Nevin Manimala

Acta Anaesthesiol Scand. 2021 Dec 24. doi: 10.1111/aas.14023. Online ahead of print.

ABSTRACT

BACKGROUND: Respiratory failure is the main cause of mortality and morbidity among ICU patients with coronavirus disease 2019 (COVID-19). In these patients, supplemental oxygen therapy is essential, but there is limited evidence the optimal target. To address this, the ongoing handling oxygenation targets in COVID-19 (HOT-COVID) trial was initiated to investigate the effect of a lower oxygenation target (partial pressure of arterial oxygen (PaO₂ ) of 8 kPa) vs a higher oxygenation target (PaO₂ of 12 kPa) in the ICU on clinical outcome in patients with COVID-19 and hypoxaemia.

METHODS: The HOT-COVID is planned to enrol 780 patients. This paper presents the protocol and statistical analysis plan for the conduct of a secondary Bayesian analysis of the primary outcome of HOT-COVID being days alive without life-support at 90 days and the secondary outcome 90-day all-cause mortality. Further, both outcomes will be investigated for the presence heterogeneity of treatment effects based on four baseline parameters being sequential organ failure assessment score, PaO₂ /fraction of inspired oxygen ratio, highest dose of norepinephrine during the 24 hours before randomisation, and plasma concentration of lactate at randomisation.

CONCLUSION: The results of this pre-planned secondary Bayesian analysis will complement the primary frequentist analysis of the HOT-COVID trial and may facilitate a more nuanced interpretation of the trial results.

PMID:34951717 | DOI:10.1111/aas.14023

Acta Anaesthesiol Scand. 2021 Dec 24. doi: 10.1111/aas.14022. Online ahead of print.

ABSTRACT

BACKGROUND: Intubation, laryngoscopy and extubation are considered highly aerosol-generating procedures, and additional safety protocols are used during COVID-19 pandemic in these procedures. However, previous studies are mainly experimental and have neither analyzed staff exposure to aerosol generation in the real-life operating room environment nor compared the exposure to aerosol concentrations generated during normal patient care. To assess operational staff exposure to potentially infectious particle generation during general anesthesia, we measured particle concentration and size distribution with patients undergoing surgery with Optical Particle Sizer.

METHODS: A single-center observative multidisciplinary clinical study in Helsinki University Hospital with 39 adult patients who underwent general anesthesia with tracheal intubation. Mean particle concentrations during different anesthesia procedures were statistically compared with cough control data collected from 37 volunteers to assess the differences in particle generation.

RESULTS: This study measured 25 preoxygenations, 30 mask ventilations, 28 intubations and 24 extubations. The highest total aerosol concentration of 1153 particles (p)/cm³ was observed during mask ventilation. Preoxygenations, mask ventilations and extubations as well as uncomplicated intubations generated mean aerosol concentrations statistically comparable to coughing. It is noteworthy that difficult intubation generated significantly fewer aerosols than either uncomplicated intubation (p=0.007) or coughing (p=0.006).

CONCLUSIONS: Anesthesia induction generates mainly small (<1 µm) aerosol particles. Based on our results, general anesthesia procedures are not highly aerosol-generating compared with coughing. Thus, their definition as high-risk aerosol-generating procedures should be re-evaluated due to comparable exposures during normal patient care.

PMID:34951703 | DOI:10.1111/aas.14022

J Am Geriatr Soc. 2021 Dec 24. doi: 10.1111/jgs.17633. Online ahead of print.

ABSTRACT

BACKGROUND: Lower urinary tract symptoms (LUTS) are associated with frailty phenotype, a risk factor for functional decline. Our objective was to determine the association between baseline LUTS and 2-year risk of new functional limitation among older men.

METHODS: We analyzed data from the Osteoporotic Fractures in Men (MrOS) study with baseline at Year 7 and follow-up through Year 9. Participants included 2716 community-dwelling men age ≥ 71 years without any baseline self-reported functional limitation. LUTS severity (American Urologic Association Symptom Index) was classified as none/mild (score 0-7), moderate (8-19), and severe (20-35). At baseline and follow-up, men reported their ability to complete several mobility, activities of daily living (ADLs), and cognition-dependent tasks. Risk was estimated for 3 incident functional limitation outcomes: (1) mobility (any difficulty walking 2-3 blocks or climbing 10 steps), (2) ADL (any difficulty bathing, showering, or transferring), and (3) cognition-dependent (any difficulty managing money or medications). We used Poisson regression with a robust variance estimator to model adjusted risk ratios (ARR) and 95% CIs controlling for age, site, and comorbidities; other demographic/lifestyle factors did not meet criteria for inclusion.

RESULTS: Overall, the 2-year risk was 15% for mobility, 10% for ADLs, and 4% for cognition-dependent task limitations. Compared to none/mild LUTS, risk of incident mobility limitations was increased for moderate (ARR = 1.35, 95% CI: 1.12, 1.63) and severe LUTS (ARR = 1.98, 95% CI: 1.48, 2.64). Men were also at higher risk for incident ADL limitations if they reported moderate (ARR = 1.32, 95% CI: 1.05, 1.67) and severe LUTS (ARR = 1.62, 95% CI: 1.07,2.43). Results were somewhat attenuated after adjusting for the frailty phenotype but remained statistically significant. LUTS were not associated with incident cognition-dependent task limitations.

CONCLUSIONS: LUTS severity is associated with incident mobility and ADL limitations among older men. Increased clinical attention to risk of functional limitations among older men with LUTS is likely warranted.

PMID:34951697 | DOI:10.1111/jgs.17633

MAGMA. 2021 Dec 24. doi: 10.1007/s10334-021-00990-5. Online ahead of print.

ABSTRACT

OBJECTIVE: We tried to reveal how the normal appearing white matter (NAWM) was affected in patients with glioblastoma treated with chemo-radiotherapy (CRT) in the period following the treatment, by multiparametric MRI.

MATERIALS AND METHODS: 43 multiparametric MRI examinations of 17 patients with glioblastoma treated with CRT were examined. A total of six different series or maps were analyzed in the examinations: Apparent Diffusion Coefficient (ADC) and Fractional Anisotropy (FA) maps, Gradient Echo (GRE) sequence, Dynamic susceptibility contrast (DSC) and Arterial spin labeling (ASL) perfusion sequences. Each sequence in each examination was examined in detail with 14 Region of Interest (ROI) measurements. The obtained values were proportioned to the contralateral NAWM values and the results were recorded as normalized values. Time dependent changes of normalized values were statistically analyzed.

RESULTS: The most prominent changes in follow-up imaging occurred in the perilesional region. In perilesional NAWM, we found a decrease in normalized FA (nFA), rCBV (nrCBV), rCBF (nrCBF), ASL (nASL)values (p < 0.005) in the first 3 months after treatment, followed by a plateau and an increase approaching pretreatment values, although it did not reach. Similar but milder findings were present in other NAWM areas. In perilesional NAWM, nrCBV values were found to be positively high correlated with nrCBF and nASL, and negatively high correlated with nADC values (r: 0.963, 0.736, – 0.973, respectively). We also found high correlations between the mean values of nrCBV, nrCBF, nASL in other NAWM areas (r: 0.891, 0.864, respectively).

DISCUSSION: We showed that both DSC and ASL perfusion values decreased correlatively in the first 3 months and showed a plateau after 1 year in patients with glioblastoma treated with CRT, unlike the literature. Although it was not as evident as perfusion MRI, it was observed that the ADC values also showed a plateau pattern following the increase in the first 3 months. Further studies are needed to explain late pathophysiological changes. Because of the high correlation, our results support ASL perfusion instead of contrast enhanced perfusion methods.

PMID:34951690 | DOI:10.1007/s10334-021-00990-5

Sports Med Open. 2021 Dec 24;7(1):100. doi: 10.1186/s40798-021-00395-7.

ABSTRACT

BACKGROUND: Cardiorespiratory fitness and fatness (notably central obesity) are mediating factors of the metabolic syndrome (MetS) and consequent cardiovascular disease (CVD)/mortality risk. The fitness-fatness index (FFI) combines these factors and has been reported to be a better indicator of CVD and all-cause mortality risk, beyond the capacity of either fitness or fatness alone.

OBJECTIVE: This study sought to investigate the effects of different exercise intensities on FFI in adults with MetS.

METHODS: This was a sub-study of the ‘Exercise in the prevention of Metabolic Syndrome’ (EX-MET) multicentre trial. Ninety-nine adults diagnosed with MetS according to the International Diabetes Federation criteria were randomized to one of the following 16-week exercise interventions: i) moderate-intensity continuous training (MICT) at 60-70% HRpeak for 30 min/session (n = 34, 150 min/week); ii) 4 × 4 min bouts of high-intensity interval training at 85-95% HRpeak, interspersed with 3-min active recovery at 50-70% HRpeak (n = 34, 38 min/session, 114 min/week); and iii) 1 × 4 min bout of HIIT at 85-95% HRpeak (n = 31, 17 min/session, 51 min/week). Cardiorespiratory fitness (peak oxygen uptake, V̇O₂peak) was determined via indirect calorimetry during maximal exercise testing and fatness was the ratio of waist circumference-to-height (WtHR). FFI was calculated as V̇O₂peak in metabolic equivalents (METs) divided by WtHR. A clinically meaningful response to the exercise intervention was taken as a 1 FFI unit increase.

RESULTS: Seventy-seven participants completed pre and post testing to determine FFI. While there was no significant between group difference (p = 0.30), there was a small group x time interaction effect on FFI [F(2, 73) = 1.226; η² = 0.01], with numerically greater improvements following HIIT (4HIIT, + 16%; 1HIIT, + 11%) relative to MICT (+ 7%). There was a greater proportion of participants who had a clinically meaningful change in FFI following high-volume HIIT (60%, 15/25) and low-volume HIIT (65%, 17/26) compared to MICT (38%, 10/26), but with no significant between-group difference (p = 0.12). A similar trend was found when a sub-analysis comparing the FFI between those with type 2 diabetes (MICT, 33%, 3/9; high-volume HIIT, 64%, 7/11; and low-volume HIIT, 58%, 7/12) and without type 2 diabetes (MICT, 41%, 7/17; high-volume HIIT, 57%, 8/14; low-volume HIIT, 71%, 10/14).

CONCLUSION: Although there were no statistically significant differences detected between groups, this study suggests that the response to changes in FFI in adults with MetS may be affected by exercise intensity, when numerical differences between exercise groups are considered. Further research is warranted. Trial registration number and date of registration: ClinicalTrials.gov NCT01676870; 31/08/2012.

PMID:34951682 | DOI:10.1186/s40798-021-00395-7

Eur J Epidemiol. 2021 Dec 24. doi: 10.1007/s10654-021-00817-6. Online ahead of print.

NO ABSTRACT

PMID:34951674 | DOI:10.1007/s10654-021-00817-6

Diabetologia. 2021 Dec 24. doi: 10.1007/s00125-021-05635-9. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Type 2 diabetes is a growing global public health challenge. Investigating quantitative traits, including fasting glucose, fasting insulin and HbA_1c, that serve as early markers of type 2 diabetes progression may lead to a deeper understanding of the genetic aetiology of type 2 diabetes development. Previous genome-wide association studies (GWAS) have identified over 500 loci associated with type 2 diabetes, glycaemic traits and insulin-related traits. However, most of these findings were based only on populations of European ancestry. To address this research gap, we examined the genetic basis of fasting glucose, fasting insulin and HbA_1c in participants of the diverse Population Architecture using Genomics and Epidemiology (PAGE) Study.

METHODS: We conducted a GWAS of fasting glucose (n = 52,267), fasting insulin (n = 48,395) and HbA_1c (n = 23,357) in participants without diabetes from the diverse PAGE Study (23% self-reported African American, 46% Hispanic/Latino, 40% European, 4% Asian, 3% Native Hawaiian, 0.8% Native American), performing transethnic and population-specific GWAS meta-analyses, followed by fine-mapping to identify and characterise novel loci and independent secondary signals in known loci.

RESULTS: Four novel associations were identified (p < 5 × 10^-9), including three loci associated with fasting insulin, and a novel, low-frequency African American-specific locus associated with fasting glucose. Additionally, seven secondary signals were identified, including novel independent secondary signals for fasting glucose at the known GCK locus and for fasting insulin at the known PPP1R3B locus in transethnic meta-analysis.

CONCLUSIONS/INTERPRETATION: Our findings provide new insights into the genetic architecture of glycaemic traits and highlight the continued importance of conducting genetic studies in diverse populations.

DATA AVAILABILITY: Full summary statistics from each of the population-specific and transethnic results are available at NHGRI-EBI GWAS catalog ( https://www.ebi.ac.uk/gwas/downloads/summary-statistics ).

PMID:34951656 | DOI:10.1007/s00125-021-05635-9

Eur J Trauma Emerg Surg. 2021 Dec 24. doi: 10.1007/s00068-021-01857-z. Online ahead of print.

ABSTRACT

INTRODUCTION: In spiral fractures of the tibia, the stability of an osteosynthesis may be significantly increased by additive cerclages and, according to biomechanical studies, be brought into a state that allows immediate full weight bearing. As early as 1933, Goetze described a minimally invasive technique for classic steel cerclages. This technique was modified, so that it can be used for modern cable cerclages in a soft part saving way.

METHOD: After closed reduction, an 8 Fr redon drain is first inserted in a minimally invasive manner, strictly along the bone and placed around the tibia via 1 cm incisions on the anterolateral and dorsomedial tibial edges using a curette and a tissue protection sleeve. Via this drain, a 1.7 mm cable cerclage can be inserted. The fracture is then anatomically reduced while simultaneously tightening the cerclage. Subsequently, a nail or a minimally invasive plate osteosynthesis is executed using the standard technique. Using the hospital documentation system, data of patients that were treated with additional cerclages for tibial fractures between 01/01/2014 and 06/30/2020 were subjected to a retrospective analysis for postoperative complications (wound-healing problems, infections and neurovascular injury). Inclusion criteria were: operatively treated tibial fractures, at least one minimally invasive additive cerclage, and age of 18 years or older. Exclusion criteria were: periprosthetic or pathological fractures and the primary need of reconstructive plastic surgery. SPSS was used for statistical analysis.

RESULTS: 96 tibial shaft spiral fractures were treated with a total of 113 additive cerclages. The foregoing resulted in 10 (10.4%) postoperative wound infections, 7 of which did not involve the cerclage. One lesion of the profundal peroneal nerve was detected, which largely declined after cerclage removal. In 3 cases, local irritation from the cerclage occurred and required removal of material.

CONCLUSION: In the described technique, cerclages may be inserted additively at the tibia in a minimally invasive manner and with a few complications, thus significantly increasing the stability of an osteosynthesis. How this ultimately affects fracture healing is the subject of an ongoing study.

PMID:34951655 | DOI:10.1007/s00068-021-01857-z

Soc Psychiatry Psychiatr Epidemiol. 2021 Dec 24. doi: 10.1007/s00127-021-02215-5. Online ahead of print.

ABSTRACT

PURPOSE: It is unclear how hospitals are responding to the mental health needs of the population in England, against a backdrop of diminishing resources. We aimed to document patterns in hospital activity by psychiatric disorder and how these have changed over the last 22 years.

METHODS: In this observational time series analysis, we used routinely collected data on all NHS hospitals in England from 1998/99 to 2019/20. Trends in hospital admissions and bed days for psychiatric disorders were smoothed using negative binomial regression models with year as the exposure and rates (per 1000 person-years) as the outcome. When linear trends were not appropriate, we fitted segmented negative binomial regression models with one change-point. We stratified by gender and age group [children (0-14 years); adults (15 years +)].

RESULTS: Hospital admission rates and bed days for all psychiatric disorders decreased by 28.4 and 38.3%, respectively. Trends were not uniform across psychiatric disorders or age groups. Admission rates mainly decreased over time, except for anxiety and eating disorders which doubled over the 22-year period, significantly increasing by 2.9% (AAPC = 2.88; 95% CI: 2.61-3.16; p < 0.001) and 3.4% (AAPC = 3.44; 95% CI: 3.04-3.85; p < 0.001) each year. Inpatient hospital activity among children showed more increasing and pronounced trends than adults, including an increase of 212.9% for depression, despite a 63.8% reduction for adults with depression during the same period.

CONCLUSION: In the last 22 years, there have been overall reductions in hospital activity for psychiatric disorders. However, some disorders showed pronounced increases, pointing to areas of growing need for inpatient psychiatric care, especially among children.

PMID:34951652 | DOI:10.1007/s00127-021-02215-5

Depress Anxiety. 2021 Dec 24. doi: 10.1002/da.23231. Online ahead of print.

ABSTRACT

BACKGROUND: Although cognitive behavioral therapy (CBT) is effective in the treatment of anxiety disorders, few evidence-based alternatives exist. Autonomy enhancing treatment (AET) aims to decrease the vulnerability for anxiety disorders by targeting underlying autonomy deficits and may therefore have similar effects on anxiety as CBT, but yield broader effects.

METHODS: A multicenter cluster-randomized clinical trial was conducted including 129 patients with DSM-5 anxiety disorders, on average 33.66 years of age (SD = 12.57), 91 (70.5%) female, and most (92.2%) born in the Netherlands. Participants were randomized over 15-week groupwise AET or groupwise CBT and completed questionnaires on anxiety, general psychopathology, depression, quality of life, autonomy-connectedness and self-esteem, pre-, mid-, and posttreatment, and after 3, 6, and 12 months (six measurements).

RESULTS: Contrary to the hypotheses, effects on the broader outcome measures did not differ between AET and CBT (d = .16 or smaller at post-test). Anxiety reduction was similar across conditions (d = .059 at post-test) and neither therapy was superior on long term.

CONCLUSION: This was the first clinical randomized trial comparing AET to CBT. The added value of AET does not seem to lie in enhanced effectiveness on broader outcome measures or on long term compared to CBT. However, the study supports the effectiveness of AET and thereby contributes to extended treatment options for anxiety disorders.

PMID:34951503 | DOI:10.1002/da.23231