outcomes as much as survival, but surgical studies lack functional recovery (FR) data. The value of a standardized frailty assessment has been confirmed, yet it's infrequently utilized due to time restrictions into everyday practice. The multicenter GOSAFE study was designed to (1) evaluate the trajectory of patients' quality of life (QoL) after cancer surgery (2) assess baseline frailty indicators in unselected patients (3) clarify the most relevant tools in predicting FR and clinical outcomes. This is a report of the study design and baseline patient evaluations. Materials & Methods: GOSAFE prospectively collected a baseline multidimensional evaluation before major elective surgery in patients (≥70 years) from 26 international units. Short−/mid−/long-term surgical outcomes were recorded with QoL and FR data. Results: 1003 patients were enrolled in a 26-month span. Complete baseline data were available for 977(97.4%). Median age was 78 years (range 70–94); 52.8% males. 968(99%) lived at home, 51.6% without caregiver. 54.4% had ≥ 3 medications, 5.9% none. Patients were dependent (ADL < 5) in 7.9% of the cases. Frailty was either detected by G8 ≤ 14(68.4%), fTRST ≥ 2(37.4%), TUG > 20 s (5.2%) or ASAIII-IV (48.8%). Major comorbidities (CACI > 6) were detected in 36%; 20.9% of patients had cognitive impairment according to Mini-Cog. Conclusion: The GOSAFE showed that frailty is frequent in older patients undergoing cancer surgery. QoL and FR, for the first time, are going to be primary outcomes of a real-life observational study. The crucial role of frailty assessment is going to be addressed in the ability to predict postoperative outcomes and to correlate with QoL and FR.

ObjectiveData describing outcomes after implantable cardioverter-defibrillator (ICD) unit generator replacement in patients with heart failure (HF) with primary prevention devices are limited.MethodData on patients with HF who underwent primary prevention ICD/cardiac resynchronisation therapy-defibrillator (CRT-D) implantation from 2007 until mid-2015 who subsequently received unit generator replacement were analysed. Outcomes assessed were mortality, appropriate ICD therapy and shock, and procedural complications.Results61 of 385 patients with HF with primary prevention ICD/CRT-D undergoing unit generator replacement were identified. Follow-up period was 1.8±1.5 years after replacement. 43 (70.5%) patients had not received prior appropriate ICD therapy prior to unit replacement. The cumulative risks of appropriate ICD therapy at 1, 3 and 5 years after unit replacement in those without prior ICD therapy were 0%, 6.2% and 50% compared with 6.2%, 59.8% and 86.6%, respectively (p=0.005) in those with prior ICD therapies. No predictive factors associated with appropriate ICD therapy after replacement could be identified. 41 (32.8%) patients no longer met guideline indications at the time of unit replacement but risks of subsequent appropriate ICD interventions were not different compared with those who continued to meet primary prevention ICD indications.The 5-year mortality risk after unit replacement was 18.4% and there were high procedural complication rates (9.8%).ConclusionNo predictive marker successfully stratified patients no longer needing ICD support prospectively. Finding such a marker is important in decision-making about device replacement particularly given the concerns about the complication rates. These factors should be considered at the time of ICD unit replacement.

Background Implantable cardioverter‐defibrillator (ICD) therapy is indicated for selected heart failure patients for the primary prevention of sudden cardiac death. Little is known about the outcomes in patients selected for primary prevention device therapy in the northern region of New Zealand. Method Heart failure patients with systolic dysfunction who underwent primary prevention ICD/cardiac resynchronization therapy‐defibrillator (CRT‐D) implantation between January 1, 2007, and June 1, 2015, were included. Complications, mortality, and hospitalization events were reviewed. Results Three hundred and eighty‐five primary prevention devices were implanted (269 ICD, 116 CRT‐D). Mean age at implant was 59.1 ± 11.4 years. Mean duration of follow‐up was 3.64 ± 2.17 years. The commonest cause of death was heart failure (41.8%). Only 2 patients died from sudden arrhythmic death. The 5‐year heart failure mortality rate was 6%, whereas the 5‐year sudden arrhythmic death rate was 0.3%. Heart failure hospitalizations were commoner in those who received ICD than CRT‐D (67.7% vs 25.8%, P < .001). Maori patients have low implant rates (14%) with relatively high rates of admissions with heart failure and ventricular arrhythmia admissions, Conclusions Even in appropriately selected heart failure patients who received primary prevention devices, only a small percentage died as a result of sudden arrhythmic death. CRT‐D should be the device of choice where appropriate in heart failure patients. Significant challenges remain to improve access to device therapy and maximize benefit to those who do get implanted.

OBJECTIVES: Walking is older adults’ second most preferred mode of transport and preferred recreational activity. This leads to greater exposure to traffic, increasing their risk of pedestrian-vehicle crashes, with older adults being more likely to die as a pedestrian when compared to other modes of transport. However, less focus has been placed on this particularly vulnerable group. This review summarises issues associated with older adult pedestrian and motorised mobility scooters (MMS) safety and interventions that have been conducted. METHODS: A literature search was undertaken from Pub Med, MUARC publications, Curtin University Library Catalogue and Google Scholar. Keywords included older pedestrians, older adult road injury, mobility scooter injury, and injury prevention. Publications from 2000 onwards were used, unless an earlier publication had significant relevance and worth. CONCLUSION: Maintaining older adults’ mobility and independence during a time of decreasing physical and mental capacity is a priority. Walking provides a key mode of transport that needs to be given higher priority within the road environment by policy makers, transport planners and drivers. Therefore governments need to consider appropriate and comprehensive urban planning and road safety policies that accommodate ‘active ageing’ to provide pedestrians and MMS users with environments that facilitate active living and safe transport. In addition there is a need for community programs that raise awareness about safe road crossing for this growing vulnerable age group.

Prophylaxis for hospitalized venous-thromboembolic events (VTEs) is frequently underutilized, in part due to lack of a simple risk assessment model (RAM).To compare patient selection and administration of VTE prophylaxis according to the American College of Chest Physicians (ACCP) 2008 guidelines versus the newer 2012 guidelines, and assess the feasibility of developing simpler local RAMs.We conducted a prospective assessment of VTE risk among 300 unselected consecutive patients admitted to a medical hospital ward, using the 2008 and 2012 ACCP guidelines. The frequency and relative weight of each risk factor in the 2012 ACCP guidelines were used to develop a local VTE RAM.VTE prophylaxis was indicated by the 2008 and 2012 ACCP guidelines in 40% and 42% of the cohort respectively, and was administered in 28% and 26% of eligible patients, respectively. Contraindication to VTE prophylaxis was found in 29% of patients according to both guidelines. In comparison to the 2008 guidelines, sensitivity and specificity of the 2012 guidelines were 96% and 88%, respectively. A local RAM based on the following concise score, comprising age, malignancy and immobility, correctly identified 99% of at-risk patients based on the 2012 guidelines, with a sensitivity and specificity of 98% and 95%, respectively.Both guidelines performed to a similar degree and were poorly implemented in daily practice. A simplified RAM accurately identified the vast majority of these eligible patients. The development of local RAMs is feasible and may result in higher utilization rates.

Gilles de la Tourette syndrome is a complex neuropsychiatric disorder with a strong genetic basis. We identified a male patient with Tourette syndrome-like tics and an apparently balanced de novo translocation [46,XY,t(2;7)(p24.2;q31)]. Further analysis using array comparative genomic hybridisation (CGH) revealed a cryptic deletion at 7q31.1-7q31.2. Breakpoints disrupting this region have been reported in one isolated and one familial case of Tourette syndrome. In our case, IMMP2L, a gene coding for a human homologue of the yeast inner mitochondrial membrane peptidase subunit 2, was disrupted by the breakpoint on 7q31.1, with deletion of exons 1-3 of the gene. The IMMP2L gene has previously been proposed as a candidate gene for Tourette syndrome, and our case provides further evidence of its possible role in the pathogenesis. The deleted region (7q31.1-7q31.2) of 7.2 Mb of genomic DNA also encompasses numerous genes, including FOXP2, associated with verbal dyspraxia, and the CFTR gene.

Late graft loss (LGL) and late mortality (LM) following liver transplantation (LT) in children were analyzed from the studies of pediatric liver transplantation (SPLIT) database. Univariate and multivariate associations between pre- and postoperative factors and LGL and LM in 872 patients alive with their primary allografts 1 year after LT were reviewed. Thirty-four patients subsequently died (LM) and 35 patients underwent re-LT (LGL). Patients who survive the first posttransplant year had 5-year patient and graft survival rates of 94.2% and 89.2%, respectively. Graft loss after the first year was caused by rejection in 49% of the cases with sequelae of technical complications accounting for an additional 20% of LGL. LT for tumor, steroid resistant rejection, reoperation in the first 30 days and >5 admissions during the first posttransplant year were independently associated with LGL in multivariate analysis. Malignancy, infection, multiple system organ failure and posttransplant lymphoproliferative disease accounted for 61.8% of all late deaths after LT. LT performed for FHF and tumor were associated with LM. Patients who are at or below the mean for weight at the time of transplant were also at an increased risk of dying. Frequent readmission was also found to be associated with LM.

Damage to neonatal and adult tissues always incites an influx of inflammatory neutrophils and macrophages. Besides clearing the wound of invading microbes, these cells are believed to be crucial coordinators of the repair process, acting both as professional phagocytes to clear wound debris and as a major source of wound growth factor signals. Here we report wound healing studies in the PU.1 null mouse, which is genetically incapable of raising the standard inflammatory response because it lacks macrophages and functioning neutrophils. Contrary to dogma, we show that these “macrophageless” mice are able to repair skin wounds with similar time course to wild-type siblings, and that repair appears scar-free as in the embryo, which also heals wounds without raising an inflammatory response. The growth factor and cytokine profile at the wound site is changed, cell death is reduced, and dying cells are instead engulfed by stand-in phagocytic fibroblasts. We also show that hyperinnervation of the wound site, previously believed to be a consequence of inflammation, is present in the PU.1 null wound, too.

Objective Women have been under-represented in randomised clinical trials for primary prevention implantable cardioverter defibrillators (ICDs), and there are concerns about the efficacy of devices between genders. Our study aimed to investigate gender differences in the use of primary prevention ICD in patients with heart failure from the northern region of New Zealand. Methods Patients with heart failure with systolic dysfunction who received primary prevention ICD/cardiac resynchronisation therapy-defibrillator (CRT-D) in the northern region of New Zealand from 1 January 2007 to 1 June 2015 were included. Complications, mortality and hospitalisation events were reviewed. Results Of the 385 patients with heart failure implanted with ICD/CRT-D, women comprised 15.1% (n=58), and no change in utilisation of these devices was observed over the study period among women. Women were more likely to have non-ischaemic cardiomyopathy and have higher perioperative complications (8.6% vs 2.5%, P=0.02), with non-significant higher trend towards increased lead displacement (5.2% vs 1.8%, P=0.12). Women appeared to have lower all-cause (10.3% vs 18.7%, P=0.12), cardiovascular (5.2% vs 11.9%, P=0.13) and heart failure (3.5% vs 7.9%, P=0.22) mortalities but was not statistically significant. There were no gender differences in all-cause (70.7% vs 67%, P=0.58) or heart failure (19% vs 25%, P=0.32) readmissions. Conclusion Perioperative complications were significantly more common in women referred for ICD/CRT-D. Although there has been a significant increase in ICD implantation rates, gender differences in the use of these devices still exist in New Zealand, in keeping with the demographics of ischaemic heart disease and systolic dysfunction between genders.

We sought to assess the frequency and predictors of early and late posttransplantation anemia (PTA). In addition, we aimed to assess the outcomes of patients with anemia and to assess the impact of anemia on mortality, graft function, and graft failure. Patients who underwent kidney transplantation in a single center during a 4-year period were included. Predictors associated with the development of anemia at 6 months (early PTA) or 2 years (late PTA) were evaluated in a univariate and multivariate analyses. The effects of anemia and other variables on mortality and graft function were assessed. A total of 266 kidney transplant recipients were included. The prevalence of PTA at 6 months (early PTA) was 51.3% and at 2 years (late PTA) was 36.6%. Female sex was significantly associated with early PTA. Patients with early PTA proceeded to late PTA. Patients with both early and late PTA had a higher mortality rate at 4 years compared to patients without anemia. On multivariable analysis, lower Hb at 2 years posttransplantation (hazard ratio [HR] 0.716, 95% confidence intervals [CI] 0.541–0.948, for every increment of 1 g/dL) was significantly associated with mortality. Patients with late PTA suffered a decline in eGFR compared to patients without anemia (P = .026). Furthermore, a lower Hb at 2 years posttransplantation was also associated with graft failure (HR 0.775, 95% CI 0.619–0.969, for every increment of 1 g/dL). Post-transplantation anemia is significantly associated with late mortality, with a decline in graft function and with an increased incidence of graft failure.

OBJECTIVE: To determine the prevalence of depressive symptoms and the relationship between depressive symptoms and metabolic control. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 183 African-American adults aged 35-75 years with type 2 diabetes who were recruited from two primary care clinics in East Baltimore, Maryland. Depressive symptoms, using the Center for Epidemiological Studies Depression Scale (CES-D), HbA1c, fasting lipid profile, BMI, and blood pressure, were measured on each participant. Diabetes-related health behaviors were assessed by questionnaire. RESULTS: The prevalence of depressive symptoms (CES-D > or =22) was 30%. After adjustment for age, sex, income, social support, and duration of diabetes in linear regression models, there were significant graded relationships between greater depressive symptoms and higher serum levels of cholesterol and triglycerides (P

There have been substantial recent changes to the structure of clinical academic training. In its 2004 white paper, Science and innovation: working towards a ten-year investment framework, the government issued a call for improvements in clinical research in the NHS, to ensure that scientific advances would translate to genuine improvements in patients' care. In response to this, the UK Clinical Research Collaboration was set up to enhance the partnership between government, industry and medical sectors. They identified three current major problems in clinical academic training: lack of a clear entry route and career structure; lack of flexibility in job content and location; and a shortage of suitably structured posts on training completion. In 2004, 10% of academic posts were unfilled and there were 23% fewer junior academic staff than three years previously.

To compare mental health service utilization and its associated factors between African Americans and whites in the 1980s and 1990s.Household-based longitudinal study with baseline interviews in 1981 and follow-up interviews from 1993 to 1996.The Baltimore Epidemiologic Catchment Area (ECA) Follow-Up.Subjects included 1,662 adults (590 African Americans and 1,072 whites).Use of mental health services, defined as talking to any health professional about emotional or nervous problems or alcohol or drug-related problems within the 6 months preceding each interview.In 1981, crude rates of mental health service use in general medical (GM) settings and specialty mental health settings were similar for African Americans and whites (11.7%). However, after adjustment for predisposing, need, and enabling factors, individuals receiving mental health services were less likely to be African American. Mental health service use increased by 6.5% over follow-up, and African Americans were no longer less likely to report receiving any mental health services in the 1990s. African Americans were more likely than whites to report discussing mental health problems in GM settings without having seen a mental health specialist. They were less likely than whites to report use of specialty mental health services, but this finding was not statistically significant, possibly because of low rates of specialty mental health use by both race groups. Psychiatric distress was the strongest predictor of mental health service use. Attitudes positively associated with use of mental health services were more prevalent among African Americans than whites.Mental health service use increased in the past decade, with the greatest increase among African Americans in GM settings. Although it is possible that the racial disparity in use of specialty mental health services remains, the GM setting may offer a safety net for some mental health concerns of African Americans.

The Johns Hopkins Precursors Study, a long-term prospective study, was used to study the relation between self-reported sleep disturbances and subsequent clinical depression and psychiatric distress. A total of 1,053 men provided information on sleep habits during medical school at The Johns Hopkins University (classes of 1948-1964) and have been followed since graduation. During a median follow-up period of 34 years (range 1-45), 101 men developed clinical depression (cumulative incidence at 40 years, 12.2%), including 13 suicides. In Cox proportional hazards analysis adjusted for age at graduation, class year, parental history of clinical depression, coffee drinking, and measures of temperament, the relative risk of clinical depression was greater in those who reported insomnia in medical school (relative risk (RR) 2.0, 95% confidence interval (CI) 1.2-3.3) compared with those who did not and greater in those with difficulty sleeping under stress in medical school (RR 1.8, 95% CI 1.2-2.7) compared with those who did not report difficulty. There were weaker associations for those who reported poor quality of sleep (RR 1.6, 95% CI 0.9-2.9) and sleep duration of 7 hours or less (RR 1.5, 95% CI 0.9-2.3) with development of clinical depression. Similar associations were observed between reports of sleep disturbances in medical school and psychiatric distress assessed in 1988 by the General Health Questionnaire. These findings suggest that insomnia in young men is indicative of a greater risk for subsequent clinical depression and psychiatric distress that persists for at least 30 years.

To identify attitudes that influence patient help-seeking behavior and aspects of treatment that influence patient preferences for management of depression. Three focus group discussions (two patient groups stratified by race and one professional group). Questions addressed experience with depression, help-seeking behaviors, treatment preferences, and perceived barriers to mental health care. Academic medical, center. Eight black patients and eight white patients with depression; seven health care professionals (four physicians and three social workers). Discussions were audiotaped, transcribed, and reviewed independently by two investigators to identify and group distinct comments into categories with specific themes. Differences were adjudicated by a third investigator. Comments within categories were then checked for relevance and consistency by a health services researcher and a psychiatrist. More than 90% of the 806 comments could be grouped into one of 16 categories. Black patients raised more concerns than white patients regarding spirituality and stigma. Patients made more comments than professionals regarding the impact of spirituality, social support systems, coping strategies, life experiences, patient-provider relationships, and attributes of specific treatments. They discussed the role these factors played in their helpseeking behavior and adherence to treatment. In-depth focus group discussions with depressed patients can provide valuable and unique information about patient experiences and concerns regarding treatment for depression. Clinicians, researchers, and policymakers need to incorporate the range of factors identified by patients into their decision making for individuals with depression.

OBJECTIVES: This study examined the relationship of self-reported physical activity with subsequent depression and psychiatric distress. METHODS: Physical activity was assessed in medical school and midlife in 973 physicians as part of a prospective observational study. Outcome measures were the incidence of self-reported clinical depression and psychiatric distress on the General Health Questionnaire. RESULTS: The risk of depression was similar for nonexercisers and exercisers. No relationship was observed between physical activity level and subsequent psychiatric distress. CONCLUSIONS: This study found no evidence that exercise reduces risk for depression or psychiatric distress.

Background Chronic ruptures of the Achilles tendon cause marked functional impairment. Given the different repair techniques used, there is a need for a systematic review of the literature to investigate whether these procedure are comparable with one another when performed by experienced surgeons. Sources of data A systematic literature search using the Medline (Pubmed), EMBASE and CINHAL databases. Areas of agreement Provided there are no contraindications, surgery is regarded the best management option. Areas of controversy Most reports are case series with small sample sizes using non-validated measures. Growing points Long-term results of surgical repair procedures are now available. Areas timely for developing research The current literature does not allow clinicians to definitively determine the optimal management modality for chronic rupture of the Achilles tendon. There is a need for randomized controlled trials which use validated functional outcome measures.

The purpose of this analysis was to compare depressed patients receiving care in the general medical setting with depressed patients receiving care in specialty mental health settings. The analysis was limited to 559 respondents from the NIMH Epidemiologic Catchment Area (ECA) study who met criteria for the diagnosis of major depression sometime in the year before the interview as defined by the Diagnostic Interview Schedule. Patients who received care in the general medical sector were more likely to be black, older than age 65, have a high school education or less, and to be women, and less likely to be in the highest socioeconomic quartile. A higher proportion of specialty mental health patients reported a lifetime history of delusions, met criteria for the diagnosis of panic disorder, obsessive-compulsive disorder, or schizophrenia, and had a lifetime history of psychiatric hospitalization. Depressed patients seen in the general medical sector had a lower chance of meeting criteria for major depression one year later than those seen in the specialty mental health sector. A multivariate analysis limited to an investigation of the relative importance of sociodemographic factors indicated that the following factors were significantly associated with receiving care in the specialty mental health care sector: age groups 31-50 and 51-65, and single marital status. Black race was inversely correlated with use of specialty mental health care. These results suggest that data generated from the specialty mental health sector can be generalized to the general medical sector only after assessing demographic differences between the two groups. Demographic differences could be associated with differences in knowledge, attitudes, interpretation of symptoms, and treatment preferences related to depression.