MYCO WELL D-ONE detection of Ureaplasma spp. and Mycoplasma hominis in sexual health patients in Wales

The genital mycoplasmas are a unique group of inherently antibiotic-resistant sexually transmitted bacteria, often associated with non-gonococcal urethritis and bacterial vaginosis. The MYCO WELL D-ONE is a culture-based assay that aims to detect these organisms whilst concurrently screening them for antibiotic resistance. Urine and/or swabs from 856 informed and consented participants attending Welsh sexual health clinics were subjected to MYCO WELL D-ONE analysis, alongside qPCR and culture titration methodologies to determine sensitivity, specificity, PPV, NPV and accuracy. Resistance was confirmed by CLSI-compliant susceptibility testing and genetic mechanisms determined. The MYCO WELL D-ONE displayed a sensitivity and specificity of 91.98% and 96.44% for the detection of Ureaplasma spp., with sensitivity and specificity values of 78.23% and 98.84% for Mycoplasma hominis, compared with qPCR. Swabs harboured significantly greater bacterial loads than urine samples for both Ureaplasma spp. and M. hominis. Levofloxacin resistance rates, mediated by Ser83Leu mutation in ParC, for Ureaplasma spp. were 0.54%. Tetracycline resistance rates, mediated by tet(M), were 0.54% and 2% for Ureaplasma spp. and M. hominis, respectively; sequence analysis of tet(M)-positive Ureaplasma spp. and M. hominis strains isolated from a single individual confirmed separate resistance gene origins. The MYCO WELL D-ONE is a sensitive and specific assay for the detection of Ureaplasma spp. and M. hominis in genitourinary medicine samples, facilitating the accurate detection of these organisms within low-technology environments. While good for antibiotic resistance screening, accurate confirmation by MIC determination or molecular methods are required, and more optimally performed on urine samples

Placenta-Specific Slc38a2/SNAT2 Knockdown Causes Fetal Growth Restriction in Mice

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane (TPM) SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid (MeAIB). We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared with appropriate for gestational age (AGA) control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes FGR and could be a target for clinical therapies for late-onset FGR

Mycoplasma genitalium prevalence in Welsh sexual health patients: low antimicrobial resistance markers and no association of symptoms to bacterial load

Objectives Mycoplasma genitalium (MG) is a common cause of sexually transmitted infection, however no prevalence data is available for Wales. MG was detected by qPCR (quantitative) as well as two separate SpeeDx commercial assays, and related to clinical symptoms, age, gender and sample type. Methods Cervical swabs, urethral swabs and/or urine were collected from 1000 patients at walk-in sexual health clinics at 3 Welsh health centres from October 2017–October 2018. Extracted DNA was investigated to determine concordance between an in-house quantitative PCR, SpeeDx ResistancePlus® MG and the SpeeDx MG + parC (beta 2) assays; mutations in parC were substantiated by Sanger sequencing. Results MG was detected in 17/600 female patients (2.7%) and 13/400 (3.5%) male patients, with a 100% concordance between in-house qPCR and both SpeeDx assays. Macrolide resistance was low (relative to other studies), but more common in males (4/13; 30.8%) than females (2/17; 11.8%) and the only fluoroquinolone resistant sample (3.4% overall) was also macrolide resistant and detected from an MSM. Vaginitis was clinically apparent in 12/17 MG-positive females (2 with additional cervicitis, 1 with additional pelvic inflammatory disease), while 7 MG-positive males were asymptomatic. MG bacterial load did not correlate to clinical symptoms and females (4559 ± 1646/ml) had significantly lower MG load than males (84,714 ± 41,813/ml; p = 0.0429). Conclusions MG prevalence and antibiotic resistance in Welsh sexual health clinics is low. MG bacterial load did not correlate to clinical presentation, men have higher MG load/ml in urine than women, genders have different age bias for MG prevalence and urine and swabs are equivalent for detecting MG

Transdermal Blood Sampling for C-peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes

OBJECTIVE:C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative.RESEARCH DESIGN AND METHODS:Ninety-one individuals (71 with type 1 diabetes, 20 controls; individuals with type 1 diabetes: aged median 14.8 years [interquartile range (IQR) 9.1–17.1], diabetes duration 4.0 years [1.5–7.7]; controls: 42.2 years [38.0–52.1]) underwent contemporaneous venous and TCB sampling for measurement of plasma C-peptide. Participants with type 1 diabetes also provided venous serum and plasma, and TCB plasma for measurement of autoantibodies to glutamate decarboxylase, islet antigen-2, and zinc transporter 8. The ability of TCB plasma to detect significant endogenous insulin secretion (venous C-peptide ≥200 pmol/L) was compared along with agreement in levels, using Bland-Altman. Venous serum was compared with venous and TCB plasma for detection of autoantibodies, using established thresholds. Acceptability was assessed by age-appropriate questionnaire.RESULTS:Transdermal sampling took a mean of 2.35 min (SD 1.49). Median sample volume was 50 µL (IQR 40–50) with 3 of 91 (3.3%) failures, and 13 of 88 (14.7%) <35 µL. TCB C-peptide showed good agreement with venous plasma (mean venous ln[C-peptide] – TCB ln[C-peptide] = 0.008, 95% CI [−0.23, 0.29], with 100% [36 of 36] sensitivity/100% [50 of 50] specificity to detect venous C-peptide ≥200 pmol/L). Where venous serum in multiple autoantibody positive TCB plasma agreed in 22 of 32 (sensitivity 69%), comparative specificity was 35 of 36 (97%). TCB was preferred to venous sampling (type 1 diabetes: 63% vs. 7%; 30% undecided).CONCLUSIONS:Transdermal capillary testing for C-peptide is a sensitive, specific, and acceptable alternative to venous sampling; TCB sampling for islet autoantibodies needs further assessment

Substance use disorders and risk of suicide in a general US population: a case control study

BACKGROUND: Prior research suggests that substance use disorders (SUDs) are associated with risk of suicide mortality, but most previous work has been conducted among Veterans Health Administration patients. Few studies have examined the relationship between SUDs and suicide mortality in general populations. Our study estimates the association of SUDs with suicide mortality in a general US population of men and women who receive care across eight integrated health systems. METHODS: We conducted a case-control study using electronic health records and claims data from eight integrated health systems of the Mental Health Research Network. Participants were 2674 men and women who died by suicide between 2000-2013 and 267,400 matched controls. The main outcome was suicide mortality, assessed using data from the health systems and confirmed by state death data systems. Demographic and diagnostic data on substance use disorders and other health conditions were obtained from each health system. First, we compared descriptive statistics for cases and controls, including age, gender, income, and education. Next, we compared the rate of each substance use disorder category for cases and controls. Finally, we used conditional logistic regression models to estimate unadjusted and adjusted odds of suicide associated with each substance use disorder category. RESULTS: All categories of substance use disorders were associated with increased risk of suicide mortality. Adjusted odds ratios ranged from 2.0 (CI 1.7, 2.3) for patients with tobacco use disorder only to 11.2 (CI 8.0, 15.6) for patients with multiple alcohol, drug, and tobacco use disorders. Substance use disorders were associated with increased relative risk of suicide for both women and men across all categories, but the relative risk was more pronounced in women. CONCLUSIONS: Substance use disorders are associated with significant risk of suicide mortality, especially for women, even after controlling for other important risk factors. Experiencing multiple substance use disorders is particularly risky. These findings suggest increased suicide risk screening and prevention efforts for individuals with substance use disorders are needed

Evaluating a pre-surgical health optimisation programme: a feasibility study

BACKGROUND: Health optimisation programmes are increasingly popular and aim to support patients to lose weight or stop smoking ahead of surgery, yet there is little published evidence about their impact. This study aimed to assess the feasibility of evaluating a programme introduced by a National Health Service (NHS) clinical commissioning group offering support to smokers/obese patients in an extra 3 months prior to the elective hip/knee surgery pathway. METHODS: Feasibility study mapping routinely collected data sources, availability and completeness for 502 patients referred to the hip/knee pathway in February–July 2018. RESULTS: Data collation across seven sources was complex. Data completeness for smoking and ethnicity was poor. While 37% (184) of patients were eligible for health optimisation, only 28% of this comparatively deprived patient group accepted referral to the support offered. Patients who accepted referral to support and completed the programme had a larger median reduction in BMI than those who did not accept referral (− 1.8 BMI points vs. − 0.5). Forty-nine per cent of patients who accepted support were subsequently referred to surgery, compared to 61% who did not accept referral to support. CONCLUSIONS: Use of routinely collected data to evaluate health optimisation programmes is feasible though demanding. Indications of the positive effects of health optimisation interventions from this study and existing literature suggest that the challenge of programme evaluation should be prioritised; longer-term evaluation of costs and outcomes is warranted to inform health optimisation policy development. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13741-022-00255-2

Wet scavenging of soluble gases in DC3 deep convective storms using WRF-Chem simulations and aircraft observations

We examine wet scavenging of soluble trace gases in storms observed during the Deep Convective Clouds and Chemistry (DC3) field campaign. We conduct high-resolution simulations with the Weather Research and Forecasting model with Chemistry (WRF-Chem) of a severe storm in Oklahoma. The model represents well the storm location, size, and structure as compared with Next Generation Weather Radar reflectivity, and simulated CO transport is consistent with aircraft observations. Scavenging efficiencies (SEs) between inflow and outflow of soluble species are calculated from aircraft measurements and model simulations. Using a simple wet scavenging scheme, we simulate the SE of each soluble species within the error bars of the observations. The simulated SEs of all species except nitric acid (HNO_3) are highly sensitive to the values specified for the fractions retained in ice when cloud water freezes. To reproduce the observations, we must assume zero ice retention for formaldehyde (CH_2O) and hydrogen peroxide (H_2O_2) and complete retention for methyl hydrogen peroxide (CH_3OOH) and sulfur dioxide (SO_2), likely to compensate for the lack of aqueous chemistry in the model. We then compare scavenging efficiencies among storms that formed in Alabama and northeast Colorado and the Oklahoma storm. Significant differences in SEs are seen among storms and species. More scavenging of HNO_3 and less removal of CH_3OOH are seen in storms with higher maximum flash rates, an indication of more graupel mass. Graupel is associated with mixed-phase scavenging and lightning production of nitrogen oxides (NO_x), processes that may explain the observed differences in HNO_3 and CH_3OOH scavenging

Cancer and psychiatric diagnoses in the year preceding suicide

BACKGROUND: Patients with cancer are known to be at increased risk for suicide but little is known about the interaction between cancer and psychiatric diagnoses, another well-documented risk factor. METHODS: Electronic medical records from nine healthcare systems participating in the Mental Health Research Network were aggregated to form a retrospective case-control study, with ICD-9 codes used to identify diagnoses in the 1 year prior to death by suicide for cases (N = 3330) or matching index date for controls (N = 297,034). Conditional logistic regression was used to assess differences in cancer and psychiatric diagnoses between cases and controls, controlling for sex and age. RESULTS: Among patients without concurrent psychiatric diagnoses, cancer at disease sites with lower average 5-year survival rates were associated with significantly greater relative risk, while cancer disease sites with survival rates of \u3e70% conferred no increased risk. Patients with most psychiatric diagnoses were at higher risk, however, there was no additional risk conferred to these patients by a concurrent cancer diagnosis. CONCLUSION: We found no evidence of a synergistic effect between cancer and psychiatric diagnoses. However, cancer patients with a concurrent psychiatric illness remain at the highest relative risk for suicide, regardless of cancer disease site, due to strong independent associations between psychiatric diagnoses and suicide. For patients without a concurrent psychiatric illness, cancer disease sites associated with worse prognoses appeared to confer greater suicide risk

Consumers as tutors – legitimate teachers?

BACKGROUND: The aim of this study was to research the feasibility of training mental health consumers as tutors for 4(th )year medical students in psychiatry. METHODS: A partnership between a consumer network and an academic unit in Psychological Medicine was formed to jointly develop a training package for consumer tutors and a curriculum in interviewing skills for medical students. Student attitudes to mental health consumers were measured pre and post the program. All tutorial evaluation data was analysed using univariate statistics. Both tutors and students evaluated the teaching program using a 4 point rating scale. The mean scores for teaching and content for both students and tutors were compared using an independent samples t-test. RESULTS: Consumer tutors were successfully trained and accredited as tutors and able to sustain delivery of tutorials over a 4 year period. The study found that whilst the medical students started with positive attitudes towards consumers prior to the program, there was a general trend towards improved attitude across all measures. Other outcomes for tutors and students (both positive and negative) are described. CONCLUSIONS: Consumer tutors along with professional tutors have a place in the education of medical students, are an untapped resource and deliver largely positive outcomes for students and themselves. Further possible developments are described