The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. ...Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription.
We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription.
Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply).
Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.
There are, to date, no MR imaging diagnostic markers for Lewy body dementia. Nigrosome 1, containing dopaminergic cells, in the substantia nigra pars compacta is hyperintense on SWI and has been ...called the swallow tail sign, disappearing with Parkinson disease. We aimed to study the swallow tail sign and its clinical applicability in Lewy body dementia and hypothesized that the sign would be likewise applicable in Lewy body dementia.
This was a retrospective cross-sectional multicenter study including 97 patients (mean age, 65 ± 10 years; 46% women), consisting of the following: controls (
= 21) and those with Lewy body dementia (
= 19), Alzheimer disease (
= 20), frontotemporal lobe dementia (
= 20), and mild cognitive impairment (
= 17). All patients underwent brain MR imaging, with susceptibility-weighted imaging at 1.5T (
= 46) and 3T (
= 51). The swallow tail sign was assessed independently by 2 neuroradiologists.
Interrater agreement was moderate (κ = 0.4) between raters. An abnormal swallow tail sign was most common in Lewy body dementia (63%; 95% CI, 41%-85%;
< .001) and had a predictive value only in Lewy body dementia with an odds ratio of 9 (95% CI, 3-28;
< .001). The consensus rating for Lewy body dementia showed a sensitivity of 63%, a specificity of 79%, a negative predictive value of 89%, and an accuracy of 76%; values were higher on 3T compared with 1.5T. The usefulness of the swallow tail sign was rater-dependent with the highest sensitivity equaling 100%.
The swallow tail sign has diagnostic potential in Lewy body dementia and may be a complement in the diagnostic work-up of this condition.
Across many species where inversions have been implicated in local adaptation, genomes often evolve to contain multiple, large inversions that arise early in divergence. Why this occurs has yet to be ...resolved. To address this gap, we built forward-time simulations in which inversions have flexible characteristics and can invade a metapopulation undergoing spatially divergent selection for a highly polygenic trait. In our simulations, inversions typically arose early in divergence, captured standing genetic variation upon mutation, and then accumulated many small-effect loci over time. Under special conditions, inversions could also arise late in adaptation and capture locally adapted alleles. Polygenic inversions behaved similarly to a single supergene of large effect and were detectable by genome scans. Our results show that characteristics of adaptive inversions found in empirical studies (e.g. multiple large, old inversions that are
outliers, sometimes overlapping with other inversions) are consistent with a highly polygenic architecture, and inversions do not need to contain any large-effect genes to play an important role in local adaptation. By combining a population and quantitative genetic framework, our results give a deeper understanding of the specific conditions needed for inversions to be involved in adaptation when the genetic architecture is polygenic. This article is part of the theme issue 'Genomic architecture of supergenes: causes and evolutionary consequences'.
It is generally accepted that complete β-cell destruction eventually occurs in individuals with type 1 diabetes, which has implications for treatment approaches and insurance coverage. The frequency ...of residual insulin secretion in a large cohort of individuals at varying ages of diagnosis and type 1 diabetes duration is unknown.
The frequency of residual insulin secretion was determined by measurement of nonfasting serum C-peptide concentration in 919 individuals with type 1 diabetes according to prespecified groups based on age at diagnosis and duration of disease (from 3 to 81 years' duration). Stimulated C-peptide was measured in those with detectable nonfasting values and a group of those with undetectable values as control.
The overall frequency of detectable nonfasting C-peptide was 29%, decreasing with time from diagnosis regardless of age at diagnosis. In all duration groups, the frequency of C-peptide was higher with diagnosis age >18 years compared with ≤18 years. Nineteen percent of those with undetectable nonfasting C-peptide were C-peptide positive upon stimulation testing.
The American Diabetes Association's definition of type 1 diabetes as "usually leading to absolute insulin deficiency" results in clinicians often considering the presence of residual insulin secretion as unexpected in this population. However, our data suggest that residual secretion is present in almost one out of three individuals 3 or more years from type 1 diabetes diagnosis. The frequency of residual C-peptide decreases with time from diagnosis regardless of age at diagnosis, yet at all durations of disease, diagnosis during adulthood is associated with greater frequency and higher values of C-peptide.
The muscle disease sarcopenia, which is characterised by a loss of muscle strength, muscle quantity, and physical performance, restricts mobility and independence in an ageing society. The aim of ...this systematic review and meta-analysis is to analyse the effects that long-term progressive resistance training interventions performed on weight machines have on sarcopenia (European Working Group on Sarcopenia in Older People) and how the interventions are composed. In total, 779 articles published between 2000 and 2020 were scanned (PubMed, Web of Science, CINAHL) and 14 randomised controlled trials were included within the review. Populations, interventions, control groups and outcomes were analysed. Subsequent meta-analysis (10 studies, 902 participants) revealed that the time needed in a chair-stand-test, as an indicator for leg strength, was predominantly reduced, whereas grip strength remained unchanged after the interventions. Data concerning the effects of machine-based progressive resistance training on muscle quantity were insufficient for meta-analysis. Physical performance measured by undergoing the Timed-Up-and-Go-test, gait speed test, Short Physical Performance Battery and 6 min-walk-test improved significantly as well. The quality of evidence (GRADE) in the analysed studies was low or moderate. In summary, machine-based progressive resistance training has the potential to reverse sarcopenia in the oldest old, as reflected by enhanced muscle strength and physical performance. The systematic review revealed promising initial results for muscle quantity.
•Muscle strength and physical performance can be improved even in the very old.•Evidence of muscle mass improvement due to machine-based resistance training is rare.•Sarcopenic status of physical performance improved throughout the interventions.•Implementing standardised methods to detect sarcopenia is important.
Abstract Unless chemically crosslinked, matrix proteins, such as collagen or silk, display a limited lifetime in vivo with significant degradation observed over a period of weeks. Likewise, ...amphiphilic peptides, lipopeptides, or glycolipids that self-assemble through hydrophobic interactions to form thin films, fiber networks, or vesicles do not demonstrate in vivo biostability beyond a few days. We report herein that a self-assembling, recombinant elastin-mimetic triblock copolymer elicited minimal inflammatory response and displayed robust in vivo stability for periods exceeding 1 year, in the absence of either chemical or ionic crosslinking. Specifically, neither a significant inflammatory response nor calcification was observed upon implantation of test materials into the peritoneal cavity or subcutaneous space of a mouse model. Moreover, serial quantitative magnetic resonance imaging, evaluation of pre- and post-explant ultrastructure by cryo-high resolution scanning electron microscopy, and an examination of implant mechanical responses revealed substantial preservation of form, material architecture, and biomechanical properties, providing convincing evidence of a non-chemically or ionically crosslinked protein polymer system that exhibits long-term stability in vivo.
To monitor inflammation in a meaningful way, the markers used must be valid: they must reflect the inflammatory process under study and they must be predictive of future health status. In 2009, the ...Nutrition and Immunity Task Force of the International Life Sciences Institute, European Branch, organized an expert group to attempt to identify robust and predictive markers, or patterns or clusters of markers, which can be used to assess inflammation in human nutrition studies in the general population. Inflammation is a normal process and there are a number of cells and mediators involved. These markers are involved in, or are produced as a result of, the inflammatory process irrespective of its trigger and its location and are common to all inflammatory situations. Currently, there is no consensus as to which markers of inflammation best represent low-grade inflammation or differentiate between acute and chronic inflammation or between the various phases of inflammatory responses. There are a number of modifying factors that affect the concentration of an inflammatory marker at a given time, including age, diet and body fatness, among others. Measuring the concentration of inflammatory markers in the bloodstream under basal conditions is probably less informative compared with data related to the concentration change in response to a challenge. A number of inflammatory challenges have been described. However, many of these challenges are poorly standardised. Patterns and clusters may be important as robust biomarkers of inflammation. Therefore, it is likely that a combination of multiple inflammatory markers and integrated readouts based upon kinetic analysis following defined challenges will be the most informative biomarker of inflammation.
XELOX or FOLFOX should be considered as standard treatment options for the adjuvant management of stage III colon cancer in all age groups and in patients with comorbidities.
Adjuvant oxaliplatin ...plus capecitabine or leucovorin/5-fluorouracil (LV/5-FU) (XELOX/FOLFOX) is the standard of care for stage III colon cancer (CC); however, there is disagreement regarding oxaliplatin benefit in patients aged >70. In most analyses, the impact of medical comorbidity (MC) has not been assessed. Efficacy and safety of adjuvant XELOX/FOLFOX versus LV/5-FU were compared with respect to age and MC using pooled data from four randomized, controlled trials, selected for access to patient-level MC data and including commonly endorsed and utilized regimens.
Individual data from patients with stage III CC in NSABP C-08, XELOXA, X-ACT, and AVANT were pooled, excluding bevacizumab-treated patients. Patients were grouped by treatment, MC (low versus high), or age (<70 versus ≥70), and compared for disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Multivariable Cox proportional hazards regression controlled for gender, T stage, and N stage.
DFS benefits were shown for XELOX/FOLFOX versus LV/5-FU regardless of age or MC, although benefits were modestly attenuated for patients aged ≥70. Hazard ratios were 0.68 (P < 0.0001) and 0.77 (P < 0.014) for <70 and ≥70 age groups; 0.69 (P < 0.0001) and 0.59 (P < 0.0001) for Charlson Comorbidity Index ≤1 and >1 groups; and 0.70 (P < 0.0001) and 0.58 (P < 0.0001) for National Cancer Institute Combined Index ≤1 and >1 groups. OS was also significantly improved in all groups. Grade 3/4 serious AE rates were comparable across cohorts and MC scores and higher in patients aged ≥70. Oxaliplatin-relevant grade 3/4 AEs, including neuropathy, were comparable across ages and MC scores.
Results further support consideration of XELOX or FOLFOX as standard treatment options for the adjuvant management of stage III CC in all age groups and in patients with comorbidities, consistent with those who were eligible for these clinical trials.
Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. ...Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable.
Abstract
Background
Physical functioning is a crucial factor for independence and quality of life in old age. The aim of the "bestform—Best function of range of motion" trial is to investigate the ...effects of a 6 months multimodal machine-based strength, coordination and endurance training on physical function, risk of falls and health parameters in older adults.
Methods
Bestform is a cluster-randomised trial including older adults ≥ 65 years living in senior care facilities in Southern Germany. Senior care facilities are randomly allocated to the control group with usual care (
n
≥ 10 care facilities) and to the intervention group (
n
≥ 10 care facilities), overall including ≥ 400 seniors. Residents belonging to the intervention group are offered a supervised machine-based exercise training programme twice weekly over 45–60 min over six months in small groups, while those in the usual care facilities will not receive active intervention. The primary outcome is the change in Short Physical Performance Battery over six months between groups. Secondary outcomes are change in risk of falling, fear of falling, number of falls and fall-related injuries, physical exercise capacity, handgrip strength, body composition, cardiac function, blood parameters, quality of life, risk of sarcopenia, activities of daily living, and cognition over three and six months.
Discussion
The bestform study investigates the change in physical function between seniors performing exercise intervention versus usual care over six months. The results of the study will contribute to the development of effective physical activity concepts in senior care facilities.
Trial registration
ClinicalTrials.gov: NCT04207307. Registered December 2019.
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