Is long term physical activity safe for older adults with knee pain: a systematic review

ObjectiveTo determine whether long-term physical activity is safe for older adults with knee pain.DesignA comprehensive systematic review and narrative synthesis of existing literature was conducted using multiple electronic databases from inception until May 2013. Two reviewers independently screened, checked data extraction and carried out quality assessment.Inclusion criteria for study designs were randomised controlled trials (RCTs), prospective cohort studies or case control studies, which included adults of mean age over 45 years old with knee pain or osteoarthritis (OA), undertaking physical activity over at least 3 months and which measured a safety related outcome (adverse events, pain, physical functioning, structural OA imaging progression or progression to total knee replacement (TKR)).ResultsOf the 8614 unique references identified, 49 studies were included in the review, comprising 48 RCTs and one case control study. RCTs varied in quality and included an array of low impact therapeutic exercise interventions of varying cardiovascular intensity. There was no evidence of serious adverse events, increases in pain, decreases in physical function, progression of structural OA on imaging or increased TKR at group level. The case control study concluded that increasing levels of regular physical activity was associated with lower risk of progression to TKR.ConclusionsLong-term therapeutic exercise lasting 3 to 30 months is safe for most older adults with knee pain. This evidence supports current clinical guideline recommendations. However, most studies investigated selected, consenting older adults carrying out low impact therapeutic exercise which may affect result generalizability

Warped Phenomenology of Higher-Derivative Gravity

We examine the phenomenological implications at colliders for the existence of higher-derivative gravity terms as extensions to the Randall-Sundrum model. Such terms are expected to arise on rather general grounds, e.g., from string theory. In 5-d, if we demand that the theory be unitary and ghost free, these new contributions to the bulk action are uniquely of the Gauss-Bonnet form. We demonstrate that the usual expectations for the production cross section and detailed properties of graviton Kaluza-Klein resonances and TeV-scale black holes can be substantially altered by existence of these additional contributions. It is shown that measurements at future colliders will be highly sensitive to the presence of such terms.Comment: 29 pages, 8 figure

Melanoma molecular subtypes: Unifying and paradoxical results

In this issue, Hacker and colleagues provide further evidence that molecular subtypes of malignant melanoma may develop along divergent pathways. The authors did not find an association between somatic BRAF-mutant melanoma and germline melanocortin-1 receptor (MC1R) gene status. We discuss this seeming paradox in light of previous studies demonstrating strong associations

Association of surgical interval and survival among hospital and non-hospital based patients with melanoma in North Carolina

Surgical excision is important for melanoma treatment. Delays in surgical excision after diagnosis of melanoma have been linked to decreased survival in hospital-based cohorts. This study was aimed at quantifying the association between the timeliness of surgical excision and overall survival in patients diagnosed with melanoma in hospital- and non-hospital-based settings, using a retrospective cohort study of patients with stage 0–III melanoma and using data linked between the North Carolina Central Cancer Registry to Medicare, Medicaid, and private health insurance plan claims across the state. We identified 6,496 patients diagnosed between 2004 and 2012 with follow-up through 2017. We categorized the time from diagnostic biopsy to surgical excision as 90 days after melanoma diagnosis. Multivariable Cox regression was used to estimate differences in survival probabilities. Five-year overall survival was lower for those with time to surgery over 90 days (78.6%) compared with those with less than 6 weeks (86%). This difference appeared greater for patients with Stage 1 melanoma. This study was retrospective, included one state, and could not assess melanoma specific mortality. Surgical timeliness may have an effect on overall survival in patients with melanoma. Timely surgery should be encouraged

Association of delays in surgery for melanoma with insurance type

IMPORTANCE: Timely receipt of treatment for cancer is an important aspect of health care quality. It is unknown how delays of surgery for melanoma vary by insurance type. OBJECTIVE: To analyze factors associated with delays between diagnosis and surgery for melanoma in patients with Medicare, Medicaid, or private insurance. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of patients who received a diagnosis of melanoma between 2004 and 2011 in North Carolina using data from the North Carolina Cancer Registry linked to administrative claims from Medicare, Medicaid, and private insurance. Inclusion criteria were incident patients with a diagnosis of melanoma stage 0 to III and with continuous insurance enrollment from at least 1 month prior to the month of diagnosis to 12 months after diagnosis of melanoma. MAIN OUTCOMES AND MEASURES: Surgical delay, defined as definitive surgical excision occurring more than 6 weeks after melanoma diagnosis. Generalized linear models with log link, Poisson distributions, and robust standard errors were used to estimate adjusted risk ratios (RRs) to model risk of delay in definitive surgery. RESULTS: A total of 7629 patients were included (4210 [55%] female; mean [SD] age, 64 [15] years), 48% (n = 3631) Medicare, 48% (n = 3667) privately insured, and 4% (n = 331) Medicaid patients. Privately insured patients were least likely to experience a delay in definitive surgery, followed by Medicare and Medicaid patients (519 [14%], 609 [17%], and 79 [24%], respectively; P < .001). After demographic adjustment, the risk of surgical delay was significantly increased in patients with Medicaid compared with private insurance (RR, 1.36; 95% CI, 1.09-1.70). Delays were more likely in nonwhite patients (RR, 1.38; 95% CI, 1.02-1.87). Surgical delays were less likely if the physician performing the surgery (RR, 0.82; 95% CI, 0.72-0.93) or the diagnosing clinician (RR, 0.81; 95% CI, 0.71-0.93) was a dermatologist as compared with a nondermatologist. CONCLUSION AND RELEVANCE: Surgical treatment delays were common but were less prevalent in patients diagnosed or surgically treated by a dermatologist. Medicaid patients experienced the most surgical delays. A reduction in delays in melanoma surgery could be achieved through better access to specialty care and cross-disciplinary coordination

The TBX21 transcription factor T-1993C polymorphism is associated with decreased IFN-γ and IL-4 production by primary human lymphocytes

T-bet is a transcription factor that drives the Th1 immune response primarily through promoting expression of the IFN-γ gene. Polymorphisms in the T-bet gene, TBX21, have been associated with immune-mediated diseases such as asthma and systemic sclerosis. We found that the TBX21 promoter polymorphism T-1993C is associated with a significant decrease in IL-4 and IFN-γ production by stimulated primary human lymphocytes from healthy participants

The effects of dietary supplementation with inulin and inulin-propionate ester on hepatic steatosis in adults with non-alcoholic fatty liver disease

The short chain fatty acid (SCFA) propionate, produced through fermentation of dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in adults with non-alcoholic fatty liver disease (NAFLD). Eighteen adults were randomised to receive 20g/day of an inulin-propionate ester (IPE), designed to deliver propionate to the colon, or an inulin-control for 42-days in a parallel design. The change in intrahepatocellular lipid (IHCL) following the supplementation period was not different between groups (P=0.082), however IHCL significantly increased within the inulin-control group (20.9±2.9 to 26.8±3.9%; P=0.012; n=9), which was not observed within the IPE group (22.6±6.9 to 23.5±6.8%; P=0.635; n=9). The predominant SCFA from colonic fermentation of inulin is acetate, which in a background of NAFLD and a hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetate- mediated increase in IHC