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JAMA Network Open Jun 2024Obstructive sleep apnea (OSA) is a common condition in older adult (aged >65 years) populations, but more mechanistic research is needed to individualize treatments....
IMPORTANCE
Obstructive sleep apnea (OSA) is a common condition in older adult (aged >65 years) populations, but more mechanistic research is needed to individualize treatments. Previous evidence has suggested an association between OSA and posttraumatic stress disorder (PTSD) but is limited by possible selection bias. High-quality research on this association with a careful evaluation of possible confounders may yield important mechanistic insight into both conditions and improve treatment efforts.
OBJECTIVE
To investigate the association of current PTSD symptoms and PTSD diagnosis with OSA.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study of twin pairs discordant for PTSD, which allows for adjustment for familial factors, was conducted using in-laboratory polysomnography from March 20, 2017, to June 3, 2019. The study sample comprised male veteran twins recruited from the Vietnam Era Twin Registry. The data analysis was performed between June 11, 2022, and January 30, 2023.
EXPOSURE
Symptoms of PTSD in twins who served in the Vietnam War. Diagnosis of PTSD was a secondary exposure.
MAIN OUTCOMES AND MEASURES
Obstructive sleep apnea was assessed using the apnea-hypopnea index (AHI) (≥4% oxygen saturation criterion as measured by events per hour) with overnight polysomnography. Symptoms of PTSD were assessed using the PTSD Checklist (PCL) and structured clinical interview for PTSD diagnosis.
RESULTS
A total of 181 male twins (mean [SD] age, 68.4 [2.0] years) including 66 pairs discordant for PTSD symptoms and 15 pairs discordant for a current PTSD diagnosis were evaluated. In models examining the PCL and OSA within pairs and adjusted for body mass index (BMI) and other sociodemographic, cardiovascular, and psychiatric risk factors (including depression), each 15-point increase in PCL was associated with a 4.6 (95% CI, 0.1-9.1) events-per-hour higher AHI. Current PTSD diagnosis was associated with an adjusted 10.5 (95% CI, 5.7-15.3) events-per-hour higher AHI per sleep-hour. Comparable standardized estimates of the association of PTSD symptoms and BMI with AHI per SD increase (1.9 events per hour; 95% CI, 0.5-3.3 events per hour) were found.
CONCLUSIONS AND RELEVANCE
This cross-sectional study found an association between PTSD and sleep-disordered breathing. The findings have important public health implications and may also enhance understanding of the many factors that potentially affect OSA pathophysiology.
Topics: Humans; Stress Disorders, Post-Traumatic; Male; Sleep Apnea, Obstructive; Cross-Sectional Studies; Aged; Veterans; Middle Aged; Vietnam Conflict; Polysomnography; Diseases in Twins; Twins
PubMed: 38913378
DOI: 10.1001/jamanetworkopen.2024.16352 -
JMIR Cardio May 2024Background: Although telemedicine has been proven to have significant potential for improving cardiac patient care, there remains a substantial risk of introducing...
Analysis of Demographic and Socioeconomic Factors Influencing the Adherence to a Web-based Intervention Among Patients after Acute Coronary Syndrome: a Prospective Observational Cohort Study.
BACKGROUND
Background: Although telemedicine has been proven to have significant potential for improving cardiac patient care, there remains a substantial risk of introducing disparities linked to the utilization of digital technology, especially for older or socially vulnerable subgroups.
OBJECTIVE
We investigated factors influencing adherence to a telemedicine-delivered health education intervention in ischemic patients, emphasizing demographic and socioeconomic considerations.
METHODS
We conducted a descriptive, observational, prospective cohort study in consecutive patients referred to our cardiology center for acute coronary syndrome, from February 2022 to January 2023. Patients were invited to join a web-based health educational meeting (WHEM) after hospital discharge, as part of a secondary prevention program. The WHEM sessions were scheduled monthly and used a teleconference software program for remote synchronous videoconferencing, accessible through standard computer, tablet, or smartphone based on patient preference or availability.
RESULTS
Out of the 252 patients (median age 70 years [interquartile range: 61.0-77.3 years]; 189 males [75%]), 98 (39%) declined the invitation to participate in the WHEM. The reasons for non-acceptance were mainly challenges in handling digital technology (70/98, 71.4%), followed by lack of confidence in telemedicine as an integrative tool for managing their medical condition (45/98, 45.9%), and lack of Internet-connected devices (43/98, 43.8%). Out of the 154 patients who agreed to participate in the WHEM, 40 (26%) were unable to attend. Univariable logistic regression analysis showed that the presence of a caregiver with digital proficiency and a higher education level were associated with increased likelihood of attendance to the WHEM, while the converse was true for increasing age and female gender. After multivariable adjustment, higher education level (odds ratio, 2.26 [95% confidence interval, 1.53-3.32], p<0.001) and caregiver with digital proficiency (odds ratio, 12.83 [95% confidence interval, 5.93-27.75], p<0.001) remained independently associated with the outcome. The model discrimination was good even when corrected for optimism (optimism corrected C-index, 0.812), as was the agreement between observed and predicted probability of participation (optimism corrected calibration intercept and slope, 0.010 and 0.948).
CONCLUSIONS
The current study identifies a notable lack of suitability for a specific cohort of ischemic patients to participate in our telemedicine intervention, emphasizing the risk of digital marginalization for a significant portion of the population. Addressing low digital literacy rates among patients or their informal caregivers, and overcoming cultural bias against remote care, were identified as critical issues in our study findings to facilitate the broader adoption of telemedicine as an inclusive tool in healthcare.
PubMed: 38912920
DOI: 10.2196/57058 -
Renal Failure Dec 2024The monocyte-to-lymphocyte multiplying platelets ratio (MLPR) is a novel systemic inflammatory marker, deriving from the monocyte-to-lymphocyte ratio (MLR). However, the...
Monocytes to lymphocytes multiplying platelets ratio as an early indicator of acute kidney injury in cardiac surgery with cardiopulmonary bypass: a retrospective analysis.
OBJECTIVE
The monocyte-to-lymphocyte multiplying platelets ratio (MLPR) is a novel systemic inflammatory marker, deriving from the monocyte-to-lymphocyte ratio (MLR). However, the link between MLPR and acute kidney injury following cardiac surgery (CSA-AKI) with cardiopulmonary bypass (CPB) has not been investigated yet. We comprehensively explored the potential linear and nonlinear relationship between MLPR or MLR and CSA-AKI.
METHODS
Data of patients who underwent cardiac surgery with CPB between December 2018 and April 2021 were retrospectively collected at Fuwai Hospital, Beijing, China. MLPR was defined as monocyte count (×10/L) × 1000/(lymphocyte count (×10/L) × platelets (×10/L)). MLR was defined as monocyte count (×10/L)/lymphocyte count (×10/L). Logistic regression and restricted cubic spline (RCS) were used for linear and nonlinear analysis. The primary outcome was postoperative AKI within 48 h of after cardiac surgery.
RESULTS
Of the 2420 patients screened, 2387 eligible patients were enrolled in the final analysis; the mean age was 54.7 years, and 1501 [62.9%] were men. The incidence of AKI was 25.8%. Logistic regression showed that MLPR (odds ratio [OR] = 1.31, 95% confidence interval [CI]: 1.16-1.48, < .001) and MLR (OR = 3.06, 95% CI: 1.29-7.29, = .012) were independent risk factors for AKI. Moreover, in the RCS model with adjustment for age (median: 56), female sex, and history of diabetes, a significant statistical difference was detected between preoperative MLPR, MLR, and AKI ( for non-linearity <.001). The subgroup analyses revealed similar results.
CONCLUSIONS
The study revealed a nonlinear relationship between MLPR and MLR with AKI. MLPR exhibited a J-shaped curve, and MLR showed a favorable S-shaped curve in relation to AKI. Particularly, MLPR emerges as a promising clinical composite index for early CSA-AKI prediction. These findings emphasize the significance of MLPR as a valuable tool in clinical practice for timely identification and management of CSA-AKI.
Topics: Humans; Acute Kidney Injury; Male; Female; Middle Aged; Retrospective Studies; Cardiopulmonary Bypass; Monocytes; Cardiac Surgical Procedures; Lymphocytes; Aged; China; Postoperative Complications; Blood Platelets; Adult; Biomarkers; Platelet Count; Lymphocyte Count; Risk Factors
PubMed: 38912831
DOI: 10.1080/0886022X.2024.2364776 -
Annals of Surgery Open : Perspectives... Jun 2024This study examined whether there is an association between opioid-related mortality and surgical procedures.
OBJECTIVE
This study examined whether there is an association between opioid-related mortality and surgical procedures.
METHODS
A case-control study design using deceased controls compared individuals with and without opioid death and their exposure to common surgeries in the preceding 4 years. This population-based study used linked death and hospitalization databases in Canada (excluding Quebec) from January 01, 2008 to December 31, 2017. Cases of opioid death were identified and matched to 5 controls who died of other causes by age (±4 years), sex, province of death, and date of death (±1 year). Patients with HIV infection and alcohol-related deaths were excluded from the control group. Logistic regression was used to determine if there was an association between having surgery and death from an opioid-related cause by estimating the crude and adjusted odds ratios (ORs) with the corresponding 95% confidence interval (CI). Covariates included sociodemographic characteristics, comorbidities, and the number of days of hospitalization in the previous 4 years.
RESULTS
We identified 11,865 cases and matched them with 59,345 controls. About 11.2% of cases and 12.5% of controls had surgery in the 4 years before their death, corresponding to a crude OR of 0.89 (95% CI: 0.83-0.94). After adjustment, opioid mortality was associated with surgical procedure with OR of 1.26 (95% CI: 1.17-1.36).
CONCLUSIONS
After adjusting for comorbidities, patients with opioid mortality were more likely to undergo surgical intervention within 4 years before their death. Clinicians should enhance screening for opioid use and risk factors when considering postoperative opioid prescribing.
PubMed: 38911620
DOI: 10.1097/AS9.0000000000000412 -
The Lancet. Microbe Jun 2024Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria...
Association between butyrate-producing gut bacteria and the risk of infectious disease hospitalisation: results from two observational, population-based microbiome studies.
BACKGROUND
Microbiota alterations are common in patients hospitalised for severe infections, and preclinical models have shown that anaerobic butyrate-producing gut bacteria protect against systemic infections. However, the relationship between microbiota disruptions and increased susceptibility to severe infections in humans remains unclear. We investigated the relationship between gut microbiota and the risk of future infection-related hospitalisation in two large population-based cohorts.
METHODS
In this observational microbiome study, gut microbiota were characterised using 16S rRNA gene sequencing in independent population-based cohorts from the Netherlands (HELIUS study; derivation cohort) and Finland (FINRISK 2002 study; validation cohort). HELIUS was conducted in Amsterdam, Netherlands, and included adults (aged 18-70 years at inclusion) who were randomly sampled from the municipality register of Amsterdam. FINRISK 2002 was conducted in six regions in Finland and is a population survey that included a random sample of adults (aged 25-74 years). In both cohorts, participants completed questionnaires, underwent a physical examination, and provided a faecal sample at inclusion (Jan 3, 2013, to Nov 27, 2015, for HELIUS participants and Jan 21 to April 19, 2002, for FINRISK participants. For inclusion in our study, a faecal sample needed to be provided and successfully sequenced, and national registry data needed to be available. Primary predictor variables were microbiota composition, diversity, and relative abundance of butyrate-producing bacteria. Our primary outcome was hospitalisation or mortality due to any infectious disease during 5-7-year follow-up after faecal sample collection, based on national registry data. We examined associations between microbiota and infection risk using microbial ecology and Cox proportional hazards.
FINDINGS
We profiled gut microbiota from 10 699 participants (4248 [39·7%] from the derivation cohort and 6451 [60·3%] from the validation cohort). 602 (5·6%) participants (152 [3·6%] from the derivation cohort; 450 [7·0%] from the validation cohort) were hospitalised or died due to infections during follow-up. Gut microbiota composition of these participants differed from those without hospitalisation for infections (derivation p=0·041; validation p=0·0002). Specifically, higher relative abundance of butyrate-producing bacteria was associated with a reduced risk of hospitalisation for infections (derivation cohort cause-specific hazard ratio 0·75 [95% CI 0·60-0·94] per 10% increase in butyrate producers, p=0·013; validation cohort 0·86 [0·77-0·96] per 10% increase, p=0·0077). These associations remained unchanged following adjustment for demographics, lifestyle, antibiotic exposure, and comorbidities.
INTERPRETATION
Gut microbiota composition, specifically colonisation with butyrate-producing bacteria, was associated with protection against hospitalisation for infectious diseases in the general population across two independent European cohorts. Further studies should investigate whether modulation of the microbiome can reduce the risk of severe infections.
FUNDING
Amsterdam UMC, Porticus, National Institutes of Health, Netherlands Organisation for Health Research and Development (ZonMw), and Leducq Foundation.
PubMed: 38909617
DOI: 10.1016/S2666-5247(24)00079-X -
Journal of Hazardous Materials Jun 2024Increased cardiometabolic risk is associated with abnormalities in blood biomarkers profile and adiposity measurements. Some substances found in the food matrix and the...
Increased cardiometabolic risk is associated with abnormalities in blood biomarkers profile and adiposity measurements. Some substances found in the food matrix and the environment, called endocrine-disrupting chemicals, may impair cardiometabolic health in the early and later stages of life. Bisphenol A (BPA) is a food contaminant that migrates from food contact materials and may act as an endocrine disruptor, negatively affecting human health. The present work aims to longitudinally assess the association between BPA exposure and cardiometabolic outcomes, considering data from Portuguese population-based birth cohort Generation XXI. Blood insulin (0.06stdβ; 95 %CI:0.03,0.09) and insulin resistance (0.05stdβ; 95 %CI:0.02,0.08) presented a significant longitudinal association with BPA daily exposure after adjustment for important variables and energy. The same findings were observed for fat mass (0.03stdβ; 95 %CI 0.01,0.06) and waist circumference (0.06stdβ; 95 %CI:0.04,0.08). For z-BMI, a significant cross-sectional (0.03stdβ; 95 %CI:0.01,0.04) and longitudinal (0.02stdβ; 95 %CI:0.00,0.04) association was found. This was the first study assessing the association between BPA exposure and health outcomes from childhood to adolescence. We found an association between BPA exposure and increased blood insulin level, insulin resistance, fat mass percentage, waist circumference and z-BMI. Our results point to the need to reduce exposure to BPA in the early stages of life.
PubMed: 38909471
DOI: 10.1016/j.jhazmat.2024.135000 -
Biological Psychiatry. Cognitive... Jun 2024Recent neuroimaging studies and publicly-disseminated analytic tools advocate that regional morphometric analyses covary for global thickness. We empirically demonstrate...
Adjustment of Regional Cortical Thickness Measures for Global Cortical Thickness Obscures Deficits Across the Schizophrenia Spectrum: A Cautionary Note about Normative Modeling of Brain Imaging Data.
Recent neuroimaging studies and publicly-disseminated analytic tools advocate that regional morphometric analyses covary for global thickness. We empirically demonstrate that this statistical approach severely underestimates regional thickness dysmorphology in psychiatric disorders. Study 1 included 90 healthy controls, 51 clinical high-risk for psychosis, and 78 early illness schizophrenia participants. Study 2 included 56 healthy controls, 83 non-affective psychosis, and 30 affective psychosis participants. We examined global and regional thickness correlations, global thickness group differences, and regional thickness group differences with/without global thickness covariation. Global and regional thickness were strongly correlated across groups. Global thickness was lower in schizophrenia-spectrum groups versus other groups. Regional thickness deficits in schizophrenia-spectrum groups were attenuated/eliminated with global thickness covariation. Depriving regional thickness of its shared variance with global thickness removes disease-related effects. This statistical method results in erroneous conclusions that regional thickness is normal in disorders like schizophrenia or clinical high-risk syndrome.
PubMed: 38908749
DOI: 10.1016/j.bpsc.2024.06.001 -
BMC Geriatrics Jun 2024Increase in functional disability in aging societies is an international medical and public health issue. Masticatory function may be a potential risk factor for... (Observational Study)
Observational Study
BACKGROUND
Increase in functional disability in aging societies is an international medical and public health issue. Masticatory function may be a potential risk factor for functional disability, but the role of frailty in the association has not been clarified.
METHODS
Forty thousand five hundred sixty-two community-dwelling older adults aged 65 years and over who were insured by public health insurance as of April 2018 were followed up for a median of 3.0 years. Masticatory function was categorized as good, moderate, or poor based on a self-reported questionnaire. The development of functional disability was defined as a new certification of the need for long-term care. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs).
RESULTS
During the follow-up period, 1,397 individuals experienced functional disability. After adjusting for age, sex, comorbidities, medical history, and lifestyle behaviors, the HR for incident functional disability was significantly higher in the moderate and poor groups compared to the good group (moderate, HR 1.21 [95% CI, 1.07-1.37]; poor, HR 1.64 [95% CI, 1.03-2.62]). However, after additional adjustment for frailty-related factors-namely, underweight, regular exercise, and gait speed-the association was attenuated in both the moderate group (HR 1.06 [95% CI, 0.94-1.21]) and the poor group (HR 1.51 [95% CI, 0.94-2.41]).
CONCLUSIONS
Masticatory dysfunction was significantly associated with incident functional disability in a community-dwelling older Japanese population. Our findings suggest that masticatory dysfunction may be a surrogate of frailty rather than a direct cause of functional disability.
Topics: Humans; Aged; Male; Female; Frailty; Mastication; Aged, 80 and over; Independent Living; Frail Elderly; Disabled Persons; Disability Evaluation; Risk Factors; Geriatric Assessment; Japan
PubMed: 38907214
DOI: 10.1186/s12877-024-05131-w -
Renal Failure Dec 2024Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Shrunken pore syndrome (SPS) is defined as eGFR/eGFR ratio...
BACKGROUND
Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Shrunken pore syndrome (SPS) is defined as eGFR/eGFR ratio <0.70 and predicts high CVD mortality. The Framingham Risk Score (FRS) is used to estimate an individual's 10-year CVD risk. This study investigated the association between FRS and eGFR/eGFR ratio in T2DM patients.
METHODS
Patients aged 18-80 years who were newly diagnosed with T2DM were included in this retrospective study. Ordinal logistic regression analysis was used to investigate the association between risk factors of T2DM and FRS. A Generalized Linear Model was used to calculate odds ratios (OR) and 95% confidence intervals (CI).
RESULTS
There were 270 patients included in the study. Only 27 patients (10%) met the diagnostic criteria of SPS. Ordinal logistic regression analysis showed that SPS was not correlated with FRS risk (OR = 1.99, 95%CI = 0.94-4.23, = 0.07), whereas eGFR/eGFR (OR = 0.86, 95%CI = 0.77-0.97, = 0.01) showed a significant negative association with FRS risk. Compared with eGFR/eGFR>0.85, eGFR/eGFR≤0.85 increased FRS risk (OR = 1.95, 95%CI = 1.18-3.21, < 0.01). After adjustment for confounding factors, increased eGFR/eGFR ratio was associated with decreased FRS risk when considered as a continuous variable (OR = 0.87, 95%CI = 0.77-0.99, = 0.03). The FRS risk in patients with eGFR/eGFR≤0.85 is 1.86 times higher than that in patients with eGFR/eGFR>0.85 (OR = 1.86, 95%CI = 1.08-3.21, = 0.03).
CONCLUSIONS
In the current study, no significant association between SPS and FRS was identified. However, lower eGFR/eGFR and eGFR/eGFR≤0.85 were associated with a significantly increased CVD risk in T2DM.
Topics: Humans; Female; Male; Middle Aged; Diabetes Mellitus, Type 2; Retrospective Studies; Aged; Cardiovascular Diseases; Glomerular Filtration Rate; Adult; Creatinine; China; Cystatin C; Logistic Models; Young Adult; Aged, 80 and over; Risk Assessment; Adolescent; Risk Factors; Heart Disease Risk Factors; East Asian People
PubMed: 38905298
DOI: 10.1080/0886022X.2024.2346267 -
Human Reproduction Open 2024Is acute haemoperitoneum that is managed conservatively a precursor of deep endometriosis?
STUDY QUESTION
Is acute haemoperitoneum that is managed conservatively a precursor of deep endometriosis?
SUMMARY ANSWER
Our study provides evidence to suggest that acute haemoperitoneum may lead to the development of deep endometriosis in a significant proportion of cases.
WHAT IS KNOWN ALREADY
A recent pilot study was the first to suggest that acute haemoperitoneum could be a precursor of deep endometriosis. However, the sample size was small, and the follow-up was not standardized owing to unknown rates of clot absorption and development of endometriosis.
STUDY DESIGN SIZE DURATION
This was a prospective observational cohort study conducted at a single centre over a 31-month period. A required sample size of 30 was calculated using results from a previous study, with a minimum of 15 women each in the groups with and without significant haemoperitoneum (study and control groups, respectively). A total of 59 women were recruited to the study and eight were lost to follow-up. The final sample comprised 51 women, 15 in the study group and 36 in the control group.
PARTICIPANTS/MATERIALS SETTING METHODS
All non-pregnant, premenopausal women aged 18-50 years who consecutively presented to our dedicated gynaecological diagnostic unit with severe acute lower abdominal pain were eligible for this study. We only included women who were clinically stable and were suitable for conservative management. Those with prior history or evidence of endometriosis on their initial ultrasound scan, previous hysterectomy, or bilateral oophorectomy were excluded. Participants had standardized follow-up visits for 6 months, with pelvic ultrasound scans and the British Society of Gynaecological Endoscopy pelvic pain questionnaires completed at each visit. The primary outcome was the sonographically confirmed presence of newly formed endometriosis. Secondary outcomes were the presence and change of pelvic pain symptoms and health-related quality of life (HR-QOL).
MAIN RESULTS AND THE ROLE OF CHANCE
After completion of follow-up, 7/15 (47%; 95% CI 21.3-71.4%) women presenting with acute haemoperitoneum (study group) developed sonographic evidence of deep endometriosis, compared to 0/36 (0%; 97.5% CI 0.0-9.7%) women in the control group. A ruptured functional haemorrhagic cyst was the most common cause of haemoperitoneum, occurring in 13/15 cases (87%). The time from the initial event to sonographic evidence of endometriosis varied from 2 to 6 months. The EuroQol visual analogue scores were not significantly different at baseline between the groups that developed and did not develop endometriosis [28 (interquartile range (IQR) 15-40, n = 6) vs 56 (IQR 35-75, n = 44), =0.09], while the EuroQol-5D values were lower in the endometriosis group [-0.01 (IQR -0.07 to 0.19, n = 6) vs 0.62 (IQR 0.24-0.73, n = 44), =0.002]. At 6 months, the EuroQol-5D scores were improved in both groups, but remained significantly lower in the endometriosis group compared to the no endometriosis group [0.69 (IQR 0.66-0.80, n = 6) vs 0.85 (IQR 0.76-1.00, n = 44), =0.03]. There was no clinically relevant difference in the pelvic pain scores at either time point.
LIMITATIONS REASONS FOR CAUTION
It remains uncertain whether minimal, superficial endometriosis existed at commencement of the study and had a role in the development of deep endometriosis. Although the ultrasound findings were in keeping with deep endometriosis, this was not confirmed histologically. The pelvic pain and HR-QOL findings could have been influenced by the baseline scores being taken when the patient was admitted with acute pain. Also, the sample size was too small to draw reliable conclusions regarding the impact of newly developed endometriosis on QoL.
WIDER IMPLICATIONS OF THE FINDINGS
Our study provides further evidence showing that significant haemoperitoneum may be a precursor of deep endometriosis. Haemodynamically stable women presenting with acute pelvic pain and significant haemoperitoneum should be counselled about the risk of developing deep endometriosis. Interventional studies should be carried out in the future to see whether laparoscopy and pelvic washout could prevent development of deep endometriosis. Preventative strategies, including treatment to suppress ovulation and formation of functional cysts, should be further investigated. This includes the combined and progesterone-only contraceptive pills. Larger future studies are also required to assess women over a longer period of time, with adjustment for confounding factors, to evaluate a possible effect on HR-QOL and pain symptoms.
STUDY FUNDING/COMPETING INTERESTS
Funding was obtained from The Gynaecology Ultrasound Centre, London, UK. TT received personal fees from GE, Samsung, Medtronic, and Merck for lectures on ultrasound. TT also received a postdoctoral grant from the South-Eastern Norwegian Health Authority (grant number 2020083).
TRIAL REGISTRATION NUMBER
researchregistry6472.
PubMed: 38905001
DOI: 10.1093/hropen/hoae036