Advance Care Planning (ACP) in Medicare Beneficiaries with Heart Failure.

BACKGROUND: Heart failure is a leading cause of death in the USA, contributing to high expenditures near the end of life. Evidence remains lacking on whether billed advance care planning changes patterns of end-of-life healthcare utilization among patients with heart failure. Large-scale claims evaluation assessing billed advance care planning and end-of-life hospitalizations among patients with heart failure can fill evidence gaps to inform health policy and clinical practice. OBJECTIVE: Assess the association between billed advance care planning delivered and Medicare beneficiaries with heart failure upon the type and quantity of healthcare utilization in the last 30 days of life. DESIGN: This retrospective cross-sectional cohort study used Medicare fee-for-service claims from 2016 to 2020. PARTICIPANTS: A total of 48,466 deceased patients diagnosed with heart failure on Medicare. MAIN MEASURES: Billed advance care planning services between the last 12 months and last 30 days of life will serve as the exposure. The outcomes are end-of-life healthcare utilization and total expenditure in inpatient, outpatient, hospice, skilled nursing facility, and home healthcare services. KEY RESULTS: In the final cohort of 48,466 patients (median [IQR] age, 83 [76-89] years; 24,838 [51.2%] women; median [IQR] Charlson Comorbidity Index score, 4 [2-5]), 4406 patients had an advance care planning encounter. Total end-of-life expenditure among patients with billed advance care planning encounters was 19% lower (95% CI, 0.77-0.84) compared to patients without. Patients with billed advance care planning encounters had 2.65 times higher odds (95% CI, 2.47-2.83) of end-of-life outpatient utilization with a 33% higher expected total outpatient expenditure (95% CI, 1.24-1.42) compared with patients without a billed advance care planning encounter. CONCLUSIONS: Billed advance care planning delivery to individuals with heart failure occurs infrequently. Prioritizing billed advance care planning delivery to these individuals may reduce total end-of-life expenditures and end-of-life inpatient expenditures through promoting use of outpatient end-of-life services, including home healthcare and hospice.

Effects of transcutaneous electrical nerve stimulation on pain, function, and descending inhibition in people with non-specific chronic low-back pain: a study protocol for a randomized crossover trial.

BACKGROUND: Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP. METHODS/DESIGN: This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2-125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05. DISCUSSION: This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants. TRIAL REGISTRATION: ClinicalTrials.gov NCT05812885. Registered on 24th May 2023.

SP-CHAP, an endolysin with enhanced activity against biofilm pneumococci and nasopharyngeal colonization.

Streptococcus pneumoniae (Spn), a Gram-positive bacterium, is responsible for causing a wide variety of invasive infections. The emergence of multi-drug antibiotic resistance has prompted the search for antimicrobial alternatives. Phage-derived peptidoglycan hydrolases, known as endolysins, are an attractive alternative. In this study, an endolysin active against Spn, designated SP-CHAP, was cloned, produced, purified, biochemically characterized, and evaluated for its antimicrobial properties. Cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domains are widely represented in bacteriophage endolysins but have never previously been reported for pneumococcal endolysins. Here, we characterize the first pneumococcal endolysin with a CHAP catalytic domain. SP-CHAP was antimicrobial against all Spn serovars tested, including capsular and capsule-free pneumococci, and it was found to be more active than the most widely studied pneumococcal endolysin, Cpl-1, while not affecting various oral or nasal commensal organisms tested. SP-CHAP was also effective in eradicating Spn biofilms at concentrations as low as 1.56 µg/mL. In addition, a Spn mouse nasopharyngeal colonization model was employed, which showed that SP-CHAP caused a significant reduction in Spn colony-forming units, even more than Cpl-1. These results indicate that SP-CHAP may represent a promising alternative to combating Spn infections. IMPORTANCE: Considering the high rates of pneumococcal resistance reported for several antibiotics, alternatives are urgently needed. In the present study, we report a Streptococcus pneumoniae-targeting endolysin with even greater activity than Cpl-1, the most characterized pneumococcal endolysin to date. We have employed a combination of biochemical and microbiological assays to assess the stability and lytic potential of SP-CHAP and demonstrate its efficacy on pneumococcal biofilms in vitro and in an in vivo mouse model of colonization. Our findings highlight the therapeutic potential of SP-CHAP as an antibiotic alternative to treat Streptococcus pneumoniae infections.

Is there 'trustworthy' evidence for using manual therapy to treat patients with shoulder dysfunction?: A systematic review.

The primary objective of this review was to create a 'trustworthy,' living systematic review and meta-analysis for the application of manual therapy interventions in treating patients with shoulder dysfunction. Included studies were English-language randomized controlled trials published between 1/1/2010 and 8/3/2023, with searches performed in: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINHAL, ProQuest Nursing & Allied Health, EBSCO Medline, and PEDro. The population of focus included adults 18 years and older with musculoskeletal impairments related to shoulder dysfunction. Our primary outcomes included pain and region-specific outcome measures. We excluded trials, including participants having shoulder dysfunction resulting from surgery, radicular pain, instability/dislocation, fracture, lymphedema, and radiation. Our screening methodology was based upon a previously published 'trustworthy' systematic review protocol. This included the application of our PICOTS criteria in addition to screening for prospective clinical trial registration and following of prospective intent, as well as assessment of PEDro scores, risk-of-bias ratings, GRADE scoring, and examination of confidence in estimated effects. Twenty-six randomized controlled trials met our PICOTS criteria; however, only 15 of these were registered. Only three were registered prospectively. Two of these did not have discussions and conclusions that aligned with their primary outcome. The remaining single study was found to have a high risk-of-bias, meaning the remainder of the protocol could not be employed and that no randomized controlled trials could undergo further assessment or meta-analysis. The results of this systematic review indicate there are no 'trustworthy' randomized controlled trials examining the effectiveness of manual therapy interventions for the treatment of patients with shoulder dysfunction, as defined by the prospectively established methodology. Therefore, these findings signal that creating a 'trustworthy,' living systematic review on this clinically relevant topic is not yet possible due to a lack of 'trustworthy' randomized controlled trials.

Does manual therapy meaningfully change quantitative sensory testing and patient reported outcome measures in patients with musculoskeletal impairments related to the spine?: A 'trustworthy' systematic review and meta-analysis.

OBJECTIVES: To perform a 'trustworthy' systematic review (SR) with meta-analysis on the potential mechanisms of manual therapy used to treat spinal impairments. DESIGN: SR with meta-analysis. LITERATURE SEARCH: Articles published between January 2010 and October 2022 from CENTRAL, CINAHL, MEDLINE, PubMed, ProQuest, and PEDro. METHODS: This SR included English-language randomized clinical trials (RCTs) involving manual therapy to treat spinal impairments in adults. The primary outcome was pressure pain thresholds (PPTs). To synthesize RCTs with high confidence in estimated effects using the GRADE, RCTs with questionable prospective, external, and internal validity, and high risk of bias (RoB) were excluded. RESULTS: Following title and abstract screening, 89 full-text RCTs were reviewed. Twenty-two studies included the criteria of interest. Sixteen were not prospectively registered, two contained discussion/conclusions judged to be inconsistent with the registry, and one was rated as having a high RoB. Three studies met the inclusion criteria; heterogeneous interventions and locations for PPT testing prevented synthesis into practice recommendations. The two studies with high confidence in estimated effects had small effect sizes, and one study had confidence intervals that crossed zero for the outcome measures of interest. DISCUSSION: Standardized PPT testing, as a potential measure of centrally mediated pain, could provide clues regarding the mechanisms of manual therapy or help identify/refine research questions. CONCLUSION: High-quality RCTs could not be synthesized into strong conclusions secondary to the dissimilarity in research designs. Future research regarding quantitative sensory testing should develop RCTs with high confidence in estimated effects that can be translated into strong recommendations.

Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis.

Importance: Alcohol use disorder affects more than 28.3 million people in the United States and is associated with increased rates of morbidity and mortality. Objective: To compare efficacy and comparative efficacy of therapies for alcohol use disorder. Data Sources: PubMed, the Cochrane Library, the Cochrane Central Trials Registry, PsycINFO, CINAHL, and EMBASE were searched from November 2012 to September 9, 2022 Literature was subsequently systematically monitored to identify relevant articles up to August 14, 2023, and the PubMed search was updated on August 14, 2023. Study Selection: For efficacy outcomes, randomized clinical trials of at least 12 weeks' duration were included. For adverse effects, randomized clinical trials and prospective cohort studies that compared drug therapies and reported health outcomes or harms were included. Data Extraction and Synthesis: Two reviewers evaluated each study, assessed risk of bias, and graded strength of evidence. Meta-analyses used random-effects models. Numbers needed to treat were calculated for medications with at least moderate strength of evidence for benefit. Main Outcomes and Measures: The primary outcome was alcohol consumption. Secondary outcomes were motor vehicle crashes, injuries, quality of life, function, mortality, and harms. Results: Data from 118 clinical trials and 20 976 participants were included. The numbers needed to treat to prevent 1 person from returning to any drinking were 11 (95% CI, 1-32) for acamprosate and 18 (95% CI, 4-32) for oral naltrexone at a dose of 50 mg/d. Compared with placebo, oral naltrexone (50 mg/d) was associated with lower rates of return to heavy drinking, with a number needed to treat of 11 (95% CI, 5-41). Injectable naltrexone was associated with fewer drinking days over the 30-day treatment period (weighted mean difference, -4.99 days; 95% CI, -9.49 to -0.49 days) Adverse effects included higher gastrointestinal distress for acamprosate (diarrhea: risk ratio, 1.58; 95% CI, 1.27-1.97) and naltrexone (nausea: risk ratio, 1.73; 95% CI, 1.51-1.98; vomiting: risk ratio, 1.53; 95% CI, 1.23-1.91) compared with placebo. Conclusions and Relevance: In conjunction with psychosocial interventions, these findings support the use of oral naltrexone at 50 mg/d and acamprosate as first-line pharmacotherapies for alcohol use disorder.

Mentorship and self-efficacy are associated with lower burnout in physical therapists in the United States: a cross-sectional survey study.

PURPOSE: This study investigated the prevalence of burnout in physical therapists in the United States and the relationships between burnout and education, mentorship, and self-efficacy. METHODS: This was a cross-sectional survey study. An electronic survey was distributed to practicing physical therapists across the United States over a 6-week period from December 2020 to January 2021. The survey was completed by 2,813 physical therapists from all states. The majority were female (68.72%), White or Caucasian (80.13%), and employed full-time (77.14%). Respondents completed questions on demographics, education, mentorship, self-efficacy, and burnout. The Burnout Clinical Subtypes Questionnaire 12 (BCSQ-12) and self-reports were used to quantify burnout, and the General Self-Efficacy Scale (GSES) was used to measure self-efficacy. Descriptive and inferential analyses were performed. RESULTS: Respondents from home health (median BCSQ-12=42.00) and skilled nursing facility settings (median BCSQ-12=42.00) displayed the highest burnout scores. Burnout was significantly lower among those who provided formal mentorship (median BCSQ-12=39.00, P=0.0001) compared to no mentorship (median BCSQ-12=41.00). Respondents who received formal mentorship (median BCSQ-12=38.00, P=0.0028) displayed significantly lower burnout than those who received no mentorship (median BCSQ-12=41.00). A moderate negative correlation (rho=-0.49) was observed between the GSES and burnout scores. A strong positive correlation was found between self-reported burnout status and burnout scores (rrb=0.61). CONCLUSION: Burnout is prevalent in the physical therapy profession, as almost half of respondents (49.34%) reported burnout. Providing or receiving mentorship and higher self-efficacy were associated with lower burnout. Organizations should consider measuring burnout levels, investing in mentorship programs, and implementing strategies to improve self-efficacy.

Anaphylatoxin signaling activates macrophages to control intracellular Rickettsia proliferation.

IMPORTANCE: Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can "win" by taking over the host, or the bacteria can "lose" if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that "activate" innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.

Inhibition of ATM-directed antiviral responses by HIV-1 Vif.

Emerging evidence indicates that HIV-1 hijacks host DNA damage repair (DDR) pathways to facilitate multiple facets of virus replication. Canonically, HIV-1 engages proviral DDR responses through the accessory protein Vpr, which induces constitutive activation of DDR kinases ATM and ATR. However, in response to prolonged DDR signaling, ATM directly induces pro-inflammatory NF-κB signaling and activates multiple members of the TRIM family of antiviral restriction factors, several of which have been previously implicated in antagonizing retroviral and lentiviral replication. Here, we demonstrate that the HIV-1 accessory protein Vif blocks ATM-directed DNA repair processes, activation of NF-κB signaling responses, and TRIM protein phosphorylation. Vif function in ATM antagonism occurs in clinical isolates and in common HIV-1 Group M subtypes/clades circulating globally. Pharmacologic and functional studies combine to suggest that Vif blocks Vpr-directed activation of ATM but not ATR, signifying that HIV-1 utilizes discrete strategies to fine-tune DDR responses that promote virus replication while simultaneously inhibiting immune activation.

Vividness as the similarity between generated imagery and an internal model.

Vividness in visual mental imagery has been relatively under-explored compared to imagery's representational format and neural mechanisms. In this paper, we take a deeper look at vividness and suggest that in re-framing it, we can potentially reconcile disparate findings regarding visual cortex activation during imagery. Unlike traditional views of vividness that define the concept in terms of perception, we frame vividness in terms of imagery's relation to an internal model; the closer the generated imagery is to this model, the more vivid it is. This view is considered alongside existing neuroscientific, psychological, and philosophical research, as well as directions for future research.

Screening for Latent Tuberculosis Infection in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Latent tuberculosis infection (LTBI) can progress to active tuberculosis disease, causing morbidity and mortality. Objective: To review the evidence on benefits and harms of screening for and treatment of LTBI in adults to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through December 3, 2021; references; experts; literature surveillance through January 20, 2023. Study Selection: English-language studies of LTBI screening, LTBI treatment, or accuracy of the tuberculin skin test (TST) or interferon-gamma release assays (IGRAs). Studies of LTBI screening and treatment for public health surveillance or disease management were excluded. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when a sufficient number of similar studies were available. Main Outcomes and Measures: Screening test accuracy; development of active tuberculosis disease, transmission, quality of life, mortality, and harms. Results: A total of 113 publications were included (112 studies; N = 69 009). No studies directly evaluated the benefits and harms of screening. Pooled estimates for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI, 0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled estimates for specificity of screening tests ranged from 0.95 to 0.99. For treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial found a relative risk (RR) for progression to active tuberculosis at 5 years of 0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI, 2.03-10.39]; number needed to harm, 279). A previously published meta-analysis reported that multiple regimens were efficacious compared with placebo or no treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339). Conclusions and Relevance: No studies directly evaluated the benefits and harms of screening for LTBI compared with no screening. TST and IGRAs were moderately sensitive and highly specific. Treatment of LTBI with recommended regimens reduced the risk of progression to active tuberculosis. Isoniazid was associated with higher rates of hepatotoxicity than placebo or rifampin.

Manual therapy for non-radicular cervical spine related impairments: establishing a 'Trustworthy' living systematic review and meta-analysis.

OBJECTIVES: To establish a 'trustworthy' living systematic review (SR) with a meta-analysis of manual therapy for treating non-radicular cervical impairments. DESIGN: SR with meta-analysis. LITERATURE SEARCH: Articles published between January 2010 and September 2022 were included from: Cochrane Central Register of Controlled Trials (CENTRAL); CINAHL; MEDLINE; PubMed; PEDro, and ProQuest Nursing and Allied Health. METHODS: This SR included English-language randomized clinical trials (RCTs) of manual therapy involving adults used to treat non-radicular cervical impairments. The primary outcomes were pain and region-specific outcome measures. Cervicogenic headaches and whiplash were excluded to improve homogeneity. Two reviewers independently assessed RCTs. The prospective plan was to synthesize results with high confidence in estimated effects using GRADE. RESULTS: Thirty-five RCTs were screened for registration status. Twenty-eight were not registered or registered prospectively. In 5 studies, the discussion and conclusion did not match the registry, or this could not be determined. One study did not meet the external validity criterion, and another was rated as having a high risk of bias. One study met the inclusion and exclusion criteria, so practice recommendations could not be made. The remaining study did not identify any clinically meaningful group differences. DISCUSSION: Only one prospectively registered RCT met this SR's strict, high-quality standards. The single identified paper provides initial high-quality evidence on this topic. CONCLUSION: This SR establishes a foundation of trustworthiness and can be used to generate research agendas to determine the potential clinical utility of manual therapy directed at the cervical spine for non-radicular cervical complaints.

"Trustworthiness," confidence in estimated effects, and confidently translating research into clinical practice.

Trustworthy, preprocessed sources of evidence, such as systematic reviews and clinical practice guidelines, are crucial for practicing clinicians. Confidence in estimated effects is related to how different the outcome data were between the two groups. Factors including the effect size, variability of the effect, research integrity, research methods, and selected outcome measures impact confidence in the estimated effect. The current evidence suggests that post-randomization biases cannot be ruled out with a high degree of certainty in published research, limiting the utility of preprocessed sources for clinicians. Research should be prospectively registered to improve this situation, and fidelity with prospective intent should be verified to minimize biases and strengthen confidence in estimated effects. Otherwise, discussions related to preprocessed literature, including P-values, point estimates of effect, confidence intervals, post-randomization biases, external and internal validity measures, and the confidence in estimated effects required to translate research into practice confidently, are all moot points.

Correlation of SARS-CoV-2 Neutralization with Antibody Levels in Vaccinated Individuals.

Neutralizing antibody titers are an important measurement of the effectiveness of vaccination against SARS-CoV-2. Our laboratory has set out to further verify the functionality of these antibodies by measuring the neutralization capacity of patient samples against infectious SARS-CoV-2. Samples from patients from Western New York who had been vaccinated with the original Moderna and Pfizer vaccines (two doses) were tested for neutralization of both Delta (B.1.617.2) and Omicron (BA.5). Strong correlations between antibody levels and neutralization of the delta variant were attained; however, antibodies from the first two doses of the vaccines did not have good neutralization coverage of the subvariant omicron BA.5. Further studies are ongoing with local patient samples to determine correlation following updated booster administration.

Is the quality of systematic reviews influenced by prospective registration: a methods review of systematic musculoskeletal physical therapy reviews.

INTRODUCTION: It is unknown if verified prospective registration of systematic reviews (SRs) and the randomized clinical trials (RCTs) that they use affect an SR's methodological quality on A MeaSurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). METHODS: Data originated from interventional SRs published in International Society of Physiotherapy Journals Editors (ISPJE) member journals, indexed in MEDLINE, between 1 January 2018 and 18 August 2021. Blinded reviewers identified the SRs and extracted the data for the variables of interest for the SRs and the RCTs. RESULTS: Two of 14 ISPJE member journals required prospective SR registration. Twenty SRs were identified, and 169 unique, retrievable RCTs were included within those SRs. One (5.0%) of the 20 SRs and 15 of the 169 (8.9%) RCTs were prospectively registered and published consistent with this intent. Nineteen (95.0%) of the 20 identified SRs was categorized as 'critically low' on the AMSTAR 2. DISCUSSION: SRs and the RCTs identified within them were infrequently prospectively registered, prospectively verifiable, or prospectively verified based on the established research record. CONCLUSIONS: Ensuring that SRs and RCTs have fidelity with the research record from conception to publication may help rule out low-value interventions, decrease variability in physical therapy practice, and solidify evidence-based physical therapy practice.

Lack of standardization in dry needling dosage and adverse event documentation limits outcome and safety reports: a scoping review of randomized clinical trials.

OBJECTIVES: Examine: (1) whether variability in dry needling (DN) dosage affects pain outcomes, (2) if effect sizes are clinically important, and (3) how adverse events (AE) were documented and whether DN safety was determined. METHODS: Nine databases were searched for randomized controlled trials (RCTs) investigating DN in symptomatic musculoskeletal disorders. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. Included RCTs met PEDro criteria #1 and scored > 7/10. Data extraction included DN dosage, pain outcome measures, dichotomous AE reporting (yes/no), and AE categorization. Clinically meaningful differences were determined using the minimum clinically important difference (MCID) for pain outcomes . RESULTS: Out of 22 identified RCTs, 11 demonstrated significant between-group differences exceeding the MCID, suggesting a clinically meaningful change in pain outcomes. Nine documented whether AE occurred. Only five provided AEs details and four cited a standard means to report AE. DISCUSSION: There was inconsistency in reporting DN dosing parameters and AE. We could not determine if DN dosing affects outcomes, whether DN consistently produces clinically meaningful changes, or establish optimal dosage. Without more detailed reporting, replication of methods in future investigations is severely limited. A standardized method is lacking to report, classify, and provide context to AE from DN. Without more detailed AE reporting in clinical trials investigating DN efficacy, a more thorough appraisal of relative risk, severity, and frequency was not possible. Based on these inconsistencies, adopting a standardized checklist for reporting DN dosage and AE may improve internal and external validity and the generalizability of results.

Protocol for the development of a 'trustworthy' living systematic review and meta analyses of manual therapy interventions to treat neuromusculoskeletal impairments.

BACKGROUND: Preprocessed research resources are believed to be highly 'trustworthy' when translating research to clinical practice. However, the overall 'trustworthiness' is unknown if this evidence contains randomized clinical trials (RCTs) where prospective has not been/cannot be verified, has low confidence in estimated effects, and if they are not up to date. OBJECTIVES: This protocol will be used to create a baseline benchmark for a series of trustworthy living systematic reviews (SRs) regarding manual therapy interventions. METHODS: Data will originate from RCTs related to manual therapy neuromusculoskeletal interventions, indexed in 6 search engines in English from 1 January 2010, to the present. Two blinded reviewers will identify the RCTs and extract data using Covidence. The data will be synthesized based on consensus and analyzed using the Cochrane collaboration's Review Manager. EXPECTED OUTCOMES: It is expected that there will be a shortage of RCTs with at least a moderate confidence in estimated effects that will allow for strong practice recommendations. DISCUSSION: Identifying evidence that can be translated into strong practice recommendations is essential to identify beneficial and harmful interventions, decrease practice variability, and identify neuromusculoskeletal manual therapy interventions that require further disciplined methodological focus.

Watching the watchmen: changing tides in the oversight of medical assistance in dying.

The recent wave of medical assistance in dying legalisation raises questions about proper oversight of the practice as new systems for data collection, case assessment and public reporting emerge. Newer systems, such as in Spain, New Zealand and Colombia, are eschewing the retrospective approach used for case assessment in older systems, particularly those in the Netherlands, Belgium and the USA, in favour of an approach requiring more extensive review prior to the procedure. This shift aims to increase compliance with each jurisdiction's specific safeguards and legal criteria as well as to protect vulnerable patients, but also risks stifling access to the practice and increasing administrative burden on clinicians and patients. Newer systems also tend to favour more extensive data collection than older systems, while failing to be as transparent with public reporting. Inconsistency in data collection and public reporting make it difficult for researchers, policymakers and the public to assess the practice and help achieve a balance between access and compliance. Research on oversight activities is sparse, and there is a need for clarity to determine how best to handle violations of the law and how to create best practices.

Screening for Prediabetes and Type 2 Diabetes in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Of youths diagnosed with type 2 diabetes, many develop microvascular complications by young adulthood. Objective: To review the evidence on benefits and harms of screening children and adolescents for prediabetes and type 2 diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through May 3, 2021; references; experts; literature surveillance through July 22, 2022. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or type 2 diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: This review included 8 publications (856 participants; mean age, 14 years [range, 10-17 years]). Of those, 6 were from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. No eligible studies directly evaluated the benefits or harms of screening. One randomized clinical trial (RCT) (TODAY; n = 699 adolescents with obesity; mean age, 14 years) comparing metformin, metformin plus rosiglitazone, and metformin plus lifestyle intervention reported that 2 youths with recently diagnosed diabetes developed kidney impairment (0 vs 1 vs 1, respectively; P > .99) and 11 developed diabetic ketoacidosis (5 vs 3 vs 3, respectively; P = .70). One RCT of 75 adolescents (mean age, 13 years) with obesity with prediabetes compared an intensive lifestyle intervention with standard care and reported that no participants in either group developed diabetes, although follow-up was only 6 months. Regarding harms of interventions, 2 RCTs assessing different comparisons enrolled youths with recently diagnosed diabetes. Major hypoglycemic events were reported by less than 1% of participants. Minor hypoglycemic events were more common among youths treated with metformin plus rosiglitazone than among those treated with metformin or metformin plus lifestyle intervention in TODAY (8.2% vs 4.3% vs 3.4%, P = .05). In 1 study, gastrointestinal adverse events were more commonly reported by those taking metformin than by those taking placebo (abdominal pain: 25% vs 12%; nausea/vomiting: 17% vs 10%; P not reported). Conclusions and Relevance: No eligible studies directly evaluated the benefits or harms of screening for prediabetes and type 2 diabetes in children and adolescents. For youths with prediabetes or recently diagnosed (not screen-detected) diabetes, the only eligible trials reported few health outcomes and found no difference between groups, although evidence was limited by substantial imprecision and a duration of follow-up likely insufficient to assess health outcomes.