Adjusted Mean Difference Research Articles

Cannabis-Containing Cream for CKD-Associated Pruritus: A Double-Blind, Placebo Controlled Trial

Rationale & ObjectiveThis study aims to compare the efficacy of a cannabis cream and a placebo in the treatment of chronic kidney disease (CKD)-associated pruritus. Study DesignA double-blind randomized controlled study. Setting & ParticipantsSixty hemodialysis patients with the Worst Itching Intensity Numerical Rating Scale (WI-NRS) ≥ 3. ExposurePatients received cannabis cream or placebo. OutcomesThe primary endpoint was the WI-NRS score at week 4. The secondary endpoints included the WI-NRS at week 2, Skindex-10 score at week 2 and 4, and the mean difference score between baseline and week 4 for WI-NRS and the Skindex-10 score Analytical ApproachWe utilized unpaired t-tests or Mann–Whitney U tests, along with Chi-square or Fisher’s exact tests as appropriate. Adjusted mean differences were determined using ANCOVA, adjusting for baseline scores. ResultsAmong 60 participants, mean age was 61.6 ± 14.4 years and mean baseline WI-NRS was 6.7 ± 1.7. The placebo and cannabis cream groups were similar at baseline, although more individuals in the placebo group had diabetes. At 4 weeks, the WI-NRS dropped to 2.6 in the cannabis group and 3.6 in the placebo group (mean difference after adjustment for baseline scores:-1.1, 95% CI: -2.1 to -0.2, p = 0.02). Skindex-10 scores at week 4 were also lower in the cannabis group, but after adjustment for baseline scores, statistical significance was not maintained. No side effects were observed in either group. LimitationsA single study with a small sample size restricts its generalizability. Variances in participants' diabetes statuses might have impacted itch outcomes. The absence of cannabinoid level assessment in blood prevents conclusive determination of potential systemic impacts. A four-week follow-up period inadequately captures long-term effect. ConclusionsIn CKD-associated pruritus, the topical cream containing cannabis significantly reduced the severity of itching symptoms compared to the placebo.

Outcomes of the My Therapy self-management program in people admitted for rehabilitation: A stepped wedge cluster randomized clinical trial

BackgroundSelf-management programs can increase the time spent on prescribed therapeutic exercises and activities in rehabilitation inpatients, which has been associated with better functional outcomes and shorter hospital stays. ObjectivesTo determine whether implementation of a self-management program (‘My Therapy’) improves functional independence relative to routine care in people admitted for physical rehabilitation. MethodsThis stepped wedge, cluster randomized trial was conducted over 54 weeks (9 periods of 6-week duration, April 2021 - April 2022) across 9 clusters (general rehabilitation wards) within 4 hospitals (Victoria, Australia). We included all adults (≥18 years) admitted for rehabilitation to participating wards. The intervention included routine care plus ‘My Therapy’, comprising a sub-set of exercises and activities from supervised sessions which could be performed safely, without supervision or assistance. The primary outcomes were the proportion of participants achieving a minimal clinically important difference (MCID) in the Functional Independence Measure, (FIM™) and change in total FIM™ score from admission to discharge. Results2550 participants (62 % women) were recruited (control: n = 1458, intervention: n = 1092), with mean (SD) age 77 (13) years and 37 % orthopedic diagnosis. Under intervention conditions, participants reported a mean (SD) of 29 (21) minutes/day of self-directed therapy, compared to 4 (SD 14) minutes/day, under control conditions. There was no evidence of a difference between control and intervention conditions in the odds of achieving an MCID in FIM™ (adjusted odds ratio 0.93, 95 % CI 0.65 to 1.31), or in the change in FIM™ score (adjusted mean difference: -0.27 units, 95 % CI -2.67 to 2.13). ConclusionsMy Therapy was delivered safely to a large, diverse sample of participants admitted for rehabilitation, with an increase in daily rehabilitation dosage. However, given the lack of difference in functional improvement with participation in My Therapy, self-management programs may need to be supplemented with other strategies to improve function in people admitted for rehabilitation. Trial registrationAustralian New Zealand Clinical Trials Registry (ACTRN12621000313831), https://www.anzctr.org.au/

Early parenteral nutrition is associated with improved growth in very low birth weight infants: a retrospective study

ObjectiveTo assess the association between early initiation of parenteral nutrition (PN) and body growth in preterm infants with very low birth weight (VLBW).DesignCausal inference analysis with confounders preselected by causal...

Polyp detection with colonoscopy assisted by the GI Genius artificial intelligence endoscopy module compared with standard colonoscopy in routine colonoscopy practice (COLO-DETECT): a multicentre, open-label, parallel-arm, pragmatic randomised controlled trial

Increased polyp detection during colonoscopy is associated with decreased post-colonoscopy colorectal cancer incidence and mortality. The COLO-DETECT trial aimed to assess the clinical effectiveness of the GI Genius intelligent endoscopy module for polyp detection, comparing colonoscopy assisted by GI Genius (computer-aided detection [CADe]-assisted colonoscopy) with standard colonoscopy in routine practice. We did a multicentre, open-label, parallel-arm, pragmatic randomised controlled trial in 12 National Health Service (NHS) hospitals (ten NHS Trusts) in England, among adults (aged ≥18 years) undergoing planned colonoscopy for gastrointestinal symptoms or for surveillance due to personal or family history (ie, symptomatic indications), or colorectal cancer screening. Randomisation (1:1) to CADe-assisted colonoscopy or standard colonoscopy was done with a web-based dynamic adaptive algorithm, immediately before colonoscopy, with stratification by age group, sex, colonoscopy indication (screening or symptomatic), and NHS Trust. Recruiting staff, participants, and colonoscopists were unmasked to trial allocation; histopathologists, co-chief investigators, and trial statisticians were masked. CADe-assisted colonoscopy consisted of standard colonoscopy plus the GI Genius module active for at least the entire inspection phase of colonoscope withdrawal. The primary outcome was mean adenomas per procedure (total number of adenomas detected divided by total number of procedures); the key secondary outcome was adenoma detection rate (proportion of colonoscopies with at least one adenoma). Analysis was by intention to treat (ITT), with outcomes compared between groups by mixed-effects regression modelling, in which effect estimates were adjusted for randomisation stratification variables. Data were imputed for outcome measures with more than 5% missing values. All participants who underwent colonoscopy were assessed for safety. The trial is registered on ISRCTN (ISRCTN10451355) and ClinicalTrials.gov (NCT04723758), and is complete. Between March 29, 2021, and April 6, 2023, 2032 participants (1132 [55·7%] male, 900 [44·3%] female; mean age 62·4 years [SD 10·8]) were recruited and randomly assigned: 1015 to CADe-assisted colonoscopy and 1017 to standard colonoscopy. 1231 (60·6%) participants were undergoing screening and 801 (39·4%) had symptomatic indications. Mean adenomas per procedure was 1·56 (SD 2·82; n=1001 participants with available data) in the CADe-assisted colonoscopy group versus 1·21 (1·91; n=1009) in the standard colonoscopy group, representing an adjusted mean difference of 0·36 (95% CI 0·14-0·57; adjusted incidence rate ratio 1·30 [95% CI 1·15-1·47], p<0·0001). Adenomas were detected in 555 (56·6%) of 980 participants in the CADe-assisted colonoscopy group versus 477 (48·4%) of 986 in the standard colonoscopy group, representing a proportion difference of 8·3% (95% CI 3·9-12·7; adjusted odds ratio 1·47 [95% CI 1·21-1·78], p<0·0001). Numbers of adverse events were similar between the CADe-assisted colonoscopy and standard colonoscopy groups (adverse events: 25 vs 19; serious adverse events: four vs six), and no adverse events in the CADe-assisted colonoscopy group were deemed to be related to GI Genius use on independent review. Results of the COLO-DETECT trial support the use of GI Genius to increase detection of premalignant colorectal polyps in routine colonoscopy practice. Medtronic.

Prefabricated contoured foot orthoses to reduce pain and increase physical activity in people with hip osteoarthritis: A randomised feasibility trial.

Hip osteoarthritis (OA) is a prevalent and burdensome condition that leads to impaired quality of life and a substantial economic burden. Encouraging physical activity, particularly walking, is crucial for OA management, but many individuals with hip OA fail to meet recommended activity levels. Prefabricated contoured foot orthoses have shown promise in improving hip muscle efficiency during walking in laboratory settings, but their real-world feasibility and efficacy remain uncertain. The aim of this study was to assess the feasibility of conducting a fully powered randomised controlled trial (RCT) to evaluate the effectiveness of prefabricated contoured foot orthoses, prescribed via telehealth, in people with hip OA. This feasibility trial randomised 27 participants with hip OA into two groups: prefabricated contoured foot orthoses or flat shoe inserts. Feasibility outcomes were assessed, including recruitment rate, adherence, logbook completion, and dropout rate. Patient-reported outcomes and accelerometer-measured physical activity were collected as secondary outcomes. While the recruitment rate was low (0.88 people/week), adherence to the intervention (59%), logbook completion (93%), and dropout rates (7%) met or exceeded our predefined feasibility parameters. Participants found the intervention acceptable, and practicality was demonstrated with minor adverse events. Preliminary efficacy testing indicated that prefabricated contoured foot orthoses positively affected physical activity (adjusted mean difference=2590 [260 to 4920] steps/day), with comparable outcomes for hip-related quality of life and pain. This trial supports proceeding to a fully powered RCT to assess the effect of teleheath prescribed prefabricated contoured foot orthoses on physical activity in people with hip OA. National Institutes of Health Trial Registry (NCT05138380).

Proactive integrated consultation-liaison psychiatry and time spent in hospital by older medical inpatients in England (The HOME Study): a multicentre, parallel-group, randomised controlled trial

Older people admitted to hospital in an emergency often have prolonged inpatient stays that worsen their outcomes, increase health-care costs, and reduce bed availability. Growing evidence suggests that the biopsychosocial complexity of their problems, which include cognitive impairment, depression, anxiety, multiple medical illnesses, and care needs resulting from functional dependency, prolongs hospital stays by making medical treatment less efficient and the planning of post-discharge care more difficult. We aimed to assess the effects of enhancing older inpatients' care with Proactive Integrated Consultation-Liaison Psychiatry (PICLP) in The HOME Study. We have previously described the benefits of PICLP reported by patients and clinicians. In this Article, we report the effectiveness and cost-effectiveness of PICLP-enhanced care, compared with usual care alone, in reducing time in hospital. We did a parallel-group, multicentre, randomised controlled trial in 24 medical wards of three English acute general hospitals. Patients were eligible to take part if they were 65 years or older, had been admitted in an emergency, and were expected to remain in hospital for at least 2 days from the time of enrolment. Participants were randomly allocated to PICLP or usual care in a 1:1 ratio by a database software algorithm that used stratification by hospital, sex, and age, and randomly selected block sizes to ensure allocation concealment. PICLP clinicians (consultation-liaison psychiatrists supported by assisting clinicians) made proactive biopsychosocial assessments of patients' problems, then delivered discharge-focused care as integrated members of ward teams. The primary outcome was time spent as an inpatient (during the index admission and any emergency readmissions) in the 30 days post-randomisation. Secondary outcomes were the rate of discharge from hospital for the total length of the index admission; discharge destination; the length of the index admission after random allocation truncated at 30 days; the number of emergency readmissions to hospital, the number of days spent as an inpatient in an acute general hospital, and the rate of death in the year after random allocation; the patient's experience of the hospital stay; their view on the length of the hospital stay; anxiety (Generalized Anxiety Disorder-2); depression (Patient Health Questionnaire-2); cognitive function (Montreal Cognitive Assessment-Telephone version); independent functioning (Barthel Index of Activities of Daily Living); health-related quality of life (five-level EuroQol five-dimension questionnaire); and overall quality of life. Statisticians and data collectors were masked to treatment allocation; participants and ward staff could not be. Analyses were intention-to-treat. The trial had a patient and public involvement panel and was registered with ISRTCN (ISRCTN86120296). 2744 participants (1399 [51·0%] male and 1345 [49·0%] female) were enrolled between May 2, 2018, and March 5, 2020; 1373 were allocated to PICLP and 1371 to usual care. Participants' mean age was 82·3 years (SD 8·2) and 2565 (93·5%) participants were White. The mean time spent in hospital in the 30 days post-randomisation (analysed for 2710 [98·8%] participants) was 11·37 days (SD 8·74) with PICLP and 11·85 days (SD 9·00) with usual care; adjusted mean difference -0·45 (95% CI -1·11 to 0·21; p=0·18). The only statistically and clinically significant difference in secondary outcomes was the rate of discharge, which was 8.5% higher (rate ratio 1·09 [95% CI 1·00 to 1·17]; p=0·042) with PICLP-a difference most apparent in patients who stayed for more than 2 weeks. Compared with usual care, PICLP was estimated to be modestly cost-saving and cost-effective over 1 and 3, but not 12, months. No intervention-related serious adverse events occurred. This is the first randomised controlled trial of PICLP. PICLP is experienced by older medical inpatients and ward staff as enhancing medical care. It is also likely to be cost-saving in the short-term. Although the trial does not provide strong evidence that PICLP reduces time in hospital, it does support and inform its future development and evaluation. UK National Institute for Health and Care Research.

Opioid agonist treatment outcomes among individuals with a history of nonfatal overdose: Findings from a pragmatic, pan-Canadian, randomized control trial.

History of nonfatal overdose (NFO) is common among people who use opioids, but little is known about opioid agonist treatment (OAT) outcomes for this high-risk subpopulation. The objective of this study was to investigate the relative effectiveness of buprenorphine/naloxone and methadone on retention and suppression of opioid use among individuals with opioid use disorder (OUD) and history of NFO. Secondary analysis of a pan-Canadian pragmatic trial comparing flexible take-home buprenorphine/naloxone and supervised methadone for people with OUD and history of NFO. Logistic regression was used to examine the impact of OAT on retention in the assigned or in any OAT at 24 weeks and analysis of covariance was used to examine the mean difference in opioid use between treatment arms. Of the 272 randomized participants, 155 (57%) reported at least one NFO at baseline. Retention rates in the assigned treatment were 17.7% in the buprenorphine/naloxone group and 18.4% in the methadone group (adjusted odds ratio [AOR] = 0.54, 95% CI: 0.17-1.54). Rates of retention in any OAT were 28% and 20% in the buprenorphine/naloxone and methadone arms, respectively (AOR = 1.55, 95% CI: 0.65-3.78). There was an 11.9% adjusted mean difference in opioid-free urine drug tests, favoring the buprenorphine/naloxone arm (95% CI: 3.5-20.3; p = .0057). Among adults with OUD and a history of overdose, overall retention rates were low but improved when retention in any treatment was considered. These findings highlight the importance of flexibility and patient-centered care to improve retention and other treatment outcomes in this population.

Effectiveness of a group psychological intervention to reduce psychosocial distress in adolescents in Pakistan: a single-blind, cluster randomised controlled trial

Emotional problems in adolescents living in low-income and middle-income countries (LMICs) remain largely unaddressed; key reasons include a scarcity of trained mental health professionals and unavailability of evidence-based, scalable psychological interventions. We aimed to evaluate the effectiveness of a non-specialist-delivered, group psychological intervention to reduce psychosocial distress in school-going adolescents in Pakistan. In a two-arm, single-blind, cluster randomised controlled trial, eligible public school clusters from a rural subdistrict of Gujar Khan, Rawalpindi, Pakistan, were randomised (1:1, stratified by sex) using permuted block randomisation into intervention (n=20) and wait-list control (n=20) groups. Adolescents aged 13-15 years who provided informed assent and caregivers' consent were screened for psychosocial distress using the youth-reported Pediatric Symptoms Checklist (PSC; total psychosocial distress scores from 0 to 70), and those scoring 28 or more and their caregivers were enrolled into the trial. Adolescents in the intervention group received seven weekly group sessions and their caregivers received three biweekly group sessions in school settings from trained non-specialists. The primary outcome was change from baseline in the total PSC scores at 3 months post-intervention. The trial was registered prospectively with the International Standard Randomised Controlled Trial Number registry, ISRCTN17755448. From the 40 school clusters that were included, 282 adolescents in the intervention group and 284 adolescents in the wait-list control group were enrolled between Nov 2 and Nov 30, 2021. At 3 months, adolescents in the intervention group had significantly lower mean total score on the PSC compared with adolescents in the control group (mean difference in change from baseline 3·48 [95% CI 1·66-5·29], p=0·0002, effect size 0·38 [95% CI 0·18-0·57]; adjusted mean difference 3·26 (95% CI 1·46-5·06], p=0·0004, effect size 0·35 (0·16-0·55). No adverse events were reported in either group. The group psychological intervention most likely represents a feasible and effective option for adolescents with psychosocial distress in school settings. UK Medical Research Council, Foreign Commonwealth and Development Office, Department of Health and Social Care. For the Urdu translation of the abstract see Supplementary Materials section.

National Case Volumes and Gender Disparities in Emergency Department Utilization for Psychiatric Emergencies: A Population-Based Claims Data Analysis.

Introduction The utilization of emergency departments (EDs) for managing psychiatric emergencies has significantly increased in the United Statesbecause of the increasing prevalence of mental health disorders. This study examined national case volumes and sex disparities in ED visits for psychiatric emergencies usingdata from the Nationwide Emergency Department Sample (NEDS). Methods This retrospective analysis included adult ED visits for psychiatric emergencies identified using relevant International Classification of Diseases, 10th Revision (ICD-10) codes. Primary endpoints included national case volumes by sex. Hospitalizations with age < 18 years and those with missing data on sex were excluded. Secondary endpoints included inpatient mortality, ED and inpatient costs, admission rates, discharge disposition, length of stay (LOS), and number of procedures. Results In 2021, there were approximately 143.5 million ED visits in the United States, with 7,978,490 of these being for psychiatric emergencies. The most common presentations were substance abuse and intoxication (5,119,086 (64.2%)), severe bipolar disorder (1,912,670 (24%)), and anxiety or panic attacks (1,015,486 (12.7%)). Approximately 3,997,223 (50.1%) were women, and 3,981,267 (49.9%) were men. Men were older (mean age: 45 versus 43 years; P<0.001), were more likely to be uninsured (712,647 (17.9%) versus 497,658 (12.5%); P<0.001), and had a higher Charlson Comorbidity Index (CCI) (CCI ≥ 2: 792,272 (19.9%) versus 643,552 (16.1%); P<0.001). More men than women presented to the ED with acute substance abuse or intoxication (3,196,945 (80.3%) versus 1,922,142 (48.1%)), bipolar disorder with or without psychosis (958,275 (24.1%) versus 954,395 (23.9%); P<0.001), and suicidal ideation (267,638 (6.7%) versus 208,989 (5.2%); P<0.001). More women than men presented with severe depression (455,683 (11.4%)versus 441,921 (11.1%)), anxiety and panic attacks (615,572 (15.4%) versus402,108 (10.1%)), acute stress reaction (35,975 (0.9%) versus 23,888 (0.6%)), eating disorders (3,997 (0.1%) versus27,869 (0.07%)), and a history of abuse (21,164 (0.53%) versus19,569 (0.49%); P<0.001). Women had lower mortality rates (27,980 (0.7%) versus 63,956 (1.6%); P<0.001), lower mean ED costs (adjusted mean difference (AMD): $1,189; P<0.001), fewer in-hospital admissions (1,211,158 (30.3%) versus 1,453,162 (36.5%); P<0.001), and a higher number of prolonged hospitalizations (1,442,998 (36.1%) versus 1,194,380 (30%); P<0.001) compared with men. Conclusion Thisstudy highlights significant sex disparities in EDutilizationforpsychiatric emergencies.Men more frequently present with substance abuse and severe comorbidities, leading to higher healthcare costs and inpatient admissions. Women, while more likely to present with anxiety and depressive disorders, incur lower costs and have better overall outcomes.

Clinical and cost-effectiveness of remote-delivered, online lifestyle therapy versus psychotherapy for reducing depression: results from the CALM non-inferiority, randomised trial

We conducted the first non-inferiority, randomised controlled trial to determine whether lifestyle therapy is non-inferior to psychotherapy with respect to mental health outcomes and costs when delivered via online videoconferencing. An individually randomised, group treatment design with computer-generated block randomisation was used. Between May 2021-April 2022, 182 adults with a Distress Questionnaire-5 score=≥8 (indicative depression) were recruited from a tertiary mental health service in regional Victoria, Australia and surrounds. Participants were assigned to six 90-min sessions over 8-weeks using group-based, online videoconferencing comprising: (1) lifestyle therapy (targeting nutrition, physical activity) with a dietitian and exercise physiologist (n=91) or (2) psychotherapy (Cognitive Behavioural Therapy) with psychologists (n=91). The primary outcome was Patient Health Questionnaire-9 (PHQ-9) depression at 8-weeks (non-inferiority margin ≤2) using Generalised Estimating Equations (GEE). Cost-minimisation analysis estimated the mean difference in total costs from health sector and societal perspectives. Outcomes were assessed by blinded research assistants using Computer Assisted Telephone Interviews. Results are presented per-protocol (PP) and Intention to Treat (ITT) using beta coefficients with 95% Confidence Intervals (CIs). The sample was 80% women (mean: 45-years [SD:13.4], mean PHQ-9:10.5 [SD:5.7]. An average 4.2 of 6 sessions were completed, with complete data for n=132. Over 8-weeks, depression reduced in both arms (PP: Lifestyle (n=70) mean difference:-3.97, 95% CIs:-5.10,-2.84; and Psychotherapy (n=62): mean difference:-3.74, 95% CIs:-5.12,-2.37; ITT: Lifestyle (n=91) mean difference:-4.42, 95% CIs:-4.59,-4.25; Psychotherapy (n=91) mean difference:-3.82, 95% CIs:-4.05,-3.69) with evidence of non-inferiority (PP GEE β:-0.59; 95% CIs:-1.87, 0.70, n=132; ITT GEE β:-0.49, 95% CIs:-1.73, 0.75, n=182). Three serious adverse events were recorded. While lifestyle therapy was delivered at lower cost, there were no differences in total costs (health sector adjusted mean difference: PP AUD$156 [95% CIs-$182, $611, ITT AUD$190 [95% CIs-$155, $651] ]; societal adjusted mean difference: PP AUD$350 [95% CIs:-$222, $1152] ITT AUD$ 408 [95% CIs-$139, $1157]. Remote-delivered lifestyle therapy was non-inferior to psychotherapy with respect to clinical and cost outcomes. If replicated in a fully powered RCT, this approach could increase access to allied health professionals who, with adequate training and guidelines, can deliver mental healthcare at comparable cost to psychologists. This trial was funded by the Australian Medical Research Future Fund (GA133346) under its Covid-19 Mental Health Research Grant Scheme.

Effect of antihypertensive deprescribing on hospitalisation and mortality: long-term follow-up of the OPTiMISE randomised controlled trial

Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. The OPTiMISE trial showed that this deprescribing can be achieved with no differences in blood pressure control at 3months compared with usual care. We aimed to examine effects of deprescribing on longer-term hospitalisation and mortality. This randomised controlled trial enrolled participants from 69general practices across central and southern England. Participants aged 80years or older, with systolic blood pressure less than 150mm Hg and who were receiving two or more antihypertensive medications, were randomly assigned (1:1) to antihypertensive medication reduction (removal of one antihypertensive) or usual care. General practitioners and participants were aware of the treatment allocation following randomisation but individuals responsible for analysing the data were masked to the treatment allocation throughout the study. Participants were followed up via their primary and secondary care electronic health records at least 3years after randomisation. The primary outcome was time to all-cause hospitalisation or mortality. Intention-to-treat analyses were done using Cox regression modelling. A per-protocol analysis of the primary outcome was also done, excluding participants from the intervention group who did not reduce treatment or who had medication reinstated during the initial trial 12-week follow-up period. This study is registered with the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT2016-004236-38) and the ISRCTN Registry (ISRCTN97503221). Between March 20, 2017, and Sept 30, 2018, a total of 569participants were randomly assigned. Of these, 564(99%; intervention=280; control=284) were followed up for a median of 4·0years (IQR 3·7-4·3). Participants had a mean age of 84·8years (SD 3·4) at baseline and 273 (48%) were women. Medication reduction was sustained in 109participants at follow-up (51% of the 213participants alive in the intervention group). Participants in the intervention group had a larger reduction in antihypertensives than the control group (adjusted mean difference -0·35drugs [95% CI -0·52 to -0·18]). Overall, 202 (72%) participants in the intervention group and 218 (77%) participants in the control group experienced hospitalisation or mortality during follow-up (adjusted hazard ratio [aHR] 0·93 [95% CI 0·76to 1·12]). There was some evidence that the proportion of participants experiencing the primary outcome in the per-protocol population was lower in the intervention group (aHR 0·80 [0·64to 1·00]). Half of participants sustained medication reduction with no evidence of an increase in all-cause hospitalisation or mortality. These findings suggest that an antihypertensive deprescribing intervention might be safe for people aged 80years or older with controlled blood pressure taking two or more antihypertensives. British Heart Foundation and National Institute for Health and Care Research.

Longer-term Effect of Physical Activity Intervention on Sleep Quality: A Secondary Analysis of Cluster Randomized Controlled Trial.

To examine the longer-term effect of physical activity (PA) intervention on sleep quality and whether the effect was heterogeneous between daytime nappers and non-nappers. This study was a secondary analysis of a cluster randomized controlled trial in China. Eight villages were randomized 1:1 to intervention or control group. The intervention group received an 8-week PA intervention, while the control group did not. The primary outcome of this study was the change in the Pittsburgh Sleep Quality Index (PSQI) global score at 24 months. The 511 participants had a mean age of 70.94 years (SD 5.73) and 55.6% were female. The intervention showed improvements in the PSQI global score at 8 weeks (adjusted mean difference -1.05; P=0.002), and the effect diminished at 24 months (-0.64; P=0.06). There were statistically significant improvements in the PSQI global score for daytime nappers, but not for non-nappers at 8 weeks (adjusted mean difference -0.98; P=0.01 vs -1.27; P=0.05), 12 months (-0.86; P=0.03 vs -0.84; P=0.21), and 24 months (-0.80; P=0.04 vs -0.14; P=0.84), although these improvements were below the minimum detectible level of the PSQI which is 1 point. The 8-week PA intervention was effective in improving sleep quality, while the effect was diminished and below the minimum detectible level of the PSQI which is 1 point after 24 months. The effect of PA intervention on sleep quality was more pronounced in daytime nappers. Additional interventions (e.g., focusing on multiple behavioral interventions such as PA and healthy diet) are needed to maintain the beneficial effect of PA on sleep quality in the general older populations. Further research is required to confirm the mechanisms of the effect of napping and develop tailored interventions.

Maternal Placental Growth Factor (PlGF) levels, sonographic placental parameters, and outcomes of IVF pregnancies with and without embryo trophectoderm biopsy.

In vitro fertilization (IVF) is associated with abnormal trophoblast invasion and resultant decreased levels of circulating placental biomarkers such as placental growth factor (PlGF).Our objective was to evaluate maternal serum levels of second/third trimester PlGF, sonographic placental parameters, and clinical outcomes among IVF frozen embryo transfer (FET) pregnancies with and without embryo trophectoderm biopsy. This was a retrospective study of pregnant patients who conceived using a single frozen embryo transfer (FET) and gave birth between 30 January 2018 and 31 May 2021. We compared PlGF levels, sonographic placental parameters, and clinical outcomes between FET with biopsy and FET without biopsy groups. The median PlGF level was 614.5 pg/mL (IQR 406-1020) for FET pregnancies with biopsy, and 717.0 pg/mL (IQR 552-1215) for FET pregnancies without biopsy. The adjusted mean difference was 190.9 pg/mL lower in the FET biopsy group (95% CI, -410.6, 28.8; p = 0.088). There were no statistically significant differences in placental parameters or clinical pregnancy outcomes. This exploratory study demonstrated a possible trend toward lower maternal serum PlGF in the pregnancies conceived with FET using a biopsied embryo. Further investigation is warranted into the potential placental health effects of trophectoderm biopsy.

Health Care Needs and Costs for Children Exposed to Prenatal Substance Use to Adulthood.

Children exposed to substance use during pregnancy have increased health needs but whether these are influenced by engagement in out-of-home care is uncertain. To evaluate the association between substance use during pregnancy, out-of-home care and hospitalization utilization, and costs from birth up to age 20 years. This was a retrospective cohort study using individual-linked population birth, hospital, and out-of-home care information of all liveborn infants from New South Wales, Australia, between 2001 and 2020 using longitudinal population-based linkage records from administrative databases. Substance use during pregnancy included newborns with neonatal abstinence syndrome (n = 5946) and intrauterine exposure to drugs of addiction (n = 1260) and other substances (eg, tobacco, alcohol, and illicit drugs or misused prescription drugs; n = 202 098). Children not exposed to substance use during pregnancy were those without known exposure to substance use during pregnancy (n = 1 611 351). Data were analyzed from July 2001 to December 2021. Main outcomes were hospital readmission, length of stay, and cost burden associated with substance use during pregnancy from birth up to age 20 years. Outcomes were investigated using 2-part and Poisson regression models adjusted for sociodemographic characteristics. Mediation analysis was used to evaluate whether the association of substance use during pregnancy with risk of readmission was mediated through engagement with out-of-home care. Of the 1 820 655 live births, 935 807 (51.4%) were male. The mean (SD) age of mothers was 30.8 (5.5) years. Compared with children who were not exposed to substance use during pregnancy, those who were exposed incurred significantly higher birth hospital costs (adjusted mean difference, A$1585 per child [US$1 = A$1.51]; 95% CI, 1585-1586). If discharged alive, more children with exposure to substance use during pregnancy had at least 1 readmission (90 433/209 304 [43.4%] vs 616 425/1 611 351[38.3%]; adjusted relative risk [RR], 1.06; 95% CI, 1.06-1.07), most commonly for respiratory conditions (RR, 1.11; 95% CI, 1.09-1.12) and mental health/behavioral disorders (RR, 1.36; 95% CI, 1.33-1.41). Excess hospital costs associated with substance use during pregnancy were A$129.0 million in 2019 to 2020. Mediation analyses showed that any out-of-home care contact mediated the association between substance use during pregnancy and risk of inpatient readmission and lower health care cost (decreased by A$25.4 million). For children with neonatal abstinence syndrome, any out-of-home care contact mediated readmission risk by approximately 30%, from adjusted RR, 1.28; 95% CI, 1.19-1.35, to RR, 1.01; 95% CI, 0.98-1.02. Children who were exposed to substance use during pregnancy incurred more hospital costs than children who were not exposed up to 20 years of age, but this was reduced in association with any contact with out-of-home care. This provides insights into possible strategies for reducing health and financial burdens associated with exposure to substance use during pregnancy for children.

Race as social determinant of growth and body composition among infants born very preterm.

Racism leads to disparities in health outcomes. Our objective was to determine if black race was independently associated with differences in fat accretion at discharge in a large cohort of very preterm infants (32 weeks of gestation or less). De-identified demographic, anthropometric and body composition data were collected from seven neonatal units around the United States. Weight, length, and head circumference z-scores at birth and at the time of body composition assessment or hospital discharge were calculated. The median gestational age and birthweight for this cohort (n = 888) were 29 weeks [IQR, 27-30] and 1167 g [SD, 354], respectively. The study population included 53% black preterm infants. Birthweight was lower in black preterm infants compared with white infants (1112 ± 334 g vs. 1228 ± 366 g; p < 0.0001). After adjusting for birthweight, gestational age, and birthweight-for-age z-score, black preterm infants had more weight gain (adjusted mean difference: 0.5 g/kg/day; p = 0.03) but not higher BF% z-scores at hospital discharge (adjusted mean: 1.2 vs. 1.3; p = 0.14) than white infants. After adjusting for covariates, black race was associated with higher weight gain velocity but not higher BF% z-scores. This study presents findings from a large-scale multicenter cohort. Racial differences were observed in birth weight and the rate of weight gain; however, these differences were not associated with dissimilarities in body composition outcomes. Understanding nutrition and growth outcomes across racial groups is necessary to combat racial disparities in the neonatal intensive care unit (NICU).

Effect of music therapy combined with aerobic exercise on sleep quality among breast cancer patients undergoing chemotherapy after a radical mastectomy: a randomized controlled trial

PurposeWe aimed to study the effect of music therapy combined with aerobic exercise on the sleep quality of patients undergoing chemotherapy after a radical mastectomy.MethodsA randomized controlled trial was conducted at the Breast Disease Diagnosis and Treatment Center, Shaanxi Province Tumor Hospital, from July 2017 to June 2019. 110 female breast cancer patients who underwent a radical mastectomy were recruited and randomly allocated into an intervention group or a control group. The intervention group completed music therapy combined with aerobic exercise from the first to the sixth admission to the hospital for chemotherapy, while the control group received only routine nursing care. The sleep quality of these patients was measured using the Pittsburgh Sleep Quality Index (PSQI). A linear mixed model was used to adjust the PSQI of patients after controlling for other confounding factors.ResultsThe mean sleep quality score of the breast cancer patients who received chemotherapy after a radical mastectomy (baseline) was 8.86 ± 2.34. The intervention group had a significantly lower mean global PSQI score than the control group from the first test to the third test, with an adjusted mean difference of -1.05 (95%CI: -1.86, -0.24; P = 0.01), -2.89 (95%CI: -3.70, -2.08; P < 0.001) and − 4.84 (95%CI: -5.65, -4.03; P < 0.001), respectively. A change in the global PSQI score from baseline for the intervention group was from 0.55 (95%CI: -0.24, 1.34; P = 0.171) at the first test to 2.75 (95%CI: 1.96, 3.53; P < 0.001) at the last test, and for the control group was from − 0.51 (95%CI: -1.31, 0.29; P = 0.213 at the first test to -2.10 (95%CI: -2.91, -1.30; P < 0.001) at the last test.ConclusionsAn intervention of music therapy combined with aerobic exercise can significantly improve the sleep quality of female breast cancer patients undergoing chemotherapy after a radical mastectomy, and this intervention continuously improves many aspects of sleep reactivity.Clinical trial registrationThis study was registered in the Chinese Clinical Trial Registry (ChiCTR2100042975, 02/02/2021).

Depression and Implantable Cardioverter-Defibrillator Implantation in Black Patients at Risk for Sudden Cardiac Death.

Black patients meeting indications for implantable cardioverter-defibrillators (ICDs) have lower rates of implantation compared with White patients. There is little understanding of how mental health impacts the decision-making process among Black patients considering ICDs. Our objective was to assess the association between depressive symptoms and ICD implantation among Black patients with heart failure. This is a secondary analysis of the VIVID (Videos to Address Racial Disparities in ICD Therapy via Innovative Designs) randomized trial, which enrolled self-identified Black individuals with chronic systolic heart failure. Depressive symptoms were assessed by the Patient Health Questionnaire-2 and the Mental Component Summary of the 12-Item Short-Form Health Survey. Decisional conflict was measured by an adapted Decisional Conflict Scale (DCS). ANCOVA was used to assess differences in Decisional Conflict Scale scores. Multivariable logistic regression was used to examine the association between depressive symptoms and ICD implantation. Among 306 participants, 60 (19.6%) reported depressed mood, and 142 (46.4%) reported anhedonia. Participants with the lowest Mental Component Summary of the 12-Item Short-Form Health Survey scores (poorer mental health and higher likelihood of depression) had greater decisional conflict regarding ICD implantation compared with those with the highest Mental Component Summary of the 12-Item Short-Form Health Survey scores (adjusted mean difference in Decisional Conflict Scale score, 3.2 [95% CI, 0.5-5.9]). By 90-day follow-up, 202 (66.0%) participants underwent ICD implantation. There was no association between either the Patient Health Questionnaire-2 score or the Mental Component Summary of the 12-Item Short-Form Health Survey score and ICD implantation. Depressed mood and anhedonia were prevalent among ambulatory Black patients with chronic systolic heart failure considering ICD implantation. The presence of depressive symptoms did not impact the likelihood of ICD implantation in this population.

P-471 Anxiety, depression, and body image among infertile women with and without polycystic ovary syndrome

Abstract Study question Do women with PCOS undergoing fertility treatment experience higher anxiety and depression symptoms, along with lower body appreciation, compared to those without PCOS? Summary answer Having PCOS was not associated with symptoms of anxiety and depression, but was associated with somewhat lower body appreciation. What is known already PCOS has been associated with a higher chance to develop mental health problems, like anxiety, and body image concerns. The International Guidelines on PCOS recommend that all women with PCOS should routinely be screened for anxiety and depressive disorders. In most studies in this field, the comparison group included healthy women without fertility problems. Study design, size, duration We conducted a cross-sectional survey study between May 2021 and July 2023, using an online questionnaire. We informed women about this study at fertility clinics in the Netherlands through posters and leaflets and on the websites of the Dutch patient organizations Freya and Stichting PCOS. Participants/materials, setting, methods This study included women with infertility, with and without PCOS, undergoing fertility treatment. Women completed the Hospital Anxiety and Depression Scale and the Body Appreciation Scale-2. Primary outcomes were clinically relevant symptoms of anxiety and depression (scores&amp;gt;11), and BAS-2 scores. Secondary outcomes were mean anxiety and depression scores, along with scores of 8 and higher. Dichotomous and continuous outcomes were analysed using logistic and linear regression analyses adjusted for age, BMI, and duration of infertility. Main results and the role of chance A total of 1025 women currently undergoing infertility treatment participated, of whom 502 (49.0%) had PCOS and 523 (51.0%) had other infertility diagnoses. We found self-reported clinically relevant symptoms of anxiety in 33.1% of women with PCOS and in 31.0% of women with other infertility diagnoses (adjusted OR: 0.99, 95% CI 0.74 – 1.31). Clinically relevant symptoms of depression were reported in 15.5% of women with PCOS versus 14.5% of women with other infertility diagnoses (adjusted OR: 1.04, 95% CI 0.71 – 1.50). Women with PCOS reported slightly less body appreciation (adjusted mean difference: -1.34, 95% CI -2.32 to -0.36). Limitations, reasons for caution Results are based on self-report and may have been affected by sampling bias. Wider implications of the findings Although guidelines recommend screening women with PCOS, feelings of anxiety and depression can be present in any woman undergoing fertility treatments. We advise fertility clinics to be aware of women’s mental health issues and to offer support accordingly, as a part of routine care. Trial registration number not applicable

Effects of the discontinuation of antihypertensive treatment on neuropsychiatric symptoms and quality of life in nursing home residents with dementia (DANTON): a multicentre, open-label, blinded-outcome, randomised controlled trial.

Based on observational studies and randomised controlled trials (RCTs), the benefit-harm balance of antihypertensive treatment in older adults with dementia is unclear. To assess whether discontinuing antihypertensive treatment reduces neuropsychiatric symptoms (NPSs) and maintains quality of life (QoL) in nursing home residents with dementia. Open-label, blinded-outcome RCT. Randomisation 1:1, stratified by nursing home organisation and baseline NPS. Trial registration: NL7365. Dutch long-term care residents with moderate-to-severe dementia and systolic blood pressure (SBP) ≤160mmHg during antihypertensive treatment. Exclusion criteria included heart failure NYHA-class-III/IV, recent cardiovascular events/procedures or life expectancy <4months (planned sample size n = 492). Co-primary outcomes NPS (Neuropsychiatric Inventory-Nursing Home [NPI-NH]) and QoL (Qualidem) at 16weeks. From 9 November 2018 to 4 May 2021, 205 participants (median age 85.8 [IQR 79.6-89.5] years; 79.5% female; median SBP 134 [IQR 123-146] mmHg) were randomised to either antihypertensive treatment discontinuation (n = 101) or usual care (n = 104). Safety concerns, combined with lacking benefits, prompted the data safety and monitoring board to advice a premature cessation of randomisation. At 16-week follow-up, no significant differences were found between groups for NPI-NH (adjusted mean difference 1.6 [95% CI -2.3 to 5.6]; P = 0.42) or Qualidem (adjusted mean difference - 2.5 [95% CI -6.0 to 1.0]; P = 0.15). Serious adverse events (SAEs) occurred in 36% (discontinuation) and 24% (usual care) of the participants (adjusted hazard ratio 1.65 [95% CI 0.98-2.79]). All 32-week outcomes favoured usual care. Halfway through this study, a non-significant increased SAE risk associated with discontinuing antihypertensive treatment was observed, and an associated interim analysis showed that significant worthwhile health gain for discontinuation of antihypertensive treatment was unlikely. This unbeneficial benefit-harm balance shows that discontinuation of antihypertensive treatment in this context does not appear to be either safe or beneficial enough to be recommended in older adults with dementia.

Association Between Pharmacologic Treatment of Depression and Patient-Reported Outcomes Following Total Hip and Knee Arthroplasty

BackgroundDepression is associated with inferior outcomes following hip or knee arthroplasty, though it remains unclear if this relationship is modifiable. This study examined the association between pharmacologic treatment of depression and patient-reported outcomes. MethodsThis retrospective cohort study of 1,651 total hip arthroplasty (THA) and 1,792 total knee arthroplasty (TKA) procedures between October 2012 and June 2019 used institutional registry data linked to nationwide pharmaceutical claims. The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) global score, with pain and function subscales assessed as secondary outcomes. The TKA and THA patients were analyzed separately via mixed-effect linear regression to compare patients who had depression treated with antidepressants (TKA, n = 210; THA, n = 150) to those who had untreated depression (TKA, n = 43; THA; n = 50), and those who did not have depression (TKA, n = 1,539; THA, n = 1,451). ResultsAmong patients who had depression, not receiving preoperative antidepressant therapy was associated with smaller improvements in WOMAC global scores (TKA, adjusted mean difference [MD]: −13.1 points, 95% CI [confidence interval]: −21.4 to −4.8; THA, MD: −8.5 points, 95% CI: −15.7 to −1.2) at 2 years after surgery, but not at 1 year (TKA, MD: −5.4 points, 95% CI: −12.9 to 2.1; THA, MD: −6.3 points, 95% CI: −12.9 to 0.3). Those who did not have depression had similar improvements in WOMAC global scores to those who had treated depression at both one (TKA, MD: 0.8 points, 95% CI: −2.7 to 4.4; THA, MD: 1.8 points, 95% CI: −1.8 to 5.4) and 2 years (TKA, MD: −1.1 points, 95% CI: −4.9 to 2.7; THA, MD: −1.6 points, 95% CI: −5.6 to 2.3). The findings were consistent with secondary outcomes. ConclusionsAmong patients who have depression, antidepressant therapy before TKA or THA is associated with improved outcomes. Additional studies are needed to establish the impact of interventions to address untreated depression before surgery.