Management of Pain and Cachexia in Pancreatic Cancer: Protocol for Two Systematic Reviews, Network Meta-Analysis, Surveys, and Focus Groups.

BACKGROUND:  Approximately 75% of people with pancreatic cancer experience pain, and >50% of them have cachexia (weakness and wasting of the body). However, there is considerable uncertainty regarding the management of these distressing symptoms. OBJECTIVE:  Our primary objectives are to compare the relative benefits and harms of different interventions for pain in people with unresectable pancreatic cancer and for prevention and treatment of cachexia due to pancreatic cancer, through systematic reviews and network meta-analysis. Our secondary objectives are to develop an evidence-based clinical care pathway to manage pain and prevent and treat cachexia in people with pancreatic cancer through surveys and focus groups involving patients, carers, and health care professionals. METHODS:  We will perform 2 systematic reviews of the literature related to pain and cachexia in people with pancreatic cancer using searches from Cochrane Library, MEDLINE, Embase, Science Citation Index, and trial registries. Two researchers will independently screen for eligibility and identify randomized controlled trials (no language or publication status restriction), comparing interventions for pain or cachexia based on full-texts for articles shortlisted during screening. We will assess risk of bias in the trials using the Cochrane risk of bias tool (version 2.0) and obtain data related to baseline prognostic characteristics, potential effect modifiers and outcome data related to overall survival, health-related quality of life, treatment-related complications, and resource utilisation. We aim to conduct network meta-analysis on outcomes with multiple treatment comparisons where possible, otherwise, meta-analysis with direct comparisons, or narrative synthesis. We will perform various subgroup and sensitivity analyses. Using information obtained from both systematic reviews, we will conduct 2 surveys: one directed to patients or carers to assess acceptability of interventions, and the other to health care professionals to assess feasibility of delivery in the National Health Service. Four mixed focus groups will be conducted to evaluate findings and foster consensus in the development of the care pathway. RESULTS:  Funding was awarded from April 2022 (NIHR202727). Both systematic review protocols were prospectively registered on PROSPERO in May 2022. Formal searches began thereafter. Approval by the University College London Research Ethics Committee (23563/001) was received in December 2022. Data collection began in January 2023; data analysis will begin in May 2023 (completion expected by October 2023). CONCLUSIONS:  This study will comprehensively encompass major interventions for management of pain in people with unresectable pancreatic cancer, and prevention and treatment of cachexia in people with pancreatic cancer. Key stakeholders will facilitate the development of an evidence-based care pathway, ensuring both acceptability and feasibility. The project ends in April 2024 and published results are expected within 12 months of completion. We aim to present the findings through patient group websites, conferences, and publications, irrespective of the findings, in a peer-reviewed journal. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46335.

Social prescribing in combating loneliness and supporting physical activity.

High-prevalence rates and increased morbidity suggest that loneliness is a major public health concern warranting novel health-care strategies and interventions promoting social connectedness. Social prescribing (SP) constitutes such strategy and is, despite scarce evidence, increasingly promoted. Focusing primarily on building and maintaining social support, SP appears especially relevant in connection to community-based physical activity. In this review, we introduce and discuss the adaptation of SP in the context of the Danish healthcare system and provide examples of current research initiatives.

The Impact of COVID-19 on the Choice of Treatment for Hand Fractures: A Single-Centre Concordance Study.

Background: Management of hand trauma has evolved to incorporate assessment, treatment and rehabilitation of patients in a 'one-stop' clinic on initial presentation. Our aim was to evaluate the effect of coronavirus disease 2019 (COVID-19) on the choice of treatment for hand fractures using inter-rater agreement between surgeons. Methods: All patients with hand fractures during the COVID-19 lockdown from March to May 2020 were included in the study. Two experienced hand surgeons blinded to management and outcomes independently reviewed radiographic images and relevant clinical history to provide their opinion on optimal treatment. Weighted kappa analysis was performed to determine concordance and inter-rater agreement between the two surgeons and actual management. Results: The study included 82 patients (62 men and 20 women) with a mean age of 40.3 (SD 19.7). The injuries occurred most often at home following an accident (34%) or a fall (28%). Fractures involved the metacarpals in 29 patients and the distal phalanx in 22 patients. Thirty-five patients underwent surgery, whereas 47 were managed conservatively. Overall agreement between actual management and consultant A and consultant B was moderate (κ = 0.55, p < 0.0001 and κ = 0.63, p < 0.0001, respectively). Subgroup analysis showed a weak agreement between actual management of metacarpal fractures and consultant A and consultant B (κ = 0.22, p = 0.29 and κ = 0.47, p = 0.02, respectively). Inter-rater agreement was substantial for management of metacarpal fractures (κ = 0.73, p < 0.0001), but weak for distal phalanx fractures (κ = 0.29, p = 0.03). Conclusion: Our study has shown that overall management of hand fractures remained optimised throughout the pandemic. However, a lack of concordance was observed in the management of metacarpals. Level of Evidence: Level IV (Therapeutic).

Evaluation of the Performance of a Multiplexed Serological Assay in the Detection of SARS-CoV-2 Infections in a Predominantly Vaccinated Population.

SARS-CoV-2 seroprevalence studies may be complicated by vaccination efforts. It is important to characterize the ability of serology methods to correctly distinguish prior infection from postvaccination seroreactivity. We report the performance of the Meso Scale Discovery (MSD) V-PLEX COVID-19 Coronavirus Panel 2 IgG assay. Using serum samples from a prospective cohort of paramedics, we calculated the performance of the V-PLEX nucleocapsid ("N") assay to classify prior SARS-CoV-2 infections, defined as a (i) history of a positive SARS-CoV-2 PCR test or (ii) positive serology results using the Roche Elecsys total nucleocapsid anti-SARS-Cov-2 assay. We calculated sensitivity and specificity at the optimal threshold (defined by the highest Youden index). We compared subgroups based on vaccination status, and between models that excluded prior infections 3 to 12 months before sample collection. Of 1119 participants, 914 (81.7%) were vaccinated and 60 (5.4%) had evidence of a preceding SARS-CoV-2 infection. Overall and within vaccinated and unvaccinated subgroups, the optimal thresholds were 828 AU/mL, 827 AU/mL, and 1324 AU/mL; with sensitivities of 0.95 (95% CI: 0.94 to 0.96), 0.95 (0.94 to 0.96), 0.94 (0.92 to 0.96) and specificities of 0.88 (0.86 to 0.90), 0.87 (0.85 to 0.89), and 0.94 (0.89 to 0.98), respectively. N-assay specificity was significantly better in unvaccinated (versus vaccinated) individuals (P = 0.005). Overall optimal thresholds based on the AUC values were higher for samples from unvaccinated participants, especially when examining infections within the preceding 9 months (5855 versus 1704 AU/mL). Overall, V-PLEX nucleocapsid assay cutoff values were higher among unvaccinated individuals. Specificity was also significantly higher among unvaccinated individuals. Different thresholds were required to achieve optimal test performance, especially for detecting SARS-CoV-2 infections within the preceding 9 months. IMPORTANCE Among a cohort of adult paramedics in Canada, we investigated the performance of nucleocapsid (N) antibody detection (measured with a V-PLEX assay) to identify previous COVID-19 infections and compared differences among vaccinated and unvaccinated. Our data indicate that vaccinated and unvaccinated groups require different thresholds to achieve optimal test performance, especially for detecting COVID-19 within the preceding 9 months. Overall, specificity was significantly higher among unvaccinated, compared to vaccinated individuals.

A systematic review of adherence to physical activity interventions in individuals with type 2 diabetes.

Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.

One-year intensive lifestyle intervention and improvements in health-related quality of life and mental health in persons with type 2 diabetes: a secondary analysis of the U-TURN randomized controlled trial.

INTRODUCTION: The effects of lifestyle interventions in persons with type 2 diabetes (T2D) on health-related quality of life (HRQoL) and subjective well-being are ambiguous, and no studies have explored the effect of exercise interventions that meet or exceed current recommended exercise levels. We investigated whether a 1-year intensive lifestyle intervention is superior in improving HRQoL compared with standard care in T2D persons. RESEARCH DESIGN AND METHODS: We performed secondary analyses of a previously conducted randomized controlled trial (April 2015 to August 2016). Persons with non-insulin-dependent T2D (duration ≤10 years) were randomized to 1-year supervised exercise and individualized dietary counseling (ie, 'U-TURN'), or standard care. The primary HRQoL outcome was change in the 36-item Short Form Health Survey (SF-36) physical component score (PCS) from baseline to 12 months of follow-up, and a key secondary outcome was changes in the SF-36 mental component score (MCS). RESULTS: We included 98 participants (U-TURN group=64, standard care group=34) with a mean age of 54.6 years (SD 8.9). Between-group analyses at 12-month follow-up showed SF-36 PCS change of 0.8 (95% CI -0.7 to 2.3) in the U-TURN group and deterioration of 2.4 (95% CI -4.6 to -0.1) in the standard care group (difference of 3.2, 95% CI 0.5 to 5.9, p=0.02) while no changes were detected in SF-36 MCS. At 12 months, 19 participants (30%) in the U-TURN group and 6 participants (18%) in the standard care group achieved clinically significant improvement in SF-36 PCS score (adjusted risk ratio 2.6, 95% CI 1.0 to 4.5 corresponding to number needed to treat of 4, 95% CI 1.6 to infinite). CONCLUSION: In persons with T2D diagnosed for less than 10 years, intensive lifestyle intervention improved the physical component of HRQoL, but not the mental component of HRQoL after 1 year, compared with standard care. TRIAL REGISTRATION NUMBER: NCT02417012.

Crucial role for CA2 inputs in the sequential organization of CA1 time cells supporting memory.

There is considerable evidence for hippocampal time cells that briefly activate in succession to represent the temporal structure of memories. Previous studies have shown that time cells can be disrupted while leaving place cells intact, indicating that spatial and temporal information can be coded in parallel. However, the circuits in which spatial and temporal information are coded have not been clearly identified. Here we investigated temporal and spatial coding by dorsal hippocampal CA1 (dCA1) neurons in mice trained on a classic spatial working-memory task. On each trial, the mice approached the same choice point on a maze but were trained to alternate between traversing one of two distinct spatial routes (spatial coding phase). In between trials, there was a 10-s mnemonic delay during which the mouse continuously ran in a fixed location (temporal coding phase). Using cell-type-specific optogenetic methods, we found that inhibiting dorsal CA2 (dCA2) inputs into dCA1 degraded time cell coding during the mnemonic delay and impaired the mouse's subsequent memory-guided choice. Conversely, inhibiting dCA2 inputs during the spatial coding phase had a negligible effect on place cell activity in dCA1 and no effect on behavior. Collectively, our work demonstrates that spatial and temporal coding in dCA1 is largely segregated with respect to the dCA2-dCA1 circuit and suggests that CA2 plays a critical role in representing the flow of time in memory within the hippocampal network.

The role of ultrasonography in the assessment of ulnar collateral ligament injury of the thumb - a diagnostic test accuracy meta-analysis.

The accurate diagnosis of ulnar collateral ligament (UCL) injuries of the thumb is important in identifying patients requiring surgery. Stener lesion, the most severe form of such injuries, is debilitating and leads to chronic instability if misdiagnosed. We evaluated the diagnostic accuracy of ultrasonography (USS) in UCL injuries. A systematic review of existing literature was performed with a meta-analysis using a bivariate mixed-effects model to estimate summary sensitivity and specificity. All observational studies were assessed, with participants of any age, who sustained UCL injuries of the thumb. A hierarchical model was used to generate a hierarchical summary receiver operating characteristic (HSROC) curves. We identified 17 studies reporting a total of 593 UCL injuries. Pooled estimates for sensitivity and specificity were 0.96 (95% CI 0.89-0.99) and 0.90 (95% CI 0.81-0.94), respectively for the diagnosis of Stener lesions; 0.81 (95% CI 0.66-0.93) and 0.87 (95% CI 0.67-0.96), respectively for non-displaced complete ruptures and 0.82 (95% CI 0.66-0.92) and 0.94 (95% CI 0.85-0.98), respectively for complete ruptures without Stener lesion. The area under the curve (AUC) for Stener diagnosis using USS was 0.98, suggesting excellent diagnostic accuracy. Our meta-analysis suggests that USS is a reliable and accurate method of diagnosis for UCL injuries. Moreover, it has excellent diagnostic accuracy for Stener lesions and may be used in the diagnostic work-up of UCL injuries with magnetic resonance imaging being reserved for ambiguous cases.

Motivation and Barriers to Maintaining Lifestyle Changes in Patients with Type 2 Diabetes after an Intensive Lifestyle Intervention (The U-TURN Trial): A Longitudinal Qualitative Study.

The purpose of this study was to explore and identify factors that influence motivation for and barriers to adopting and maintaining lifestyle changes in patients with type 2 diabetes, following participation in an intensive multiple-lifestyle intervention. Participants were recruited from the U-TURN trial, a one-year, intensive lifestyle intervention for type 2 diabetes patients. This study was conducted over time; informants were interviewed twice after the trial ended with a six-month interval between interviews. The qualitative data from these individual interviews were analysed using systematic text condensation with an inductive approach. Five themes emerged: Social support and relatedness, Achievement of results, Support from healthcare professionals, Identification with and acceptance of the new lifestyle and Coping with ongoing challenges. These are all important for maintaining lifestyle changes and diabetes self-management. Changing one's lifestyle can be a constant, difficult struggle. For sustainable progress after an intensive intervention, the changes must be adopted and endorsed by patients and co-opted into their social setting. Belonging to an exercise group, confidence in managing the lifestyle adjustments and handling of challenges through continual support and professional diabetes treatment are crucial in maintaining and adhering to the new lifestyle.

Effects of an intensive lifestyle intervention on the underlying mechanisms of improved glycaemic control in individuals with type 2 diabetes: a secondary analysis of a randomised clinical trial.

AIMS/HYPOTHESIS: The aim was to investigate whether an intensive lifestyle intervention, with high volumes of exercise, improves beta cell function and to explore the role of low-grade inflammation and body weight. METHODS: This was a randomised, assessor-blinded, controlled trial. Ninety-eight individuals with type 2 diabetes (duration <10 years), BMI of 25-40 kg/m2, no use of insulin and taking fewer than three glucose-lowering medications were randomised (2:1) to either the standard care plus intensive lifestyle group or the standard care alone group. Standard care consisted of individual guidance on disease management, lifestyle advice and blinded regulation of medication following a pre-specified algorithm. The intensive lifestyle intervention consisted of aerobic exercise sessions that took place 5-6 times per week, combined with resistance exercise sessions 2-3 times per week, with a concomitant dietary intervention aiming for a BMI of 25 kg/m2. In this secondary analysis beta cell function was assessed from the 2 h OGTT-derived disposition index, which is defined as the product of the Matsuda and the insulinogenic indices. RESULTS: At baseline, individuals were 54.8 years (SD 8.9), 47% women, type 2 diabetes duration 5 years (IQR 3-8) and HbA1c was 49.3 mmol/mol (SD 9.2); 6.7% (SD 0.8). The intensive lifestyle group showed 40% greater improvement in the disposition index compared with the standard care group (ratio of geometric mean change [RGM] 1.40 [95% CI 1.01, 1.94]) from baseline to 12 months' follow-up. Plasma concentration of IL-1 receptor antagonist (IL-1ra) decreased 30% more in the intensive lifestyle group compared with the standard care group (RGM 0.70 [95% CI 0.58, 0.85]). Statistical single mediation analysis estimated that the intervention effect on the change in IL-1ra and the change in body weight explained to a similar extent (59%) the variance in the intervention effect on the disposition index. CONCLUSIONS/INTERPRETATION: Our findings show that incorporating an intensive lifestyle intervention, with high volumes of exercise, in individuals with type 2 diabetes has the potential to improve beta cell function, associated with a decrease in low-grade inflammation and/or body weight. TRIAL REGISTRATION: ClinicalTrials.gov NCT02417012 Graphical abstract.

Consolidation of vitamin A and E methods onto a multiplexing liquid chromatography tandem mass spectrometry platform simplifies laboratory workflow.

BACKGROUND: Vitamin A and E are routinely monitored to assess nutritional status. The most commonly used approach for their measurement involves laborious liquid-liquid extraction followed by high-performance liquid chromatography (HPLC) analysis on dedicated instrumentation. We describe a simple, rapid protocol for measurement of vitamin A and E and their integration into an existing online sample preparation liquid chromatography tandem mass spectrometry (SPLC-MS/MS) workflow. METHODS: We performed a method comparison between the SPLC-MS/MS and HPLC methods for vitamin A and E by measuring patient specimens across the concentration range 11-81 µg/dL for vitamin A and 1-18 mg/L for vitamin E. The analysis times on each platform were also compared. RESULTS: SPLC-MS/MS and HPLC methods were comparable with regards to analytical performance; mean bias across the measured range was 2.54% (95% CL: -11.56-16.64%) for vitamin A and -2.04% (95% CL: -18.20-14.12%) for vitamin E. Total analysis times were 7 min and 15 min for SPLC-MS/MS and HPLC respectively. CONCLUSIONS: The development of a simplified sample preparation protocol and the use of multiplexing SPLC-MS/MS have reduced sample analysis times for vitamin A and E. This method has also optimized clinical workflow through consolidation of previously independent benches.

Dose-Response Effects of Exercise on Glucose-Lowering Medications for Type 2 Diabetes: A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVE: To investigate whether a dose-response relationship exists between volume of exercise and discontinuation of glucose-lowering medication treatment in patients with type 2 diabetes. PATIENTS AND METHODS: Secondary analyses of a randomized controlled exercise-based lifestyle intervention trial (April 29, 2015 to August 17, 2016). Patients with non-insulin-dependent type 2 diabetes were randomly assigned to an intensive lifestyle intervention (U-TURN) or standard-care group. Both groups received lifestyle advice and objective target-driven medical regulation. Additionally, the U-TURN group received supervised exercise and individualized dietary counseling. Of the 98 randomly assigned participants, 92 were included in the analysis (U-TURN, n=61, standard care, n=31). Participants in the U-TURN group were stratified into tertiles based on accumulated volumes of exercise completed during the 1-year intervention. RESULTS: Median exercise levels of 178 (interquartile range [IQR], 121-213; lower tertile), 296 (IQR, 261-310; intermediate tertile), and 380 minutes per week (IQR, 355-446; upper tertile) were associated with higher odds of discontinuing treatment with glucose-lowering medication, with corresponding odds ratios of 12.1 (95% CI, 1.2-119; number needed to treat: 4), 30.2 (95% CI, 2.9-318.5; 3), and 34.4 (95% CI, 4.1-290.1; 2), respectively, when comparing with standard care. Cardiovascular risk factors such as glycated hemoglobin A1c levels, fitness, 2-hour glucose levels, and triglyceride levels were improved significantly in the intermediate and upper tertiles, but not the lower tertile, compared with the standard-care group. CONCLUSION: Exercise volume is associated with discontinuation of glucose-lowering medication treatment in a dose-dependent manner, as are important cardiovascular risk factors in well-treated participants with type 2 diabetes and disease duration less than 10 years. Further studies are needed to support these findings. STUDY REGISTRATION: ClinicalTrials.gov registration (NCT02417012).

Type 2 diabetes remission 1 year after an intensive lifestyle intervention: A secondary analysis of a randomized clinical trial.

AIM: To investigate whether an intensive lifestyle intervention induces partial or complete type 2 diabetes (T2D) remission. MATERIALS AND METHODS: In a secondary analysis of a randomized, assessor-blinded, single-centre trial, people with non-insulin-dependent T2D (duration <10 years), were randomly assigned (2:1, stratified by sex, from April 2015 to August 2016) to a lifestyle intervention group (n = 64) or a standard care group (n = 34). The primary outcome was partial or complete T2D remission, defined as non-diabetic glycaemia with no glucose-lowering medication at the outcome assessments at both 12 and 24 months from baseline. All participants received standard care, with standardized, blinded, target-driven medical therapy during the initial 12 months. The lifestyle intervention included 5- to 6-weekly aerobic and combined aerobic and strength training sessions (30-60 minutes) and individual dietary plans aiming for body mass index ≤25 kg/m2 . No intervention was provided during the 12-month follow-up period. RESULTS: Of the 98 randomized participants, 93 completed follow-up (mean [SD] age 54.6 [8.9] years; 46 women [43%], mean [SD] baseline glycated haemoglobin 49.3 [9.3] mmol/mol). At follow-up, 23% of participants (n = 14) in the intervention and 7% (n = 2) in the standard care group met the criteria for any T2D remission (odds ratio [OR] 4.4, 95% confidence interval [CI] 0.8-21.4]; P = 0.08). Assuming participants lost to follow-up (n = 5) had relapsed, the OR for T2D remission was 4.4 (95% CI 1.0-19.8; P = 0.048). CONCLUSIONS: The statistically nonsignificant threefold increased remission rate of T2D in the lifestyle intervention group calls for further large-scale studies to understand how to implement sustainable lifestyle interventions among people with T2D.

Cytokine-induced cysteine- serine-rich nuclear protein-1 (CSRNP1) selectively contributes to MMP1 expression in human chondrocytes.

Irreversible cartilage collagen breakdown by the collagenolytic matrix metalloproteinases (MMPs)-1 and MMP-13 represents a key event in pathologies associated with tissue destruction such as arthritis. Inflammation is closely associated with such pathology and occurs in both rheumatoid and osteoarthritis making it highly relevant to the prevailing tissue damage that characterises these diseases. The inflammation-induced activating protein-1 (AP-1) transcription factor is an important regulator of both MMP1 and MMP13 genes with interplay between signalling pathways contributing to their expression. Here, we have examined the regulation of MMP1 expression, and using in vivo chromatin immunoprecipitation analyses we have demonstrated that cFos bound to the AP-1 cis element within the proximal MMP1 promoter only when the gene was transcriptionally silent as previously observed for MMP13. Subsequent small interfering RNA-mediated silencing confirmed however, that cFos significantly contributes to MMP1 expression. In contrast, silencing of ATF3 (a prime MMP13 modulator) did not affect MMP1 expression whilst silencing of the Wnt-associated regulator cysteine- serine-rich nuclear protein-1 (CSRNP1) resulted in substantial repression of MMP1 but not MMP13. Furthermore, following an early transient peak in expression of CSRNP1 at the mRNA and protein levels similar to that seen for cFOS, CSRNP1 expression subsequently persisted unlike cFOS. Finally, DNA binding assays indicated that the binding of CSRNP1 to the AP-1 consensus-like sequences within the proximal promoter regions of MMP1 and MMP13 was preferentially selective for MMP1 whilst activating transcription factor 3 (ATF3) binding was exclusive to MMP13. These data further extend our understanding of the previously reported differential regulation of these MMP genes, and strongly indicate that although cFos modulates the expression of MMP1/13, downstream factors such as CSRNP1 and ATF3 ultimately serve as transcriptional regulators in the context of an inflammatory stimulus for these potent collagenolytic MMPs.

Why prescribe exercise as therapy in type 2 diabetes? We have a pill for that!

The majority of T2D cases are preventable through a healthy lifestyle, leaving little room for questions that lifestyle should be the first line of defence in the fight against the development of T2D. However, when it comes to the clinical care of T2D, the potential efficacy of lifestyle is much less clear-cut, both in terms of impacting the pathological metabolic biomarkers of the disease, and long-term complications. A healthy diet, high leisure-time physical activity, and exercise are considered to be cornerstones albeit adjunct to drug therapy in the management of T2D. The prescription and effective implementation of structured exercise and other lifestyle interventions in the treatment of T2D have not been routinely used. In this article, we critically appraise and debate our reflections as to why exercise and physical activity may not have reached the status of a viable and effective treatment in the clinical care of T2D to the same extent as pharmaceutical drugs. We argue that the reason why exercise therapy is not utilized to a satisfactory degree is multifaceted and primarily relates to a "vicious cycle" with lack of proven efficacy on T2D complications and a lack of proven effectiveness on risk factors in the primary care of T2D. Furthermore, there is a lack of experimental research establishing the optimal dose of exercise. This precludes widespread and sustained implementation of physical activity and exercise in the clinical treatment of T2D will not succeed.

The Effects of Moderate- Versus High-Load Resistance Training on Muscle Growth, Body Composition, and Performance in Collegiate Women.

Cholewa, JM, Rossi, FE, MacDonald, C, Hewins, A, Gallo, S, Micenski, A, Norton, L, and Campbell, BI. The effects of moderate- versus high-load resistance training on muscle growth, body composition, and performance in collegiate women. J Strength Cond Res 32(6): 1511-1524, 2018-Twenty young women (20.3 + 1.5 years, 164 + 6 cm, 68.7 + 13.8 kg) without prior structured resistance training experience were recruited for this study. Body composition (BodPod), compartmental water (Bioelectrical Impedance), 7-site skinfold, and arm and thigh cross-sectional area (CSA) were assessed before and after 8-week training. Performance testing consisted of vertical jump, 3-kg chest pass initial velocity, squat 1RM, and overhead press 1RM. After 2 weeks of familiarization training, subjects were matched for body composition and relative squat strength and randomly assigned to either a high-load (HL: n = 10; 4 sets of 5-7 repetitions) or moderate-load (ML: n = 10; 2 sets of 10-14 repetitions) group that completed 6-7 exercises per day performed to momentary muscular failure. Training was divided into 2 lower and one upper body training sessions per week performed on nonconsecutive days for 8 weeks. There were no statistically significant main effects for group or group × time interactions for any variable assessed. Both HL and ML resulted in similar significant increases in lean body mass (1.5 ± 0.83 kg), lean dry mass (1.32 ± 0.62 kg), thigh CSA (6.6 ± 5.6 cm), vertical jump (2.9 ± 3.2 cm), chest pass velocity (0.334 ± 1.67 m·s), back squat one repetition maximum (1RM) (22.5 ± 8.1 kg), and overhead press (3.0 ± 0.8 kg). High-load group and ML group also both resulted in significant decreases in percent body fat (1.3 ± 1.3%), total body water (0.73 ± 0.70 L), and intracellular water (0.43 ± 0.38 L). The results of this study indicate that both moderate-load and high-load training are effective at improving muscle growth, body composition, strength and power in untrained young women.

Effect of an Intensive Lifestyle Intervention on Glycemic Control in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Importance: It is unclear whether a lifestyle intervention can maintain glycemic control in patients with type 2 diabetes. Objective: To test whether an intensive lifestyle intervention results in equivalent glycemic control compared with standard care and, secondarily, leads to a reduction in glucose-lowering medication in participants with type 2 diabetes. Design, Setting, and Participants: Randomized, assessor-blinded, single-center study within Region Zealand and the Capital Region of Denmark (April 2015-August 2016). Ninety-eight adult participants with non-insulin-dependent type 2 diabetes who were diagnosed for less than 10 years were included. Participants were randomly assigned (2:1; stratified by sex) to the lifestyle group (n = 64) or the standard care group (n = 34). Interventions: All participants received standard care with individual counseling and standardized, blinded, target-driven medical therapy. Additionally, the lifestyle intervention included 5 to 6 weekly aerobic training sessions (duration 30-60 minutes), of which 2 to 3 sessions were combined with resistance training. The lifestyle participants received dietary plans aiming for a body mass index of 25 or less. Participants were followed up for 12 months. Main Outcomes and Measures: Primary outcome was change in hemoglobin A1c (HbA1c) from baseline to 12-month follow-up, and equivalence was prespecified by a CI margin of ±0.4% based on the intention-to-treat population. Superiority analysis was performed on the secondary outcome reductions in glucose-lowering medication. Results: Among 98 randomized participants (mean age, 54.6 years [SD, 8.9]; women, 47 [48%]; mean baseline HbA1c, 6.7%), 93 participants completed the trial. From baseline to 12-month follow-up, the mean HbA1c level changed from 6.65% to 6.34% in the lifestyle group and from 6.74% to 6.66% in the standard care group (mean between-group difference in change of -0.26% [95% CI, -0.52% to -0.01%]), not meeting the criteria for equivalence (P = .15). Reduction in glucose-lowering medications occurred in 47 participants (73.5%) in the lifestyle group and 9 participants (26.4%) in the standard care group (difference, 47.1 percentage points [95% CI, 28.6-65.3]). There were 32 adverse events (most commonly musculoskeletal pain or discomfort and mild hypoglycemia) in the lifestyle group and 5 in the standard care group. Conclusions and Relevance: Among adults with type 2 diabetes diagnosed for less than 10 years, a lifestyle intervention compared with standard care resulted in a change in glycemic control that did not reach the criterion for equivalence, but was in a direction consistent with benefit. Further research is needed to assess superiority, as well as generalizability and durability of findings. Trial Registration: clinicaltrials.gov Identifier: NCT02417012.

The Impact of Cervical Musculoskeletal Disorders on UK Consultant Plastic Surgeons: Can We Reduce Morbidity With Applied Ergonomics?

BACKGROUND: Based on anecdotal and observational evidence, we hypothesized that the prevalence of cervical musculoskeletal disorder (C-MSD) would be high among plastic surgeons. A questionnaire review was undertaken to test this hypothesis. Ergonomic assessment was undertaken to assess causal factors of C-MSD. METHOD: An anonymous questionnaire recording demographics, physical symptoms and behavioral responses to C-MSD was distributed to UK Plastic Surgery consultants. The postural impact of wearing loupes was assessed using motion capture techniques and recording cervical muscular activity. RESULTS: The questionnaire response rate was 81%. The prevalence of cervical spine morbidity was recorded as 32%. Employment implications included 28% of the cohort requiring sick leave. The professional impact was 7% permanently modifying their practice. There were 2 factors significant for C-MSD, the surgeons' age and the duration in hours of wearing loupes per week. Ergonomic assessment of surgeons operating in loupes demonstrated: 1. increased forward and lateral cervical flexion; 2. increased cervical muscular activity to maintain the protracted "head forward" posture; and 3. prolonged static posturing to maintain head position for visual focus. Table height adjustment and variation of loupe working distance can reduce neck flexion. CONCLUSIONS: Cervical morbidity is a prevalent problem among plastic surgeons. Long procedures, static postures and neck flexion result in the "head forward" posture. This posture exaggerates when operating with loupe magnification. Early-middle-aged consultants are more prone to cervical morbidity hence afflicted when at the top of their game. The work force is diminished for a potentially avoidable morbidity. Rather than accept this morbidity, co-operation between plastic surgeons and ergonomist may help to reduce injury.