Interventions aimed at increasing syphilis screening among non-pregnant individuals in healthcare settings: a systematic review and meta-analysis.

Syphilis remains a pressing public health concern with potential severe morbidity if left untreated. To improve syphilis screening, targeted interventions are crucial, especially in at-risk populations. This systematic review synthesises studies that compare syphilis screening in the presence and absence of an intervention. A systematic search of four databases was conducted (Medline, Embase, Cinahl and Scopus). The primary outcomes evaluated included syphilis screening, re-screening and detection rates. Findings were synthesised narratively. Where multiple studies were clinically heterogenous, a pooled odds ratio was calculated. Twenty-four studies were included. A variety of interventions showed promise including clinician alerts, which increased syphilis screening rate (OR range, 1.25-1.45) and patient SMS reminders that mostly improved re-screening/re-attendance rates (OR range, 0.93-4.4). Coupling syphilis serology with routine HIV monitoring increased the proportion of HIV-positive individuals undergoing both tests. However, pooling three studies with this intervention using the outcome of syphilis detection rate yielded inconclusive results (pooled OR 1.722 [95% CI 0.721-2.723], I 2 =24.8%, P =0.264). The introduction of hospital-based packaged testing for screening high-risk individuals is unique given hospitals are not typical locations for public health initiatives. Nurse-led clinics and clinician incentives were successful strategies. Including syphilis screening with other existing programs has potential to increase screening rates (OR range, 1.06-2.08), but requires further investigation. Technology-driven interventions produced cost-effective, feasible and positive outcomes. Challenges were evident in achieving guideline-recommended screening frequencies for men who have sex with men, indicating the need for multifaceted approaches. Wider application of these interventions may improve syphilis screening and detection rates.

Validation of shear wave elastography as a noninvasive measure of pelvic floor muscle stiffness.

OBJECTIVES: To investigate the validity of shear wave elastography (SWE) as a measure of stiffness of the puborectalis muscle by examining: (1) the relationship between puborectalis muscle stiffness and pelvic floor muscle (PFM) activation at different intensities; and (2) the relationship between puborectalis stiffness and pelvic floor morphometry during contractions at different intensities. METHODS: Fifteen healthy asymptomatic women performed 6-s isometric PFM contractions at different intensities (0, 10%, 20%, 30%, 50%, 75%, and 100% of maximal voluntary contraction) guided by intravaginal electromyography (EMG). Stiffness of the puborectalis muscle was measured using SWE by calculating the average shear modulus in regions of interest that contained puborectalis muscle fibers parallel to the transducer. Pelvic floor morphometry was assessed in the mid-sagittal plane using transperineal B-mode ultrasound imaging. Shear modulus, EMG (root mean square amplitude) and pelvic floor morphometry parameters were normalized to the value recorded during maximal voluntary contraction. To assess the relationship between stiffness and pelvic floor activation/morphometry, coefficient of determination (r2 ) was calculated for each participant and a group average was computed. RESULTS: Shear modulus and EMG were highly correlated (average r2 ; left 0.90 ± 0.08, right 0.87 ± 0.15). Shear modulus also strongly correlated with bladder neck position (x-axis horizontal coordinates relative to the pubic symphysis), anorectal rectal angle and position, levator plate angle, and antero-posterior diameter of the levator hiatus (average r2 : range 0.62-0.78). CONCLUSIONS: These findings support the validity of SWE to assess puborectalis muscle stiffness in females. Stiffness measures were strongly associated with PFM EMG and pelvic floor morphometry and may be used to indirectly assess the level of activation of the puborectalis muscle without the use of more invasive techniques. By overcoming limitations of current assessment tools, this promising noninvasive and real-time technique could enable important breakthrough in the pathophysiology and management of pelvic floor disorders.

Genome-wide association study identifies 74 loci associated with educational attainment.

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.

International comparison of guidelines for management of impetigo: a systematic review.

BACKGROUND: Impetigo is a common superficial skin infection that affects people worldwide and is usually treated with antibiotics; therefore, its management has implications for global antibiotic stewardship. OBJECTIVE: This systematic review and narrative synthesis compares and contrasts international impetigo management guidelines. METHODS: Guidelines for treatment of impetigo that were produced by a national authority; available to primary care physicians; and published since 2008 were included. Following a comprehensive search strategy, data extraction from eligible studies was performed independently in duplicate. Details of antiseptic and antibiotic treatment; methicillin-resistant Staphylococcus aureus treatment; and conservative management and preventative measures were tabulated and analysed descriptively. RESULTS: Fifty-one guidelines were included from 42 different countries. All guidelines recommended systemic antibiotics, 78% of these only for widespread lesions or failure of topical antibiotic treatment. The first-line systemic antibiotic treatment was restricted to narrow-spectrum options in 21 (41%) whilst 7 (14%) recommended only broad-spectrum antibiotics first-line. Thirty-four (67%) guidelines included recommendations for topical antibiotic use. Twenty guidelines (39%) did not mention antiseptic treatment for impetigo. Guidelines did not always provide clear indications for different treatment options. CONCLUSIONS: Despite potentially equal efficacy to systemic antibiotics, only two-thirds of guidelines include topical antibiotic options. Many fail to include recommendations for non-antibiotic treatments such as antiseptics, preventative measures and conservative management, despite potential for antibiotic-sparing. Provision of clear definitions of disease severity and indications for treatment would enhance the ability of clinicians to adhere to recommendations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018117770.

Muscle spindles of the multifidus muscle undergo structural change after intervertebral disc degeneration.

PURPOSE: Proprioceptive deficits are common in low back pain. The multifidus muscle undergoes substantial structural change after back injury, but whether muscle spindles are affected is unclear. This study investigated whether muscle spindles of the multifidus muscle are changed by intervertebral disc (IVD) degeneration in a large animal model. METHODS: IVD degeneration was induced by partial thickness annulus fibrosus lesion to the L3-4 IVD in nine sheep. Multifidus muscle tissue at L4 was harvested at six months after lesion, and from six age-/sex-matched naïve control animals. Muscle spindles were identified in Van Gieson's-stained sections by morphology. The number, location and cross-sectional area (CSA) of spindles, the number, type and CSA of intrafusal fibers, and thickness of the spindle capsule were measured. Immunofluorescence assays examined Collagen I and III expression. RESULTS: Multifidus muscle spindles were located centrally in the muscle and generally near connective tissue. There were no differences in the number or location of muscle spindles after IVD degeneration and only changes in the CSA of nuclear chain fibers. The thickness of connective tissue surrounding the muscle spindle was increased as was the expression of Collagen I and III. CONCLUSION: Changes to the connective tissue and collagen expression of the muscle spindle capsule are likely to impact their mechanical properties. Changes in capsule stiffness may impact the transmission of length change to muscle spindles and thus transduction of sensory information. This change in muscle spindle structure may explain some of the proprioceptive deficits identified with low back pain.

Characterisation of motor cortex organisation in patients with different presentations of persistent low back pain.

Persistence of low back pain is thought to be associated with different underlying pain mechanisms, including ongoing nociceptive input and central sensitisation. We hypothesised that primary motor cortex (M1) representations of back muscles (a measure of motor system adaptation) would differ between pain mechanisms, with more consistent observations in individuals presumed to have an ongoing contribution of nociceptive input consistently related to movement/posture. We tested 28 participants with low back pain sub-grouped by the presumed underlying pain mechanisms: nociceptive pain, nociplastic pain and a mixed group with features consistent with both. Transcranial magnetic stimulation was used to study M1 organisation of back muscles. M1 maps of multifidus (deep and superficial) and longissimus erector spinae were recorded with fine-wire electromyography and thoracic erector spinae with surface electromyography. The nociplastic pain group had greater variability in M1 map location (centre of gravity) than other groups (p < .01), which may suggest less consistency, and perhaps relevance, of motor cortex adaptation for that group. The mixed group had greater overlap of M1 representations between deep/superficial muscles than nociceptive pain (deep multifidus/longissimus: p = .001, deep multifidus/thoracic erector spinae: p = .008) and nociplastic pain (deep multifidus/longissimus: p = .02, deep multifidus/thoracic erector spinae: p = .02) groups. This study provides preliminary evidence of differences in M1 organisation in subgroups of low back pain classified by likely underlying pain mechanisms. Despite the sample size, differences in cortical re-organisation between subgroups were detected. Differences in M1 organisation in subgroups of low back pain supports tailoring of treatment based on pain mechanism and motor adaptation.

Effect of a Consumer-Focused Website for Low Back Pain on Health Literacy, Treatment Choices, and Clinical Outcomes: Randomized Controlled Trial.

BACKGROUND: The internet is used for information related to health conditions, including low back pain (LBP), but most LBP websites provide inaccurate information. Few studies have investigated the effectiveness of internet resources in changing health literacy or treatment choices. OBJECTIVE: This study aims to evaluate the effectiveness of the MyBackPain website compared with unguided internet use on health literacy, choice of treatments, and clinical outcomes in people with LBP. METHODS: This was a pragmatic, web-based, participant- and assessor-blinded randomized trial of individuals with LBP stratified by duration. Participants were randomly allocated to have access to the evidence-based MyBackPain website, which was designed with input from consumers and expert consensus or unguided internet use. The coprimary outcomes were two dimensions of the Health Literacy Questionnaire (dimension 2: "having sufficient information to manage my health;" dimension 3: "actively managing my health;" converted to scores 1-100) at 3 months. Secondary outcomes included additional Health Literacy Questionnaire dimensions, quality of treatment choices, and clinical outcomes. RESULTS: A total of 453 participants were recruited, and 321 (70.9%) completed the primary outcomes. Access to MyBackPain was not superior to unguided internet use on primary outcomes (dimension 2: mean difference -0.87 units, 95% CI -3.56 to 1.82; dimension 3: mean difference -0.41 units, 95% CI -2.78 to 1.96). Between-group differences in other secondary outcomes had inconsistent directions and were unlikely to be clinically important, although a small improvement of unclear importance in the quality of stated treatment choices at 1 month was found (mean difference 0.93 units, 95% CI 0.03 to 1.84). CONCLUSIONS: MyBackPain was not superior to unguided internet use for health literacy, but data suggest some short-term improvement in treatment choices. Future research should investigate if greater interactivity and engagement with the website may enhance its impact. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001292369; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372926. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2018-027516.

Do features of randomized controlled trials of pelvic floor muscle training for postprostatectomy urinary incontinence differentiate successful from unsuccessful patient outcomes? A systematic review with a series of meta-analyses.

AIMS: Efficacy of pelvic floor muscle training (PFMT) for postprostatectomy incontinence (PPI) differs between randomized clinical trials (RCT). This might be explained by variation in content/delivery of PFMT (eg, biofeedback, muscles targeted, and time of commencement of training). This review investigated whether outcome of meta-analysis differs based on presence or not of specific RCT features. METHODS: PubMed, CINAHL, EMBASE, Physiotherapy Evidence Database (PEDro), and Cochrane were searched for RCTs that investigated efficacy of PFMT on PPI. PFMT details and outcomes were extracted. Methodological quality and comprehensiveness of PFMT reporting was assessed using the PEDro scale and Consensus on Reporting Template, respectively. Effect size and 95% confidence intervals were calculated for incontinence rate at 3 months. To identify features that influenced efficacy, separate meta-analyses were performed for studies with and without specific features. RESULTS: Twenty-two trials were included, and 15 were used for meta-analysis of 3-month outcomes. Overall, meta-analysis showed reduced incontinence with PFMT (risk ratio [RR] = 0.85; I2 = 55%; P = .005). Meta-analyses showed better outcomes for PFMT than control groups when the study included preoperative PFMT (RR = 0.76; I2 = 30%; P = .006), biofeedback (RR = 0.73; I2 = 58%; P = .006), instruction to contract around the urethra (RR = 0.9; I2 = 43%; P = .009), a control group without PFMT instruction (RR = 0.85; I2 = 69%; P = .05), inclusion of all men irrespective of continence status (RR = 0.84; I2 = 30%; P = .003) and continence defined as no leakage (RR = 0.85; I2 = 48%; P = .05). CONCLUSIONS: Preoperative PFMT, biofeedback, urethral instructions, no PFMT instruction for controls, inclusion of all men, and continence defined as no leakage are features associated with successful patient outcomes. Future studies should consider these features in design of interventions and pooling data for meta-analysis.

Design, Delivery, Maintenance, and Outcomes of Peer-to-Peer Online Support Groups for People With Chronic Musculoskeletal Disorders: Systematic Review.

BACKGROUND: Online support groups (OSGs) are one way for people with chronic diseases, their family or friends, and health professionals to communicate, gain information, and provide social support. As the number of peer-to-peer OSGs for chronic musculoskeletal conditions grows, it is important to gain insight into the different designs of groups available, who is accessing them, if and how they may be effective, and what strategies are being used to implement or increase consumer engagement. OBJECTIVE: The objectives of this systematic review of people with musculoskeletal conditions were to (1) describe the design features (functions, usage options, moderation, and expert input) of peer-to-peer OSGs, (2) describe the characteristics of the individuals using peer-to-peer OSGs, (3) synthesize the evidence on outcomes of participation, and (4) identify strategies used in the delivery and maintenance of OSGs. METHODS: A search comprising terms related to the population (people with musculoskeletal disorders) and the intervention (peer-to-peer OSGs) was conducted in 6 databases. Results were filtered from 1990 (internet inception) to February 2019. Studies identified in the search were screened according to predefined eligibility criteria using a 2-step process. Quantitative studies were appraised by 2 reviewers using the Risk Of Bias In Non-Randomized Studies of Interventions tool. Qualitative studies were appraised by 2 different reviewers using the Critical Appraisal Skills Programme checklist. Extracted data were synthesized narratively. RESULTS: We examined 21 studies with low to moderate risk of bias. Of these studies, 13 studies included OSGs hosted on public platforms, 11 studies examined OSGs that were conducted in English, and 6 studies used moderators or peer leaders to facilitate engagement. Studies either reported the number of OSG members (n=1985 across all studies) or the number of posts (range: 223-200,000). The majority of OSG members were females who were not full-time employees and with varied levels of education. There were no randomized controlled trials measuring the efficacy of OSGs. Qualitative and quantitative studies identified empowerment, social support, self-management behavior, and health literacy as primary constructs to measure OSG efficacy. Neutral or marginal improvement was reported in these constructs. Sharing experiences and a greater level of engagement appeared to have an important influence on OSGs efficacy. The extent to which members posted on the website influenced engagement. CONCLUSIONS: Across a diverse range of designs, languages, included features, and delivery platforms, peer-to-peer OSGs for chronic musculoskeletal conditions attract predominantly female participants of all ages and education levels. The level of participation of a member appears to be related to their perceived benefit, health literacy, and empowerment. Future studies are needed to identify which design and maintenance strategies have superior efficacy and whether there are concomitant improvements in health outcomes for people with chronic musculoskeletal conditions resulting from participation in OSGs. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42018090326; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018090326.

Australian women's self-perceived barriers to participation in cervical cancer screening: A systematic review.

BACKGROUND: Australia has recently introduced a new screening program for cervical cancer. There has also been a decline in participation rates for cervical screening. AIM: To complete a systematic literature review of the factors that prevent Australian women from participating in cervical screening. METHODS: Authors searched CINAHL, Medline, SCOPUS and the Cochrane Library to obtain articles discussing Australian women's self-identified barriers to cervical screening. Quantitative studies published in peer-reviewed journals after 1991 were considered. PROSPERO Registration Number: CRD42018105028. RESULTS: The final search produced 1749 studies, with 13 quantitative papers included in the narrative synthesis after screening by two independent reviewers. No articles were excluded due to bias. DISCUSSION: Self-identified barriers to screening were categorised into personal, practitioner, test-related and logistical factors. The most commonly stated barriers included lack of time, embarrassment, fear of results, irrelevance and male health professionals. The use of HPV triage in cervical screening was not a barrier to screening, however, some women regarded self-collected HPV testing as a barrier. Barriers to self-collection included desire for the general practitioner to complete the test, fear of doing the test incorrectly, wishing to include it in a general check-up and concerns about the test itself. CONCLUSION: A variety of personal, practitioner, test-related and logistical barriers negatively impact the screening participation of Australian women. Further research into barriers in the Australian population, and women's attitudes towards HPV testing and self-collection is required to create effective health interventions to improve participation in cervical screening.

Discovery of novel heart rate-associated loci using the Exome Chip.

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.

Activity of Deep and Superficial Pelvic Floor Muscles in Women in Response to Different Verbal Instructions: A Preliminary Investigation Using a Novel Electromyography Electrode.

INTRODUCTION: Verbal instructions are used clinically to encourage activation of the pelvic floor muscles (PFM). Whether separate layers of PFM activate differently in response to instructions remains unknown. AIM: To test the hypotheses that (i) instructions that aimed to bias activity of a specific muscle layer would increase activation of the targeted layer to a greater extent than the other layer, (ii) activity of individual PFM layers would differ between instructions, and (iii) PFM activity would be symmetrical for all instructions. METHOD: PFM electromyography (EMG) was recorded using custom-designed surface electrodes in 12 women without PFM dysfunction. The electrode included 4 pairs of recording surfaces orientated to measure EMG from deep and superficial PFM on each side. 3 submaximal contractions were performed for 5 seconds in response to 7 verbal instructions. Root-mean-squared EMG amplitude was calculated for 1 second during the period when participants most closely matched the target activation level. A repeated-measures anova was used to test whether PFM EMG differed between instructions and between regions. The EMG increase of individual muscles relative to that of the reference muscle [deep/right PFM] was compared to no change with t-tests for single samples. MAIN OUTCOME MEASURE: PFM EMG amplitude. RESULTS: Superficial PFM EMG was greater than deep PFM for all instructions (P = .039). 2 instructions induced the greatest amplitude of EMG for the superficial PFM: "squeeze the muscles around the vaginal opening as if to purse lips of your mouth" and "draw the clitoris in a posterior direction" (P = .036). Asymmetry was found in the deeper PFM in 3 instructions designed to bias the superficial PFM. STRENGTH & LIMITATIONS: This preliminary study recorded activation of deep and superficial PFM layers in females with a custom-designed novel electrode. Some cross-talk of recording between muscle layers is possible but unlikely to impact the major findings. CONCLUSION: Verbal instructions used to teach PFM contractions can influence their pattern of activity. This study provides preliminary evidence that, in a selection of verbal instructions, the superficial PFM activates more than the deep PFM, and that the deep PFM can have asymmetrical activation. Aljuraifani R, Stafford RE, Hall LM, et al. Activity of Deep and Superficial Pelvic Floor Muscles in Women in Response to Different Verbal Instructions: A Preliminary Investigation Using a Novel Electromyography Electrode J Sex Med 2019;16:673-679.

Exploring the Characteristics and Preferences for Online Support Groups: Mixed Method Study.

BACKGROUND: Osteoarthritis (OA) is a chronic, disabling, and prevalent disorder. As there is no cure for OA, long-term self-management is paramount. Support groups (SGs) can facilitate self-management among people living with OA. Understanding preferences in design and features of SGs, including online SGs (OSGs), among people with OA can inform future development of SG interventions for this condition. OBJECTIVE: The objective of this study was to investigate health care- and health information-seeking behavior, digital literacy, and preferences for the design of SGs in people with OA. The study also explored the perceived barriers and enablers to being involved in OSGs. METHODS: An online survey study was conducted with a mixed method design (quantitative and qualitative). Individuals aged ≥45 years with knee, hip, or back pain for ≥3 months were recruited from an extant patient database of the Institute of Bone and Joint Research via email invitations. Quantitative elements of the survey included questions about sociodemographic background; health care- and health information-seeking behavior; digital literacy; and previous participation in, and preferences for, SGs and OSGs. Respondents were classified into 2 groups (Yes-SG and No-SG) based on previous participation or interest in an SG. Group differences were assessed with Chi-square tests (significance level set at 5%). Responses to free-text questions relating to preferences regarding OSG engagement were analyzed qualitatively using an inductive thematic analysis. RESULTS: A total of 415 people with OA completed the survey (300/415, 72.3% females; 252/415, 61.0% lived in a major city). The Yes-SG group included 307 (307/415, 73.9%) participants. Between the Yes-SG and No-SG groups, there were no differences in sociodemographic characteristics, health care- and health information-seeking behavior, and digital literacy. An online format was preferred by 126/259 (48.7%) of the Yes-SG group. Trained peer facilitators were preferred, and trustworthiness of advice and information were highly prioritized by the respondents. Qualitative analysis for OSG participation revealed 5 main themes. Lack of time and motivation were the main barriers identified. The main enablers were related to accessibility, enjoyment of the experience, and the content of the discussed information. CONCLUSIONS: These findings highlight the preferences in design features and content of SGs and OSGs and may assist in the further development of such groups.

Design of programs to train pelvic floor muscles in men with urinary dysfunction: Systematic review.

AIMS: Pelvic floor muscle training (PFMT) is a first line conservative treatment for men with urinary dysfunction, but reports of its efficacy are variable. This study aimed to systematically review the content of PFMT programs used for urinary dysfunction in men. METHODS: Electronic databases (PubMed, CINAHL, EMBASE, Cochrane, PEDro) were searched for studies that used PFMT in the treatment of adult men with urinary dysfunction. Details of PFMT treatment sessions and home exercise protocols were extracted. Criteria specific to PFMT were developed, based on the Consensus on Exercise Reporting Template, and applied to all studies to measure the comprehensiveness of the PFMT description in the manuscript. RESULTS: Results from the 108 included studies indicate substantial heterogeneity in both the content of PFMT and the quality of reporting of the components of the exercise regimes. There was notable disparity in the muscles targeted by the interventions (and few focused on urethral control despite the use in management of urinary conditions) and the intensity of the programs (eg, 18-240 contractions per day). Most studies were missing key details of description of the PFMT programs (eg, the position in which the pelvic floor muscle [PFM] contraction was taught and how it was assessed, methods used to ensure exercise adherence). CONCLUSIONS: Variation in content of PFMT programs is likely to contribute to variation in the reported efficacy for management of urinary dysfunction in men, and unclear description of the details of the evaluated programs makes it difficult to identify the effective/ineffective components. PROSPERO registration number CRD42017071038.

Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury.

PURPOSE: Intervertebral disk (IVD) lesion and its subsequent degeneration have a profound effect on the multifidus muscle. The subacute/early chronic phase of multifidus remodeling after IVD lesion has been proposed to be regulated by inflammatory processes. The balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages plays an important role in maintaining tissue integrity after injury. The localization, polarization of macrophage subtypes and their mediation of the pro-inflammatory cytokine tumor necrosis factor (TNF) are unknown in paraspinal muscles during IVD degeneration. A sheep model of IVD degeneration was used to investigate the role of macrophages and TNF in the structural alterations that occur within the multifidus muscle. METHODS: Anterolateral lesions were induced at L3-4 IVD in sheep. Multifidus muscle tissue at L4 was harvested 3 and 6 months after lesion and used for immunofluorescence assays to examine total macrophage number, macrophage polarization between M1 and M2, and to assess the localization of TNF expression in muscle, adipose and connective tissues from injured and naïve control animals. RESULTS: A greater proportion of M1 macrophages is present in muscle at both 3 and 6 months after IVD lesion, and adipose tissue at 6 months. Total number of macrophages is unchanged. At 6 months, expression of TNF is increased in adipose and connective tissue and the proportion of TNF expressed by M1 macrophages is increased. CONCLUSIONS: These data support the proposal that macrophages and TNF (pro-inflammatory cytokine) play an active role in the subacute/early chronic phase of remodeling in muscle, adipose and connective tissues of the multifidus during IVD degeneration. This presents a novel target for treatment. These slides can be retrieved under Electronic Supplementary Material.

Planned dose reduction of ocrelizumab in relapsing-remitting multiple sclerosis: a single-centre observational study.

Background: Ocrelizumab, a humanised anti-CD20 monoclonal, is a highly effective treatment for relapsing-remitting multiple sclerosis (RRMS). The long-term safety of B-cell depletion in RRMS, however, is uncertain and there are no data on dose reduction of ocrelizumab as a risk mitigation strategy. This study aimed to evaluate the effectiveness and safety of reducing ocrelizumab dose from 600 to 300 mg in patients with RRMS. Method: Data were collected through the Townsville neurology service. Following the standard randomised controlled trial regimen of 600 mg every 6 months for 2 years, sequential patients consented to dose reduction to 300 mg every 6 months. Patients were included if they were diagnosed with RRMS and received at least one reduced dose of ocrelizumab. Relapse, disability progression, new MRI lesions, CD19+ cell counts and immunoglobulin concentrations were analysed. Results: A total of 35 patients, treated with 177 full and 107 reduced doses, were included. The mean follow-up on reduced dose was 17 (1-31) months. We observed no relapses or new MRI activity in the cohort receiving the reduced dose, accompanied by persistent CD19+B cell depletion (≤0.05×109/L). Mean IgG, IgA and IgM levels remained stable throughout the study. No new safety concerns arose. Conclusions: In this single-centre observational study, dose reduction of ocrelizumab from 600 to 300 mg every 6 months after 2 years appeared to maintain efficacy in terms of new inflammatory disease activity. A randomised trial may be warranted to confirm this and explore the impact of dose reduction on long-term safety.

The effect of COVID-19 on medical student clinical skill practice and self-perceived proficiency.

Background: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted medical education. This study aimed to determine how COVID-19 affected students' opportunity to practice core clinical skills across specialty rotations and their self-perceived proficiency at performing these. Methods: Routinely administered surveys of fifth year medical student' experiences and perceptions of medical training from 2016 to 2021 were analysed. Number of times core clinical skills were performed and self-perceived proficiency of each skill were compared pre- (years 2016-2019) and during-COVID (years 2020-2021). Results: Data from 219 surveys showed a reduction in the opportunity to perform "a cervical screen test" (p<0.001), "a mental health assessment" (p=0.006), "assess the risk of suicide" (p=0.004) and "bladder catheterisation" (p=0.007) during-COVID. Self-reported skill proficiency was also less during-COVID for performance of: "a mental health assessment" (p=0.026) and "an ECG" (p=0.035). Conclusions: The impact of COVID-19 on mental health skills was greatest, potentially due to a shift toward telehealth services and consequent reduced ability for students to engage in consultations. In a time of potential long-term change in the healthcare landscape, it is imperative to ensure adequate opportunity to practice all core clinical skills during medical training. Inclusion of telehealth earlier into the curriculum may benefit student confidence.

Impact of new diagnostic pathway for gestational diabetes in time of COVID-19.

Background: In April 2020, the diagnostic criteria for gestational diabetes mellitus (GDM) changed in Queensland, with the goal of reducing exposure of pregnant women to COVID-19. Methods: A retrospective clinical audit was conducted at a regional hospital to compare the incidence of GDM, and specific maternal and neonatal outcomes four months before and after the change in guidelines was implemented. Results: Less than 50% of diagnostic tests were performed according to new guidelines. There was a non-significant increase in the incidence of GDM (13.3% to 15.3%), and pharmacological treatments. Instrumental deliveries (p = 0.01) and shoulder dystocia (p = 0.04) increased following the change in guidelines. There were no differences in the incidence of elective and emergency caesarean delivery, macrosomia and fetal weight. Maternal pre-pregnancy body mass index (BMI) was higher in the COVID-19 GDM cohort (p = 0.02). Conclusions: Despite the change in guidelines, there was a non-significant increase in the incidence of diagnosis of gestational diabetes.

A study protocol for a randomised controlled trial of ice to reduce the pain of immunisation: The ICE trial.

BACKGROUND AND OBJECTIVES: Vaccine injections commonly cause iatrogenic pain. Ice may reduce pain. This is a study protocol for a prospective randomised controlled trial aiming to investigate the efficacy of ice packs to decrease vaccine-related pain in adults. METHOD: The intervention group (n = 45) will receive ice packs (0 °C) and the control group (n = 45) receive placebo cold packs (10 °C) on the injection site for 30 seconds prior to vaccination. RESULTS: The primary outcomes will test the hypothesis that applying an ice pack will significantly reduce pain of vaccination when compared with a cold pack. The primary dependent variable will be pain score recorded on a visual analogue scale. Secondary outcomes aim to assess potential adverse reactions. The main analysis of data will follow the intention-to-treat principle. The primary dependent variable will be compared using an independent t-test or a Mann-Whitney U test. Multivariable logistic regression analysis may be used. DISCUSSION: The trial may guide general practitioners in the use of ice packs to reduce injection-related pain in adults.

Risk factors for low back pain outcome: Does it matter when they are measured?

BACKGROUND: The early identification of factors that increase risk of poor recovery from acute low back pain (LBP) is critical to prevent the transition to chronicity. Although most studies of risk factors for poor outcome in LBP tend to investigate the condition once it is already persistent, there is evidence to suggest that this differs from risk factors measured during the early-acute stage. This study aimed to identify early risk factors for poor outcome in the short- and long-term in individuals with acute LBP, and to compare this with factors identified at 3 months in the same cohort. METHODS: One hundred and thirty-three individuals were recruited within 2 weeks of an acute LBP episode and completed questionnaires related to their sociodemographic, psychological, clinical and history/treatment status at baseline and 3 months later, and their pain-level fortnightly for 12 months. RESULTS: Of the 133 participants recruited, follow-up data were provided by 120 at 3 months, 97 at 6 months, 85 at 9 months and 94 at 12 months. Linear regression identified various factors at baseline (acute phase) and 3 months later that predicted short- and long-term outcome (pain level, change in pain). Key findings were that: (1) depressive symptoms at baseline most consistently predicted worse outcome; (2) psychological factors in general at 3 months were more predictive of outcome than when measured at baseline; (3) early health care utilization predicted better outcome, whereas use of pain medication later (3 months) predicted worse outcome; and (4) sex and BMI predicted outcome inconsistently over 12-months. CONCLUSIONS: The results highlight the multidimensional nature of risk factors for poor outcome in LBP and the need to consider time variation in these factors. Significance This study attempts to consider the impact of time variation of candidate risk factors on long-term outcome from the very early onset of acute low back pain. Risk factors across domains (sociodemographic, psychological, clinical, history/treatment) were identified, but their relationship with outcome often depended on when (acute phase vs. 3 months later) they were measured after back pain onset. Findings highlight the need to consider both a diverse range of factors and their potential time variance when assessing risk of poor outcome.