Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of l-folinic or folic acid

Distribution of plasma folate forms in hemodialysis patients receiving high daily doses of l-folinic or folic acid.BackgroundWe have previously reported that a daily oral high dose of l-folinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients does not provide significantly greater reduction in fasting total homocysteine (tHcy) levels than an equimolar dose of folic acid. The present study uses the affinity/HPLC method to analyze the distribution of plasma folate forms in patients who received l-folinic acid versus those who received folic acid. This was done to investigate claims that renal insufficiency is associated with impaired folate interconversion, a stance that is supportive of the premise that tHcy lowering in these patients is more efficacious with folinic acid and other reduced folates, than folic acid.MethodsForty-eight chronic and stable hemodialysis patients were block-randomized, based on their screening predialysis tHcy levels, sex, and dialysis center, into two groups treated for 12 weeks with oral folic acid at 15 mg/day or an equimolar amount (20 mg/day) of oral l-folinic acid. All 48 subjects also received 50 mg/day of oral vitamin B6 and 1 mg/day of oral vitamin B12. Folate distribution was determined in plasma of 46 participants (Folinic acid group, N = 22; Folic acid group, N = 24) by using the affinity/HPLC method, with electrochemical (coulometric) detection.ResultsBoth groups had similar baseline geometric means of plasma total folate and similar folate forms distribution. Following treatment, both groups demonstrated similar marked elevation in plasma total folate (geometric mean of the increase: Folinic acid group, +337 ng/mL; Folic acid group, +312 ng/mL; P = 0.796). In the folinic acid-treated group, practically all of the increase in total folate was due to 5-methyltetrahydrofolate. In the folic acid-treated group 5-methyltetrahydrofolate accounted for 35% of the increase in total folate and the remainder was unmethylated folic acid.ConclusionsData from the present findings suggest that defects in folate absorption or impairment in folate interconversion are not the cause of the persistent hyperhomocysteinemia in hemodialysis patients

Associations between toenail arsenic concentration and dietary factors in a New Hampshire population

AbstractBackgroundDietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown.MethodsAs part of a population-based case–control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We used general linear models to examine the associations between toenail arsenic and each dietary factor, taking into account potentially confounding effects.ResultsAs expected, we found an inverse association between ln-transformed toenail arsenic and consumption of vitamin B12 (excluding supplements) and animal protein. Unexpectedly, there were also inverse associations with numerous dietary lipids (e.g., total fat, total animal fat, total vegetable fat, total monounsaturated fat, total polyunsaturated fat, and total saturated fat). Finally, increased toenail arsenic concentrations were associated with increased consumption of long chain n-3 fatty acids.ConclusionIn a relatively well-nourished population exposed to relatively low levels of arsenic via water, consumption of certain dietary lipids may decrease toenail arsenic concentration, while long chain n-3 fatty acids may increase toenail arsenic concentration, possibly due to their association with arsenolipids in fish tissue

Implementing evidence-based practices in rural settings: a scoping review of theories, models, and frameworks

BackgroundRural healthcare has unique characteristics that affect the dissemination and implementation of evidence-based interventions. Numerous theories, models, and frameworks have been developed to guide implementation of healthcare interventions, though not specific to rural healthcare. The present scoping review sought to identify the theories, models, and frameworks most frequently applied to rural health and propose an approach to rural health research that harnesses selected constructs from these theories, models, and frameworks. This resulting synthesis can serve as a guide to researchers, policy makers, and clinicians seeking to employ commonly used theories, models, and frameworks to rural health.MethodsWe used the Scopus abstract indexing service to identify peer-reviewed literature citing one or more of theories, models, or frameworks used in dissemination and implementation research and including the word “rural” in the Title, Abstract, or Keywords. We screened the remaining titles and abstracts to ensure articles met additional inclusion criteria. We conducted a full review of the resulting 172 articles to ensure they identified one or more discrete theory, model, or framework applied to research or quality improvement projects. We extracted the theories, models, and frameworks and categorized these as process models, determinant frameworks, classic theories, or evaluation frameworks.ResultsWe retained 61 articles of which 28 used RE-AIM, 11 used Community-Based Participatory Research (CBPR) framework, eight used the Consolidated Framework for Implementation Research (CFIR), and six used the integrated-Promoting Action on Research Implementation in Health Services (iPARIHS). Additional theories, models, and frameworks were cited in three or fewer reports in the literature. The 14 theories, models, and frameworks cited in the literature were categorized as seven process models, four determinant frameworks, one evaluation framework, and one classic theory.ConclusionsThe RE-AIM framework was the most frequently cited framework in the rural health literature, followed by CBPR, CFIR, and iPARIHS. A notable advantage of RE-AIM in rural healthcare settings is the focus on reach as a specified outcome, given the challenges of engaging a geographically diffuse and often isolated population. We present a rationale for combining the strengths of these theories, models, and frameworks to guide a research agenda specific to rural healthcare research.Systematic Review Registrationhttps://osf.io/fn2cd/

The Maristán stigma scale: a standardized international measure of the stigma of schizophrenia and other psychoses

Background: People with schizophrenia face prejudice and discrimination from a number of sources including professionals and families. The degree of stigma perceived and experienced varies across cultures and communities. We aimed to develop a cross-cultural measure of the stigma perceived by people with schizophrenia.Method: Items for the scale were developed from qualitative group interviews with people with schizophrenia in six countries. The scale was then applied in face-to-face interviews with 164 participants, 103 of which were repeated after 30 days. Principal Axis Factoring and Promax rotation evaluated the structure of the scale; Horn’s parallel combined with bootstrapping determined the number of factors; and intra-class correlation assessed test-retest reliability.Results: The final scale has 31 items and four factors: informal social networks, socio-institutional, health professionals and self-stigma. Cronbach’s alpha was 0.84 for the Factor 1; 0.81 for Factor 2; 0.74 for Factor 3, and 0.75 for Factor 4. Correlation matrix among factors revealed that most were in the moderate range [0.31-0.49], with the strongest occurring between perception of stigma in the informal network and self-stigma and there was also a weaker correlation between stigma from health professionals and self-stigma. Test-retest reliability was highest for informal networks [ICC 0.76 [0.67 -0.83]] and self-stigma [ICC 0.74 [0.64-0.81]]. There were no significant differences in the scoring due to sex or age. Service users in Argentina had the highest scores in almost all dimensions.Conclusions: The MARISTAN stigma scale is a reliable measure of the stigma of schizophrenia and related psychoses across several cultures. A confirmatory factor analysis is needed to assess the stability of its factor structure.We are also grateful for support from the Pan-American Health Office (PAHO), Camden and Islington NHS Foundation Trust and University College London (UCL)

Brief of Amici Curiae 56 Professors of Law and Economics in Support of Petition of Writ of Certiorari

28 U.S.C. § 1400(b) provides that a defendant in a patent case may be sued where the defendant is incorporated or has a regular and established place of business and has infringed the patent. This Court made clear in Fourco Glass Co. v. Transmirra Prods. Corp., 353 U.S. 222, 223 (1957), that those were the only permissible venues for a patent case. But the Federal Circuit has rejected Fourco and the plain meaning of § 1400(b), instead permitting a patent plaintiff to file suit against a defendant anywhere there is personal jurisdiction over that defendant. The result has been rampant forum shopping, particularly by patent trolls. 44% of 2015 patent lawsuits were filed in a single district: the Eastern District of Texas, a forum with plaintiff-friendly rules and practices, and where few of the defendants are incorporated or have established places of business. And an estimated 86% of 2015 patent cases were filed somewhere other than the jurisdictions specified in the statute. Colleen V. Chien & Michael Risch, Recalibrating Patent Venue, Santa Clara Univ. Legal Studies Research Paper No. 10-1 (Sept. 1, 2016), Table 3. This Court should grant certiorari to review the meaning of 28 U.S.C. § 1400(b) because the Federal Circuit’s dubious interpretation of the statute plays an outsized and detrimental role, both legally and economically, in the patent system

Brief of Amici Curiae 56 Professors of Law and Economics in Support of Petition of Writ of Certiorari

28 U.S.C. § 1400(b) provides that a defendant in a patent case may be sued where the defendant is incorporated or has a regular and established place of business and has infringed the patent. This Court made clear in Fourco Glass Co. v. Transmirra Prods. Corp., 353 U.S. 222, 223 (1957), that those were the only permissible venues for a patent case. But the Federal Circuit has rejected Fourco and the plain meaning of § 1400(b), instead permitting a patent plaintiff to file suit against a defendant anywhere there is personal jurisdiction over that defendant. The result has been rampant forum shopping, particularly by patent trolls. 44% of 2015 patent lawsuits were filed in a single district: the Eastern District of Texas, a forum with plaintiff-friendly rules and practices, and where few of the defendants are incorporated or have established places of business. And an estimated 86% of 2015 patent cases were filed somewhere other than the jurisdictions specified in the statute. Colleen V. Chien & Michael Risch, Recalibrating Patent Venue, Santa Clara Univ. Legal Studies Research Paper No. 10-1 (Sept. 1, 2016), Table 3. This Court should grant certiorari to review the meaning of 28 U.S.C. § 1400(b) because the Federal Circuit’s dubious interpretation of the statute plays an outsized and detrimental role, both legally and economically, in the patent system

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Should all women with pregnancy-related pelvic girdle pain be treated with exercise?

NoThis paper presents the main findings of a systematic literature review that was undertaken to investigate whether physiotherapist-guided exercise is effective in reducing the severity of pregnancy-related pelvic girdle pain (PPGP). Seven electronic databases were systematically searched. Studies that met the inclusion criteria were assessed for methodological quality and internal validity. Five primary randomized controlled trials (RCTs) and one post-partum follow-up study were included in the review. The authors of all six studies incorporated advice and physiotherapist-guided exercise, either in a group setting or as part of an individualized exercise programme, into at least one of their intervention groups, with or without the addition of a pelvic support belt, acupuncture or other physiotherapy treatment modality. Two of the primary RCTs found that exercise and advice effectively reduced pre-partum PPGP. One study concluded that exercise had no additional value beyond simply supplying a pelvic support belt and advice. The results of another trial supported the use of physiotherapist-guided stabilization exercises for the treatment of post-partum PPGP. Yet another study did not find any differences between the intervention groups involved. The works included in this review all reported that PPGP reduced over time, regardless of the intervention used to treat it, suggesting that the greatest factor influencing the resolution of PPGP is time rather than exercise. The findings do not support the routine use of physiotherapist-guided exercise in the treatment of all women with PPGP. Advice, information and a non-elastic pelvic support belt should be offered to women with pre-partum PPGP, whereas patients with persistent symptoms of post-partum PPGP should receive individualized physiotherapist-guided exercise aimed at stabilizing the pelvic area as part of a wider package of physiotherapy treatment

Do physiotherapy staff record treatment time accurately? An observational study

OBJECTIVE: To assess the reliability of duration of treatment time measured by physiotherapy staff in early-stage stroke patients. DESIGN: Comparison of physiotherapy staff's recording of treatment sessions and video recording. SETTING: Rehabilitation stroke unit in a general hospital. SUBJECTS: Thirty-nine stroke patients without trunk control or who were unable to stand with an erect trunk without the support of two therapists recruited to a randomized trial evaluating the Oswestry Standing Frame. Twenty-six physiotherapy staff who were involved in patient treatment. MAIN MEASURES: Contemporaneous recording by physiotherapy staff of treatment time (in minutes) compared with video recording. STATISTICAL ANALYSIS: Intraclass correlation with 95% confidence interval and the Bland and Altman method for assessing agreement by calculating the mean difference (standard deviation; 95% confidence interval), reliability coefficient and 95% limits of agreement for the differences between the measurements. RESULTS: The mean duration (standard deviation, SD) of treatment time recorded by physiotherapy staff was 32 (11) minutes compared with 25 (9) minutes as evidenced in the video recording. The mean difference (SD) was -6 (9) minutes (95% confidence interval (CI) -9 to -3). The reliability coefficient was 18 minutes and the 95% limits of agreement were -24 to 12 minutes. Intraclass correlation coefficient for agreement between the two methods was 0.50 (95% CI 0.12 to 0.73). CONCLUSIONS: Physiotherapy staff's recording of duration of treatment time was not reliable and was systematically greater than the video recording