Estimate Group Differences Research Articles

The association between the circadian misalignment of serum cortisol acrophase and sleep end time with chemotherapy-induced peripheral neuropathy

ABSTRACT Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of chemotherapy. The objective of this prospective observational study was to examine the association between circadian misalignment (CM), as measured by phase angle difference (PAD) of biological and behavioral rhythms and CIPN. The PAD of cortisol acrophase and actigraphy-based sleep end time in breast cancer patients was measured and categorized into low PAD (n = 11) and high PAD (n = 12) groups based on median value. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN20 (CIPN20). The assessment of CM revealed that the sleep end time of the low PAD group was more delayed in relation to cortisol acrophase compared to the high PAD group. The low PAD group demonstrated significantly higher CIPN20 global and sensory scale scores compared to the high-PAD group at one month post-chemotherapy, with an estimated group difference of 17.63 ± 4.75 and 27.07 ± 6.70 (p = 0.001 and p < 0.001, respectively). The present findings indicate that the low PAD group, which exhibited a relatively delayed behavioral rhythm with respect to its biological rhythm, displayed an increased susceptibility to CIPN. Further large-sample research is necessary to attain a comprehensive understanding of the mechanisms through which CM affects CIPN.

Peer-assisted telemedicine for hepatitis C in people who use drugs: A randomized controlled trial.

Hepatitis C virus (HCV) elimination requires treating people who use drugs (PWUD), yet fewer than 10% of PWUD in the United States access HCV treatment and access is especially limited in rural communities. We randomized PWUD with HCV viremia and past 90-day injection drug or non-prescribed opioid use in seven rural Oregon counties to peer-assisted telemedicine HCV treatment (TeleHCV) versus peer-assisted referral to local providers (enhanced usual care; EUC). Peers supported screening and pre-treatment laboratory evaluation for all participants and facilitated telemedicine visits, medication delivery, and adherence for TeleHCV participants. Generalized linear models estimated group differences in HCV viral clearance (primary outcome) and HCV treatment initiation and completion (secondary outcomes). Of the 203 randomized participants (100 TeleHCV, 103 EUC), most were male (62%), white (88%), with recent houselessness (70%), and used methamphetamines (88%) or fentanyl/heroin (58%) in the past 30 days. Eighty-five of 100 TeleHCV participants (85%) initiated treatment versus 13 of 103 (12%) EUC participants (RR = 6.7, 95% CI 4.0 to 11.3, p<0.001). Sixty-three of 100 (63%) TeleHCV participants vs. 16 of 103 (16%) EUC participants achieved viral clearance 12 weeks after anticipated treatment completion date (RR = 4.1, 95% CI 2.5 to 6.5, p <0.001). The Peer TeleHCV treatment model substantially increased HCV treatment initiation and viral clearance compared to EUC. Replication in other rural and low-resource settings could further World Health Organization HCV elimination goals by expanding and decentralizing treatment access for PWUD. NCT04798521.

Association of the COVID-19 Pandemic With Outcomes After Anterior Cruciate Ligament Reconstruction: A Retrospective Comparative Study Examining Changes in Health Care Access, Delivery, and Functional Outcomes.

Structured rehabilitation optimizes outcomes and reduces reinjury risk after anterior cruciate ligament reconstruction (ACLR). The coronavirus 2019 (COVID-19) pandemic interrupted standard rehabilitation, possibly affecting ACLR outcomes. To characterize changes to ACLR functional outcomes related to the COVID-19 pandemic. Cohort study; Level of evidence, 3. Patients who underwent ACLR between June 11, 2019, and March 11, 2020, (postpandemic group) were compared retrospectively with those who underwent ACLR the year before (June 11, 2018, to March 11, 2019). A mixed-effects linear regression model was used to estimate group differences in isokinetic quadriceps testing. A Kaplan-Meier analysis assessed the probability of achieving >90% limb symmetry index (LSI) for isokinetic quadriceps strength at 60 deg/s and passing all return-to-sport functional outcomes at 1 year postoperatively. A total of 176 patients (80 in the control group and 96 in the postpandemic group) were included. The rate of achieving >90% LSI in isokinetic strength at 60 deg/s at 1 year postoperatively was 39% (95% CI, 27%-49%) for the control group versus 22% (95% CI, 13%-30%) for the postpandemic group (P = .01). Similarly, the rate of achieving >90% LSI in all functional tests at 1 year postoperatively was 15% (95% CI, 7%-22%) for the control group versus 7% (95% CI, 2%-12%) for the postpandemic group (P = .04). The number of in-person physical therapy visits per patient was 25.8 ± 6.8 in the control group versus 24.4 ± 7.5 in the postpandemic group (P = .23). Only the postpandemic group accessed physical therapy using remote telemedicine. Each additional telehealth rehabilitation visit was associated with a 1-week delay in achieving >90% LSI in isokinetic quadriceps strength for the postpandemic group. The COVID-19 pandemic was associated with a decrease in lower extremity strength and a lower probability of achieving limb symmetry and passing the criteria for return to sport at 1 year postoperatively. These results were not due to lack of access to physical therapy.

Are They Prepared? Comparing Intern Milestone Performance of Accelerated 3-Year and 4-Year Medical Graduates.

Accelerated 3-year programs (A3YPs) at medical schools were developed to address student debt and mitigate workforce shortage issues. This study investigated whether medical school length (3 vs 4 years) was associated with early residency performance. The primary research question was as follows: Are the Accreditation Council for Graduate Medical Education Milestones (MS) attained by A3YP graduates comparable to graduates of traditional 4-year programs (T4YPs) at 6 and 12 months into internship? The MS data from students entering U.S. medical schools in 2021 and 2022 from the 6 largest specialties were used: emergency medicine, family medicine, internal medicine, general surgery, psychiatry, and pediatrics. Three-year and 4-year graduates were matched for analysis (2,899 matched learners: 182 in A3YPs and 2,717 in T4YPs). The study used a noninferiority study design to examine data trends between the study cohort (A3YP) and control cohort (T4YP). To account for medical school and residency program effects, the authors used cross-classified random-effects regression to account for clustering and estimate group differences. The mean Harmonized MS ratings for the midyear and end-year reporting periods showed no significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = 0.01 [0.02], P = .77). Mean MS ratings across internal medicine MS for the midyear and end-year reporting periods showed no significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = -0.03 [0.03], P = .31). Similarly, for family medicine, there were no statistically significant differences between the A3YP and T4YP groups (mean [SE] cross-classified coefficient = 0.01 [0.02], P = .96). For the specialties studied, there were no significant differences in MS performance between 3-year and 4-year graduates at 6 and 12 months into internship. These results support comparable efficacy of A3YPs in preparing medical students for residency.

Effects of smoking cessation on endothelial function as assessed by flow-mediated total dilation

BackgroundIn assessing the effects of smoking cessation on endothelial function, low-flow-mediated constriction (L-FMC) may provide complementary information to flow-mediated dilation (FMD). However, the value of flow-mediated total dilation (FMTD), an index that incorporates L-FMC into FMD, remains underreported. We aimed to evaluate the effect of smoking cessation on endothelial function, as assessed by FMD and FMTD, and clarify its associated clinical factors.MethodsWe enrolled 118 consecutive current smokers without previous coronary artery disease (72.9% were men; age: 59 ± 11 years) who underwent smoking cessation treatment. The clinical variables %FMD, %L-FMC, and %FMTD were examined before and 20 weeks after treatment initiation. A multivariate linear regression model was used to investigate the effects of smoking cessation on %FMD and %FMTD and the interaction between smoking cessation and baseline clinical variables.ResultsAfter 20 weeks, 85 smokers (69.4% were men; age: 59 ± 12 years) ceased smoking (abstainers), whereas 33 smokers (81.8% were men; age: 58 ± 11 years) did not (continued smokers). The estimated group differences (abstainers - continued smokers) in changes in the %FMD and %FMTD were 0.77% (95% confidence interval [CI], -0.22–1.77%; p = 0.129) and 1.17% (95% CI, 0.16–2.18%; p = 0.024), respectively. Smoking cessation-associated improvement in %FMTD was greater in women than in men (5.41% [95% CI, 3.15–7.67%] versus 0.24% [95% CI, -0.81–1.28%]; p-value for interaction, < 0.001). Additionally, a greater %FMTD improvement was observed in patients who smoked fewer cigarettes per day (p-value for interaction, 0.042) and those who had a smaller resting baseline lumen diameter (Dbase) (p-value for interaction, 0.023).ConclusionsSmoking cessation was associated with an improvement in %FMTD. Sex, cigarettes smoked per day, and Dbase significantly affected this improvement. The FMTD may help in risk stratification after smoking cessation.

Characteristics and outcomes of patients with low back pain with and without radiating leg pain following the GLA:D back program

BackgroundSome patients with low back pain (LBP) also report radiating leg pain which is a prognostic factor for poorer clinical outcomes. We aimed: 1) to compare the baseline characteristics of patients with LBP with - (LBP + leg pain) and without radiating leg pain (LBP - alone); 2) to investigate whether patients with LBP + leg pain show similar post-treatment outcomes as compared to LBP – alone, after participation in an exercise and patient education program, i.e. the GLA:D Back program. MethodsThe patient sample included 3508 patients in the GLA:D Back program between March 2018 and August 2022. The outcomes were mean changes in LBP intensity, back-related activity limitation, self-efficacy and fear of movement measured from baseline to 3, 6 and 12 months. Baseline characteristics were compared with descriptive statistics, and linear mixed models were used to estimate group differences in changes from baseline to 3-, 6- and 12 months. Results1915 (55%) of the patients were in the group LBP- alone and 1593 (45%) in the LBP + leg pain. The LBP + leg pain group displayed higher STarT back classification (greater risk of chronicity) compared to the LBP–alone. The LBP + leg pain group showed almost similar improvements in all outcomes compared to LBP – alone after the GLA:D Back program. ConclusionIn long-lasting (chronic) LBP patients, the LBP + leg pain group improved to the same extent as LBP - alone regarding LBP intensity, disability, and fear of movement following an exercise and patient education program, GLA:D Back.

Association of Psychological Resilience, Cognitive Reserve, and Brain Reserve with Post-Concussive Symptoms in Children with Mild Traumatic Brain Injury and Orthopedic Injury: An A-CAP Study.

Protective factors, including psychological resilience, cognitive reserve, and brain reserve, may be positively associated with recovery after pediatric mild traumatic brain injury (mTBI) but have yet to be studied concurrently. We sought to examine these factors as moderators of post-concussive symptoms (PCS) in pediatric mTBI compared to mild orthopedic injury (OI). Participants included 967 children (633 mTBI, 334 OI) aged 8-16.99 years, recruited from 5 Canadian pediatric emergency departments as part of a prospective longitudinal cohort study. At 10 days post-injury, psychological resilience was measured using the Connor-Davidson Resilience Scale (CD-RISC) and brain reserve was measured using total brain volume (TBV) derived from structural magnetic resonance imaging . Cognitive reserve was measured at 3 months post-injury using IQ scores from the Wechsler Abbreviated Scale of Intelligence-Second Edition. Cognitive and somatic PCS were measured using child and parent ratings on the Health and Behavior Inventory, completed weekly for 3 months and bi-weekly to 6 months. Analyses involved generalized least squares regression models using restricted cubic splines. Covariates included age at injury, sex, racialized identity, material and social deprivation, pre-injury migraine and concussion history, and retrospective pre-injury PCS. Psychological resilience moderated group differences in parent-reported PCS. At 30 days post-injury, estimated group differences in parent-reported cognitive and somatic PCS (mTBI > OI) were larger at higher (75th percentile) resilience scores (Est = 2.25 [0.87, 3.64] and Est = 2.38 [1.76, 3.00], respectively) than at lower (25th percentile) resilience scores (Est = 1.44 [0.01, 2.86] and Est = 2.08 [1.45, 2.71], respectively). Resilience did not moderate group differences in child-reported PCS but was negatively associated with child-reported PCS in both groups (ps < .001). Brain reserve (i.e., TBV) also moderated group differences, but only for parent-reported somatic PCS (p = .018). Group difference (mTBI > OI) at 30 days were larger at smaller (25th percentile) TBV (Est = 2.78 [2.17, 3.38]) than at larger (75th percentile) TBV (Est = 1.95 [1.31, 2.59]). TBV was not associated with parent-reported cognitive PCS or child-reported PCS. IQ did not moderate PCS in either group but had a significant non-linear association in both groups with child-reported somatic PCS (p = .018) and parent-reported PCS (p < .001), with higher PCS scores at both lower and higher IQs. These findings suggest that higher resilience predicts fewer PCS, but less strongly after mTBI than OI; greater brain reserve may reduce the effect of mTBI on somatic PCS; and cognitive reserve has an unexpected curvilinear association with PCS across injury types. The results highlight the importance of protective factors as predictors of recovery and potential targets for intervention following pediatric mTBI.

Outcomes of Aural Rehabilitation Provided in Person or by Telehealth Among Deaf/Hard of Hearing Young Children with Cochlear Implants or Hearing Aids.

Background: Cochlear implants and hearing aids may facilitate the development of listening and spoken language (LSL) in deaf/hard of hearing young children, but they require aural rehabilitation therapy-often unavailable outside urban areas-for optimal outcomes. This trial assessed the relative effectiveness of LSL therapy delivered either in person or by interactive video. The hypothesis was that telehealth service delivery would be noninferior to in-person therapy. Methods: Most parents refused randomization of their children to telehealth or in-person conditions; therefore, randomization was impossible. In consultation with the funder (NIDCD), the study design was modified. Parents were allowed to select their preferred study condition, and the study team was blinded to group membership. Forty-two families were in the in-person group and 35 in telehealth (40 and 30, respectively, after attrition). Primary endpoints were total score, auditory comprehension, and expressive communication on the Preschool Language Scale, 5th edition. There were several secondary speech, hearing, and language outcome measures. Assessments occurred at baseline and at follow-up after 6 months of LSL therapy. Results: Propensity scores were used to create two matched groups. At baseline, groups did not differ on PLS-5 scores. Change from baseline to F/U on age-equivalents for all three scores was nearly identical for both groups, although the telehealth group was younger, on average, than the in-person group. Discussion: Telehealth was noninferior to in-person services for all primary endpoints. For secondary outcomes, neither group demonstrated a significant advantage. Magnitudes of estimated group differences were small, suggesting nonsignificant differences not predominantly because of sample size. The telehealth group showed greater improvement on 15/24 of secondary language outcome measures. The findings provide evidence that telehealth is equivalent to in-person care for providing LSL therapy to young children with cochlear implants and hearing aids.

Move for Life an intervention for inactive adults aged 50 years and older: a cluster randomised feasibility trial.

Move for Life (MFL) is a theory-informed intervention that was developed to augment established physical activity (PA) programmes and enable inactive adults aged 50 years and older to be more active. This study examined the feasibility of MFL and sought to provide evidence of its potential for improving PA and associated health outcomes. A 3-arm cluster randomised feasibility trial compared MFL intervention, usual provision (UP) and control (CON) groups at baseline (T0), post-intervention (T1, at 8, 10 or 12- weeks) and 6-month follow up (T2). We used purposive sampling strategies to recruit participants according to characteristics of interest. Feasibility outcomes assessed recruitment, fidelity, adherence, retention and data completion rates based on pre-set criteria. Primary outcomes were accelerometer-based moderate-to-vigorous intensity PA (MVPA) and self-reported compliance with physical activity guidelines (PAGL). Secondary outcomes included light intensity PA (LiPA), standing time, sedentary time, body composition (adiposity), physical function and psychological well-being. We used linear mixed models (continuous outcomes) or generalized estimated equations (categorical outcomes) to estimate group differences over time in the study outcomes. Progression criteria for feasibility outcomes were met, and 733 individuals were recruited. Considering a 6-month period (T0-T2), while self-reported compliance with PAGL increased in MFL relative to UP and CON and in UP relative to CON, standing time decreased in MFL relative to CON and sedentary time increased in the latter compared to UP. Waist circumference decreased in MFL relative to UP and CON. MFL outperformed UP in the Timed Up and Go Test while MFL and UP increased the distance covered in the Six-Minute Walk Test compared to CON. Psychological well-being increased in MFL relative to CON (all p < 0.05). Findings show that MFL is feasible, while data are promising with regards to the potential of improving community PA programmes for adults aged 50 or more years. https://www.isrctn.com/Registration#ISRCTN11235176.

Modeling Risk for Lower Extremity Musculoskeletal Injury in U.S. Military Academy Cadet Basic Training.

Sport and tactical populations are often impacted by musculoskeletal injury. Many publications have highlighted that risk is correlated with multiple variables. There do not appear to be existing studies that have evaluated a predetermined combination of risk factors that provide a pragmatic model for application in tactical and/or sports settings. To develop and test the predictive capability of multivariable risk models of lower extremity musculoskeletal injury during cadet basic training at the U.S.Military Academy. Cadets from the class of 2022 served as the study population. Sex and injury history were collected by questionnaire. Body Mass Index (BMI) and aerobic fitness were calculated during testing in the first week of training. Movement screening was performed using the Landing Error Scoring System during week 1 and cadence was collected using an accelerometer worn throughout initial training. Kaplan-Meier survival curves estimated group differences in time to the first musculoskeletal injury during training. Cox regression was used to estimate hazard ratios (HRs) and Akaike Information Criterion (AIC) was used to compare model fit. Cox modeling using HRs indicated that the following variables were associated with injury risk : Sex, history of injury, Landing Error Scoring System Score Category, and Physical Fitness Test (PT) Run Score. When controlling for sex and history of injury, amodel including aerobic fitness and BMI outperformed the model including movement screening risk and cadence (AIC: 1068.56 vs. 1074.11) and a model containing all variables that were significant in the univariable analysis was the most precise (AIC: 1063.68). In addition to variables typically collected in this tactical setting (Injury History, BMI, and aerobic fitness), the inclusion of kinematic testing appears to enhance the precision of the risk identification model and will likely continue to be included in screening cadets at greater risk.

Impact and process evaluation of a primary-school Food Education and Sustainability Training (FEAST) program in 10-12-year-old children in Australia: pragmatic cluster non-randomized controlled trial

BackgroundEnvironmentally sustainable food initiatives accompanying nutrition education, such as the Food Education and Sustainability Training (FEAST) program, have gained traction in school settings. The aim of this trial was to conduct an impact and process evaluation of FEAST, to evaluate its effect on children’s fruit and vegetable (F&V) intakes, and secondary outcomes: F&V variety consumed, nutrition knowledge, food preparation/cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours, and food production knowledge.MethodsFEAST was a 10-week curriculum-aligned program, designed to educate children about healthy eating, food waste, and sustainability, while teaching cooking skills. It was implemented by classroom teachers, face-to-face and online, during COVID-19 school closures, in Australia in 2021. A custom designed survey was used to collect baseline and post-intervention data from students. Generalised linear mixed models (GLMM) estimated group differences in pre-post changes for primary and secondary outcomes. Surveys were also administered to students and teachers to evaluate intervention implementation.ResultsTwenty schools participated and self-selected to be either intervention schools (n = 10) or wait-list control (WLC) schools (n = 10). A total of 977, 5th and 6th grade children participated in the trial with a mean age of 11.1 years (SD ± 0.7). The FEAST intervention, compared to WLC, did not result in significant increases in primary outcomes nor secondary outcomes. The process evaluation revealed FEAST was well-received by students and teachers, but COVID-19 school closures hindered implementation fidelity with a less intense program delivered under the constraints of pandemic lockdowns.ConclusionsThis is the first cluster non-randomized controlled trial designed to independently evaluate FEAST in the primary-school setting. No evidence was found for improved F&V intakes in children, nor secondary outcomes. However, the positive process evaluation results suggest that further trials of the program are warranted. If implemented as originally designed (pre-pandemic), with increased duration and complemented by supporting school policies, such programs have the potential to improve children’s daily F&V intakes, cooking skills and food waste behaviours. This would support the Australian curriculum and contribute to: health promotion within schools and sustainable schools initiatives, the national agenda to reduce food waste and sustainable development goals.Australian and New Zealand Clinical Trials Registry[ACTRN12620001347954]- Registered prospectively on 14/12/2020.

Changes in Cognitive Function After Kidney Transplantation: A Longitudinal Cohort Study

Rationale & ObjectiveKidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains. Study DesignProspective cohort study. Setting & ParticipantsWe examined pre- to post-KT cognition in patients waitlisted for KT at an academic center. PredictorsTransplant status. We measured cognitive function pre-KT (n=101), three months post-KT (n=78), and 1-year post-KT (n=83). OutcomesOur primary outcome was change in cognitive function pre- to post-KT. We used standard neuropsychological tests to assess global cognition (Mini Mental State Exam [MMSE], episodic/declarative memory (Logical Memory), psychomotor speed/visuospatial function (Digit Symbol Substitution Test [DSST], Trailmaking A), working memory/attention (Digit Span), executive function (Trailmaking B), and semantic memory/verbal fluency/language (Category Fluency). Analytical ApproachUsing linear mixed model analysis, we evaluated the change in neuropsychological test scores adjusted for age, sex, race, education, and number of assessments. ResultsLogical Memory I and II, DSST, MMSE, Category Fluency (animal naming), and Digit Span backward scores were low pre-KT compared to normative values from the National Alzheimer’s Coordinating Center data. Logical memory I and II improved post-KT (pre- vs. post-KT: estimated group difference (d)=3.3, p<0.001 for Logical Memory I, d=4.27, p<0.001 for Logical Memory II), such that post-KT scores were similar to normative values (post-KT vs. normative values: d=-0.37, p=0.06 for Logical Memory I, d=-0.89, p=0.08 for Logical Memory II). Category Fluency (animal naming) (d=2.4, p<0.001) and DSST (d=3.12, p=0.01) scores also improved with KT, but post-KT DSST scores remained lower than normative values (post-KT vs. normative values: d=-5.17, p<0.001). MMSE, Digit Span, and Trailmaking A and B did not change with KT. LimitationsSingle center study. ConclusionsEpisodic and verbal declarative memory normalize after KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function show partial improvement. Cognitive impairment in kidney disease is thus, at least partly reversible with KT.

Erythropoiesis and estimated fluid volume regulation following initiation of ipragliflozin treatment in patients with type 2 diabetes mellitus and chronic kidney disease: A post-hoc analysis of the PROCEED trial.

To analyse the changes in erythropoietic and estimated fluid volume parameters after the initiation of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). This was a post-hoc analysis of the PROCEED trial, which evaluated the effect of 24-week ipragliflozin treatment on endothelial dysfunction in patients with T2DM and CKD. We evaluated the changes in erythropoietic and estimated fluid volume parameters from baseline to 24 weeks post-treatment in 53 patients who received ipragliflozin (ipragliflozin group) and 55 patients with T2DM and CKD without sodium-glucose co-transporter 2 inhibitors (control group), a full analysis set of the PROCEED trial. The increases in haemoglobin [estimated group difference, 0.5 g/dl; 95% confidence interval (CI), 0.3-0.8; p < .001], haematocrit (estimated group difference, 2.2%; 95% CI, 1.3-3.1; p < .001) and erythropoietin (estimated log-transformed group difference, 0.1; 95% CI, 0.01-0.3; p = .036) were significantly greater in the ipragliflozin group than those in the control group. Ipragliflozin treatment was significantly associated with an increase in erythropoietin, independent of the corresponding change in haemoglobin (β = 0.253, p < .001) or haematocrit (β = 0.278, p < .001). Reductions in estimated plasma volume (estimated group difference, -7.94%; 95% CI, -11.6 to -4.26%; p < .001) and estimated extracellular volume (estimated group difference, -181.6 ml; 95% CI, -275.7 to -87.48 ml; p < .001) were significantly greater in the ipragliflozin group than those in the control group. Erythropoiesis was enhanced and estimated fluid volumes were reduced by ipragliflozin in patients with T2DM and CKD. PROCEED trial (registration number: jRCTs071190054).

Nurse-guided mobile health care program to reduce emotional distress experienced by parents of infants prenatally diagnosed with critical congenital heart disease: A pilot study

BackgroundFollowing prenatal diagnosis of critical congenital heart disease (CCHD), parents encounter emotional distress while facing caregiving challenges. Supportive psycho-educational interventions using mobile health (mHealth) can make care more accessible. ObjectivesWe tested a novel nurse-guided mHealth care program, Preparing Heart and Mind™ (PHM™), with the objectives of examining feasibility and estimating the effect of the intervention on parents' emotional distress. MethodsThis pilot study design randomized participants using a 2:1 intervention to control ratio. Analysis involved description of retention, intervention attendance and engagement, and adjusted linear mixed models to estimate group differences in depressive (CES-D), anxiety (STAI-S), and traumatic stress (IES-r) symptoms. ResultsThe sample included 55 parents (n = 38 PHM™ group, n = 17 control). Complete retention of 37 (67 %) parents included 29 (76 %) in the PHM™ group and 8 (47 %) control. Most attrition was due to infant death (7 parents), transplant referral (2 parents), or postnatal diagnostic ineligibility (4 parents). For the PHM™ group, ≥96 % of parents attended pre- and postnatal sessions, and most (65 %) messaged with the nurse. mHealth engagement was highest prenatally, with handling uncertainty the most viewed topic (average 94 % pages viewed). In linear mixed models analyses, the PHM™ group had on average 4.84 points lower depression (95 % CI: −10.68–1.04), 6.56 points lower anxiety (−14.04–0.92), and 6.28 points lower trauma (−14.44–1.88) scores by study end. ConclusionFindings suggest that a nurse-guided mHealth approach is feasible and may contribute to a clinically important reduction in parents' emotional distress.

Administration of Oxycodone Hydrochloride by Target Controlled Infusion - Does the Timing Matter?

Background: In spite of long-term clinical experience with oxycodone hydrochloride/OxyNorm (OH), analgesic concentrations of OH in acute postoperative pain management have not been established. There are assumably different opinions regarding intraoperative timing of OH administration among anaesthesiologists and nurse anaesthetists, hence different practices. Aim: The aim of the study was to determine to which extent intraoperative timing of OH administration affects the need for postoperative OH during target-controlled propofol and remifentanil infusion (TCI) for patients undergoing laparoscopic cholecystectomy. Method: Anesthetic and postoperative journals from 100 patients were included in this retrospective observational study. Patients in category 1 (n = 20) received OH towards the end in addition to the introduction/maintenance of TCI. Patients in category 2 (n = 66) received OH in the beginning/during the maintenance of TCI, but not towards the end. Patients in category 3 (n = 14) received OH only towards the end of TCI. Multiple regression models were used to analyze the data. Result: Mean total postoperative doses of OH and standard deviations (SD) were 4.7 (3.1), 6.9 (5.1) and 4.7 (3.4) mg for patients in categories 1–3, respectively; with an overall p-value for equality of group means of 0.032. Adjusting for age, gender, weight, operating time and medications given during operation did not affect the results substantially (p = 0.012). In total during the per- and postoperative course, observed means (SD) of OH administered were 11.0 (2.9), 12.1 (5.5) and 9.0 (3.5) mg for patients in categories 1- , respectively (p = 0.039). The estimated group differences were only slightly affected by adjusting for patient and operational variables, however the result was no longer statistically significant (p = 0.057). Conclusion: Our retrospective analysis suggested that intraoperative timing of OH administration affects the need for OH postoperatively after laparoscopic cholecystectomy with TCI anaesthesia. To reduce the total amount of OH, it may be beneficial to administer OH only towards the end of anaesthesia.

Multivariate analysis of PET pharmacokinetic parameters improves inferential efficiency

PurposeIn positron emission tomography quantification, multiple pharmacokinetic parameters are typically estimated from each time activity curve. Conventionally all but the parameter of interest are discarded before performing subsequent statistical analysis. However, we assert that these discarded parameters also contain relevant information which can be exploited to improve the precision and power of statistical analyses on the parameter of interest. Properly taking this into account can thereby draw more informative conclusions without collecting more data.MethodsBy applying a hierarchical multifactor multivariate Bayesian approach, all estimated parameters from all regions can be analysed at once. We refer to this method as Parameters undergoing Multivariate Bayesian Analysis (PuMBA). We simulated patient–control studies with different radioligands, varying sample sizes and measurement error to explore its performance, comparing the precision, statistical power, false positive rate and bias of estimated group differences relative to univariate analysis methods.ResultsWe show that PuMBA improves the statistical power for all examined applications relative to univariate methods without increasing the false positive rate. PuMBA improves the precision of effect size estimation, and reduces the variation of these estimates between simulated samples. Furthermore, we show that PuMBA yields performance improvements even in the presence of substantial measurement error. Remarkably, owing to its ability to leverage information shared between pharmacokinetic parameters, PuMBA even shows greater power than conventional univariate analysis of the true binding values from which the parameters were simulated. Across all applications, PuMBA exhibited a small degree of bias in the estimated outcomes; however, this was small relative to the variation in estimated outcomes between simulated datasets.ConclusionPuMBA improves the precision and power of statistical analysis of PET data without requiring the collection of additional measurements. This makes it possible to study new research questions in both new and previously collected data. PuMBA therefore holds great promise for the field of PET imaging.

Retrospective study of more than 5 million emergency admissions to hospitals in England: Epidemiology and outcomes for people with dementia.

People living with dementia (PwD) admitted in emergency to an acute hospital may be at higher risk of inappropriate care and poorer outcomes including longer hospitalisations and higher risk of emergency re-admission or death. Since 2009 numerous national and local initiatives in England have sought to improve hospital care for PwD. We compared outcomes of emergency admissions for cohorts of patients aged 65+ with and without dementia at three points in time. We analysed emergency admissions (EAs) from the Hospital Episodes Statistics datasets for England 2010/11, 2012/13 and 2016/17. Dementia upon admission was based on a diagnosis in the patient's hospital records within the last five years. Outcomes were length of hospital stays (LoS), long stays (> = 15 days), emergency re-admissions (ERAs) and death in hospital or within 30 days post-discharge. A wide range of covariates were taken into account, including patient demographics, pre-existing health and reasons for admission. Hierarchical multivariable regression analysis, applied separately for males and females, estimated group differences adjusted for covariates. We included 178 acute hospitals and 5,580,106 EAs, of which 356,992 (13.9%) were male PwD and 561,349 (18.6%) female PwD. Uncontrolled differences in outcomes between the patient groups were substantial but were considerably reduced after control for covariates. Covariate-adjusted differences in LoS were similar at all time-points and in 2016/17 were 17% (95%CI 15%-18%) and 12% (10%-14%) longer for male and female PwD respectively compared to patients without dementia. Adjusted excess risk of an ERA for PwD reduced over time to 17% (15%-18%) for males and 17% (16%-19%) for females, but principally due to increased ERA rates amongst patients without dementia. Adjusted overall mortality was 30% to 40% higher for PwD of both sexes throughout the time-period; however, adjusted in-hospital rates of mortality differed only slightly between the patient groups, whereas PwD had around double the risk of dying within 30 days of being discharged. Over the six-year period, covariate-adjusted hospital LoS, ERA rates and in-hospital mortality rates for PwD were only slightly elevated compared to similar patients without dementia and remaining differences potentially reflect uncontrolled confounding. PwD however, were around twice as likely to die shortly after discharge, the reasons for which require further investigation. Despite being widely used for service evaluation, LoS, ERA and mortality may lack sensitivity to changes in hospital care and support to PwD.

Estimating accelerated biological ageing using machine learning and metabolomics data in people with mental disorders

IntroductionAccelerated biological ageing might contribute to the higher prevalence of age-related diseases and excess mortality amongst individuals with mental disorders. Recent advances in machine learning and the collection of high-dimensional molecular “omics” data allow for the quantification of biological age.ObjectivesThe aim of this study was to use machine learning methods to predict biological age from nuclear magnetic resonance spectroscopy metabolomics data and to identify psychiatric traits associated with accelerated biological ageing.MethodsThe UK Biobank is a multicentre community-based observational study that recruited &gt;500,000 middle-aged and older adults. 168 metabolomic measures were quantified using the Nightingale Health platform. Phase 1 release of these data included a random subset of 118,462 UK Biobank participants. Metabolomic age delta (MetaboAgeΔ) was defined as the difference between predicted biological age and observed chronological age. We estimated group differences in MetaboAgeΔ between individuals with and without mental disorders and examined whether polygenic scores for mental disorders predicted MetaboAgeΔ.ResultsUp to 110,780 participants with complete data on all metabolomic measures were included in the analysis. Individuals with a history of mental disorders had higher MetaboAgeΔ values than people without a mental illness. For example, MetaboAgeΔ suggested that the difference between predicted biological age and observed chronological age was about two-years greater amongst individuals with bipolar disorder than amongst people without mental illness. Polygenic scores for mental disorders were positively correlated with MetaboAgeΔ.ConclusionsThese findings suggest that individuals with a history of mental disorders or with higher polygenic scores for mental disorders were biologically older than their chronological age.Disclosure of InterestNone Declared

Haematological indices in acute coronary syndromes: Could there be a hidden message?

Introduction and Aim: The routine markers of CAD show elevation after the development of acute manifestations. There exists a need for the establishment/validation of biomarkers that predict preclinical atherosclerotic changes. This study assesses the utility of haematological indices in the prediction and prognostication of CAD. Materials and Methods: This retrospective study includes 830 patient reports investigated for serum Troponin T retrieved from the laboratory information system. Reports were grouped into positive and negative categories. Relevant haematological and biochemical data were retrieved. Statistical analysis was carried out to estimate group differences, correlation, sensitivity, specificity, and AUC. Results: Troponin T positive group showed significantly elevated WBCs, neutrophils, CRP, NLR, PLR, and SII with significantly low lymphocytes, monocytes, basophils and RBC count. None of the lipid profile parameters, except serum triglyceride, showed significant differences between groups. Males showed a higher baseline but a blunter elevation CRP during acute coronary events. ROC showed maximum sensitivity (75.9%) and NPV (77.9%) for NLR, while PLR showed maximum specificity (76.4%). Conclusion: Haematological indices may have a better predictive value than conventional lipid profile and might serve as key markers in novel cardiac risk screening panels and aid in the risk stratification and management of coronary artery diseases.

Early Developmental Trajectories in Infants With Neurofibromatosis 1.

ObjectiveTo examine the trajectories of cognitive, motor and behavioural development in infants with NF1 compared to infants without a family history of neurodevelopmental difficulties.Study designInfants with NF1 and low-risk controls were recruited from 5 months of age and followed longitudinally. Data from standardised tests was gathered at 5, 10 and 14 months and developmental trajectories of motor, language, behaviour, sleep, social development and parent–infant interaction were examined. Linear mixed modelling was used to estimate group differences in cognitive and behavioural measures over time.ResultsNo group differences were observed on Mullen Scale of Early Learning, overall adaptive functioning, temperament or behavioural measures. There were no group differences observed on measures of social communication or parent–infant interaction. Over the course of development, the NF1 group slept less and took more time to settle to sleep as compared to the control group. Maternal education was significantly associated with cognitive and behavioural developmental outcomes in both groups.ConclusionCognitive, social and behavioural impairments are a cause of significant functional morbidity in children with NF1. This report is the first study to investigate the trajectories of cognitive, motor and behavioural development in infancy in NF1. Our results demonstrate that overall cognitive and behavioural developmental trajectories of the NF1 group in the infancy period are similar to controls. Given previous reports of delayed development in the NF1 cohort by 40 months, early clinical interventions strategies to promote sleep hygiene may be beneficial to optimise developmental outcomes.