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Determining outcomes using the total neoadjuvant therapy (TNT) in patients with local advanced rectal cancer is important for stratifying patients according to expected outcomes in future studies in the era of treatment combination. The present meta-analysis estimated the pathological complete response, disease-free survival, and overall survival probabilities of rectal cancer patients and identified predictors of outcomes.Studies reporting pathological complete response rate and time-dependent outcomes (progression or death) after total neoadjuvant treatment of locally advanced rectal cancer (LARC) were identified in MEDLINE through January 2022. Three independent observers extracted data on patient populations and outcomes and combined the data using a distribution-free summary survival curve. The primary outcomes were actuarial probabilities of recurrence and survival.Fourteen RCTs, including 18 TNT arms, met the inclusion criteria. The pooled estimate of pathological complete response (pCR) probability was 23.6%, with moderate heterogeneity between studies. The pooled estimates of actuarial disease-free survival rate were 70.6% at 3 years and 65.4% at 5 years. The pooled estimates of actuarial survival rates were 93% at 3 years and 81.6% at 5 years. In both these outcomes, heterogeneity between studies was highly significant.This meta-analysis showed that Total Neoadjuvant Therapy is an optimal approach for LARC patients. The results provide a useful benchmark for future comparisons of the benefits of combinations of other drug families as target therapies or immunotherapies.

Determining the risk for progression or survival after standard androgen deprivation treatment (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) is essential for stratifying patients according to expected outcomes in future studies of treatment combination. This systematic review and meta-analysis aims to estimate the progression-free survival (PFS) and overall survival (OS) probabilities in the control group of randomized controlled trials (RCTs) of different regimens of standard androgen deprivation treatment (ADT) in mHSPC and to identify possible predictors of outcomes.Studies reporting time-dependent outcomes (progression or death) after standard ADT treatment of mHSPC were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through June 2021. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of disease progression and survival. Fifteen studies met the inclusion criteria. The pooled estimate of the actuarial PFS rate was 35.2% at two years. The pooled actuarial OS rate was 62.5% at three years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, high-volume disease and the presence of visceral metastases were associated with shorter survival. Our findings show that PFS and OS are highly variable in patients with mHSPC treated with ADT, providing a helpful benchmark for indirect comparisons of the benefits of the combination of chemotherapy and second-generation hormonotherapy.

Rationale: High circulating galectin-3 is associated with poor outcomes in patients with COVID-19. We hypothesised that GB0139, a potent inhaled thiodigalactoside galectin-3 inhibitor with anti-inflammatory and antifibrotic actions, would be safely and effectively delivered in COVID-19 pneumonitis. Objectives: Primary outcomes were safety and tolerability of inhaled GB0139 as an add-on therapy for patients hospitalised with COVID-19 pneumonitis. Methods: We present the findings of two arms of a phase Ib/IIa randomised controlled platform trial in hospitalised patients with confirmed COVID-19 pneumonitis. Patients received standard of care (SoC) or SoC plus 10 mg inhaled GB0139 twice daily for 48 hours, then once daily for up to 14 days or discharge. Results: Data are reported from 41 patients, 20 of which were assigned randomly to receive GB0139. Primary outcomes: the GB0139 group experienced no treatment-related serious adverse events. Incidences of adverse events were similar between treatment arms (40 with GB0139+SoC vs 35 with SoC). Secondary outcomes: plasma GB0139 was measurable in all patients after inhaled exposure, and demonstrated target engagement with decreased circulating galectin (overall treatment effect post-hoc ANCOVA over days 2–7: p=0.0099 vs SoC). Plasma biomarkers associated with inflammation, fibrosis, coagulopathy and major organ function were evaluated. Conclusions: In COVID pneumonitis, inhaled GB013 was well-tolerated, achieved clinically relevant plasma concentrations with target engagement. The data support larger clinical trials to determine clinical efficacy. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT04473053. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).Keywords: Covid-19; Galectin-3; GB0139

Purpose Studies have shown an increased risk for mortality in patients with psoriasis. Furthermore, research has demonstrated an inverse relationship between 25-hydroxyvitamin D (25[OH]D) level and all-cause mortality. This study investigated the association between 25(OH)D level and all-cause mortality in US adults with psoriasis. Methods Data from NHANES (1999–2014 and mortality data through December 31, 2015) were analyzed. Quartiles of 25(OH)D level were created based on 25(OH)D levels among patients. Cox proportional hazards models were used for estimating hazard ratios (95% CI) for all-cause mortality. Findings A total of 82,091 participants were enrolled in the NHANES study from 1999 to 2014. Overall, 610 patients with psoriasis were identified in NHANES. The mean (SD) duration of follow-up was 5.61 (3.38) years (3427.92 person-years). The hazard ratio for mortality in the fully adjusted model was 0.12 (95% CI, 0.02–0.60; Ptrend = 0.01) in patients with a high 25(OH)D concentration compared to those with 25(OH)D deficiency. Implications The 25(OH)D concentration was significantly inversely associated with all-cause mortality among these patients with psoriasis. Studies have shown an increased risk for mortality in patients with psoriasis compared to the general population. Vitamin D is not regularly metabolized in patients with psoriasis due to their skin abnormality. Vitamin D supplementation has been associated with a reduced mortality in patients with psoriasis. In practice, attention to vitamin D level is crucial, as is the use of vitamin D supplementation, for improving the health of these patients.

A highly sensitive optical probe for the detection of activated neutrophils and Neutrophil Extracellular Traps (NETs) is reported. It is based on a triple-quenched, super-silent tri-branched probe that generates >20 fold increase in fluorescence upon cleavage. The probe was highly specific for human neutrophil elastase, a protease that mediates a variety of inflammatory diseases, and detected NETosis and neutrophil activation in in vitro differentiated neutrophils and isolated human neutrophils.

Propolis is a resin-like substance collected by honeybees from certain plants that have been shown to positive effect on inflammatory factors. Therefore, the aim of this study was to systematically review and meta-analyse the effects of Propolis supplementation on CRP, TNF-a, IL-1, and IL-6 in Randomized Controlled Trials (RCTs). A comprehensive systematic search of articles was conducted in PubMed/MEDLINE, Web of sciences, and Scopus to identify the potential titles up to August 2019. PRISMA guidelines were performed for this study. Inclusion was 1-study design was parallel or cross over randomized controlled trial (RCT), 2- consumption of Propolis as intervention, 3- reported sufficient information about inflammatory factors, CRP, IL1, IL6, TNF-a. Six studies were identified by comprehensive search. This meta-analysis study found a significant reduction in IL-6, CRP, and TNF-α following Propolis consumption (Weighted mean differences (WMD): −17.96 pg/ml, 95% CI: −35.53, −0.38, I2 = 98%), (WMD: −1.16 pg/ml, 95% CI: −2.28, −0.03, I2 = 97%), and (WMD: −34.08 pg/ml, 95% CI: −60.25, −7.91, I2 = 97%), respectively. Propolis did not showed any significant effect on IL-1 (WMD: −17.36 pg/ml, 95% CI: −37.60, 2.87, I2 = 97%). In conclusion, the results demonstrated that CRP, TNF-a and IL-6 were significantly reduced following propolis supplementation. Keywords: Propolis, CRP, TNF, Interleukin-1, Interleukin-6, Inflammation, CRP: c-reactive protein, TNF-a: Tumor necrosis factor alpha, IL-6: Interleukin 6, IL-1: Interleukin 1, WMD: Weighted mean differences

ObjectiveThis systematic review aims to explore and synthesise existing literature on the direct and indirect costs from road traffic injuries (RTIs) in sub-Saharan Africa (SSA), the quality of existing evidence, methods used to estimate and report these costs, and the factors that drive the costs.MethodologyMEDLINE, SCOPUS, ProQuest Central, Web of Science, Global Index Medicus, Embase, World Bank Group e-Library, Econlit, Google Scholar and WHO webpages were searched for relevant literature. References of selected papers were also examined for related articles. Screening was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were included in this review if they were published by March 2019, written in English, conducted in SSA and reported original findings on the cost of illness or economic burden of RTIs. The results were systematically examined, and the quality assessed by two reviewers using a modified Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist.ResultsEleven studies met the inclusion criteria. RTIs can cost between INT$119 and 178 634 per injury and INT$486 and 12 845 per hospitalisation. Findings show variability in costing methods and inadequacies in the quality of existing evidence. Prolonged hospital stays, surgical sundries and severity of injury were the most common factors associated with cost.ConclusionWhile available data are limited, evidence shows that the economic burden of RTIs in SSA is high. Poor quality of existing evidence and heterogeneity in costing methods limit the generalisability of costs reported.

Fish erythrocytes remain nucleated for their life-span, unlike mammalian erythrocytes which undergo enucleation. Asides transportation of oxygen, fish erythrocytes are capable of several immune defence processes. Nucleated fish erythrocytes represent prime candidates for carrying out ETotic responses. ETosis is an evolutionary conserved innate immune defence process found in both vertebrates and invertebrates, which involves the extrusion of DNA studded with antimicrobial proteins into the extracellular space serving to trap and kill microorganisms. In this report, we demonstrate that fish erythrocytes isolated from Danio rerio (zebrafish) produce ETotic-like responses when exposed to chemical and physiological stimuli. Furthermore, we found Salmo salar (Atlantic salmon) erythrocytes produce similar ETotic responses. We have termed these ET-like formations Fish Erythrocyte Extracellular Traps (FEETs). Interestingly, we discovered that mammalian inducers of NETosis, such as the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate and the calcium ionophore ionomycin, induced FEETs. Moreover, we found that FEETs are dependent upon activation of PKC and generation of mitochondrial reactive oxygen species. Thus, this brief report represents the first demonstration that fish erythrocytes can exhibit ETotic-like responses, unveiling a previously unknown function of nucleated erythrocytes, which sheds new light on the innate immune arsenal of erythrocytes.

Background Scabies is an extremely fastidious infestation caused by the Sarcoptes scabiei mite. It causes a persistent itch that can disrupt a person’s mental health, sleep, and overall quality of life. In endemic areas, treatment by targeting symptomatic individuals and their contacts is often unsuccessful due to an asymptomatic period and high rates of re-infection. To overcome this, Mass Drug Administration (MDA) is often used to treat the whole community, irrespective of whether individuals presently have scabies. This review summarises the evidence for the effectiveness of MDA in treating scabies. Methods An exhaustive literature review was conducted on MEDLINE, EMBASE, Web of Science and Scopus. All peer-reviewed articles published in English January 1990 to March 2020 were eligible and only if the studies were primary and interventional. Furthermore, the intervention had to be a pharmacological MDA method involving human subjects. Results TWELVE articles that qualified for inclusion were identified. MDA for scabies significantly reduced its prevalence in communities at follow up. Some of the drivers of success were communities with low levels of migration, an uptake of MDA of > 85%, the use of oral Ivermectin therapy, the treatment of children and pregnant women within the treated population, and repeated treatment for participants diagnosed with scabies at baseline. Conclusions The average absolute reduction in prevalence of scabies was 22.0% and the relative reduction average was 73.4%. These results suggest MDA is effective in treating scabies in the endemic community. Further evidence is needed surrounding MDA use in urban areas with increased levels of migration. Importantly, MDA should not substitute the tackling of socioeconomic factors which contribute to endemic disease such as good sanitation and hygiene.

Current research suggests conflicting evidence surrounding the association between serum magnesium levels and the diagnosis of attention deficit hyperactivity disorder (ADHD). This systematic review and meta-analysis aims to explore, summarize and quantify the published literature addressing this topic. We conducted an exhaustive literature search on Scopus and PubMed for all the relevant observational studies published up to August 2018. A meta-analysis using a random-effects model was used to summarize the overall association between serum magnesium level and ADHD from the available data. We identified seven studies which reported the mean and standard deviation (SD) of magnesium concentration in both ADHD and control groups. The random-effects meta-analysis showed that subjects with ADHD had 0.105 mmol/l (95 CI:-0.188, -0.022; P < 0.013) lower serum magnesium levels compared with to their healthy controls. Moreover, we observed striking and statistically significant heterogeneity among the included studies (I-2 = 96.2, P = 0.0103). The evidence from this meta-analysis supports the theory that an inverse relationship between serum magnesium deficiency and ADHD exists. High heterogeneity amongst the included studies suggests that there is a residual need for observational and community-based studies to further investigate this issue.

Patients with recalcitrant facial port wine stains (rfPWS) can be challenging to manage, often leaving the clinician with difficult decisions for treatment options. ‘Triple therapy’ consists of using three different laser wavelengths at each treatment setting. The evidence on outcomes is limited as this treatment approach has not been previously reported to the best of our knowledge. Children who received triple therapy at least once for rfPWS, and for whom SIAscopy readings had been taken, were retrospectively identified. SIAscope readings were compared before the first triple therapy treatment and at final the most recent clinical follow-up. The clinical appearance was also assessed using a Visual Analogue Scale comparing clinical photographs taken before triple therapy to those taken at the most recent clinical follow-up. A total of 47 children were identified and included in our review. The SIAscope readings showed an overall significant (p

Neutrophils are predominantly glycolytic cells that derive little ATP from oxidative phosphorylation; however, they possess an extensive mitochondrial network and maintain a mitochondrial membrane potential. Although studies have shown neutrophils need their mitochondria to undergo apoptosis and regulate NETosis, the metabolic role of the respiratory chain in these highly glycolytic cells is still unclear. Recent studies have expanded on the role of reactive oxygen species (ROS) released from the mitochondria as intracellular signaling molecules. Our study shows that neutrophils can use their mitochondria to generate ROS and that mitochondrial ROS release is increased in hypoxic conditions. This is needed for the stabilization of a high level of the critical hypoxic response factor and pro-survival protein HIF-1α in hypoxia. Further, we demonstrate that neutrophils use the glycerol 3-phosphate pathway as a way of directly regulating mitochondrial function through glycolysis, specifically to maintain polarized mitochondria and produce ROS. This illustrates an additional pathway by which neutrophils can regulate HIF-1α stability and will therefore be an important consideration when looking for treatments of inflammatory conditions in which HIF-1α activation and neutrophil persistence at the site of inflammation are linked to disease severity.

Despite the success of vaccines and selected repurposed treatments, COVID-19 is likely to remain a global health problem and further chemotherapeutics are required. Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials without characterisation of Pharmacokinetics (PK)/Pharmacodynamics (PD) including safety in COVID-19. One such drug is Nafamostat Mesylate (Nafamostat), a synthetic serine protease inhibitor with anticoagulant and anti-inflammatory properties. Preclinical data has demonstrated that it is has potent antiviral activity against SARS-CoV-2 by directly inhibiting the transmembrane protease serine 2 (TMPRSS2) dependent stage of host cell entry.MethodsWe present the findings of a phase Ib/II open label, platform randomised controlled trial (RCT), exploring the safety of intravenous Nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly to standard of care (SoC), Nafamostat or an alternative therapy. Secondary endpoints included clinical endpoints such as number of oxygen free days and clinical improvement/ deterioration, PK/PD, thromboelastometry, D Dimers, cytokines, immune cell flow cytometry and viral load.ResultsData is reported from 42 patients, 21 of which were randomly assigned to receive intravenous Nafamostat. The Nafamostat group developed significantly higher plasma creatinine levels, more adverse events and a lower number of oxygen free days. There were no other statistically significant differences in the primary or secondary endpoints between Nafamostat and SoC. PK data demonstrated that intravenous Nafamostat was rapidly broken down to inactive metabolites. We observed an antifibrinolytic profile, and no significant anticoagulant effects in thromboelastometry. Participants in the Nafamostat group had higher D Dimers compared to SoC. There were no differences in cytokine profile and immune cell phenotype and viral loads between the groups.ConclusionIn hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous Nafamostat. Given the number of negative trials with repurposed drugs, our experimental medicine trial highlights the value of PK/PD studies prior to selecting drugs for efficacy trials. Given the mechanism of action, further evaluation of Nafamostat delivered via a different route may be warranted. This trial demonstrates the importance of experimental trials in new disease entities such as COVID-19 prior to selecting drugs for larger trials.

A favourable option to management symptoms during menopausal transition is menopausal hormone therapy (MHT) but relation among MHT and risk of melanoma is controversial. This study aims to identify, analyse and present the evidence surrounding post-menopausal exogenous hormone therapy and the risk for melanoma in women. A systematic searches of database was conducted in PubMed/MEDLINE, Scopus, and Cochrane without time, region, and language restrictions from inception to April 2020. The DerSimonian and Laird random-effects model was used to estimate combined risk ratio (RR) and 95% confidence intervals (CI). Subgroup analysis and time-response analysis was conducted based on the formulation of used hormone and length of hormone therapy. Combined results from fourteen studies that containing 19 arms with 1,164,077 participants which 4273 of them had melanoma cancer showed increase risk of melanoma in the hormone-treated versus control group 1.14 (95% CI 1.05-1.24, I2: 21%). The stronger and significant relationship between MHT and risk of melanoma was in participants who used oestrogen formulation (RR 1.32, 95% CI 1.17-1.49, I2 = 0%). Moreover, a significant non-linear time-response relation between MHT and melanoma was also in initial three years of MHT (Coef1 = 0.2423, p1 < 0.01). This study reveals a significant direct relationship between the MHT and risk of melanoma in postmenopausal women.

The effect of roxadustat (FG-4592) on individuals with chronic kidney diseases (CKD) patients receiving or not receiving the dialysis was unclear. The aim of this study was to evaluate the efficacy of roxadustat for the treatment of anemia in patients who are dialysis dependent (DD) or dialysis independent (NDD) CKD. We performed a systematic review of randomised controlled trials (RCTs) comparing treatment with roxadustat versus placebo or epoetin alfa up to November 2019. We investigated the efficacy of roxadustat in the levels of hemoglobin and other clinical parameters in renal anemia in patients with NDD and DD-CKD. We estimated weighted-mean difference (WMD) using random effect models. We included six RCTs comprising 1001 patients of whom 70.6 % were treated with roxadustat and 294 controls. The control group for studies of NDD-CKD patients was placebo whereas an active control of epoetin-alfa was used in studies of DD-CKD patients. Median follow-up time was 8 weeks. All trials were industry-sponsored. Overall, roxadustat increased hemoglobin levels by 1.20 g/dl (95 % CI:0.66, 1.75,P < 0.0001,I2 = 99.3 %). Hemoglobin levels increased by 1.99 g/dl in NDD-CKD patients versus placebo and 0.52 g/dl in DD-CKD patients versus epoetin-alfa. Roxadustat was associated with a decrease the levels of hepcidin by -49.3 ng/dl (-38.5 ng/dl in NDD patients versus placebo and -27.7 ng/dl in DD patients versus epoetin alfa), a decrease in ferritin of -49.7 μmol/l (-52.2 μmol/l in NDD patients versus placebo and -7.3 μmol/l in DD patients versus epoetin alfa), and increase in total iron-binding capacity of 32.2 μmol/l (14.1 μmol/l in NDD patients versus placebo and 13.6 μmol/l in DD patients versus epoetin alfa). The percentage change in the transferrin saturation levels was -2.07 % (-6%, NDD patients versus placebo, and +3.7 % in DD patients versus epoetin alfa) in anemia associated CKD patients. This review found roxadustast increases the levels of hemoglobin, serum transferrin, intestinal iron absorption, and reduces hepcidin in both NDD and DD-CKD patients. Safety data is still emerging.

In the last three decades there have been major advances in the use of lasers for cutaneous vascular anomalies.

Importance Superior labrum from anterior to posterior (SLAP) pathology can result in significant pain and functional limitation for a wide variety of patients. Although many different options have been described for the diagnosis and treatment of SLAP pathology, there is little high-quality evidence to support a given diagnosis/treatment method. Objective The aim of this study was to review the global demographics and trends of SLAP literature, diagnosis, management and consistency of reported outcomes Evidence review We performed a systematic search for studies addressing SLAP pathology published over the last 10 years. Extracted data included sample size, study location, intervention, outcome measures reported, sex distribution and level of evidence. Management was compared between geographic areas. Findings We identified 363 studies reporting on SLAP management over the past decade that met our inclusion and exclusion criteria. The majority of studies originated from North America (50.4%), followed by Asia (22.3%) and Europe (20.9%) with most studies describing results of operative intervention originating from the USA (58.5%). We found the majority of literature related to SLAP pathology was case series level data (44.0%) consisting of sample sizes of less than 40 patients (50.1%). The majority of studies presented clinical outcome scores with the ASES score being the most commonly reported (28.3%). The most common complications reported were pain (32.6%) and stiffness (30.4%) following surgical intervention. Conclusions Current literature related to the management of SLAP pathology demonstrates a predominance of North American studies with low levels of evidence consisting of small sample sizes and variably reported clinical outcome scores. Future research should focus on multicentre, randomised studies to clarify current controversies in the surgical versus non-operative management of SLAP pathology. Relevance Significant demographic and geographic differences exist in the diagnosis and treatment of SLAP. Level of evidence Level IV, systematic review of level I–IV studies.

Background. We describe a case of elastosis perforans serpiginosa and its successful management with PDL laser. Case Presentation. A 15-year-old male presented with a history of itchy, raised, red and unsightly lesions on the back of his neck. He was diagnosed with Elastosis Perforans Serpiginosa on tissue biopsy and underwent pulse dye laser therapy over four years with excellent results. Conclusions. Our results show that pulse dye laser therapy is a safe and effective treatment for elastosis perforans serpiginosa.

Background Current guidelines recommend a Drug Reaction Assessment (DRA) before beginning inhaled therapies to assess for bronchoconstriction and tolerability. There is limited evidence to support this recommendation. Methods In this study we aimed to establish the predictors of successful DRAs in different patient groups using a cohort of all DRAs performed in adults between 2011 and 2016 at the Royal Brompton Hospital. Spirometry, age, gender, height, and underlying lung disease were recorded. A multivariable logistic regression model was constructed to ascertain variables associated with successful DRAs. Results There were 1492 DRA trials using hypertonic saline (32%), antimicrobials (63%), or rhDNase (5%). The majority of patients (94%, n = 1408) passed the DRA. Mean FEV1% predicted was 58.03 (SD 23.36). Female sex, type of inhaled product, and FEV1% predicted were established as significant predictors for DRA success. An FEV1% predicted > 55% was associated with greater probability of DRA success (Odds Ratio [OR]: 2.96 (1.80,4.86) p Conclusion This study classifies distinct patient groups with varying baseline risks which can be used to predict tolerability when adding an inhaled product to their management plan. Some “low risk” patients may in future be able to self-assess their tolerability for inhaled therapies at home to avoid unneeded hospital monitoring.

A 36-year-old immunocompetent man who have sex with men first presented to the plastics team with an ulcerating lesion on his left first toe. The lesion was suggestive of pyogenic granuloma (PG) clinically and histologically. Two years later, the same patient presented to the dermatology clinic with a new erythematous lesion with intermittent bleeding on the left second toe. Clinically, this lesion was suggestive of another PG. However, the histology of the skin curettage revealed part of a PG merging with an atypical spindle cell proliferation with characteristic ‘sieve-like’ appearance in keeping with Kaposi sarcoma. This was confirmed with human herpesvirus-8 immunohistochemistry staining. PG-like Kaposi sarcoma is an uncommon variant of Kaposi sarcoma. Often not considered clinically or histologically, a deep skin biopsy is essential to establish the right diagnosis. Our case highlights the need to consider Kaposi sarcoma as a differential diagnosis in all patients, including HIV-negative individuals, presenting with PG-like lesions.

The prevalence of type 2 diabetes mellitus continues to rise and simultaneously technology has contributed to the growth of MHealth interventions for its prevention, monitoring and management. This systematic review aimed to summarize and evaluate the quality of the published evidence on cost and cost-effectiveness of mHealth interventions for T2DM. A systematic literature search of PubMed, EMBASE, and Web of Science was conducted for papers up to end of April 2019. We included all partial or full economic evaluations providing cost or cost-effectiveness results for mHealth interventions targeting individuals diagnosed with, or at risk of, type 2 diabetes mellitus. Twenty-three studies met the inclusion criteria. Intervention cost varied substantially based on the type and numbers or combination of technologies used, ranging from 1.8 INT $ to 10101.1 INT $ per patient per year. The studies which presented cost effectiveness results demonstrated highly cost-effective interventions, with cost per QALY gained ranging from 0.4 to 62.5 percent of GDP per capita of the country. The quality of partial economic evaluations was on average lower than that of full economic evaluations. Cost of mHealth interventions varied substantially based on type and combination of technology used, however, where cost-effectiveness results were reported, the intervention was cost-effective. PROSPERO registration number: CRD42019123476; Registered: 27/01/2019.

Aim: This study investigated time trend and regional disparities in hospitalisations due to osteoarthritis (OA) among people aged ≥20 years in Sweden from 1998 through 2015. Methods: National and regional data on hospital admissions with a primary diagnosis of OA were collected from the National Patient Register. The absolute and relative regional disparities were assessed using the absolute weighted mean difference from overall mean and the index of disparity. We applied joinpoint regression for temporal trend analysis of hospitalisations and the Mann–Kendall trend test for disparity measures. Changes in number of OA hospitalisations between 1998–2000 and 2013–2015 were analysed using two counterfactual scenarios. Results: During 1998–2015, OA hospitalisations constituted 2.0% of all hospitalisations, with higher proportions among women (58.7%) and those aged 70–74 years (18.0%). The age-standardised rate of OA hospitalisation and its proportions from all and musculoskeletal disorders hospitalisations rose, on average, by >2.0% per year during the study period. OA hospitalisation rates rose statistically significantly in all age groups except for the youngest and oldest age groups. The proportion of hip OA from all OA hospitalisations declined, while the opposite was observed for knee OA. The relative regional disparities declined in men, and the absolute regional disparities rose among women over time. The population growth and ageing could explain only about one third of the observed increases in the absolute number of OA hospitalisations between 1998–2000 and 2013–2015. Conclusions: OA hospitalisations have increased substantially, suggesting the need to improve OA prevention and primary-care management in Sweden.

Summary Background & aims To establish reference values for limb composition, fat-free mass (FFM) and fat mass (FM) in Italian adults for gender-specific age brackets 20–80 years old and to assess age-related regional changes in body composition. Methods A multicenter, retrospective study was conducted on 1571 healthy subjects, 1240 women and 331 men. Regional FFM and FM were measured by dual-energy X-ray absorptiometry. FM was expressed as % of limb weight. Results FFM in men diminished with age in both arms and legs, with reference ranges (25th −75th percentile) of 3.8–4.6 kg and 10.4–12.2 kg, respectively for 20–29 year-olds, and 3.1–3.9 kg and 8.2–10.4 kg for 70–79 year-olds. Women’s arm FFM remained stable with aging (reference values 1.7–2.2 kg), decreasing in their legs (6.2–7.2 kg for 20–29 year-olds, 5.5–6.5 kg for 70–79 year-olds). Limb FM% increased with age in both genders: the reference values were 9–15% (arms) and 12–21% (legs) for 20–29 year-old men, and 19–26% and 19–29%, respectively, for 70–79 year-olds; for women’s arms, they were 25–36% for 20–29 year-olds and 36–48% for 70–79 year-olds, while their leg FM remained the same with aging, i.e. 32–40%. Conclusions These data complete the published reference values for whole body composition, enabling physiological or pathological changes in limb composition to be identified in Caucasian populations living in the Mediterranean area.

Osteoporosis (OP) and osteoarthritis (OA) are age-related diseases often considered to be mutually exclusive. We previously found that 25% of women with advanced OA had occult OP, and that femoral neck (FN) bone mineral density (BMD) T-scores were significantly higher for osteoarthritic vs. contralateral hips. The FRAX® calculator incorporates clinical risk factors and FN BMD T-score to estimate 10-year total fracture probability and hip fracture probability. In 35 women and men ≥41 years with unilateral hip OA scheduled for hip replacement, we tested whether FRAX® fracture probability is underestimated when using data for the OA rather than the contralateral hip. There were between-hip differences for FN BMD T-score (p < 0.0001), total fracture probability (p = 0.0004), and hip fracture probability (p = 0.0009). Use of FN BMD T-scores resulted in OP treatment recommendations for 0% and 11% of subjects compared with 11% and 17% for total fracture probability and hip fracture probability, respectively. In 6-11% of subjects in this series, the FRAX® calculator underestimated fracture probability with data for the OA hip. With the increased use of FRAX® in clinical use, these data suggest that measurement of BMD at the contralateral hip may yield higher calculated FRAX® total and hip fracture probabilities.

Background: To investigate the impact on bone and muscle of pathological conditions involving only one of the upper limbs, it is important to know the physiological differences due to the dominance effect. Aim: To evaluate any physiological differences between dominant and non-dominant upper limbs in terms of bone mineral density (BMD), muscle mass, and muscle density at different levels. Subjects and methods: The study considered 60 right-handed healthy adults, 30 men and 30 women. Cortical BMD, muscle area, and muscle density were investigated by pQCT-XCT-3000 Stratec at the proximal radius, trabecular and total BMD at the distal radius, and trabecular and cortical BMD at the second phalanx of the third finger. Hand grip strength was also measured. Results: No significant differences in BMD were found between the dominant and non-dominant upper limbs at any of the sites considered, in men or women. Muscle density was also similar on the two sides, whereas muscle area at the proximal radius was significantly lower on the non-dominant side in both men [4177.5±475.1 vs 4009.3±552.7 mm2; Δ%: 4.1%; 95% confidence interval (CI) 1.7%–6.5%] and women (2903.9±470.9 vs 2720.3±411.7 mm2; Δ%: 6.1%; 95%CI 4.3%–7.9%). Hand grip strength proved greater on the right side in both men (48.5±8.8 vs 45.2±8.7 kg; Δ% 7.1; p

e12000 Background: Transitory or definitive amenorrhea (A) is a related side effect, specifically affecting young women diagnosed with breast cancer and treated with adjuvant chemotherapy (CT). Pre...

Purpose. The association between serum 25-h ydroxyvitamin D values and cortical/trabecular bone parameters in older adults has been incompletely explored. This study was designed to investigate the relationship between serum 25-hydroxyvitamin D levels and bone parameters for the tibia and radius using peripheral quantitative computed tomography in free-living healthy older adults. Methods. The study in volved 134 older adults attending a twice-weekly low-intensity fitness program. In addition to clinical history and serum parameters, we assessed fat-free mass using dual-energy X-ray absorptiometry, total bone and cortical bone cross-sectional areas, and trabecular and cortical bone mineral density for the tibia and radius by peripheral quantitative computed tomography. Results. After applying multi variate linear regression models, adjusting for sex, age, body mass index, fat mass and fat-free mass, and creatinine, the association between 25-hydroxyvitamin D and bone parameters was significant for total bone and cortical bone cross-sectional areas in the radius (partial R 2 = 0.05 and 0.09, respectively) and for trabecular bone mineral density and cortical bone cross-sectional area in the tibia (partial R 2 = 0.11 and 0.02, respectively). Conclusion. These findings support the idea that serum 25-h ydroxyvitamin D levels and bone parameters are linked in older adults. Longitudinal studies are needed to establish whether vitamin D levels over time are associated with changes in these parameters.