A New Tool for Estimating the Number of Pregnant People in the United States.

BACKGROUND: Knowing the approximate number of women of reproductive age (ie, 15-49 years) who are pregnant at a point in time in the United States can aid in emergency preparedness resource allocation. The Centers for Disease Control and Prevention (CDC) released a pregnancy estimator toolkit in 2012, which could be used to estimate the number of pregnant people in a geographic area at a point in time. This original toolkit did not account for pregnancy losses before 20 weeks of gestation; however, an updated toolkit released by the CDC in May 2024 uses a ratio of live births to estimate the number of pregnancy losses before 20 weeks at a point in time for improved estimation of total pregnant people at a point in time. INSTRUMENT: We used the CDC's updated reproductive health tool, "Estimating the Number of Pregnant Women in a Geographic Area." EXPERIENCE: Using publicly available data for 2020, we gathered the necessary input values, including total births, fetal deaths, and induced abortions, and applied the equation available in the CDC toolkit to estimate the number of pregnant people in the United States at any point in time in 2020. CONCLUSION: In 2020, there were 75,582,028 women of reproductive age in the United States, and we estimate that approximately 2,962,052 or 3.9% of women of reproductive age were pregnant at any point in time in the United States.

Short-term intermittent fasting and energy restriction do not impair rates of muscle protein synthesis: A randomised, controlled dietary intervention.

BACKGROUND: Intermittent fasting (IF) is an effective energy restricted dietary strategy to reduce body and fat mass and improve metabolic health in individuals with either an overweight or obese status. However, dietary energy restriction may impair muscle protein synthesis (MPS) resulting in a concomitant decline in lean body mass. Due to periods of prolonged fasting combined with irregular meal intake, we hypothesised that IF would reduce rates of MPS compared to an energy balanced diet with regular meal patterns. AIMS: We assessed the impact of a short-term, ten days, alternate day fasting or a continuous energy restricted diet to a control diet on integrated rates of skeletal MPS in middle-aged males with overweight or obesity. METHODS: Twenty-seven middle-aged males with overweight or obesity (age: 44.6 ± 5.4 y; BMI: 30.3 ± 2.6 kg/m2) consumed a three-day lead-in diet, followed by a ten-day controlled dietary intervention matched for protein intake, as alternate day fasting (ADF: 62.5 energy (En)%, days of 25 En% alternated with days of 100 En% food ingestion), continuous energy restriction (CER: 62.5 En%), or an energy balanced, control diet (CON: 100 En%). Deuterated water (D2O) methodology with saliva, blood, and skeletal muscle sampling were used to assess integrated rates of MPS over the ten-day intervention period. Secondary measures included fasting plasma glucose, insulin, and gastrointestinal hormone concentrations, continuous glucose monitoring, and assessment of body composition. RESULTS: There were no differences in daily rates of MPS between groups (ADF: 1.18 ± 0.13, CER: 1.13 ± 0.16, and CON: 1.18 ± 0.18 %/day, P > 0.05). The reductions in body mass were greater in ADF and CER compared to CON (P < 0.001). Lean and fat mass were decreased by a similar magnitude across groups (main time effect, P < 0.001; main group effect, P > 0.05). Fasting plasma leptin concentrations decreased in ADF and CER (P < 0.001), with no differences in fasting plasma glucose or insulin concentrations between groups. CONCLUSION: Short-term alternate day fasting does not lower rates of MPS compared to continuous energy restriction or an energy balanced, control diet with matched protein intake. The prolonged effects of IF and periods of irregular energy and protein intake patterns on muscle mass maintenance remain to be investigated. This trial was registered under Australian New Zealand Clinical Trial Registry (https://www.anzctr.org.au), identifier no. ACTRN12619000757112.

Comparing the effects of time-restricted eating on glycaemic control in people with type 2 diabetes with standard dietetic practice: A randomised controlled trial.

AIMS: To test the efficacy of time-restricted eating (TRE) in comparison to dietitian-led individualised dietary guidance to improve HbA1c in people with Type 2 diabetes mellitus. METHODS: In a parallel groups design, 51 adults (35-65 y) with Type 2 diabetes mellitus and overweight/obesity (HbA1c ≥6.5% (48 mmol/mol), BMI ≥25-≤40 kg/m2) commenced a six-month intervention. Following baseline, participants were randomised to TRE (1000-1900 h) or DIET (individualised dietetic guidance) with four consultations over four months. Changes in HbA1c (primary), body composition, and self-reported adherence (secondary) were analysed using linear mixed models. A non-inferiority margin of 0.3% (4 mmol/mol) HbA1c was set a priori. RESULTS: Forty-three participants (56 ± 8 y, BMI: 33 ± 5 kg/m2, HbA1c: 7.6 ± 0.8%) completed the intervention. HbA1c was reduced (P=0.002; TRE: -0.4% (-5 mmol/mol), DIET: -0.3% (-4 mmol/mol)) with no group or interaction effects; TRE was non-inferior to DIET (-0.11%, 95%CI: -0.50% to 0.28%). Body mass reduced in both groups (TRE: -1.7 kg; DIET: -1.2 kg) via ∼900 kJ/d spontaneous energy reduction (P<0.001). Self-reported adherence was higher in TRE versus DIET (P<0.001). CONCLUSIONS: When individualised dietary guidance is not available, effective, and/or suitable, TRE may be an alternative dietary strategy to improve glycaemic control in people with Type 2 diabetes mellitus.

Health Catch-UP!: a realist evaluation of an innovative multi-disease screening and vaccination tool in UK primary care for at-risk migrant patients.

BACKGROUND: Migrants to the UK face disproportionate risk of infections, non-communicable diseases, and under-immunisation compounded by healthcare access barriers. Current UK migrant screening strategies are unstandardised with poor implementation and low uptake. Health Catch-UP! is a collaboratively produced digital clinical decision support system that applies current guidelines (UKHSA and NICE) to provide primary care professionals with individualised multi-disease screening (7 infectious diseases/blood-borne viruses, 3 chronic parasitic infections, 3 non-communicable disease or risk factors) and catch-up vaccination prompts for migrant patients. METHODS: We carried out a mixed-methods process evaluation of Health Catch-UP! in two urban primary healthcare practices to integrate Health Catch-UP! into the electronic health record system of primary care, using the Medical Research Council framework for complex intervention evaluation. We collected quantitative data (demographics, patients screened, disease detection and catch-up vaccination rates) and qualitative participant interviews to explore acceptability and feasibility. RESULTS: Ninety-nine migrants were assessed by Health Catch-UP! across two sites (S1, S2). 96.0% (n = 97) had complete demographics coding with Asia 31.3% (n = 31) and Africa 25.2% (n = 25), the most common continents of birth (S1 n = 92 [48.9% female (n = 44); mean age 60.6 years (SD 14.26)]; and S2 n = 7 [85.7% male (n = 6); mean age 39.4 years (SD16.97)]. 61.6% (n = 61) of participants were eligible for screening for at least one condition and uptake of screening was high 86.9% (n = 53). Twelve new conditions were identified (12.1% of study population) including hepatitis C (n = 1), hypercholesteraemia (n = 6), pre-diabetes (n = 4), and diabetes (n = 1). Health Catch-UP! identified that 100% (n = 99) of patients had no immunisations recorded; however, subsequent catch-up vaccination uptake was poor (2.0%, n = 1). Qualitative data supported acceptability and feasibility of Health Catch-UP! from staff and patient perspectives, and recommended Health Catch-UP! integration into routine care (e.g. NHS health checks) with an implementation package including staff and patient support materials, standardised care pathways (screening and catch-up vaccination, laboratory, and management), and financial incentivisation. CONCLUSIONS: Clinical Decision Support Systems like Health Catch-UP! can improve disease detection and implementation of screening guidance for migrant patients but require robust testing, resourcing, and an effective implementation package to support both patients and staff.

Emergency department visits, inpatient hospitalizations, and non-fatal and fatal drug overdoses during COVID-19 among Veterans with opioid use disorder.

BACKGROUND: The COVID-19 pandemic had dramatic adverse impacts on people with opioid use disorder (OUD), as evidenced by significant disruptions to care and unprecedented increases in drug overdoses. In this study, we evaluated the impacts of COVID-19 on utilization of emergency and inpatient care, and fatal and non-fatal overdoses among veterans with OUD. METHODS: We used Veterans Health Administration (VHA) electronic medical record and mortality data to compare emergency department (ED) visits, inpatient hospitalizations, and fatal and non-fatal overdoses between a pandemic-exposed cohort of veterans with OUD observed both pre- and post-pandemic onset (n = 53,803; observed January 2019-March 2021) to a matched pre-pandemic control group (n = 53,803; observed October 2017-December 2019). RESULTS: Compared to pre-pandemic trends, there were significant decreases in the odds of ED and inpatient admissions and total number of ED and inpatient admissions during COVID-19. There was a significant decrease in the odds of having a recorded non-fatal overdose. The odds of overdose death increased during the pandemic compared to pre-pandemic trends. CONCLUSION: We observed significant decreases in the utilization of ED and inpatient care services, and fewer non-fatal overdoses, post-pandemic onset. Healthcare disruptions limiting access to emergency and inpatient care could account for the lower number of recorded non-fatal overdoses, potentially reflecting an underestimate of risk. In contrast, fatal overdoses increased during the pandemic compared to pre-pandemic trends. Lower utilization of emergency and inpatient care, and higher rates of fatal overdoses during the pandemic, suggest an exacerbation of unmet treatment need post-pandemic onset.

Changing hearts and minds: theorizing how, when, and under what conditions three social influence implementation strategies work.

Background: Opinion leadership, educational outreach visiting, and innovation championing are commonly used strategies to address barriers to implementing innovations and evidence-based practices in healthcare settings. Despite voluminous research, ambiguities persist in how these strategies work and under what conditions they work well, work poorly, or work at all. The current paper develops middle-range theories to address this gap. Methods: Conceptual articles, systematic reviews, and empirical studies informed the development of causal pathway diagrams (CPDs). CPDs are visualization tools for depicting and theorizing about the causal process through which strategies operate, including the mechanisms they activate, the barriers they address, and the proximal and distal outcomes they produce. CPDs also clarify the contextual conditions (i.e., preconditions and moderators) that influence whether, and to what extent, the strategy's causal process unfolds successfully. Expert panels of implementation scientists and health professionals rated the plausibility of these preliminary CPDs and offered comments and suggestions on them. Findings: Theoretically, opinion leadership addresses potential adopters' uncertainty about likely consequences of innovation use (determinant) by promoting positive attitude formation about the innovation (mechanism), which results in an adoption decision (proximal outcome), which leads to innovation use (intermediate outcome). As this causal process repeats, penetration, or spread of innovation use, occurs (distal outcome). Educational outreach visiting addresses knowledge barriers, attitudinal barriers, and behavioral barriers (determinants) by promoting critical thinking and reflection about evidence and practice (mechanism), which results in behavioral intention (proximal outcome), behavior change (intermediate outcome), and fidelity, or guideline adherence (distal outcome). Innovation championing addresses organizational inertia, indifference, and resistance (determinants) by promoting buy-in to the vision, fostering a positive implementation climate, and increasing collective efficacy (mechanisms), which leads to participation in implementation activities (proximal outcome), initial use of the innovation with increasing skill (intermediate outcome) and, ultimately, greater penetration and fidelity (distal outcomes). Experts found the preliminary CPDs plausible or highly plausible and suggested additional mechanisms, moderators, and preconditions, which were used to amend the initial CPD. Discussion: The middle-range theories depicted in the CPDs furnish testable propositions for implementation research and offer guidance for selecting, designing, and evaluating these social influence implementation strategies in both research studies and practice settings.

Strengthening Maternal and Infant Health Resilience Before Weather and Climate Disasters: Preparedness Resources from CDC's Division of Reproductive Health.

This report describes opportunities to address emergency preparedness to incorporate the needs of pregnant and postpartum populations. This report briefly summarizes data on the impacts of weather and climate disasters on maternal and infant health and outlines opportunities for individuals, health care providers, and public health practitioners to increase capacity to prepare for these occurrences, which are becoming more frequent and costly. Specific resources from the U.S. Centers for Disease Control and Prevention's Division of Reproductive Health are shared to support individual preparedness, communication of disaster safety messages, and emergency preparedness planning capacity among health care providers and health departments.

Impact of antiretroviral therapy during primary HIV infection on T-cell immunity after treatment interruption.

This study aims to understand the impact of early antiretroviral therapy (ART) on HIV-specific T-cell responses measured after treatment interruption may inform strategies to deliver ART-free immune-mediated viral suppression. HIV-specific T-cell immunity was analysed using gamma interferon enzyme-linked immunospot assays in two studies. SPARTAC included individuals with primary HIV infection randomised to 48 weeks of ART (n = 24) or no immediate therapy (n = 37). The PITCH (n = 7) cohort started antiretroviral therapy in primary infection for at least one year, followed by TI. In SPARTAC, participants treated in PHI for 48 weeks followed by TI for 12 weeks, and those who remained untreated for 60 weeks made similar HIV Gag-directed responses (both magnitude and breadth) at week 60. However, the treated group made a greater proportion of novel HIV Gag-directed responses by Week 60, suggestive of a greater reserve to produce new potentially protective responses. In the more intensively followed PITCH study, 6/7 participants showed dominant Gag and/or Pol-specific responses post-TI compared with pre-TI. Although early ART in PHI was not associated with major differences in HIV-specific immunity following TI compared with untreated participants, the potential to make more new Gag-directed responses warrants further investigation as this may inform strategies to achieve ART-free control.

Caesarean section and anal incontinence in women after obstetric anal sphincter injury: A systematic review and meta-analysis.

BACKGROUND: Approximately 50% women who give birth after obstetric anal sphincter injury (OASI) develop anal incontinence (AI) over their lifetime. OBJECTIVE: To evaluate current evidence for a protective benefit of planned caesarean section (CS) to prevent AI after OASI. SEARCH STRATEGY: MEDLINE/PubMed, Embase 1974-2024, CINAHL and Cochrane to 7 February 2024 (PROSPERO CRD42022372442). SELECTION CRITERIA: All studies reporting outcomes after OASI and a subsequent birth, by any mode. DATA COLLECTION AND ANALYSIS: Eighty-six of 2646 screened studies met inclusion criteria, with nine studies suitable to meta-analyse the primary outcome of 'adjusted AI' after OASI and subsequent birth. Subgroups: short-term AI, long-term AI, AI in asymptomatic women. SECONDARY OUTCOMES: total AI, quality of life, satisfaction/regret, solid/liquid/flatal incontinence, faecal urgency, AI in women with and without subsequent birth, change in AI pre- to post- subsequent birth. MAIN RESULTS: There was no evidence of a difference in adjusted AI after subsequent vaginal birth compared with CS after OASI across all time periods (OR = 0.92, 95% CI 0.72-1.20; 9 studies, 2104 participants, I2 = 0% p = 0.58), for subgroup analyses or secondary outcomes. There was no evidence of a difference in AI in women with or without subsequent birth (OR = 1.00 95% CI 0.65-1.54; 10 studies, 970 participants, I2 = 35% p = 0.99), or pre- to post- subsequent birth (OR = 0.79 95% CI 0.51-1.25; 13 studies, 5496 participants, I2 = 73% p = 0.31). CONCLUSIONS: Due to low evidence quality, we are unable to determine whether planned caesarean is protective against AI after OASI. Higher quality evidence is required to guide personalised decision-making for asymptomatic women and to determine the effect of subsequent birth mode on long-term AI outcomes.

Comparing the potential of benchtop and handheld mid-infrared spectrometers for predicting soil phosphorus (P) sorption capacity and evaluating the influence of sample preparation.

Traditional soil phosphorus (P) sorption capacity is examined from a Langmuir isotherm batch technique, which is time-consuming, labour intensive and generates chemical waste. In this work, we provide an efficient and convenient technique with MIR spectroscopy to predict the Langmuir parameter of soil P sorption maximum capacity (Smax, mg·kg-1). Four spectral libraries from benchtop (Bruker) and handheld (Agilent) MIR spectrometers were built with samples in two particle size ranges, <0.100 mm (ball-milled) and <2 mm. respectively. Using an archive of samples with a database of sorption parameters, soils were classified into 'low' and 'high' sorption capacities. Chemometric regression models of partial least squares (PLS), Cubist, support vector machine (SVM) regression and random forest (RF) were evaluated for Smax prediction. Bruker spectral libraries with both soil particle sizes yielded 'excellent models', with SVM predicting Smax values with high accuracy (RPIQV = 4.50 and 4.25 for the spectral libraries of the ball-milled and <2 mm samples, respectively). In comparison, the Agilent handheld spectral libraries contained more noise and less resolution. For Agilent MIR spectroscopy, more homogeneous samples after ball milling resulted in a higher accurate Smax prediction. For Agilent libraries of ball-milled samples, an 'approximate quantitative model' (RPIQV = 2.74) was obtained from the raw spectra using the Cubist algorithm. However, for Agilent spectroscopy of <2 mm samples, the best performing Cubist algorithm can only achieve a 'fair model' (RPIQV=2.23) with the potential to discriminate between 'low' and 'high' Smax values. The results suggest that the benchtop spectrometer can predict the Langmuir Smax value with high accuracy without the need to ball mill samples. However, the handheld spectrometer can only make approximate quantitative predictions of Smax for ball-milled samples. For <2 mm samples, Agilent can only be used to classify 'low' and 'high' sorption capacity soils.

Health Care Utilization and Clinical Management of All-Cause and Norovirus-Associated Acute Gastroenteritis Within a US Integrated Health Care System.

Background: Norovirus-associated acute gastroenteritis (AGE) exacts a substantial disease burden, yet the health care utilization for and clinical management of norovirus-associated AGE are not well characterized. Methods: We describe the health care encounters and therapeutics used for patients with all-cause and norovirus-associated AGE in the Kaiser Permanente Northwest health system from 1 April 2014 through 30 September 2016. Medical encounters for patients with AGE were extracted from electronic health records, and encounters within 30 days of one another were grouped into single episodes. An age-stratified random sample of patients completed surveys and provided stool samples for norovirus testing. Results: In total, 40 348 individuals had 52 509 AGE episodes; 460 (14%) of 3310 participants in the substudy tested positive for norovirus. An overall 35% of all-cause AGE episodes and 29% of norovirus-associated AGE episodes had ≥2 encounters. While 80% of norovirus-associated AGE episodes had at least 1 encounter in the outpatient setting, all levels of the health care system were affected: 10%, 22%, 10%, and 2% of norovirus-associated AGE episodes had at least 1 encounter in virtual, urgent care, emergency department, and inpatient settings, respectively. Corresponding proportions of therapeutic use between norovirus-positive and norovirus-negative episodes were 13% and 10% for intravenous hydration (P = .07), 65% and 50% for oral rehydration (P < .001), 7% and 14% for empiric antibiotic therapy (P < .001), and 33% and 18% for antiemetics (P < .001). Conclusions: Increased health care utilization and therapeutics are likely needed for norovirus-associated AGE episodes during peak norovirus winter seasons, and these data illustrate that effective norovirus vaccines will likely result in less health care utilization.

Differences in neuroinflammation in people who started antiretroviral treatment during primary versus chronic HIV infection: an 18kDa Translocator protein (TSPO) positron emission tomography (PET) study.

Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [11C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population. This was a cross-sectional, observational study. All participants underwent [11C]PBR28 PET-CT neuroimaging. Using a two-tissue compartment model, total volume of distribution (VT) and distribution volume ratios (DVR) using cortical grey matter as a pseudo-reference region at 20 regions of interest (ROIs) were calculated. Differences in VT and DVR were compared between groups using the Kruskall-Wallis test. Seventeen neuro-asymptomatic male PWH on ART (9 aPWH, 8 cPWH) and 8 male control participants (CPs) were included. Median (interquartile range, IQR) age was 40 (30, 46), 44 (41, 47) and 21 (20, 25) years in aPWH, cPWH and CPs, respectively. Median (IQR) CD4 (cells/µL) and CD4:CD8 were 687 (652, 1014) and 1.37 (1.24, 1.42), and 700 (500, 720) and 0.67 (0.64, 0.82) in aPWH and cPWH, respectively. Overall, no significant difference in VT and DVR were observed between the three groups at any ROIs. cPWH demonstrated a trend towards higher mean VT compared with aPWH and CPs at most ROIs. No significant differences in neuroinflammation, using [11C]PBR28 binding as a proxy, were identified between cPWH, aPWH and CPs. A trend towards lower absolute [11C]PBR28 binding was seen amongst aPWH and CPs, suggesting early ART may mitigate neuroinflammation.

Formylated Peptide Receptor-1-Mediated Gut Inflammation as a Therapeutic Target in Inflammatory Bowel Disease.

Background: Formylated peptide receptor (FPR)-1 is a G-coupled receptor that senses foreign bacterial and host-derived mitochondrial formylated peptides (FPs), leading to innate immune system activation. Aim: We sought to investigate the role of FPR1-mediated inflammation and its potential as a therapeutic target in inflammatory bowel disease (IBD). Methods: We characterized FPR1 gene and protein expression in 8 human IBD (~1000 patients) datasets with analysis on disease subtype, mucosal inflammation, and drug response. We performed in vivo dextran-sulfate sodium (DSS) colitis in C57/BL6 FPR1 knockout mice. In ex vivo studies, we studied the role of mitochondrial FPs and pharmacological blockade of FPR1 using cyclosporin H in human peripheral blood neutrophils. Finally, we assess mitochondrial FPs as a potential mechanistic biomarker in the blood and stools of patients with IBD. Results: Detailed in silico analysis in human intestinal biopsies showed that FPR1 is highly expressed in IBD (n = 207 IBD vs 67 non-IBD controls, P < .001), and highly correlated with gut inflammation in ulcerative colitis (UC) and Crohn's disease (CD) (both P < .001). FPR1 receptor is predominantly expressed in leukocytes, and we showed significantly higher FPR1+ve neutrophils in inflamed gut tissue section in IBD (17 CD and 24 UC; both P < .001). Further analysis in 6 independent IBD (data available under Gene Expression Omnibus accession numbers GSE59071, GSE206285, GSE73661, GSE16879, GSE92415, and GSE235970) showed an association with active gut inflammation and treatment resistance to infliximab, ustekinumab, and vedolizumab. FPR1 gene deletion is protective in murine DSS colitis with lower gut neutrophil inflammation. In the human ex vivo neutrophil system, mitochondrial FP, nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) is a potent activator of neutrophils resulting in higher CD62L shedding, CD63 expression, reactive oxygen species production, and chemotactic capacity; these effects are inhibited by cyclosporin H. We screened for mitochondrial ND6 in IBD (n = 54) using ELISA and detected ND6 in stools with median values of 2.2 gg/mL (interquartile range [IQR] 0.0-4.99; range 0-53.3) but not in blood. Stool ND6 levels, however, were not significantly correlated with paired stool calprotectin, C-reactive protein, and clinical IBD activity. Conclusions: Our data suggest that FPR1-mediated neutrophilic inflammation is a tractable target in IBD; however, further work is required to clarify the clinical utility of mitochondrial FPs as a potential mechanistic marker for future stratification.

Multidrug resistance plasmids commonly reprogram the expression of metabolic genes in Escherichia coli.

Multidrug-resistant Escherichia coli is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance between lineages is driving the rising rates of hard-to-treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and while a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared the impacts of different MDR plasmids in a common bacterial host. As such, our ability to predict which MDR plasmids are the most likely to be maintained and spread in bacterial populations is limited. Here, we introduced eight diverse MDR plasmids encoding resistances against a range of clinically important antibiotics into E. coli K-12 MG1655 and measured their fitness costs and transcriptional impacts. The scale of the transcriptional responses varied substantially between plasmids, ranging from >650 to <20 chromosomal genes being differentially expressed. However, the scale of regulatory disruption did not correlate significantly with the magnitude of the plasmid fitness cost, which also varied between plasmids. The identities of differentially expressed genes differed between transconjugants, although the expression of certain metabolic genes and functions were convergently affected by multiple plasmids, including the downregulation of genes involved in L-methionine transport and metabolism. Our data show the complexity of the interaction between host genetic background and plasmid genetic background in determining the impact of MDR plasmid acquisition on E. coli. IMPORTANCE: The increase in infections that are resistant to multiple classes of antibiotics, including those isolates that carry carbapenamases, beta-lactamases, and colistin resistance genes, is of global concern. Many of these resistances are spread by conjugative plasmids. Understanding more about how an isolate responds to an incoming plasmid that encodes antibiotic resistance will provide information that could be used to predict the emergence of MDR lineages. Here, the identification of metabolic networks as being particularly sensitive to incoming plasmids suggests the possible targets for reducing plasmid transfer.

Utility of Repetitive Transcranial Magnetic Stimulation for Chronic Daily Headache Prophylaxis: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Management of chronic daily headaches (CDH) remains challenging due to the limited efficacy of standard prophylactic pharmacological measures. Several studies have reported that repetitive transcranial magnetic stimulation (rTMS) can effectively treat chronic headaches. The objective was to determine the utility of rTMS for immediate post-treatment and sustained CDH prophylaxis. RECENT FINDINGS: All procedures were conducted per PRISMA guidelines. PubMed, Scopus, Web of Science, and ProQuest databases were searched for controlled clinical trials that have tested the efficacy of rTMS on populations with CDH. DerSimonian-Laird random-effects meta-analyses were performed using the 'meta' package in R to examine the post- vs. pre-rTMS changes in standardized headache intensity and frequency compared to sham-control conditions. Thirteen trials were included with a combined study population of N = 538 patients with CDH (rTMS, N = 284; Sham, N = 254). Patients exposed to rTMS had significantly reduced standardized CDH intensity and frequency in the immediate post-treatment period (Hedges' g = -1.16 [-1.89, -0.43], p = 0.002 and Δ = -5.07 [-10.05, -0.11], p = 0.045 respectively). However, these effects were sustained marginally in the follow-up period (Hedges' g = -0.43 [-0.76, -0.09], p = 0.012 and Δ = -3.33 [-5.52, -1.14], p = 0.003). Significant between-study heterogeneity was observed, at least partially driven by variations in rTMS protocols. Despite the observed clinically meaningful and statistically significant benefits in the immediate post-treatment period, the prophylactic effects of rTMS on CDH do not seem to sustain with discontinuation. Thus, the cost-effectiveness of the routine use of rTMS for CDH prophylaxis remains questionable. REGISTRATION: Protocol preregistered in PROSPERO International Prospective Register of Systematic Reviews (CRD42021250100).

Multi-infection screening for migrant patients in UK primary care: Challenges and opportunities.

Background: Migrants in Europe face a disproportionate burden of undiagnosed infection, including tuberculosis, blood-borne viruses, and parasitic infections and many belong to an under-immunised group. The European Centre for Disease Control (ECDC) has called for innovative strategies to deliver integrated multi-disease screening to migrants within primary care, yet this is poorly implemented in the UK. We did an in-depth qualitative study to understand current practice, barriers and solutions to infectious disease screening in primary care, and to seek feedback on a collaboratively developed digitalised integrated clinical decision-making tool called Health Catch UP!, which supports multi-infection screening for migrant patients. Methods: Two-phase qualitative study of UK primary healthcare professionals, in-depth semi-structured telephone-interviews were conducted. In Phase A, we conducted interviews with clinical staff (general practitioners (GPs), nurses, health-care-assistants (HCAs)); these informed data collection and analysis for phase B (administrative staff). Data were analysed iteratively, using thematic analysis. Results: In phase A, 48 clinicians were recruited (25 GPs, 15 nurses, seven HCAs, one pharmacist) and 16 administrative staff (11 Practice-Managers, five receptionists) in phase B. Respondents were positive about primary care's ability to effectively deliver infectious disease screening. However, we found current infectious disease screening lacks a standardised approach and many practices have no system for screening meaning migrant patients are not always receiving evidence-based care (i.e., NICE/ECDC/UKHSA screening guidelines). Barriers to screening were reported at patient, staff, and system-levels. Respondents reported poor implementation of existing screening initiatives (e.g., regional latent TB screening) citing overly complex pathways that required extensive administrative/clinical time and lacked financial/expert support. Solutions included patient/staff infectious disease champions, targeted training and specialist support, simplified care pathways for screening and management of positive results, and financial incentivisation. Participants responded positively to Health Catch-UP!, stating it would systematically integrate data and support clinical decision-making, increase knowledge, reduce missed screening opportunities, and normalisation of primary care-based infectious disease screening for migrants. Conclusions: Our results suggest that implementation of infectious disease screening in migrant populations is not comprehensively done in UK primary care. Primary health care professionals support the concept of innovative digital tools like Health Catch-UP! and that they could significantly improve disease detection and effective implementation of screening guidance but that they require robust testing and resourcing.

Rapid antiretroviral therapy in primary HIV-1 infection enhances immune recovery.

OBJECTIVE: We present findings from a large cohort of individuals treated during primary HIV infection (PHI) and examine the impact of time from HIV-1 acquisition to antiretroviral therapy (ART) initiation on clinical outcomes. We also examine the temporal changes in the demographics of individuals presenting with PHI to inform HIV-1 prevention strategies. METHODS: Individuals who fulfilled the criteria of PHI and started ART within 3 months of confirmed HIV-1 diagnosis were enrolled between 2009 and 2020. Baseline demographics of those diagnosed between 2009 and 2015 (before preexposure prophylaxis (PrEP) and universal ART availability) and 2015-2020 (post-PrEP and universal ART availability) were compared. We examined the factors associated with immune recovery and time to viral suppression. RESULTS: Two hundred four individuals enrolled, 144 from 2009 to 2015 and 90 from 2015 to 2020; median follow-up was 33 months. At PHI, the median age was 33 years; 4% were women, 39% were UK-born, and 84% were MSM. The proportion of UK-born individuals was 47% in 2009-2015, compared with 29% in 2015-2020. There was an association between earlier ART initiation after PHI diagnosis and increased immune recovery; each day that ART was delayed was associated with a lower likelihood of achieving a CD4 + cell count more than 900 cells/µl [hazard ratio 0.99 (95% confidence interval, 95% CI 0.98-0.99), P  = 0.02) and CD4/CD8 more than 1.0 (hazard ratio 0.98 (95% CI 0.97-0.99). CONCLUSION: Early initiation of ART at PHI diagnosis is associated with enhanced immune recovery, providing further evidence to support immediate ART in the context of PHI. Non-UK-born MSM accounts for an increasing proportion of those with primary infection; UK HIV-1 prevention strategies should better target this group.

CDC Division of Reproductive Health's Emergency Preparedness Resources and Activities for Radiation Emergencies: Public Health Considerations for Women's Reproductive Health.

Pregnant, postpartum, and lactating people, and infants have unique needs during public health emergencies, including nuclear and radiological incidents. This report provides information on the CDC Division of Reproductive Health's emergency preparedness and response activities to address the needs of women of reproductive age (aged 15-49 years), people who are pregnant, postpartum, or lactating, and infants during a radiation emergency. Highlighted preparedness activities include: (1) development of a quick reference guide to inform key questions about pregnant, postpartum, and lactating people, and infants during radiation emergencies; and (2) exercising the role of reproductive health experts during nuclear and radiological incident preparedness activities.

Patient-Reported Outcome Measures for Severe Recurrent Bilateral Nasal Polyps: Psychometric Evaluation and Content Validity.

Objective: To date, no patient-reported outcome measures have been specifically developed to assess pharmacological treatment effect in participants with severe chronic rhinosinusitis (CRS) with recurrent bilateral nasal polyps (NP). These studies aimed to assess (1) the psychometric properties and (2) content validity of Visual Analogue Scales (VAS) assessing NP symptom severity. Study Design: (1) Retrospective psychometric validation study using clinical trial data and (2) cross-sectional qualitative patient interview study. Setting: (1) Multicentre trial; (2) real-world. Methods: (1) Psychometric validation was performed using data from a randomized, double-blind, placebo-controlled, Phase II study (NCT01362244) investigating the effect of mepolizumab in 105 participants with severe, recurrent bilateral NP currently needing polypectomy surgery. (2) Content validity was explored through cognitive debriefing interviews in 27 adults with severe CRS with recurrent bilateral NP who had received NP surgery in the past 10 years (NCT03221192). Results: (1) Acceptable reliability, validity, and responsiveness were shown for individual VAS items, although the loss of smell VAS item performed poorly in several analyses, suggesting further evaluation of this item is needed. (2) All individual VAS items were well understood, considered relevant and were consistently interpreted by most participants, providing evidence for their content validity. Conclusion: These findings support the use of symptom VAS measures to evaluate disease experience and treatment effect in clinical trials of participants with severe CRS with recurrent bilateral NP.