Effectiveness of postsurgical rehabilitation following lumbar disc herniation surgery: A systematic review.

Introduction: The effectiveness of post-surgical rehabilitation following lumbar disc herniation (LDH) surgery is unclear. Research question: To investigate the effectiveness and safety of rehabilitation interventions initiated within three months post-surgery for adults treated surgically for LDH. Material and methods: This systematic review searched seven databases from inception to November 2023. Independent reviewers screened studies, assessed and extracted data, and rated the certainty of the evidence using the GRADE approach. Results: This systematic review retrieved 20,531 citations and included 25 randomized controlled trials. The high certainty evidence suggests that adding Pilates exercise to routine care and cognitive behavioral therapy may improve function immediately post-intervention (1 RCT), and that adding whole-body magnetic therapy to exercise, pharmacological and aquatic therapy may reduce low back pain intensity (1 RCT) immediately post-intervention. Compared to placebo, pregabalin did not reduce low back pain or leg pain intensity (1 RCT) (moderate to high certainty evidence). We found no differences between: 1) behavioral graded activity vs. physiotherapy (1 RCT); 2) exercise and education vs. neck massage or watchful waiting (1 RCT); 3) exercise, education, and in-hospital usual care vs. in-hospital usual care (1 RCT); 4) functional or staged exercise vs. usual post-surgical care including exercise (2 RCTs); and 5) supervised exercise with education vs. education (1 RCT). No studies assessed adverse events. Discussion and conclusion: Evidence on effective and safe post-surgical rehabilitation interventions is sparse. This review identified two interventions with potential short-term benefits (Pilates exercises, whole-body magnetic therapy) but safety is unclear, and one with an iatrogenic effect (pregabalin).

Rehabilitation of back pain in the pediatric population: a mixed studies systematic review.

BACKGROUND: A significant proportion of children and adolescents experience back pain. However, a comprehensive systematic review on the effectiveness of rehabilitation interventions is lacking. OBJECTIVES: To evaluate benefits and harms of rehabilitation interventions for non-specific low back pain (LBP) or thoracic spine pain in the pediatric population. METHODS: Seven bibliographic electronic databases were searched from inception to June 16, 2023. Moreover, reference lists of relevant studies and systematic reviews, three targeted websites, and the WHO International Clinical Trials Registry Platform were searched. Paired reviewers independently conducted screening, assessed risk of bias, and extracted data related to study characteristics, methodology, subjects, and results. Certainty of evidence was evaluated based on the GRADE approach. RESULTS: We screened 8461 citations and 307 full-text articles. Ten quantitative studies (i.e., 8 RCTs, 2 non-randomized clinical trials) and one qualitative study were included. With very low to moderate certainty evidence, in adolescents with LBP, spinal manipulation (1-2 sessions/week over 12 weeks, 1 RCT) plus exercise may be associated with a greater likelihood of experiencing clinically important pain reduction versus exercise alone; and group-based exercise over 8 weeks (2 RCTs and 1 non-randomized trial) may reduce pain intensity. The qualitative study found information provided via education/advice and compliance of treatment were related to effective treatment. No economic studies or studies examining thoracic spine pain were identified. CONCLUSIONS: Spinal manipulation and group-based exercise may be beneficial in reducing LBP intensity in adolescents. Education should be provided as part of a care program. The overall evidence is sparse. Methodologically rigorous studies are needed. TRIAL REGISTRATION: CRD42019135009 (PROSPERO).

Hypothiocyanous acid reductase is critical for host colonization and infection by Streptococcus pneumoniae.

The major human pathogen Streptococcus pneumoniae encounters the immune-derived oxidant hypothiocyanous acid (HOSCN) at sites of colonization and infection. We recently identified the pneumococcal hypothiocyanous acid reductase (Har), a member of the flavoprotein disulfide reductase enzyme family, and showed that it contributes to the HOSCN tolerance of S. pneumoniae in vitro. Here, we demonstrate in mouse models of pneumococcal infection that Har is critical for colonization and invasion. In a colonization model, bacterial load was attenuated dramatically in the nasopharynx when har was deleted in S. pneumoniae. The Δhar strain was also less virulent compared to wild type in an invasion model as reflected by a significant reduction in bacteria in the lungs and no dissemination to the blood and brain. Kinetic measurements with recombinant Har demonstrated that this enzyme reduced HOSCN with near diffusion-limited catalytic efficiency, using either NADH (kcat/KM = 1.2 × 108 M-1s-1) or NADPH (kcat/KM = 2.5 × 107 M-1s-1) as electron donors. We determined the X-ray crystal structure of Har in complex with the FAD cofactor to 1.50 Å resolution, highlighting the active site architecture characteristic for this class of enzymes. Collectively, our results demonstrate that pneumococcal Har is a highly efficient HOSCN reductase, enabling survival against oxidative host immune defenses. In addition, we provide structural insights that may aid the design of Har inhibitors.

Introduction to target trial emulation in rehabilitation: a systematic approach to emulate a randomized controlled trial using observational data.

Rehabilitation providers and policymakers need valid evidence to make informed decisions about the healthcare needs of the population. Whenever possible, these decisions should be informed by randomized controlled trials (RCTs). However, there are circumstances when evidence needs to be generated rapidly, or when RCTs are not ethical or feasible. These situations apply to studying the effects of complex interventions, including rehabilitation as defined by Cochrane Rehabilitation. Therefore, we explore using the target trial emulation framework by Hernán and colleagues to obtain valid estimates of the causal effects of rehabilitation when RCTs cannot be conducted. Target trial emulation is a framework guiding the design and analysis of non-randomized comparative effectiveness studies using observational data, by emulating a hypothetical RCT. In the context of rehabilitation, we outline steps for applying the target trial emulation framework using real world data, highlighting methodological considerations, limitations, potential mitigating strategies, and causal inference and counterfactual theory as foundational principles to estimating causal effects. Overall, we aim to strengthen methodological approaches used to estimate causal effects of rehabilitation when RCTs cannot be conducted.

A good night's sleep: pain trajectories and sleep disturbance in children with cerebral palsy.

STUDY OBJECTIVES: Sleep quality is important during childhood and adolescence. Given the high prevalence of pain in children/youth with cerebral palsy, we aimed to measure the association between short-term pain trajectories and sleep disturbance in these individuals. METHODS: We accrued the cohort between November 2019 and October 2020 and recruited children/youth who (1) were 8-18 years old; (2) had cerebral palsy with any Gross Motor Function Classification System level; and (3) could self-report pain and sleep disturbance. We collected self-reported baseline and weekly follow-up data using electronic questionnaires completed every week for 5 weeks. Sleep disturbance at 5 weeks was the primary outcome (pediatric Patient-Reported Outcomes Measurement Information System short form, v1.0-4a). We used general linear regression to assess the association between pain intensity trajectory group and sleep disturbance controlling for confounders. RESULTS: A total of 190 individuals were eligible; 102 were enrolled and 89 were included in our final analysis. Pain trajectory groups had estimated crude mean sleep disturbance scores at 5 weeks ranging from 56.0 (95% confidence interval, 51.8, 60.8) to 61.8 (55.7, 67.9). Compared to those with stable, no/very mild pain, those in the stable, high-pain group had the greatest sleep disturbance (adjusted ß = 5.7; 95% confidence interval, 1.2, 10.2). CONCLUSIONS: Irrespective of pain trajectory, children and youth with cerebral palsy reported sleep disturbances. Those with a stable, high pain intensity in the previous 5 weeks reported the greatest sleep disturbance. The results highlight the importance of considering pain trajectories and their impact on sleep in children with cerebral palsy. CITATION: Shearer HM, Côté P, Hogg-Johnson S, Fehlings DL. A good night's sleep: pain trajectories and sleep disturbance in children with cerebral palsy. J Clin Sleep Med. 2024;20(5):719-726.

Systematic Review Procedures for the World Health Organization (WHO) Evidence Syntheses on Benefits and Harms of Structured and Standardized Education/Advice, Structured Exercise Programs, Transcutaneous Electrical Nerve Stimulation (TENS), and Needling Therapies for the Management of Chronic Low Back Pain in Adults.

As commissioned by the WHO, we updated and expanded the scope of four systematic reviews to inform its (in development) clinical practice guideline for the management of CPLBP in adults, including older adults. Methodological details and results of each review are described in the respective articles in this series. In the last article of this series, we discuss methodological considerations, clinical implications and recommendations for future research.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Structured Exercise Programs for Chronic Primary Low Back Pain in Adults.

PURPOSE: Evaluate benefits and harms of structured exercise programs for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: We searched for randomized controlled trials (RCTs) in electronic databases (inception to 17 May 2022). Eligible RCTs targeted structured exercise programs compared to placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of exercise could be isolated). We extracted outcomes, appraised risk of bias, conducted meta-analyses where appropriate, and assessed certainty of evidence using GRADE. RESULTS: We screened 2503 records (after initial screening through Cochrane RCT Classifier and Cochrane Crowd) and 398 full text RCTs. Thirteen RCTs rated with overall low or unclear risk of bias were synthesized. Assessing individual exercise types (predominantly very low certainty evidence), pain reduction was associated with aerobic exercise and Pilates vs. no intervention, and motor control exercise vs. sham. Improved function was associated with mixed exercise vs. usual care, and Pilates vs. no intervention. Temporary increased minor pain was associated with mixed exercise vs. no intervention, and yoga vs. usual care. Little to no difference was found for other comparisons and outcomes. When pooling exercise types, exercise vs. no intervention probably reduces pain in adults (8 RCTs, SMD = - 0.33, 95% CI - 0.58 to - 0.08) and functional limitations in adults and older adults (8 RCTs, SMD = - 0.31, 95% CI - 0.57 to - 0.05) (moderate certainty evidence). CONCLUSIONS: With moderate certainty, structured exercise programs probably reduce pain and functional limitations in adults and older people with CPLBP.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Transcutaneous Electrical Nerve Stimulation (TENS) for Chronic Primary Low Back Pain in Adults.

PURPOSE: To evaluate benefits and harms of transcutaneous electrical nerve stimulation (TENS) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: We searched for randomized controlled trials (RCTs) from various electronic databases from July 1, 2007 to March 9, 2022. Eligible RCTs targeted TENS compared to placebo/sham, usual care, no intervention, or interventions with isolated TENS effects (i.e., combined TENS with treatment B versus treatment B alone) in adults with CPLBP. We extracted outcomes requested by the WHO Guideline Development Group, appraised the risk of bias, conducted meta-analyses where appropriate, and graded the certainty of evidence using GRADE. RESULTS: Seventeen RCTs (adults, n = 1027; adults ≥ 60 years, n = 28) out of 2010 records and 89 full text RCTs screened were included. The evidence suggested that TENS resulted in a marginal reduction in pain compared to sham (9 RCTs) in the immediate term (2 weeks) (mean difference (MD) = -0.90, 95% confidence interval -1.54 to -0.26), and a reduction in pain catastrophizing in the short term (3 months) with TENS versus no intervention or interventions with TENS specific effects (1 RCT) (MD = -11.20, 95% CI -17.88 to -3.52). For other outcomes, little or no difference was found between TENS and the comparison interventions. The certainty of the evidence for all outcomes was very low. CONCLUSIONS: Based on very low certainty evidence, TENS resulted in brief and marginal reductions in pain (not deemed clinically important) and a short-term reduction in pain catastrophizing in adults with CPLBP, while little to no differences were found for other outcomes.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Needling Therapies for Chronic Primary Low Back Pain in Adults.

PURPOSE: Evaluate benefits and harms of needling therapies (NT) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing NT compared with placebo/sham, usual care, or no intervention (comparing interventions where the attributable effect could be isolated). We conducted meta-analyses where indicated and graded the certainty of evidence. RESULTS: We screened 1831 citations and 109 full text RCTs, yeilding 37 RCTs. The certainty of evidence was low or very low across all included outcomes. There was little or no difference between NT and comparisons across most outcomes; there may be some benefits for certain outcomes. Compared with sham, NT improved health-related quality of life (HRQoL) (physical) (2 RCTs; SMD = 0.20, 95%CI 0.07; 0.32) at 6 months. Compared with no intervention, NT reduced pain at 2 weeks (21 RCTs; MD = - 1.21, 95%CI - 1.50; - 0.92) and 3 months (9 RCTs; MD = - 1.56, 95%CI - 2.80; - 0.95); and reduced functional limitations at 2 weeks (19 RCTs; SMD = - 1.39, 95%CI - 2.00; - 0.77) and 3 months (8 RCTs; SMD = - 0.57, 95%CI - 0.92; - 0.22). In older adults, NT reduced functional limitations at 2 weeks (SMD = - 1.10, 95%CI - 1.71; - 0.48) and 3 months (SMD = - 1.04, 95%CI - 1.66; - 0.43). Compared with usual care, NT reduced pain (MD = - 1.35, 95%CI - 1.86; - 0.84) and functional limitations (MD = - 2.55, 95%CI - 3.70; - 1.40) at 3 months. CONCLUSION: Based on low to very low certainty evidence, adults with CPLBP experienced some benefits in pain, functioning, or HRQoL with NT; however, evidence showed little to no differences for other outcomes.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Structured and Standardized Education or Advice for Chronic Primary low back pain in Adults.

PURPOSE: Evaluate benefits and harms of education/advice for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) assessing education/advice compared with placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of education/advice could be isolated). We conducted meta-analyses and graded the certainty of evidence. RESULTS: We screened 2514 citations and 86 full text RCTs and included 15 RCTs. Most outcomes were assessed 3 to 6 months post-intervention. Compared with no intervention, education/advice improved pain (10 RCTs, MD = -1.1, 95% CI -1.63 to -0.56), function (10 RCTs, SMD = -0.51, 95% CI -0.89 to -0.12), physical health-related quality of life (HRQoL) (2 RCTs, MD = 24.27, 95% CI 12.93 to 35.61), fear avoidance (5 RCTs, SMD = -1.4, 95% CI -2.51 to -0.29), depression (1 RCT; MD = 2.10, 95% CI 1.05 to 3.15), and self-efficacy (1 RCT; MD = 4.4, 95% CI 2.77 to 6.03). Education/advice conferred less benefit than sham Kinesio taping for improving fear avoidance regarding physical activity (1 RCT, MD = 5.41, 95% CI 0.28 to 10.54). Compared with usual care, education/advice improved pain (1 RCT, MD = -2.10, 95% CI -3.13 to -1.07) and function (1 RCT, MD = -7.80, 95% CI -14.28 to -1.32). There was little or no difference between education/advice and comparisons for other outcomes. For all outcomes, the certainty of evidence was very low. CONCLUSION: Education/advice in adults with CPLBP was associated with improvements in pain, function, HRQoL, and psychological outcomes, but with very low certainty.

Improving Rehabilitation Research to Optimize Care and Outcomes for People with Chronic Primary Low Back Pain: Methodological and Reporting Recommendations from a WHO Systematic Review Series.

Chronic primary low back pain (CPLBP) is a prevalent and disabling condition that often requires rehabilitation interventions to improve function and alleviate pain. This paper aims to advance future research, including systematic reviews and randomized controlled trials (RCTs), on CPLBP management. We provide methodological and reporting recommendations derived from our conducted systematic reviews, offering practical guidance for conducting robust research on the effectiveness of rehabilitation interventions for CPLBP. Our systematic reviews contributed to the development of a WHO clinical guideline for CPLBP. Based on our experience, we have identified methodological issues and recommendations, which are compiled in a comprehensive table and discussed systematically within established frameworks for reporting and critically appraising RCTs. In conclusion, embracing the complexity of CPLBP involves recognizing its multifactorial nature and diverse contexts and planning for varying treatment responses. By embracing this complexity and emphasizing methodological rigor, research in the field can be improved, potentially leading to better care and outcomes for individuals with CPLBP.

Identification of Streptococcus pneumoniae genes associated with hypothiocyanous acid tolerance through genome-wide screening.

Streptococcus pneumoniae is a commensal bacterium and invasive pathogen that causes millions of deaths worldwide. The pneumococcal vaccine offers limited protection, and the rise of antimicrobial resistance will make treatment increasingly challenging, emphasizing the need for new antipneumococcal strategies. One possibility is to target antioxidant defenses to render S. pneumoniae more susceptible to oxidants produced by the immune system. Human peroxidase enzymes will convert bacterial-derived hydrogen peroxide to hypothiocyanous acid (HOSCN) at sites of colonization and infection. Here, we used saturation transposon mutagenesis and deep sequencing to identify genes that enable S. pneumoniae to tolerate HOSCN. We identified 37 genes associated with S. pneumoniae HOSCN tolerance, including genes involved in metabolism, membrane transport, DNA repair, and oxidant detoxification. Single-gene deletion mutants of the identified antioxidant defense genes sodA, spxB, trxA, and ahpD were generated and their ability to survive HOSCN was assessed. With the exception of ΔahpD, all deletion mutants showed significantly greater sensitivity to HOSCN, validating the result of the genome-wide screen. The activity of hypothiocyanous acid reductase or glutathione reductase, known to be important for S. pneumoniae tolerance of HOSCN, was increased in three of the mutants, highlighting the compensatory potential of antioxidant systems. Double deletion of the gene encoding glutathione reductase and sodA sensitized the bacteria significantly more than single deletion. The HOSCN defense systems identified in this study may be viable targets for novel therapeutics against this deadly pathogen. IMPORTANCE Streptococcus pneumoniae is a human pathogen that causes pneumonia, bacteremia, and meningitis. Vaccination provides protection only against a quarter of the known S. pneumoniae serotypes, and the bacterium is rapidly becoming resistant to antibiotics. As such, new treatments are required. One strategy is to sensitize the bacteria to killing by the immune system. In this study, we performed a genome-wide screen to identify genes that help this bacterium resist oxidative stress exerted by the host at sites of colonization and infection. By identifying a number of critical pneumococcal defense mechanisms, our work provides novel targets for antimicrobial therapy.

Multivariable prediction models for the recovery of and claim closure related to post-collision neck pain and associated disorders.

OBJECTIVE: Few clinical prediction models are available to clinicians to predict the recovery of patients with post-collision neck pain and associated disorders. We aimed to develop evidence-based clinical prediction models to predict (1) self-reported recovery and (2) insurance claim closure from neck pain and associated disorders (NAD) caused or aggravated by a traffic collision. METHODS: The selection of potential predictors was informed by a systematic review of the literature. We used Cox regression to build models in an incident cohort of Saskatchewan adults (n = 4923). The models were internally validated using bootstrapping and replicated in participants from a randomized controlled trial conducted in Ontario (n = 340). We used C-statistics to describe predictive ability. RESULTS: Participants from both cohorts (Saskatchewan and Ontario) were similar at baseline. Our prediction model for self-reported recovery included prior traffic-related neck injury claim, expectation of recovery, age, percentage of body in pain, disability, neck pain intensity and headache intensity (C = 0.643; 95% CI 0.634-0.653). The prediction model for claim closure included prior traffic-related neck injury claim, expectation of recovery, age, percentage of body in pain, disability, neck pain intensity, headache intensity and depressive symptoms (C = 0.637; 95% CI 0.629-0.648). CONCLUSIONS: We developed prediction models for the recovery and claim closure of NAD caused or aggravated by a traffic collision. Future research needs to focus on improving the predictive ability of the models.

MerA functions as a hypothiocyanous acid reductase and defense mechanism in Staphylococcus aureus.

The major pathogen Staphylococcus aureus has to cope with host-derived oxidative stress to cause infections in humans. Here, we report that S. aureus tolerates high concentrations of hypothiocyanous acid (HOSCN), a key antimicrobial oxidant produced in the respiratory tract. We discovered that the flavoprotein disulfide reductase (FDR) MerA protects S. aureus from this oxidant by functioning as a HOSCN reductase, with its deletion sensitizing bacteria to HOSCN. Crystal structures of homodimeric MerA (2.4 Å) with a Cys43 -Cys48 intramolecular disulfide, and reduced MerACys43 S (1.6 Å) showed the FAD cofactor close to the active site, supporting that MerA functions as a group I FDR. MerA is controlled by the redox-sensitive repressor HypR, which we show to be oxidized to intermolecular disulfides under HOSCN stress, resulting in its inactivation and derepression of merA transcription to promote HOSCN tolerance. Our study highlights the HOSCN tolerance of S. aureus and characterizes the structure and function of MerA as a major HOSCN defense mechanism. Crippling the capacity to respond to HOSCN may be a novel strategy for treating S. aureus infections.

Post-Concussion Symptoms and Disability in Adults With Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Studies investigating long-term symptoms and disability after mild traumatic brain injury (mTBI) have yielded mixed results. This systematic review and meta-analysis aimed to determine the prevalence of self-reported post-concussion symptoms (PCS) and disability following mTBI. We systematically searched MEDLINE, Embase, CINAHL, CENTRAL, and PsycInfo to identify inception cohort studies of adults with mTBI. Paired reviewers independently extracted data and assessed risk of bias with the Scottish Intercollegiate Guidelines Network criteria. We identified 43 eligible studies for the systematic review; 41 were rated as high risk of bias, primarily due to high attrition (> 20%). Twenty-one studies (49%) were included in the meta-analyses (five studies were narratively synthesized; 17 studies were duplicate reports). At 3-6 months post-injury, the estimated prevalence of PCS from random-effects meta-analyses was 31.3% (95% confidence interval [CI] = 25.4-38.4) using a lenient definition of PCS (2-4 mild severity PCS) and 18.3% (95% CI = 13.6-24.0) using a more stringent definition. The estimated prevalence of disability was 54.0% (95% CI = 49.4-58.6) and 29.6% (95% CI = 27.8-31.5) when defined as Glasgow Outcome Scale-Extended <8 and <7, respectively. The prevalence of symptoms similar to PCS was higher in adults with mTBI versus orthopedic injury (prevalence ratio = 1.57, 95% CI = 1.22-2.02). In a meta-regression, attrition rate was the only study-related factor significantly associated with higher estimated prevalence of PCS. Setting attrition to 0%, the estimated prevalence of PCS (lenient definition) was 16.1%. We conclude that nearly one in three adults who present to an emergency department or trauma center with mTBI report at least mild severity PCS 3-6 months later, but controlling for attrition bias, the true prevalence may be one in six. Studies with representative samples and high retention rates are needed.

Clinical course of pain intensity in individuals with cerebral palsy: A prognostic systematic review.

AIM: To describe the clinical course of pain intensity in individuals with cerebral palsy (CP) resulting from usual care or specific interventions. METHOD: We conducted an exploratory prognostic systematic review searching electronic databases from inception to 31st December 2021. Evidence from low and moderate risk-of-bias studies was synthesized. RESULTS: We retrieved 2275 citations; 18 studies met the inclusion criteria and 10 were synthesized. The course of pain intensity in children with CP receiving usual care was stable over 15 weeks (χ2 [2]  = 1.8, p = 0.5). Children who received continuous intrathecal baclofen (CITB) reported significant pain intensity reduction (visual analogue scale [VAS] = -4.2 out of 10, 95% confidence interval [CI] = -6.3 to -2.1]) 6 months postinsertion but similar children receiving usual care had no significant change over 6 months (VAS = 1.3 out of 10, 95% CI = -1.3 to 3.6). Children receiving botulinum neurotoxin A (BoNT-A) injections had significant decreases in pain after 1 month (numeric rating scale = -6.5, 95% CI = -8.0 to -5.0). Adults with chronic pain receiving usual care reported stable pain intensity over time; pain intensity improved in ambulatory adults exercising and those treated surgically for cervical myelopathy. INTERPRETATION: The course of pain intensity in individuals with CP is unclear. Evidence suggests that children and adults receiving usual care had stable pain intensity over the short or long term. Interventions (CITB and BoNT-A in children and exercise and surgical treatment for cervical myelopathy in adults) had pain intensity reduction. Larger study samples are needed to confirm these results. WHAT THIS PAPER ADDS: Pain intensity was stable in children with cerebral palsy (CP) receiving usual care. Adults with CP and chronic pain receiving usual care had stable, persistent pain intensity. Children receiving continuous intrathecal baclofen via pump and botulinum neurotoxin A reported significantly lower pain intensities. Adults with chronic pain and dyskinetic CP and cervical myelopathy reported significantly lower pain intensity with exercise or cervical decompression. Limited high-quality evidence exists describing non-procedural pain changes in individuals with CP.

A newly identified flavoprotein disulfide reductase Har protects Streptococcus pneumoniae against hypothiocyanous acid.

Hypothiocyanous acid (HOSCN) is an antimicrobial oxidant produced from hydrogen peroxide and thiocyanate anions by heme peroxidases in secretory fluids such as in the human respiratory tract. Some respiratory tract pathogens display tolerance to this oxidant, which suggests that there might be therapeutic value in targeting HOSCN defense mechanisms. However, surprisingly little is known about how bacteria protect themselves from HOSCN. We hypothesized that tolerant pathogens have a flavoprotein disulfide reductase that uses NAD(P)H to directly reduce HOSCN, similar to thioredoxin reductase in mammalian cells. Here, we report the discovery of a previously uncharacterized flavoprotein disulfide reductase with HOSCN reductase activity, which we term Har (hypothiocyanous acid reductase), in Streptococcus pneumoniae, a bacterium previously found to be tolerant of HOSCN. S. pneumoniae generates large amounts of hydrogen peroxide that can be converted to HOSCN in the respiratory tract. Using deletion mutants, we demonstrate that the HOSCN reductase is dispensable for growth of S. pneumoniae in the presence of lactoperoxidase and thiocyanate. However, bacterial growth in the HOSCN-generating system was completely crippled when deletion of HOSCN reductase activity was combined with disruption of GSH import or recycling. Our findings identify a new bacterial HOSCN reductase and demonstrate a role for this protein in combination with GSH utilization to protect S. pneumoniae from HOSCN.

Improving the annual monitoring rates of testosterone replacement therapy patients in primary care.

INTRODUCTION: Testosterone replacement therapy (TRT) is the treatment of choice for male hypogonadism. British Society for Sexual Medicine (BSSM) guidelines on adult testosterone deficiency recommend that TRT patients undergo annual monitoring of their testosterone levels and potential complications of treatment; though evidence suggests that substantial numbers of men on TRT are not monitored adequately. METHODS: Review of the electronic patient record from a single general practice in southwest Scotland revealed that only 1 of 26 (4%) TRT patients had been monitored as per BSSM guidelines in the previous 12 months. Additionally, when monitoring was undertaken there was inconsistency in the blood tests requested. The use of quality improvement (QI) tools including process mapping and cause-and-effect diagram identified staff and patient knowledge of monitoring requirements and the lack of an effective recall system as areas for improvement. We tested three change ideas: the utilisation of an existing recall system for long-term therapies; a TRT Ordercomms blood group template (OBGT) to standardise monitoring; and a patient information leaflet (PIL) to improve patient education. The aim of this project was to achieve 60% annual monitoring rate. RESULTS: The percentage of patients monitored for testosterone levels and potential TRT complications increased from 4% (1/26) to 65% (17/26) over a 7-week test period. The utilisation of the existing recall system was a particularly effective intervention, leading to an increase from 4% (1/26) to 31% (8/26) in the first 2 weeks. CONCLUSION: The use of QI tools was associated with over 60% of male TRT patients receiving comprehensive annual monitoring, as per BSSM guidelines. Our findings support the hypothesis that a patient recall system, combined with an OBGT and a PIL led to this increase.

Teledermatology to reduce face-to-face appointments in general practice during the COVID-19 pandemic: a quality improvement project.

Teledermatology is an important subspecialty of telemedicine that continues to evolve with advances in telecommunication and mobile phone technology. A 19-week primary care quality improvement project collected baseline data and tested three change ideas, using the Model for Improvement method, with primary and secondary aims: to increase the weekly percentage of remote dermatological consultations with supporting images that were successfully concluded remotely to greater than 80% and to reduce the weekly percentage of dermatological face-to-face consultations to less than 50%. We hypothesised that by improving the quality of patient images and the confidence of reception staff in triaging skin complaints, there would be a decrease in the weekly number of face-to-face dermatological appointments, thereby decreasing the risk of COVID-19 transmission within the practice and community. Two change ideas focused on supporting patients to improve image quality by introducing '4 Key Instructions' and a patient information leaflet (PIL). The third focused on increasing reception staff confidence in triaging skin complaints by introducing a triage pathway guidance tool. A total of 253 dermatological consultations were analysed: 170 of these were telephone consultations with 308 supporting images. Process measures showed clear improvements in the quality of images provided by patients which likely contributed to an increase in completed remote consultation. Our primary outcome measure was achieved. Our secondary outcome measure suggested that in the absence of high-quality images, it might not be possible to reduce dermatological face-to-face consultations much below 50% in primary care. Process measures showed clear improvements in the quality of images provided by patients which likely contributed to the increase in remote consultation. The implications of these findings for the theory of change are discussed.