The impact of long-term care interventions on healthcare utilisation among older persons: a scoping review of reviews.

BACKGROUND: As the ageing population grows, the demand for long-term care (LTC) services will rise, concurrently amplifying healthcare utilisation. This review aims to examine and consolidate information on LTC interventions that influence healthcare utilisation among older persons. METHODS: A scoping review was performed through a systematic search in PubMed, EBSCO CINAHL, EBM Reviews - Cochrane Database of Systematic Reviews, Embase, APA PsycInfo, EBM Reviews - Health Technology Assessment, and EBM Reviews - NHS Economic Evaluation Database. Systematic reviews with meta-analyses published between 1 January 2010 and 2 June 2022 among older persons aged 60 and above were included. The characteristics of LTC interventions were mapped to the World Health Organization (WHO) Healthy Ageing Framework. The effect sizes of healthcare utilisations for LTC interventions were recalculated using a random-effects model. The methodological quality was assessed with the AMSTAR-2 checklist, while the quality of evidence for each association was evaluated using GRADE. RESULTS: Thirty-seven meta-analyses were included. The most prominent domain of the healthy ageing framework was managing chronic conditions. One hundred twelve associations between various LTC interventions and healthcare utilisations were identified, with 22 associations impacting healthcare utilisation. Four interventions were supported by suggestive or convincing evidence. Preventive home visits were found to reduce hospital admission (OR: 0.73, 95% CI: 0.59, 0.91, p = 0.005), caregiver integration during discharge planning (OR: 0.68, 95% CI: 0.57, 0.81, p < 0.001), and continuity of care (OR: 0.76, 95% CI: 0.61, 0.95, p = 0.018) reduced hospital readmission, and perioperative geriatric interventions reduced the length of hospital stay (MD: -1.50, 95% CI: -2.24, -0.76, p < 0.001). None of the associations impacted emergency department visits, medication use, and primary care utilisations with convincing evidence. Most reviews received low methodological quality. CONCLUSION: The findings suggest that LTC interventions could benefit from transitioning to a community-based setting involving a multidisciplinary team, including carers. The spectrum of services should incorporate a comprehensive assessment to ensure continuous care.

Association Between Cytomegalovirus Infection and Tuberculosis Disease: A Systematic Review and Meta-Analysis of Epidemiological Studies.

BACKGROUND: Tuberculosis is one of the leading causes of mortality worldwide from an infectious disease. This review aimed to investigate the association between prior cytomegalovirus infection and tuberculosis disease. METHODS: Six bibliographic databases were searched from their respective inception to 31 December 2021. Data were pooled using random-effects meta-analysis. RESULTS: Of 5476 identified articles, 15 satisfied the inclusion criteria with a total sample size of 38 618 patients. Pooled findings showed that individuals with cytomegalovirus infection had a higher risk of tuberculosis disease compared to those not infected with cytomegalovirus (odds ratio [OR], 3.20; 95% confidence interval [CI], 2.18-4.70). Age was the only covariate that exerted a significant effect on the result of the association. Meta-analysis of risk estimates reported in individual studies showed a marked and significant correlation of cytomegalovirus infection with active tuberculosis (adjusted hazard ratio, 2.92; 95% CI, 1.34-4.51; adjusted OR, 1.14; 95% CI, .71-1.57). A clear dose-response relation was inferred between the levels of cytomegalovirus antibodies and the risks of tuberculosis events (OR for high levels of cytomegalovirus antibodies, 4.07; OR for medium levels of cytomegalovirus antibodies, 3.58). CONCLUSIONS: The results suggest an elevated risk of tuberculosis disease among individuals with a prior cytomegalovirus infection.

Evolution of Streptococcus pyogenes has maximized the efficiency of the Sortase A cleavage motif for cell wall transpeptidation.

Trafficking of M-protein (Mprt) from the cytosol of Group A Streptococcus pyogenes (GAS) occurs via Sec translocase membrane channels that associate with Sortase A (SrtA), an enzyme that catalyzes cleavage of Mprt at the proximal C-terminal [-LPST355∗GEAA-] motif and subsequent transpeptidation of the Mprt-containing product to the cell wall (CW). These steps facilitate stable exposure of the N-terminus of Mprt to the extracellular milieu where it interacts with ligands. Previously, we found that inactivation of SrtA in GAS cells eliminated Mprt CW transpeptidation but effected little reduction in its cell surface exposure, indicating that the C-terminus of Mprt retained in the cytoplasmic membrane (CM) extends its N-terminus to the cell surface. Herein, we assessed the effects of mutating the Thr355 residue in the WT SrtA consensus sequence (LPST355∗GEAA-) in a specific Mprt, PAM. In vitro, we found that synthetic peptides with mutations (LPSX355GEAA) in the SrtA cleavage site displayed slower cleavage activities with rSrtA than the WT peptide. Aromatic residues at X had the lowest activities. Nonetheless, PAM/[Y355G] still transpeptidated the CW in vivo. However, when using isolated CMs from srtA-inactivated GAS cells, rapid cleavage of PAM/[LPSY355GEAA] occurred at E357∗ but transpeptidation did not take place. These results show that another CM-resident enzyme nonproductively cleaved PAM/[LPSYGE357∗AA]. However, SrtA associated with the translocon channel in vivo cleaved and transpeptidated PAM/[LPSX355∗GEAA] variants. These CM features allow diverse cleavage site variants to covalently attach to the CW despite the presence of other potent nonproductive CM proteases.

Treatment of a Delayed Type IIIb Endoleak 20 Years Post EVAR With Inverted Contralateral Limb Custom-Made Device: A Case Report.

PURPOSE: Type III endoleak can be difficult to distinguish from Type I endoleak. Depending on the stent graft anatomy, the use of standard bifurcated endografts may not be technically feasible, and patients may have to be subject to an aorto-uni-iliac repair with femoral-femoral bypass or open surgery. CASE REPORT: We report a case of an 86-year-old male who had a Type IIIb endoleak 20 years post EVAR which was characterized on angiography to be from a hole close to the bifurcation limb origin. The initial Talent (Medtronic, Santa Rosa, California) device had a 50 mm main body common trunk, which was not amenable to treatment with standard devices. He was successfully treated with a custom-made device with an inverted contralateral limb. CONCLUSIONS: Our case highlights the need for lifelong surveillance post EVAR as endoleak may present decades post initial EVAR. It also demonstrates that many Type III endoleak which were otherwise deemed unsuitable for treatment with standard devices may potentially be treatable with custom-made device (CMD). This solution preserves a percutaneous option in a now older person which avoids surgical bypass. Further studies are required to establish the durability of this treatment and survey for recurrence.

Interventions for people with type 2 diabetes mellitus fasting during Ramadan.

BACKGROUND: Fasting during Ramadan is obligatory for adult Muslims, except those who have a medical illness. Many Muslims with type 2 diabetes (T2DM) choose to fast, which may increase their risks of hypoglycaemia and dehydration. OBJECTIVES: To assess the effects of interventions for people with type 2 diabetes fasting during Ramadan. SEARCH METHODS: We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, WHO ICTRP and ClinicalTrials.gov (29 June 2022) without language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) conducted during Ramadan that evaluated all pharmacological or behavioural interventions in Muslims with T2DM. DATA COLLECTION AND ANALYSIS: Two authors screened and selected records, assessed risk of bias and extracted data independently. Discrepancies were resolved by a third author. For meta-analyses we used a random-effects model, with risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes with their associated 95% confidence intervals (CIs). We assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included 17 RCTs with 5359 participants, with a four-week study duration and at least four weeks of follow-up. All studies had at least one high-risk domain in the risk of bias assessment. Four trials compared dipeptidyl-peptidase-4 (DPP-4) inhibitors with sulphonylurea. DPP-4 inhibitors may reduce hypoglycaemia compared to sulphonylureas (85/1237 versus 165/1258, RR 0.53, 95% CI 0.41 to 0.68; low-certainty evidence). Serious hypoglycaemia was similar between groups (no events were reported in two trials; 6/279 in the DPP-4 versus 4/278 in the sulphonylurea group was reported in one trial, RR 1.49, 95% CI 0.43 to 5.24; very low-certainty evidence). The evidence was very uncertain about the effects of DPP-4 inhibitors on adverse events other than hypoglycaemia (141/1207 versus 157/1219, RR 0.90, 95% CI 0.52 to 1.54) and HbA1c changes (MD -0.11%, 95% CI -0.57 to 0.36) (very low-certainty evidence for both outcomes). No deaths were reported (moderate-certainty evidence). Health-related quality of life (HRQoL) and treatment satisfaction were not evaluated. Two trials compared meglitinides with sulphonylurea. The evidence is very uncertain about the effect on hypoglycaemia (14/133 versus 21/140, RR 0.72, 95% CI 0.40 to 1.28) and HbA1c changes (MD 0.38%, 95% CI 0.35% to 0.41%) (very low-certainty evidence for both outcomes). Death, serious hypoglycaemic events, adverse events, treatment satisfaction and HRQoL were not evaluated. One trial compared sodium-glucose co-transporter-2 (SGLT-2) inhibitors with sulphonylurea. SGLT-2 may reduce hypoglycaemia compared to sulphonylurea (4/58 versus 13/52, RR 0.28, 95% CI 0.10 to 0.79; low-certainty evidence). The evidence was very uncertain for serious hypoglycaemia (one event reported in both groups, RR 0.90, 95% CI 0.06 to 13.97) and adverse events other than hypoglycaemia (20/58 versus 18/52, RR 1.00, 95% CI 0.60 to 1.67) (very low-certainty evidence for both outcomes). SGLT-2 inhibitors result in little or no difference in HbA1c (MD 0.27%, 95% CI -0.04 to 0.58; 1 trial, 110 participants; low-certainty evidence). Death, treatment satisfaction and HRQoL were not evaluated. Three trials compared glucagon-like peptide 1 (GLP-1) analogues with sulphonylurea. GLP-1 analogues may reduce hypoglycaemia compared to sulphonylurea (20/291 versus 48/305, RR 0.45, 95% CI 0.28 to 0.74; low-certainty evidence). The evidence was very uncertain for serious hypoglycaemia (0/91 versus 1/91, RR 0.33, 95% CI 0.01 to 7.99; very low-certainty evidence). The evidence suggests that GLP-1 analogues result in little to no difference in adverse events other than hypoglycaemia (78/244 versus 55/255, RR 1.50, 95% CI 0.86 to 2.61; very low-certainty evidence), treatment satisfaction (MD -0.18, 95% CI -3.18 to 2.82; very low-certainty evidence) or change in HbA1c (MD -0.04%, 95% CI -0.45% to 0.36%; 2 trials, 246 participants; low-certainty evidence). Death and HRQoL were not evaluated. Two trials compared insulin analogues with biphasic insulin. The evidence was very uncertain about the effects of insulin analogues on hypoglycaemia (47/256 versus 81/244, RR 0.43, 95% CI 0.13 to 1.40) and serious hypoglycaemia (4/131 versus 3/132, RR 1.34, 95% CI 0.31 to 5.89) (very low-certainty evidence for both outcomes). The evidence was very uncertain for the effect of insulin analogues on adverse effects other than hypoglycaemia (109/256 versus 114/244, RR 0.83, 95% CI 0.44 to 1.56; very low-certainty evidence), all-cause mortality (1/131 versus 0/132, RR 3.02, 95% CI 0.12 to 73.53; very low-certainty evidence) and HbA1c changes (MD 0.03%, 95% CI -0.17% to 0.23%; 1 trial, 245 participants; very low-certainty evidence). Treatment satisfaction and HRQoL were not evaluated. Two trials compared telemedicine with usual care. The evidence was very uncertain about the effect of telemedicine on hypoglycaemia compared with usual care (9/63 versus 23/58, RR 0.42, 95% CI 0.24 to 0.74; very low-certainty evidence), HRQoL (MD 0.06, 95% CI -0.03 to 0.15; very low-certainty evidence) and HbA1c change (MD -0.84%, 95% CI -1.51% to -0.17%; very low-certainty evidence). Death, serious hypoglycaemia, AEs other than hypoglycaemia and treatment satisfaction were not evaluated. Two trials compared Ramadan-focused patient education with usual care. The evidence was very uncertain about the effect of Ramadan-focused patient education on hypoglycaemia (49/213 versus 42/209, RR 1.17, 95% CI 0.82 to 1.66; very low-certainty evidence) and HbA1c change (MD -0.40%, 95% CI -0.73% to -0.06%; very low-certainty evidence). Death, serious hypoglycaemia, adverse events other than hypoglycaemia, treatment satisfaction and HRQoL were not evaluated. One trial compared drug dosage reduction with usual care. The evidence is very uncertain about the effect of drug dosage reduction on hypoglycaemia (19/452 versus 52/226, RR 0.18, 95% CI 0.11 to 0.30; very low-certainty evidence). No participants experienced adverse events other than hypoglycaemia during the study (very low-certainty evidence). Death, serious hypoglycaemia, treatment satisfaction, HbA1c change and HRQoL were not evaluated. AUTHORS' CONCLUSIONS: There is no clear evidence of the benefits or harms of interventions for individuals with T2DM who fast during Ramadan. All results should be interpreted with caution due to concerns about risk of bias, imprecision and inconsistency between studies, which give rise to low- to very low-certainty evidence. Major outcomes, such as mortality, health-related quality of life and severe hypoglycaemia, were rarely evaluated. Sufficiently powered studies that examine the effects of various interventions on these outcomes are needed.

Low glycaemic index or low glycaemic load diets for people with overweight or obesity.

BACKGROUND: The prevalence of obesity is increasing worldwide, yet nutritional management remains contentious. It has been suggested that low glycaemic index (GI) or low glycaemic load (GL) diets may stimulate greater weight loss than higher GI/GL diets or other weight reduction diets. The previous version of this review, published in 2007, found mainly short-term intervention studies. Since then, randomised controlled trials (RCTs) with longer-term follow-up have become available, warranting an update of this review. OBJECTIVES: To assess the effects of low glycaemic index or low glycaemic load diets on weight loss in people with overweight or obesity. SEARCH METHODS: We searched CENTRAL, MEDLINE, one other database, and two clinical trials registers from their inception to 25 May 2022. We did not apply any language restrictions. SELECTION CRITERIA: We included RCTs with a minimum duration of eight weeks comparing low GI/GL diets to higher GI/GL diets or any other diets in people with overweight or obesity. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We conducted two main comparisons: low GI/GL diets versus higher GI/GL diets and low GI/GL diets versus any other diet. Our main outcomes included change in body weight and body mass index, adverse events, health-related quality of life, and mortality. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: In this updated review, we included 10 studies (1210 participants); nine were newly-identified studies. We included only one study from the previous version of this review, following a revision of inclusion criteria. We listed five studies as 'awaiting classification' and one study as 'ongoing'. Of the 10 included studies, seven compared low GI/GL diets (233 participants) with higher GI/GL diets (222 participants) and three studies compared low GI/GL diets (379 participants) with any other diet (376 participants). One study included children (50 participants); one study included adults aged over 65 years (24 participants); the remaining studies included adults (1136 participants). The duration of the interventions varied from eight weeks to 18 months. All trials had an unclear or high risk of bias across several domains.  Low GI/GL diets versus higher GI/GL diets Low GI/GL diets probably result in little to no difference in change in body weight compared to higher GI/GL diets (mean difference (MD) -0.82 kg, 95% confidence interval (CI) -1.92 to 0.28; I2 = 52%; 7 studies, 403 participants; moderate-certainty evidence). Evidence from four studies reporting change in body mass index (BMI) indicated low GI/GL diets may result in little to no difference in change in BMI compared to higher GI/GL diets (MD -0.45 kg/m2, 95% CI -1.02 to 0.12; I2 = 22%; 186 participants; low-certainty evidence)at the end of the study periods. One study assessing participants' mood indicated that low GI/GL diets may improve mood compared to higher GI/GL diets, but the evidence is very uncertain (MD -3.5, 95% CI -9.33 to 2.33; 42 participants; very low-certainty evidence). Two studies assessing adverse events did not report any adverse events; we judged this outcome to have very low-certainty evidence. No studies reported on all-cause mortality.    For the secondary outcomes, low GI/GL diets may result in little to no difference in fat mass compared to higher GI/GL diets (MD -0.86 kg, 95% CI -1.52 to -0.20; I2 = 6%; 6 studies, 295 participants; low certainty-evidence). Similarly, low GI/GL diets may result in little to no difference in fasting blood glucose level compared to higher GI/GL diets (MD 0.12 mmol/L, 95% CI 0.03 to 0.21; I2 = 0%; 6 studies, 344 participants; low-certainty evidence).  Low GI/GL diets versus any other diet Low GI/GL diets probably result in little to no difference in change in body weight compared to other diets (MD -1.24 kg, 95% CI -2.82 to 0.34; I2 = 70%; 3 studies, 723 participants; moderate-certainty evidence). The evidence suggests that low GI/GL diets probably result in little to no difference in change in BMI compared to other diets (MD -0.30 kg in favour of low GI/GL diets, 95% CI -0.59 to -0.01; I2 = 0%; 2 studies, 650 participants; moderate-certainty evidence). Two adverse events were reported in one study: one was not related to the intervention, and the other, an eating disorder, may have been related to the intervention. Another study reported 11 adverse events, including hypoglycaemia following an oral glucose tolerance test. The same study reported seven serious adverse events, including kidney stones and diverticulitis. We judged this outcome to have low-certainty evidence. No studies reported on health-related quality of life or all-cause mortality. For the secondary outcomes, none of the studies reported on fat mass. Low GI/GL diets probably do not reduce fasting blood glucose level compared to other diets (MD 0.03 mmol/L, 95% CI -0.05 to 0.12; I2 = 0%; 3 studies, 732 participants; moderate-certainty evidence).  AUTHORS' CONCLUSIONS: The current evidence indicates there may be little to no difference for all main outcomes between low GI/GL diets versus higher GI/GL diets or any other diet. There is insufficient information to draw firm conclusions about the effect of low GI/GL diets on people with overweight or obesity. Most studies had a small sample size, with only a few participants in each comparison group. We rated the certainty of the evidence as moderate to very low. More well-designed and adequately-powered studies are needed. They should follow a standardised intervention protocol, adopt objective outcome measurement since blinding may be difficult to achieve, and make efforts to minimise loss to follow-up. Furthermore, studies in people from a wide range of ethnicities and with a wide range of dietary habits, as well as studies in low- and middle-income countries, are needed.

How can we improve latent tuberculosis infection management using behaviour change wheel: a systematic review.

BACKGROUND: To ensure the effective delivery of latent tuberculosis infection (LTBI) care, it is vital to overcome potential challenges in LTBI management. This systematic review aims to identify the barriers and interventions to improve LTBI management using the Capability, Opportunity, and Motivation-Behaviour (COM-B) model and Behaviour Change Wheel (BCW). METHODS: A systematic literature search was performed on five electronic databases from database inception to 3 November 2021. A two-step technique was used in the data synthesis process: (i) the barriers of LTBI management were identified using the COM-B model, followed by (ii) mapping of intervention functions from BCW to address the identified barriers. RESULTS: Forty-seven eligible articles were included in this review. The findings highlighted the need for a multifaceted approach in tackling the barriers in LTBI management across the public, provider and system levels. The barriers were summarized into suboptimal knowledge and misperception of LTBI, as well as stigma and psychosocial burden, which could be overcome with a combination of intervention functions, targeting education, environment restructuring, persuasion, modelling, training, incentivization and enablement. CONCLUSIONS: The remedial strategies using BCW to facilitate policy reforms in LTBI management could serve as a value-added initiative in the global tuberculosis control and prevention program.

Streptococcus co-opts a conformational lock in human plasminogen to facilitate streptokinase cleavage and bacterial virulence.

Virulent strains of Streptococcus pyogenes (gram-positive group A Streptococcus pyogenes [GAS]) recruit host single-chain human plasminogen (hPg) to the cell surface-where in the case of Pattern D strains of GAS, hPg binds directly to the cells through a surface receptor, plasminogen-binding group A streptococcal M-protein (PAM). The coinherited Pattern D GAS-secreted streptokinase (SK2b) then accelerates cleavage of hPg at the R561-V562 peptide bond, resulting in the disulfide-linked two-chain protease, human plasmin (hPm). hPm localizes on the bacterial surface, assisting bacterial dissemination via proteolysis of host defense proteins. Studies using isolated domains from PAM and hPg revealed that the A-domain of PAM binds to the hPg kringle-2 module (K2hPg), but how this relates to the function of the full-length proteins is unclear. Herein, we use intact proteins to show that the lysine-binding site of K2hPg is a major determinant of the activation-resistant T-conformation of hPg. The binding of PAM to the lysine-binding site of K2hPg relaxes the conformation of hPg, leading to a greatly enhanced activation rate of hPg by SK2b. Domain swapping between hPg and mouse Pg emphasizes the importance of the Pg latent heavy chain (residues 1-561) in PAM binding and shows that while SK2b binds to both hPg and mouse Pg, the activation properties of streptokinase are strictly attributed to the serine protease domain (residues 562-791) of hPg. Overall, these data show that native hPg is locked in an activation-resistant conformation that is relaxed upon its direct binding to PAM, allowing hPm to form and provide GAS cells with a proteolytic surface.

Comparative effectiveness of cardiovascular, renal and safety outcomes of second-line antidiabetic drugs use in people with type 2 diabetes: A systematic review and network meta-analysis of randomised controlled trials.

AIMS: To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second-line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non-cardiovascular adverse events. Risk ratios (RRs) and corresponding confidence intervals (CI) or credible intervals (CrI) were reported within pairwise and network meta-analysis. The quality of evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Number needed to treat (NNT) and number needed (NNH) to harm were calculated at 5 years using incidence rates and RRs. PROSPERO (CRD42020168322). RESULTS: We included 38 trials from seven classes of glucose-lowering therapies. Both sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) showed moderate to high certainty in reducing risk of 3-point major adverse cardiovascular events, 3P-MACE (network estimates: SGLT2i [RR 0.90; 95% CrI 0.84-0.96; NNT, 59], GLP1RA [RR 0.88; 95% CrI 0.83-0.93; NNT, 50]), cardiovascular death, all-cause mortality, renal composite outcome and macroalbuminuria. SGLT2i also showed high certainty in reducing risk of hospitalization for heart failure (hHF), ESRD, acute kidney injury, doubling in serum creatinine and decline in eGFR. GLP1RA were associated with lower risk of stroke (high certainty) while glitazone use was associated with an increased risk of hHF (very low certainty). The risk of developing ESRD was lower with the use of sulphonylureas (low certainty). For adverse events, sulphonylureas and insulin were associated with increased hypoglycaemic events (very low to low certainty), while GLP1RA increased the risk of gastrointestinal side effects leading to treatment discontinuation (low certainty). DPP-4i increased risk of acute pancreatitis (low certainty). SGLT2i were associated with increased risk of genital infection, volume depletion (high certainty), amputation and ketoacidosis (moderate certainty). Risk of fracture was increased with the use of glitazones (moderate certainty). CONCLUSIONS: SGLT2i and GLP1RA were associated with lower risk for different cardiorenal end points, when used as an adjunct to metformin in people with type 2 diabetes. Additionally, SGLT2i demonstrated benefits in reducing risk for surrogate end points in kidney disease progression. Safety outcomes differ among the available pharmacotherapies.

Music-based Intervention for Improving Sleep Quality of Adults without Sleep Disorder: A Systematic Review and Meta-analysis.

BACKGROUND: Listening to music is often used as a self-help intervention to improve sleep quality, but its efficacy among individuals without sleep disorder remains unclear. METHODS: A search was performed on five databases to identify for studies that examined the use of music-based intervention to improve sleep quality among individuals without sleep disorder. Random-effects meta-analysis was performed, and the certainty of evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: Twenty-two articles which recruited 1,514 participants were included for review. Meta-analysis of six studies including 424 participants did not find an improvement in sleep quality among recipients of music-based intervention compared to those with standard care (mean difference: -0.80; 95% CI: -2.15 to 0.54, low-quality evidence). Subgroup analysis showed a clear improvement in sleep quality when interventions were administered for at least 3 weeks (-2.09; -3.84 to -0.34, n = 3). No difference in terms of sleep onset latency (standardized mean difference (SMD) -0.32; 95% CI -0.88 to 0.25, n = 4, very-low quality evidence) and sleep efficiency (SMD: -0.59; 95% CI -3.15 to 1.97, n = 2, very-low quality evidence) were observed. The effect of music-based intervention on anxiety, depression and quality of life were mixed with suggestions of possible benefits. CONCLUSION: Music-based intervention in addition to standard care appears to be a promising strategy to improve sleep quality when delivered for 3 week or longer. However, effects are inconsistent across studies and larger randomized controlled studies reporting long-term outcomes are needed before it can be recommended for routine use. PROSPERO REGISTRATION: CRD42018081193.

Healthcare provider person-centred practice: relationships between prerequisites, care environment and care processes using structural equation modelling.

BACKGROUND: The translation of person-centred care concepts into practice requires fulfilment of necessary components, including person-centred values and practice held by the employees and having a supportive system. The objectives of this study were multifold: firstly, to evaluate the measurement model, secondly, to examine the roles of prerequisite or attributes of healthcare providers and care environment and how they affect delivery of person-centred processes; and finally, to examine the mediating effect of care environment towards the relationship between prerequisite and care processes. METHODS: A cross sectional study was conducted among healthcare providers working in primary care facilities in a state in Malaysia. The Person-centred Practice Inventory-Staff instrument (PCPI-S) was distributed and completed by respondents. The instrument structure, reliability and validity were assessed through confirmatory factor analysis, while the framework's unidirectional hypothesis and the mediation path hypothesis were analysed using structural equation modelling. RESULTS: The overall goodness of fit verifies the original Person-centred Practice Framework, allowing some correlation errors. There were significant relationships between prerequisites of healthcare providers and care environment (ß = 0.826, p < 0.001), as well as between care environment and care processes (ß = 0.785, p < 0.001). This analysis also proved that care environment plays a partial mediating role in the relationship between prerequisites and care processes. CONCLUSIONS: In order to successfully move towards delivering person-centred practice, it is imperative to equip healthcare providers with person-centred values and beliefs, while at the same time transform current work culture to align with person-centred care. This will allow successful delivery of person-centred processes. TRIAL REGISTRATION: NMRR-18-309-40,447.

Fluid Biomarkers in HPV and Non-HPV Related Oropharyngeal Carcinomas: From Diagnosis and Monitoring to Prognostication-A Systematic Review.

Biomarkers are crucial in oncology, from detection and monitoring to guiding management and predicting treatment outcomes. Histological assessment of tissue biopsies is currently the gold standard for oropharyngeal cancers, but is technically demanding, invasive, and expensive. This systematic review aims to review current markers that are detectable in biofluids, which offer promising non-invasive alternatives in oropharyngeal carcinomas (OPCs). A total of 174 clinical trials from the PubMed search engine in the last 5 years were identified and screened by 4 independent reviewers. From these, 38 eligible clinical trials were found and subsequently reviewed. The biomarkers involved, categorized by human papillomavirus (HPV)-status, were further divided according to molecular and cellular levels. Recent trials investigating biomarkers for both HPV-positive and HPV-negative OPCs have approaches from various levels and different biofluids including plasma, oropharyngeal swabs, and oral rinse. Promising candidates have been found to aid in detection, staging, and predicting prognosis, in addition to well-established factors including HPV-status, drinking and smoking status. These studies also emphasize the possibility of enhancing prediction results and increasing statistical significance by multivariate analyses. Liquid biopsies offer promising assistance in enhancing personalized medicine for cancer treatment, from lowering barriers towards early screening, to facilitating de-escalation of treatment. However, further research is needed, and the combination of liquid biopsies with pre-existing methods, including in vivo imaging and invasive techniques such as neck dissections, could also be explored in future trials.

How Willing Are Patients or Their Caregivers to Deprescribe: a Systematic Review and Meta-analysis.

BACKGROUND: Polypharmacy is associated with the increased use of potentially inappropriate medications, where the risks of medicine use outweigh its benefits. Stopping medicines (deprescribing) that are no longer needed can be beneficial to reduce the risk of adverse events. We summarized the willingness of patients and their caregivers towards deprescribing. METHODS: A systematic search was conducted in four databases from inception until April 30, 2021 as well as search of citation of included articles. Studies that reported patients' and/or their caregivers' attitude towards deprescribing quantitatively were included. All studies were independently screened, reviewed, and data extracted in duplicates. Patients and caregivers willingness to deprescribe their regular medication was pooled using random effects meta-analysis of proportions. RESULTS: Twenty-nine unique studies involving 11,049 participants were included. All studies focused on the attitude of the patients towards deprescribing, and 7 studies included caregivers' perspective. Overall, 87.6% (95% CI: 83.3 to 91.4%) patients were willing to deprescribe their medication, based upon the doctors' suggestions. This was lower among caregivers, with only 74.8% (49.8% to 93.8%) willing to deprescribe their care recipients' medications. Patients' or caregivers' willingness to deprescribe were not influenced by study location, study population, or the number of medications they took. DISCUSSION: Most patients and their caregivers were willing to deprescribe their medications, whenever possible and thus should be offered a trial of deprescribing. Nevertheless, as these tools have a poor predictive ability, patients and their caregivers should be engaged during the deprescribing process to ensure that the values and opinions are heard, which would ultimately improve patient safety. In terms of limitation, as not all studies may published the methods and results of measurement they used, this may impact the methodological quality and thus our findings. OPEN SCIENCE FRAMEWORK REGISTRATION: https:// osf.io/fhg94.

Large scale analyses of genotype-phenotype relationships of glycine decarboxylase mutations and neurological disease severity.

Monogenetic diseases provide unique opportunity for studying complex, clinical states that underlie neurological severity. Loss of glycine decarboxylase (GLDC) can severely impact neurological development as seen in non-ketotic hyperglycinemia (NKH). NKH is a neuro-metabolic disorder lacking quantitative predictors of disease states. It is characterized by elevation of glycine, seizures and failure to thrive, but glycine reduction often fails to confer neurological benefit, suggesting need for alternate tools to distinguish severe from attenuated disease. A major challenge has been that there are 255 unique disease-causing missense mutations in GLDC, of which 206 remain entirely uncharacterized. Here we report a Multiparametric Mutation Score (MMS) developed by combining in silico predictions of stability, evolutionary conservation and protein interaction models and suitable to assess 251 of 255 mutations. In addition, we created a quantitative scale of clinical disease severity comprising of four major disease domains (seizure, cognitive failure, muscular and motor control and brain-malformation) to comprehensively score patient symptoms identified in 131 clinical reports published over the last 15 years. The resulting patient Clinical Outcomes Scores (COS) were used to optimize the MMS for biological and clinical relevance and yield a patient Weighted Multiparametric Mutation Score (WMMS) that separates severe from attenuated neurological disease (p = 1.2 e-5). Our study provides understanding for developing quantitative tools to predict clinical severity of neurological disease and a clinical scale that advances monitoring disease progression needed to evaluate new treatments for NKH.

Cancer risk in Parkinson disease: An updated systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Increasing evidence suggests significant associations between Parkinson disease (PD) and cancer risks. We conducted an updated review of studies that examined the risks of various cancer among PD patients and how this differed when cancer preceded PD diagnosis or PD diagnosis preceded cancer. METHODS: Four databases were searched for studies that examined the association between PD and incidence of cancer from database inception to 4 June 2021. Three independent reviewers screened the articles for eligibility and extracted study data. Pooled relative risk with 95% confidence intervals were calculated using a random effects model. RESULTS: Forty studies involving 11 case-control studies, two nested case-control studies, 22 cohort studies, and five cross-sectional studies were included. Compared to controls, PD patients had lower risks of lung, genitourinary, gastrointestinal, and haematological cancers. Conversely, higher risks of melanoma and brain cancer were noted among PD patients. No association was found between PD and risk of female cancers. Subgroup analysis found negative associations between PD patients and risks of colon cancer, rectal cancer, and non-Hodgkin lymphoma. CONCLUSIONS: Findings from our meta-analysis suggest PD patients had lower risks of lung, genitourinary, gastrointestinal, and haematological cancers and increased risks of melanoma and brain cancer. Future research to investigate the underlying mechanisms between PD and cancers is warranted.

Warfarin and food, herbal or dietary supplement interactions: A systematic review.

AIMS: To present an updated overview on the safety of concurrent use of food, herbal or dietary supplement and warfarin. METHODS: A systematic literature review was performed on 5 databases from inception up to 31 December 2019. These interactions were classified depending on the likelihood of interaction and supporting evidences. RESULTS: A total of 149 articles describing 78 herbs, food or dietary supplements were reported to interact with warfarin. These reports described potentiation with 45 (57.7%) herbs, food or dietary supplements while 23 (29.5%) reported inhibition and 10 (12.8%) reported limited impact on warfarin pharmacokinetics and pharmacodynamics. Twenty unique herb and dietary supplements also reported to result in minor bleeding events, such as purpura and gum bleeding as well as major events such as intracranial bleeding that led to death. CONCLUSION: While most food, herbs and supplements can be safely taken in moderation, healthcare professionals should be aware of the increased risk of bleeding when taking several food and herbs. These include Chinese wolfberry, chamomile tea, cannabis, cranberry, chitosan, green tea, Ginkgo biloba, ginger, spinach, St. John's Wort, sushi and smoking tobacco. Patients should be counselled to continue to seek advice from their healthcare professionals when starting any new herbs, food or supplement.

Pharmacist-led intervention on chronic pain management: A systematic review and meta-analysis.

AIMS: Pharmacists have been contributing to the management of chronic pain, ensuring the quality use of medicine. However, there is diversity in the interventions provided by pharmacists and their impact. METHODS: Six electronic databases were searched from inception until June 2020 for articles published in English examining the intervention provided by the pharmacist in chronic pain management. Studies investigating the impact of pharmacist intervention individually or multidisciplinary teams including pharmacists for chronic pain management were included. RESULTS: Fourteen studies (2365 participants) were included in the current review. Six studies were randomized controlled trials while the remainder were observational studies in which pharmacists provided intervention individually or in collaboration with other healthcare professionals. Medication review was the most common intervention provided by the pharmacist. The pooled analysis found that pharmacist-led interventions reduced the pain intensity (-0.22; 95% confidence interval [CI]: -0.35 to -0.09; moderate certainty) among participants with chronic pain. Opiate stewardship provided by pharmacists was effective; however, mixed results were noted on the impact of the intervention on physical functioning, anxiety, depression and quality of life. Pharmacist intervention was more expensive than treatment as usual. CONCLUSIONS: Pharmacists contribute substantially to chronic pain management, ensuring the quality use of medicine, resulting in reduced pain intensity. Further studies with rigorous design are needed to measure the impact of pharmacist-provided intervention individually or in a multidisciplinary team on the economic benefit and other health outcomes.

A local α-helix drives structural evolution of streptococcal M-protein affinity for host human plasminogen.

Plasminogen-binding group A streptococcal M-protein (PAM) is a signature surface virulence factor of specific strains of Group A Streptococcus pyogenes (GAS) and is an important tight binding protein for human plasminogen (hPg). After activation of PAM-bound hPg to the protease, plasmin (hPm), GAS cells develop invasive surfaces that are critical for their pathogenicity. PAMs are helical dimers in solution, which are sensitive to temperature changes over a physiological temperature range. We previously categorized PAMs into three classes (I-III) based on the number and nature of short tandem α-helical repeats (a1 and a2) in their NH2-terminal A-domains that dictate interactions with hPg/hPm. Class II PAMs are special cases since they only contain the a2-repeat, while Class I and Class III PAMs encompass complete a1a2-repeats. All dimeric PAMs tightly associate with hPg, regardless of their categories, but monomeric Class II PAMs bind to hPg much weaker than their Class I and Class III monomeric counterparts. Additionally, since the A-domains of Class II PAMs comprise different residues from other PAMs, the issue emerges as to whether Class II PAMs utilize different amino acid side chains for interactions with hPg. Herein, through NMR-refined structural analyses, we elucidate the atomic-level hPg-binding mechanisms adopted by two representative Class II PAMs. Furthermore, we develop an evolutionary model that explains from unique structural perspectives why PAMs develop variable A-domains with regard to hPg-binding affinity.

Evidence of disease severity, cognitive and physical outcomes of dance interventions for persons with Parkinson's Disease: a systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's Disease (PD) usually experience worsening of both motor and non-motor symptoms. Dancing has been postulated to help patients with Parkinson's via several mechanisms that lead to improved physical, cognitive and social functions. METHODS: This systematic review was conducted following Cochrane methodology and reported following the PRISMA guideline. Four databases (up to June 2021) were searched for RCTs comparing dance to standard or other physical therapy for improvements in disease severity, quality of life, cognitive and physical outcomes as well as adverse events in patients with PD. We synthesised data using RevMan and included certainty-of-evidence rating (GRADE) for major outcomes. RESULTS: A total of 20 RCTs (N = 723) articles that evaluated Tango, Ballroom, Irish, Waltz-Foxtrot, Folk, Turo, mixed dances and a PD-tailored dance were included. Dancers (versus non-dancers) had better motor experience (MDS-UPDRS 3) (MD -6.01, 95 % CI -9.97 to -3.84; n = 148; 5 RCTs) and improved balance (MiniBest Test) (MD 4.47, 95 % CI 2.29 to 6.66; n = 95; 3 RCTs), with no consistent differences on gait, agility and cognitive outcomes. Small samples and methodological limitations resulted in low-certainty-evidence across outcomes. CONCLUSIONS: Apart from a suggestion that dance intervention modestly reduced motor disease severity and improved certain aspects of balance, there is insufficient evidence on all other outcomes, such as agility and motor function, cognitive, mood and social outcomes, quality of life as well as adverse events including the risk of fall. As evidence is insufficient to inform practice, evidence of benefits on motor disease severity and balance needs to be considered in the context of user-perception of benefit versus harm and acceptability in the development of practice guideline recommendations.

The coping strategies of community pharmacists and pharmaceutical services provided during COVID-19 in Malaysia.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has resulted in profound health challenges across the globe. Pharmacists' readiness to cope with the pandemic is critical in supporting and sustaining the healthcare workforce to meet the challenges. OBJECTIVE: This study aims to examine community pharmacists' views on their work environment, policies and preparedness for safe retail patronage to prevent the transmission of COVID-19 and assess the variables influencing coping strategies during the pandemic. SETTING: An online survey of pharmacists practising in community pharmacy setting in Malaysia. METHOD: A questionnaire-based, cross-sectional study was conducted in Malaysia to evaluate coping strategies of community pharmacists and pharmaceutical services provided during COVID-19 pandemic. Between May 1 and July 31, 2020, the questionnaire was distributed to pharmacists working in community setting nationwide utilising a snowball sampling method. MAIN OUTCOME MEASURE: Community pharmacists' perceptions on safety, resilience, organisational support, and pharmaceutical services offered during COVID-19 pandemic. RESULTS: A total of 217 pharmacists participated in the study. The vast majority of community pharmacists reported a positive outlook and were able to balance working with self-care during this period. Most reported to have access to personal protective equipment such as gloves and hand sanitisers. A large proportion of community pharmacies also installed physical barriers in doorways or in front of the counter, put markings on the ground to section areas to ensure physical distancing, and controlled the number of customers who could access the pharmacy during this period. Innovations reported to be implemented included teleconsultations and providing curb-side or drive-through delivery and pickup services. CONCLUSION: The findings suggest the frontline and essential roles of community pharmacists in delivering pandemic responses, creating the opportunity to determine areas where community pharmacy services can be incorporated to strengthen the public health system and improve patient health outcomes.