Contraceptive uptake among gender-expansive individuals in the HER Salt Lake Contraceptive Initiative.

OBJECTIVES: We examined differences in contraceptive uptake and discontinuation between gender-expansive individuals and cis-women in the HER Salt Lake Contraceptive Initiative. STUDY DESIGN: We used self-reported survey data to assess associations between gender identity, contraceptive uptake, and discontinuation. RESULTS: Of participants (n=4,289), 178/4289(4%) identified as gender-expansive with 157/178(88%) reporting recent sexual activity with men. Selection of IUD or Implant was most common, with 109/178(61%) of gender-expansive individuals choosing these options. We observed similar methods selected (p=0.2) and discontinuation rates at three years between participants (OR: 0.93, p=0.8). CONCLUSION: Gender-expansive individuals had similar method selection and discontinuation rates as cis-women.

Automated identification of abnormal infant movements from smart phone videos.

Cerebral palsy (CP) is the most common cause of physical disability during childhood, occurring at a rate of 2.1 per 1000 live births. Early diagnosis is key to improving functional outcomes for children with CP. The General Movements (GMs) Assessment has high predictive validity for the detection of CP and is routinely used in high-risk infants but only 50% of infants with CP have overt risk factors when they are born. The implementation of CP screening programs represents an important endeavour, but feasibility is limited by access to trained GMs assessors. To facilitate progress towards this goal, we report a deep-learning framework for automating the GMs Assessment. We acquired 503 videos captured by parents and caregivers at home of infants aged between 12- and 18-weeks term-corrected age using a dedicated smartphone app. Using a deep learning algorithm, we automatically labelled and tracked 18 key body points in each video. We designed a custom pipeline to adjust for camera movement and infant size and trained a second machine learning algorithm to predict GMs classification from body point movement. Our automated body point labelling approach achieved human-level accuracy (mean ± SD error of 3.7 ± 5.2% of infant length) compared to gold-standard human annotation. Using body point tracking data, our prediction model achieved a cross-validated area under the curve (mean ± S.D.) of 0.80 ± 0.08 in unseen test data for predicting expert GMs classification with a sensitivity of 76% ± 15% for abnormal GMs and a negative predictive value of 94% ± 3%. This work highlights the potential for automated GMs screening programs to detect abnormal movements in infants as early as three months term-corrected age using digital technologies.

SuPAR in major depression: Association with 26 weeks antidepressant response and 10-year depression outcomes.

Introduction: Inflammation has been associated with depression and differential antidepressant (AD) treatment response. Soluble urokinase plasminogen activator receptor (suPAR) is a novel measure of chronic inflammation. We investigated whether suPAR is associated with depression severity and AD response. Methods: We included 90 patients with major depressive disorder (MDD) who participated in a part-randomized clinical trial of 26 weeks of treatment with escitalopram or nortriptyline. suPAR levels were measured in serum samples collected at baseline and after 8, 12 and 26 weeks. Mixed effects models for the association between suPAR levels and AD response were performed. By merging with Danish nationwide registers, we included information on psychiatric hospital contacts during ten years after the GENDEP trial. Cox regression analyses calculated the hazard rate ratios between suPAR levels and subsequent hospitalizations. Results: At baseline, higher suPAR levels were not associated with overall depression severity but with greater severity of neurovegetative depressive symptoms, specifically appetite and weight changes. 57 (63.3%) patients responded positively to treatment. Among 57 (63.3%) patients who achieved response, those who responded had significantly higher baseline suPAR levels levels, and response was associated with a significant decrease in suPAR during AD treatment. Remitters decreased from 3.1 ng/ml at baseline to 2.8 ng/ml after 26 weeks (p = 0.003) and responders from 3.0 to 2.8 ng/ml (p = 0.02), whereas non-remitters and non-responders showed unchanged suPAR levels. We found no correlation between a change in suPAR and a change in MADRS, but a lowering of suPAR correlated with a decrease in neurovegetative symptoms. We found no association between suPAR levels and 10-year risk for hospitalizations. Discussion: The present study suggests that an elevated level of chronic inflammation, measured as the suPAR level, is associated with better response to AD treatment.

Estimated number of symptomatic Lyme borreliosis cases in Germany in 2021 after adjusting for under-ascertainment.

BACKGROUND: Although nine of 16 federal states in Germany conduct public health surveillance for Lyme borreliosis (LB), the extent of under-ascertainment is unknown. OBJECTIVE: As a model for European countries that conduct LB surveillance, we sought to estimate the population-based incidence of symptomatic LB after adjusting for under-ascertainment. METHODS: Estimating seroprevalence-derived under-ascertainment relies on data from seroprevalence studies, public health surveillance, and published literature. The number of symptomatic LB cases in states that conduct LB surveillance was estimated from studies reporting the seroprevalence of antibodies against Borrelia burgdorferi sensu lato, the proportion of LB cases that are asymptomatic, and the duration of antibody detection. The number of estimated incident symptomatic LB cases was compared with the number of surveillance-reported LB cases to derive under-ascertainment multipliers. The multipliers were applied to the number of 2021 surveillance-reported LB cases to estimate the population-based incidence of symptomatic LB in Germany. RESULTS: Adjusting for seroprevalence-based under-ascertainment multipliers, the estimated number of symptomatic LB cases in states that conducted surveillance was 129,870 (408 per 100,000 population) in 2021. As there were 11,051 surveillance-reported cases in 2021 in these states, these data indicate there were 12 symptomatic LB cases for every surveillance-reported LB case. CONCLUSIONS: We demonstrate that symptomatic LB is underdetected in Germany and that this seroprevalence-based approach can be applied elsewhere in Europe where requisite data are available. Nationwide expansion of LB surveillance would further elucidate the true LB disease burden in Germany and could support targeted disease prevention efforts to address the high LB disease burden.

Probing motor dynamics at the muscle level-Acoustic myography in Parkinson's disease.

Acoustic myography (AMG) noninvasively probes muscle activity. We explored whether AMG captures abnormal motor activity in patients with Parkinson's disease (PD) and how this activity is modulated by antiparkinsonian medication. Twenty patients with PD underwent AMG of the biceps, triceps, extensor carpi radialis longus, and adductor policis muscles of the more affected arm during active and passive movements, using a mobile AMG device (CURO, Denmark). AMG and assessment of motor symptoms were performed in a pragmatic off-medication state, as well as one and 3 h after oral intake of 200 mg levodopa. Three AMG parameters were calculated using the CURO analysis system. Motor efficiency was expressed by the E-score, muscle fiber recruitment by the temporal T-score, spatial summation by the S-score, and S/T ratio. Twenty age- and sex-matched healthy subjects served as controls. Group mean values were statistically compared using unpaired two-tailed adjusted t-test and ANOVA with Tukey´s correction for multiple comparison (p ≤ 0.05). For the biceps and extensor carpi radialis longus muscles, the active movement S:T ratio was lower in PD relative to healthy controls. The E-score was also lower during active and passive flexion/extension movements in the off-medication state. No significant between-group differences in the AMG scores were noted for the triceps muscle during active or passive movements. The active S:T ratio and the E-score during active elbow flexion and extension may offer a useful means to quickly assess abnormal motor activity and the effect of drug treatment in PD.

Matrix Gla Protein drives stemness and tumor initiation in ovarian cancer.

Ovarian cancer (OC) displays the highest mortality among gynecological tumors, mainly due to early peritoneal dissemination, the high frequency of tumor relapse following primary debulking, and the development of chemoresistance. All these events are thought to be initiated and sustained by a subpopulation of neoplastic cells, termed ovarian cancer stem cells (OCSC), that are endowed with self-renewing and tumor-initiating properties. This implies that interfering with OCSC function should offer novel therapeutic perspectives to defeat OC progression. To this aim, a better understanding of the molecular and functional makeup of OCSC in clinically relevant model systems is essential. We have profiled the transcriptome of OCSC vs. their bulk cell counterpart from a panel of patient-derived OC cell cultures. This revealed that Matrix Gla Protein (MGP), classically known as a calcification-preventing factor in cartilage and blood vessels, is markedly enriched in OCSC. Functional assays showed that MGP confers several stemness-associated traits to OC cells, including a transcriptional reprogramming. Patient-derived organotypic cultures pointed to the peritoneal microenvironment as a major inducer of MGP expression in OC cells. Furthermore, MGP was found to be necessary and sufficient for tumor initiation in OC mouse models, by shortening tumor latency and increasing dramatically the frequency of tumor-initiating cells. Mechanistically, MGP-driven OC stemness was mediated by the stimulation of Hedgehog signaling, in particular through the induction of the Hedgehog effector GLI1, thus highlighting a novel MGP/Hedgehog pathway axis in OCSC. Finally, MGP expression was found to correlate with poor prognosis in OC patients, and was increased in tumor tissue after chemotherapy, supporting the clinical relevance of our findings. Thus, MGP is a novel driver in OCSC pathophysiology, with a major role in stemness and in tumor initiation.

Improving seabed substrate mapping with high-resolution bottom trawl data.

Accurate seabed substrate maps are essential for marine management, as substrate is an important component of the habitat type and used as a proxy for the prevailing benthic community. The provision of substrate maps, however, is hampered by the excessive costs of at-sea observations and, consequently, the uncertainty associated with spatial models used to interpolate these observations to full-coverage maps. Here, we tested whether high-resolution distributions of bottom trawling activity, readily collected under EU law, could improve the accuracy of substrate interpolations. Fishing distributions contain indirect information of the substrate type, as targeted species often show habitat preferences and gear types are designed for particular substrates. For two study areas in the Danish North Sea, we demonstrate that including spatial distributions of bottom trawl fisheries in substrate interpolation models results in more accurate substrate predictions. This potentially opens a novel source of previously unused information for improved seabed substrate interpolation.

Cost of illness of HER2-positive and metastatic and recurrent HER2-positive breast cancer - a Danish register-based study from 2005 to 2016.

BACKGROUND: Information and knowledge about cost of illness and labour productivity in patients with HER2-positive early-stage and metastatic breast cancer treated with trastuzumab is limited. The aim of this study was to estimate the direct and indirect costs associated with treatment of HER2-positive breast cancer among patients with early-stage and metastatic breast cancer, treated with trastuzumab, in a 10-year period after diagnosis. MATERIALS AND METHODS: This study included all Danish HER2-positive breast cancer patients (≥ 18 years) treated with trastuzumab between 2005 and 2016 identified in The Danish Patient Register and the Danish Cancer Register. Furthermore, we identified patients experiencing metastatic or recurrent breast cancer. For the study populations, we estimated total direct costs and indirect costs for one year prior to the breast cancer diagnosis and up to 10 years after diagnosis compared with a group of matched controls free of breast cancer. In addition to The Danish Patient Register and Cancer Register, we applied patient level data from The Civil Registration System, The National Pathology Register, National Health Service Register for Primary Care, Register of Medicinal Product Statistics, Register of Municipal Services, The DREAM database, and Population's Education Register. RESULTS: We identified 4,153 HER2-positive breast cancer patients, whereof 27% were identified with metastatic or recurrent breast cancer. During the follow-up period of 10 years, we estimated excess direct costs of EUR 115,000 among the total study population compared to controls; EUR 211,000 among patients with metastases or recurrence; and EUR 89,000 among patients without metastases or recurrence. Direct costs were found to be highest in the first year after diagnosis and also peaked in the year after recurrence. Labour productivity was significantly lower among patients with recurrence 10 years after breast cancer diagnosis compared with controls. CONCLUSIONS: In this study, we estimated the direct and indirect cost associated with HER2-positive breast cancer. The costs were significantly higher during the 10 years after diagnosis compared to the control group, specifically among patients experiencing metastases or recurrence of breast cancer.

Reaching for equitable care: High levels of disability-related knowledge and cultural competence only get us so far.

BACKGROUND: Achieving equitable medical care for people with disabilities is a complex challenge with emphasis often placed on the need for improved physician knowledge and cultural competence. Physical medicine and rehabilitation (PM&R) is a specialty dedicated to maximizing patient function, where a focus on working with and learning from patients with complex disabilities informs physician training and patient care. OBJECTIVE: The purpose of this study was to assess barriers to equitable care in PM&R clinics through a structural checklist and semi-structured interviews with clinic staff and physicians. METHODS: We used qualitative analysis with a grounded theory approach to develop a unified explanation of how existing clinic processes and provider attitudes affect equitable access to medical care. RESULTS: We found physicians comfortable with and respectful of patient differences who described leveraging unpaid time and creativity to navigate structural, resource, and awareness barriers. Staff and physicians described current barriers as negatively affecting quality of care, clinic efficiency, and, in some cases, patient and staff safety. CONCLUSION: Our results suggest that high levels of physician disability-related knowledge and cultural competence may be insufficient to the challenge of achieving equitable care.

Does Trans-radial Longitudinal Compression Influence Myoelectric Control?

BACKGROUND: Existing trans-radial prosthetic socket designs are not optimised to facilitate reliable myoelectric control. Many socket designs pre-date the introduction of myoelectric devices. However, socket designs featuring improved biomechanical stability, notably longitudinal compression sockets, have emerged in more recent years. Neither the subsequent effects, if any, of stabilising the limb on myoelectric control nor in which arrangement to apply the compression have been reported. METHODOLOGY: Twelve able-bodied participants completed two tasks whilst wearing a longitudinal compression socket simulator in three different configurations: 1) compressed, where the compression strut was placed on top of the muscle of interest, 2) relief, where the compression struts were placed either side of the muscle being recorded and 3) uncompressed, with no external compression. The tasks were 1) a single-channel myoelectric target tracking exercise, followed by 2), a high-intensity grasping task. The wearers' accuracy during the tracking task, the pressure at opposing sides of the simulator during contractions and the rate at which the limb fatigued were observed. FINDINGS: No significant difference between the tracking-task accuracy scores or rate of fatigue was observed for the different compression configurations. Pressure recordings from the compressed configuration showed that pressure was maintained at opposing sides of the simulator during muscle contractions. CONCLUSION: Longitudinal compression does not inhibit single-channel EMG control, nor improve fatigue performance. Longitudinal compression sockets have the potential to improve the reliability of multi-channel EMG control due to the maintenance of pressure during muscle contractions.

Limited use of local anesthesia for open inguinal hernia repair: a qualitative study.

PURPOSE: Local anesthesia for open inguinal hernia repair is recommended by guidelines but is rarely used in clinical practice in several countries. This study aimed to explore physician's considerations in choosing type of anesthesia and barriers for implementing local anesthesia for open hernia repair in clinical practice. METHODS: We performed individual semi-structured interviews of surgeons and anesthesiologists. Transcribed data were condensed, coded, categorized, and formulated into themes in an inductive qualitative content analysis. RESULTS: Twenty two participants from seven public hospitals were included in the study. Participants described a standardized setup for general anesthesia with use of intravenous propofol/remifentanil and a laryngeal mask and were generally satisfied with this setup. Their considerations in choosing anesthesia could be described in four themes: (1) Intraoperative pain and quality of surgical technique, (2) Communication and teaching, (3) Logistics, and (4) Clinical routines. CONCLUSION: Participants considered intraoperative pain and quality of surgical technique, communication and teaching, logistics, and clinical routines as important factors when choosing anesthesia for open inguinal hernia repair and these factors acted as barriers for implementing of local anesthesia in Danish public hospitals. In this setting, implementation strategies should, therefore, be multimodal to address these barriers. The potential workload in such an effort should be justified by evidence supporting specific types of local anesthesia comapared with general anesthesia with use of propofol/remifentanil and a laryngeal mask.

Shock decision algorithm for use during load distributing band cardiopulmonary resuscitation.

AIM: Chest compressions delivered by a load distributing band (LDB) induce artefacts in the electrocardiogram. These artefacts alter shock decisions in defibrillators. The aim of this study was to demonstrate the first reliable shock decision algorithm during LDB compressions. METHODS: The study dataset comprised 5813 electrocardiogram segments from 896 cardiac arrest patients during LDB compressions. Electrocardiogram segments were annotated by consensus as shockable (1154, 303 patients) or nonshockable (4659, 841 patients). Segments during asystole were used to characterize the LDB artefact and to compare its characteristics to those of manual artefacts from other datasets. LDB artefacts were removed using adaptive filters. A machine learning algorithm was designed for the shock decision after filtering, and its performance was compared to that of a commercial defibrillator's algorithm. RESULTS: Median (90% confidence interval) compression frequencies were lower and more stable for the LDB than for the manual artefact, 80 min-1 (79.9-82.9) vs. 104.4 min-1 (48.5-114.0). The amplitude and waveform regularity (Pearson's correlation coefficient) were larger for the LDB artefact, with 5.5 mV (0.8-23.4) vs. 0.5 mV (0.1-2.2) (p < 0.001) and 0.99 (0.78-1.0) vs. 0.88 (0.55-0.98) (p < 0.001). The shock decision accuracy was significantly higher for the machine learning algorithm than for the defibrillator algorithm, with sensitivity/specificity pairs of 92.1/96.8% (machine learning) vs. 91.4/87.1% (defibrillator) (p < 0.001). CONCLUSION: Compared to other cardiopulmonary resuscitation artefacts, removing the LDB artefact was challenging due to larger amplitudes and lower compression frequencies. The machine learning algorithm achieved clinically reliable shock decisions during LDB compressions.

Mortality and Urological Complications After Open Groin Hernia Repair in Local, General, and Regional Anesthesia: A Nationwide Linked Register Study.

BACKGROUND AND AIMS: The choice of anesthesia method may influence mortality and postoperative urological complications after open groin hernia repair. We aimed to investigate the association between type of anesthesia and incidence of urinary retention, urethral stricture, prostate surgery, and 1-year mortality after open groin hernia repair. MATERIALS AND METHODS: Data were linked from the Danish Hernia Database, the national patient register, and the register of causes of death. We investigated data on male adult patients receiving open groin hernia repair from 1999 to 2013 with either local anesthesia, regional anesthesia, or general anesthesia. In relation to the type of anesthesia, we compared mortality and urological complications up to 1 year postoperatively. We adjusted for covariates in a logistic regression assessing urological complications and with the Cox regression assessing mortality. RESULTS: We included 113,069 open groin hernia repairs in local anesthesia, regional anesthesia, or general anesthesia. The risk of urinary retention adjusted for covariates was higher after both general anesthesia (adjusted odds ratio = 1.64, 95% confidence interval = 1.05-2.57, p = 0.031) and regional anesthesia (odds ratio = 2.99, 95% confidence interval = 1.67-5.34, p < 0.0005) compared with local anesthesia. The adjusted risk of prostate surgery was also higher for both general anesthesia (odds ratio = 1.58, 95% confidence interval = 1.23-2.03, p < 0.0005) and regional anesthesia (odds ratio = 1.90, 95% confidence interval = 1.40-2.58, p < 0.0005) compared with local anesthesia. Type of anesthesia did not influence 1-year mortality or the risk for urethral stricture. CONCLUSION: Patients undergoing open groin hernia repair in local anesthesia experience the lowest rate of urological complications and have equally low mortality compared with patients undergoing repair in general anesthesia or regional anesthesia.

Effect of ampicillin, cephalexin, ceftiofur and tetracycline treatment on selection of resistant coliforms in a swine faecal microcosmos.

AIMS: To analyse and compare the effect of selection power for antimicrobial resistance (AMR) in coliforms of two kinds of ß-lactams-aminopenicillins; ampicillin (Amp) and cephalosporins; cephalexin (Cpn) and ceftiofur (Cef)-and tetracycline (Tet) using an approach based on a swine faecal microcosmos. METHODS AND RESULTS: Sixteen faecal samples from 32 pigs (mixed two by two) were treated with Amp, Cpn, Cef and Tet for 6 h (T6h) at concentrations expected to reach the animals gut when using in vivo standard doses. Controls (no drug added) were also tested. Next, samples were 1 : 100 diluted and left under the same conditions (no antimicrobial added) for further 20 h (T20h). The proportion of resistant coliform bacteria (R coliforms) to each antimicrobial was analysed just before starting the treatment (T0), at T6h and at T20h. Coselection was also studied by replica plating. Treatment for 6 h yielded significant increase in proportion of R coliforms, regardless of the drug and lack of selection pressure showed different effects at T20h depending on the antimicrobial used. Selective pressure was associated with the type of the ß-lactam with Amp selecting for significantly higher numbers of R coliforms than cephalosporins. CONCLUSIONS: AMR development was observed following short treatment, and for Amp and Tet treatment, resistance persisted 20 h beyond the interruption of treatment. An association between kind of ß-lactam and power of selection was found. SIGNIFICANCE AND IMPACT OF THE STUDY: AMR represents a threat to human health globally and antimicrobial treatment of livestock has a direct impact on this problem. Through our approach based on a swine faecal microcosmos, we demonstrated the effect on AMR development of several drugs commonly used in livestock. Cephalosporins, representing last-line antimicrobials in human medicine, exerted lower selective pressure than Amp under the conditions used and yielded higher proportion of multidrug-R strains.

Marine resource abundance drove pre-agricultural population increase in Stone Age Scandinavia.

How climate and ecology affect key cultural transformations remains debated in the context of long-term socio-cultural development because of spatially and temporally disjunct climate and archaeological records. The introduction of agriculture triggered a major population increase across Europe. However, in Southern Scandinavia it was preceded by ~500 years of sustained population growth. Here we show that this growth was driven by long-term enhanced marine production conditioned by the Holocene Thermal Maximum, a time of elevated temperature, sea level and salinity across coastal waters. We identify two periods of increased marine production across trophic levels (P1 7600-7100 and P2 6400-5900 cal. yr BP) that coincide with markedly increased mollusc collection and accumulation of shell middens, indicating greater marine resource availability. Between ~7600-5900 BP, intense exploitation of a warmer, more productive marine environment by Mesolithic hunter-gatherers drove cultural development, including maritime technological innovation, and from ca. 6400-5900 BP, underpinned a ~four-fold human population growth.

Evaluation of novel multiplex qPCR assays for diagnosis of pathogens associated with the bovine respiratory disease complex.

Bovine respiratory disease complex is the most common disease requiring the use of antimicrobials in industrial calf production worldwide. Pathogenic bacteria (Mannheimia haemolytica (Mh), Pasteurella multocida (Pm), Histophilus somni (Hs), and Mycoplasma bovis) and a range of viruses (bovine respiratory syncytial virus, bovine coronavirus, bovine parainfluenza virus type 3, bovine viral diarrhea virus and bovine herpesvirus type 1) are associated with this complex. As most of these pathogens can be present in healthy and diseased calves, simple detection of their presence in diseased calves carries low predictive value. In other multi-agent diseases of livestock, quantification of pathogens has added substantially to the predictive value of microbiological diagnosis. The aim of this study was to evaluate the ability of two recently developed quantitative PCR (qPCR) kits (Pneumo4B and Pneumo4V) to detect and quantify these bacterial and viral pathogens, respectively. Test efficiencies of the qPCR assays, based on nucleic acid dilution series of target bacteria and viruses, were 93-106% and 91-104%, respectively, with assay detection limits of 10-50 copies of nucleic acids. All 44 strains of target bacteria were correctly identified, with no false positive reactions in 135strains of non-target bacterial species. Based on standard curves of log10 CFU versus cycle threshold (Ct) values, quantification was possible over a 5-log range of bacteria. In 92 tracheal aspirate samples, the kappa values for agreement between Pneumo4B and bacterial culture were 0.64-0.84 for Mh, Pm and Hs. In an additional 84 tracheal aspirates, agreement between Pneumo4B or Pneumo 4V and certified diagnostic qPCR assays was moderate (0.57) for M. bovis and high (0.71-0.90) for viral pathogens. Thus Pneumo4 kits specifically detected and quantified the relevant pathogens.

Towards high-quality peri-operative care: a global perspective.

Article 25 of the United Nations' Universal Declaration of Human Rights enshrines the right to health and well-being for every individual. However, universal access to high-quality healthcare remains the purview of a handful of wealthy nations. This is no more apparent than in peri-operative care, where an estimated five billion individuals lack access to safe, affordable and timely surgical care. Delivery of surgery and anaesthesia in low-resource environments presents unique challenges that, when unaddressed, result in limited access to low-quality care. Current peri-operative research and clinical guidance often fail to acknowledge these system-level deficits and therefore have limited applicability in low-resource settings. In this manuscript, the authors priority-set the need for equitable access to high-quality peri-operative care and analyse the system-level contributors to excess peri-operative mortality rates, a key marker of quality of care. To provide examples of how research and investment may close the equity gap, a modified Delphi method was adopted to curate and appraise interventions which may, with subsequent research and evaluation, begin to address the barriers to high-quality peri-operative care in low- and middle-income countries.