Standard Care Group Research Articles

Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma.

Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%). A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).

Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma

BackgroundIn an analysis of the primary outcome of this phase 3 trial, patients with early relapsed or refractory large B-cell lymphoma who received axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor T-cell therapy, as second-line treatment had significantly longer event-free survival than those who received standard care. Data were needed on longer-term outcomes.MethodsIn this trial, we randomly assigned patients with early relapsed or refractory large B-cell lymphoma in a 1:1 ratio to receive either axi-cel or standard care (two to three cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had a response). The primary outcome was event-free survival, and key secondary outcomes were response and overall survival. Here, we report the results of the prespecified overall survival analysis at 5 years after the first patient underwent randomization.ResultsA total of 359 patients underwent randomization to receive axi-cel (180 patients) or standard care (179 patients). At a median follow-up of 47.2 months, death had been reported in 82 patients in the axi-cel group and in 95 patients in the standard-care group. The median overall survival was not reached in the axi-cel group and was 31.1 months in the standard-care group; the estimated 4-year overall survival was 54.6% and 46.0%, respectively (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.54 to 0.98; P=0.03 by stratified two-sided log-rank test). This increased survival with axi-cel was observed in the intention-to-treat population, which included 74% of patients with primary refractory disease and other high-risk features. The median investigator-assessed progression-free survival was 14.7 months in the axi-cel group and 3.7 months in the standard-care group, with estimated 4-year percentages of 41.8% and 24.4%, respectively (hazard ratio, 0.51; 95% CI, 0.38 to 0.67). No new treatment-related deaths had occurred since the primary analysis of event-free survival.ConclusionsAt a median follow-up of 47.2 months, axi-cel as second-line treatment for patients with early relapsed or refractory large B-cell lymphoma resulted in significantly longer overall survival than standard care. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.)

Acupuncture after valve surgery is feasible and shows promise in reducing postoperative atrial fibrillation: The ACU-Heart pilot trial

ObjectiveAcupuncture is an effective treatment for arrythmias and postoperative symptoms but has not been investigated after cardiac surgery. Acupuncture After Heart Surgery is a prospective, randomized, controlled pilot trial of daily inpatient acupuncture or standard care after valve surgery with the primary end point being feasibility and secondary end points being reduction in postoperative atrial fibrillation incidence and postoperative symptoms. MethodsA total of 100 patients without a history of atrial fibrillation underwent primary valve surgery via sternotomy and randomized 1:1 to acupuncture (51) or standard care (49). The acupuncture group received daily inpatient sessions starting on postoperative day 1. Postoperative symptoms (pain, nausea, stress, anxiety) were assessed once daily in the standard care group and before/after daily intervention in the acupuncture group. The groups were comparable except for age (acupuncture: 55.6 ± 11.4 years, standard care: 61.0 ± 9.3 years; P = .01). ResultsThe Acupuncture After Heart Surgery pilot trial met primary and secondary end points. There were no adverse events. An average of 3.8 (±1.1) acupuncture sessions were delivered per patient during a mean hospital stay of 4.6 days (±1.3). Acupuncture was associated with a reduction in pain, nausea, stress, and anxiety after each session (P < .0001), and patients receiving acupuncture had reduced postoperative stress and anxiety across admission compared with standard care (P = .049 and P = .036, respectively). Acupuncture was associated with reduced postoperative atrial fibrillation incidence (acupuncture: 7 [13.7%], standard care: 16 [32.7%]; P = .028), fewer discharges on amiodarone (acupuncture: 5 [9.8%], standard care: 13 [26.5%]; P = .03), and fewer hours in the intensive care unit (acupuncture: 30.3 ± 10.0, standard care: 37.0 ± 22.5; P = .057). ConclusionsAcupuncture after valve surgery is feasible, is well tolerated, and has clinical benefit. The reduction noted in postoperative atrial fibrillation incidence will inform larger trials designed to further investigate the impact of acupuncture on postoperative atrial fibrillation and medical outcomes.

Safety and Efficacy of a Single Procedure of Extraction and Reimplantation of Infected Cardiovascular Implantable Electronic Device (CIED) in Comparison with Deferral Timing: An Observational Retrospective Multicentric Study

(1) Background: Infections are among the most frequent and life-threatening complications of cardiovascular implantable electronic device (CIED) implantation. The aim of this study is to compare the outcome and safety of a single-procedure device extraction and contralateral implantation versus the standard-of-care (SoC) two-stage replacement for infected CIEDs. (2) Methods: We retrospectively included 66 patients with CIED infections who were treated at two Italian hospitals. Of the 66 patients enrolled in the study, 27 underwent a single procedure, whereas 39 received SoC treatment. All patients were followed up for 12 months after the procedure. (3) Results: Considering those lost to follow-up, there were no differences in the mortality rates between the two cohorts, with survival rates of 81.5% in the single-procedure group and 84.6% in the SoC group (p = 0.075). (4) Conclusions: Single-procedure reimplantation associated with an active antibiofilm therapy may be a feasible and effective therapeutic option in CIED-dependent and frail patients. Further studies are warranted to define the best treatment regimen and strategies to select patients suitable for the single-procedure reimplantation.

Clinical trial versus standard of care in EGFR-wild type and ALK- negative lung adenocarcinoma: A propensity-matched analysis.

e21116 Background: Clinical trials have been a vital role for survival improvement in recurrent or metastatic lung cancer. Recent advances in targeted therapy for EGFR-mutant or ALK-positive lung adenocarcinoma dramatically increased survival. However, EGFR-wild type and ALK negative lung adenocarcinoma still had relatively poor survival outcome. Clinical trial of targeted therapy for rare driver mutation or immunotherapy was introduced in 2015. Moreover, next-generation sequencing was reimbursed in 2017 in Korea. This study evaluated the benefit of clinical trials for EGFR-wild type and ALK negative lung adenocarcinoma in recent 5 years. Methods: This study included patients with recurrent or metastatic lung adenocarcinoma who received systemic treatment between March 2017 and June 2022 at Samsung Medical Center. We compared overall survival in group with clinical trial and the standard of care (SOC) by using propensity score matching (PSM) (1:1). We used cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval while accounting for clustering among matched pairs. Results: Of total, 1,686 EGFR-wild type and ALK negative lung adenocarcinoma were included for final analysis. Among them, 1,380 received SOC only and 306 patients enrolled at least one clinical trial. In a group of clinical trial, 41.5%, 29.1%, and 23,2% of patients were enrolled for first-, second-, and third-line treatment, respectively. To achieve the balance between the SOC group and the clinical trial group, 8 baseline characteristics (age, sex, smoking history, ECOG performance status, brain metastasis, liver metastasis, bone metastasis, and rare driver mutation) were included. After PSM, 612 patients were matched to group of the SOC (n = 306) and the group of clinical trial (n = 306). Among the clinical trial, 27.8% was a clinical trial of targeted therapy and 72.2% was a clinical trial of immunotherapy or others. Median follow-up duration was 32.8 months (range, 5.0–64.4). Median overall survival was 17.1 months (95% CI, 13.2–21.4) for SOC and 27.3 months (95% CI, 22.1–32.4) for group of clinical trial (HR = 0.71 (95% CI, 0.58–0.88, P = 0.002). Conclusions: This study showed the performance of clinical trials for patients with EGFR-wild type and ALK-negative lung adenocarcinoma at tertiary hospital. After PSM, clinical trials showed survival benefits that reduced the risk of death by 29% in patients with EGFR-wild type and ALK-negative lung adenocarcinoma.

Relative time in physical activity and sedentary behaviour across a 2-year pedometer-based intervention in people with prediabetes or type 2 diabetes: a secondary analysis of a randomised controlled trial

BackgroundPeople with prediabetes or type 2 diabetes (T2D) need to be physically active, including moderate-to-vigorous intensity physical activity (MVPA) and light-intensity physical activity (LIPA) and reduce time in sedentary behaviour (SB). Few studies have evaluated the effect of randomised controlled trials taking all movement behaviours into account. This study aimed to investigate the effects of a 2-year pedometer-based intervention in people with prediabetes or T2D on relative time in movement behaviours.MethodsSecondary analysis of longitudinal data on individuals with prediabetes or T2D from a three-armed randomised controlled trial, the Sophia Step Study, was conducted. The three groups were (1) a multi‑component group (self‑monitoring of steps with a pedometer plus counselling), (2) a single‑component group (self‑monitoring of steps with a pedometer, without counselling), and (3) a standard care group (control). The three behaviours MVPA, LIPA and SB during waking hours were measured with an ActiGraph GT1M accelerometer at baseline, 6, 12, 18 and 24 months. Relative time in MVPA, LIPA and SB for each participant at each time point was calculated and used as outcome measures. Linear mixed models assessed the effect of the intervention over time.ResultsIn total 184 participants with mean (SD) age 64.3 (7.6) years and 41% female was included. In the multi-component group, compared to the control group, a significant group-by-time interaction effect for relative time in all three behaviours was found at 6 and 18 months and for MVPA and SB at 24 months. In the single-component group, compared to the control group, an effect occurred in the MVPA and SB behaviours at 6 months and MVPA and LIPA at 24 months. The estimated marginal means ranged from 0.9 to 1.5% of more MVPA, 1.9–3.9% of less LIPA and from 0.5% of less SB to 1.7 more SB in the intervention groups compared to the control group.ConclusionsThe findings show a beneficial effect on all behaviours over time in the two intervention groups compared to the control group. A more pronounced effect occurred in the multi-component intervention compared to the single-component intervention, implicating the importance of counselling in pedometer-based interventions.Trial registration ClinicalTrials.gov, NCT02374788

Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial

Anticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population. The ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1). Women aged 18-42 years who had two or more pregnancy losses and confirmed inherited thrombophilia, and who were trying to conceive or were already pregnant (≤7 weeks' gestation), were eligible for inclusion. Women were randomly assigned (1:1) to use low-dose LMWH or not (alongside standard care in both groups) once they had a positive urine pregnancy test. LMWH was started at or before 7 weeks' gestation and continued until the end of pregnancy. The primary outcome measure was livebirth rate, assessed in all women with available data. Safety outcomes included bleeding episodes, thrombocytopenia, and skin reactions, and were assessed in all randomly assigned women who reported a safety event. The trial was registered within the Dutch Trial Register (NTR3361) and EudraCT (UK: 2015-002357-35). Between Aug 1, 2012, and Jan 30, 2021, 10 625 women were assessed for eligibility, 428 were registered, and 326 conceived and were randomly assigned (164 to LMWH and 162 to standard care). 116 (72%) of 162 women with primary outcome data in the LMWH group and 112 (71%) of 158 in the standard care group had livebirths (adjusted odds ratio 1·08, 95% CI 0·65 to 1·78; absolute risk difference, 0·7%, 95% CI -9·2% to 10·6%). 39 (24%) of 164 women in the LMWH group and 37 (23%) of 162 women in the standard care group reported adverse events. LMWH did not result in higher livebirth rates in women who had two or more pregnancy losses and confirmed inherited thrombophilia. We do not advise use of LMWH in women with recurrent pregnancy loss and inherited thrombophilia, and we advise against screening for inherited thrombophilia in women with recurrent pregnancy loss. National Institute for Health and Care Research and the Netherlands Organization for Health Research and Development.

Effect of the “shoulder-up” bundle on the incidence of spontaneous perineal injury after vaginal delivery: comparison of 2 historic cohorts after propensity score matching

Perineal injury following vaginal delivery represents a major cause of long-term maternal morbidity and its prevention is among the priorities of modern Obstetric practice. To investigate whether the systematic implementation of a bundle of maneuvers to prevent perineal injury (i.e. the "shoulder-up" bundle) may reduce the rate of spontaneous perineal tears in women delivering at a single tertiary maternity unit. Single-center retrospective intervention study including all vaginal deliveries between April 1st 2020 and March 31st 2022. On March 1st, 2021, a bundle focused on perineal injury prevention in vaginal deliveries has been implemented and introduced as a standard of care. The "shoulder-up" bundle includes the addition of a hands on technique for the delivery of the posterior shoulder which is slowly lifted up under the direct visualization of the perineal body, immediately after the disengagement of the anterior shoulder. The labor ward staff underwent a dedicated training to acquire expertise on the "shoulder-up" bundle. Little changes in terms of medical and midwifery staffing were recorded during the study period. The incidence of spontaneous 2nd or higher degree perineal tears was compared between the patients who gave birth prior to the clinical implementation of the bundle (Standard care Group) and those who were delivered following the implementation of the bundle (Shoulder-up Group). A 1:1 propensity score matching of the two groups was done for the variables that proved to be independently associated with the perineal outcome. From April 1st 2020 to March 31st 2022, 3671 patients had a vaginal birth at our tertiary care Unit (1786 in the Standard Care group and 1885 in the "Shoulder-up" group) and were enrolled in the study population. Of these 1191 (32.4%) experienced a spontaneous 2nd or higher degree perineal tear; at univariate analysis nulliparity (59.6% vs 39.1%, p<.001), higher gestational age at delivery (39.8 ± 1.28 vs 39.4 ± 1.97 weeks, p<.001), epidural analgesia (40.6% vs 31.2%, p<.001), vacuum assisted delivery (9.6% vs 4.0%, p<.001) and birthweight > 4Kg (11.0% vs 6.3%, p<.001) resulted independently associated with the perineal outcome. Following propensity Score matching for the above cited factors, 1703 patients of either group were compared. A significant increase in the rate of intact perineum (71.0% vs 64.1%, p = 0.014) and a reduction in the incidence of 2nd (27.2% vs 32.9%, p = 0.006) and 3rd-4th degree perineal tears (1.3% vs 3.0%, p<.001) was demonstrated in the "shoulder-up" group. Among the subgroup of patients undergoing vacuum assisted delivery a borderline significant reduction in the OASIs rate (10.4% vs 2.9%, p=0.052) was also observed. Our study showed that the clinical implementation of the "shoulder-up" bundle at vaginal delivery is associated with a significant reduction in the incidence of spontaneous 2nd or higher degree perineal tears.

The effect of Remote Monitor vs Standard of Care therapy on outcome A systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Project no. RRF-2.3.1-21-2022-00004 (MILAB) has been implemented with the support provided by the European Union. Background Remote monitoring (RM) in heart failure (HF) patients with cardiac implantable electronic devices (CIED) is a reliable approach to strictly following the device-specific and heart failure-related parameters. Despite a few positive outcome data, results are incomprehensive. Aims We aimed to assess the benefit of continuous RM vs. standard of care (SoC) in the reduction of all-cause mortality, heart failure hospitalization (HF), and cardiovascular-related hospitalization (CV), and inappropriate therapy. Methods A systematic review and meta-analysis of randomized controlled trials (RCT) testing RM vs. SoC for the management of HF patients were performed. Endpoints were all-cause mortality, CV- and HF hospitalizations and inappropriate therapy. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated. CENTRAL, EMBASE and MEDLINE were searched up to 21th of December 2021. Only randomized controlled studies were included. Results Fourteen RCTs that enrolled a total of 8370 patients were identified to evaluate all-cause mortality, resulting in an OR 0.88 (95% CI 0.75 to 1.03). When CV - and HF hospitalizations were assessed, there were no differences between the RM group and SoC group, and the OR was 0.93 (95% CI 0.82 to 1.05) and 0.95 (95% CI 0.75 to 1.19), respectively.Moreover RM did not have an effect on the rate of inappropriate therapy, OR was 0.73. (95% CI 0.30 to 1.81). Conclusions RM proved to be non-inferior in reducing all-cause mortality, CV- and HF hospitalization and rate of inappropriate therapy when compared to standard of care despite of the heterogeneous study cohorts and unstandardized alert actions.

Use of an Automated Bilingual Digital Health Tool to Reduce Unhealthy Alcohol Use Among Latino Emergency Department Patients

Alcohol use disorders have a high disease burden among US Latino groups. In this population, health disparities persist, and high-risk drinking has been increasing. Effective bilingual and culturally adapted brief interventions are needed to identify and reduce disease burden. To compare the effectiveness of an automated bilingual computerized alcohol screening and intervention (AB-CASI) digital health tool with standard care for the reduction of alcohol consumption among US adult Latino emergency department (ED) patients with unhealthy drinking. This bilingual unblinded parallel-group randomized clinical trial evaluated the effectiveness of AB-CASI vs standard care among 840 self-identified adult Latino ED patients with unhealthy drinking (representing the full spectrum of unhealthy drinking). The study was conducted from October 29, 2014, to May 1, 2020, at the ED of a large urban community tertiary care center in the northeastern US that was verified as a level II trauma center by the American College of Surgeons. Data were analyzed from May 14, 2020, to November 24, 2020. Patients randomized to the intervention group received AB-CASI, which included alcohol screening and a structured interactive brief negotiated interview in their preferred language (English or Spanish) while in the ED. Patients randomized to the standard care group received standard emergency medical care, including an informational sheet with recommended primary care follow-up. The primary outcome was the self-reported number of binge drinking episodes within the last 28 days, assessed by the timeline followback method at 12 months after randomization. Among 840 self-identified adult Latino ED patients (mean [SD] age, 36.2 [11.2] years; 433 [51.5%] male; and 697 [83.0%] of Puerto Rican descent), 418 were randomized to the AB-CASI group and 422 to the standard care group. A total of 443 patients (52.7%) chose Spanish as their preferred language at enrollment. At 12 months, the number of binge drinking episodes within the last 28 days was significantly lower in those receiving AB-CASI (3.2; 95% CI, 2.7-3.8) vs standard care (4.0; 95% CI, 3.4-4.7; relative difference [RD], 0.79; 95% CI, 0.64-0.99). Alcohol-related adverse health behaviors and consequences were similar between groups. The effect of AB-CASI was modified by age; at 12 months, the relative reduction in the number of binge drinking episodes within the last 28 days in the AB-CASI vs standard care group was 30% in participants older than 25 years (RD, 0.70; 95% CI, 0.54-0.89) compared with an increase of 40% in participants 25 years or younger (RD, 1.40; 95% CI, 0.85-2.31; P = .01 for interaction). In this study, US adult Latino ED patients who received AB-CASI had a significant reduction in the number of binge drinking episodes within the last 28 days at 12 months after randomization. These findings suggest that AB-CASI is a viable brief intervention that overcomes known procedural barriers to ED screening, brief intervention, and referral to treatment and directly addresses alcohol-related health disparities. ClinicalTrials.gov Identifier: NCT02247388.

Remote haemodynamic monitoring of pulmonary artery pressures in patients with chronic heart failure (MONITOR-HF): a randomised clinical trial

The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system. MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible patients had chronic heart failure of New York Heart Association class III and a previous heart failure hospitalisation, irrespective of ejection fraction. Patients were randomly assigned (1:1) to haemodynamic monitoring (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA) or standard care. All patients were scheduled to be seen by their clinician at 3 months and 6 months, and every 6 months thereafter, up to 48 months. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. All analyses were by intention-to-treat. This trial was prospectively registered under the clinical trial registration number NTR7673 (NL7430) on the International Clinical Trials Registry Platform. Between April 1, 2019, and Jan 14, 2022, we randomly assigned 348 patients to either the CardioMEMS-HF group (n=176 [51%]) or the control group (n=172 [49%]). The median age was 69 years (IQR 61-75) and median ejection fraction was 30% (23-40). The difference in mean change in KCCQ overall summary score at 12 months was 7·13 (95% CI 1·51-12·75; p=0·013) between groups (+7·05 in the CardioMEMS group, p=0·0014, and -0·08 in the standard care group, p=0·97). In the responder analysis, the odds ratio (OR) of an improvement of at least 5 points in KCCQ overall summary score was OR 1·69 (95% CI 1·01-2·83; p=0·046) and the OR of a deterioration of at least 5 points was 0·45 (0·26-0·77; p=0·0035) in the CardioMEMS-HF group compared with in the standard care group. The freedom of device-related or system-related complications and sensor failure were 97·7% and 98·8%, respectively. Haemodynamic monitoring substantially improved quality of life and reduced heart failure hospitalisations in patients with moderate-to-severe heart failure treated according to contemporary guidelines. These findings contribute to the aggregate evidence for this technology and might have implications for guideline recommendations and implementation of remote pulmonary artery pressure monitoring. The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories.

Effect of Kangaroo Care Following Immersion Bath on Body Temperature in Preterm Neonates

Objectives One of the aspects of routine care in stable preterm in the ward is bathing. However, during and after bath, drop in body temperature has been observed. Providing Kangaroo Mother Care (KMC) instead of routinely covering the baby with clothes following bath helps in better thermoregulation. The purpose of this study was to compare the effectiveness of standard care and KMC following immersion bathing in stable preterm neonates in postnatal ward. Patients and Methods Prospective nonrandomized interventional study done in the postnatal ward of a tertiary referral hospital. All consecutively born preterm neonates with corrected gestational age between 34 weeks and 37 weeks (mean 35 weeks +5) were enrolled in the study. Neonates received immersion bath in a tub using water temperature adjusted to 37 to 38℃. Neonates in this group were allocated to receive standard care and KMC immediately after bath on Day 1 and Day 2, respectively. Axillary temperature was recorded before bath (baseline), immediately after bath and subsequently at 15 min, 30 min, 45 min, and 60 min after bath. Data was analyzed to compare the effect of standard care and KMC immediately after bath. Results The pre-bath mean temperature between standard care and KMC were 36.27℃ and 36.47℃, respectively. In both standard care and KMC group immediately after bath there was no fall in temperature from baseline. Mean difference from baseline temperature between standard care and KMC group at 30 min, 45 min, and 60 min were 0.2℃, 0.25℃, and 0.18℃, respectively, all of which were statistically significant ( P &lt; .05). Conclusions In this pilot study on immersion bathing followed by KMC, temperature regulation was better with KMC after bathing, with a mean temperature difference ranging between 0.18 ℃ and 0.25℃ (95% CI –0.103 to0.374) between 30 min and 60 min of bathing.

Establishment of cross-cradle hold technique combined with intensive breastfeeding counselling positively impacts the weight gain rate in early infancy.

A quasiexperimental field study was undertaken in 576 exclusively breastfed (EBF) infants from 0 to 14 weeks in Gujarat, India to assess the effect of the use of appropriate breastfeeding techniques on daily weight gain rate and on reducing the underweight rate in early infancy. The interventions were delivered through the existing health system and focused primarily on counselling pregnant women during antenatal and post-natal sessions for ensuring 'effective breastfeeding' by adoption of the technique of 'cross cradle hold', appropriate breast attachment, emptying of one breast before shifting to the other along with conducting regular monitoring of infant's weight. The intervention care group (ICG) of 300 EBF infants were compared with 276 EBF infants in the control standard care group (SCG). The findings revealed that median weight gain per day between 0 and 14 weeks was significantly higher (p = 0.000) in ICG (32.7 g) as compared with SCG (28.05 g). The median weight-for-age Z at 14 weeks of age was also significantly higher in ICG compared with SCG (p = 0.000). Underweight prevalence was three times lower in ICG (5.3%) compared with SCG (16.7%) at 14 weeks of age. Infants in the ICG were noted to be 2.65-fold more likely to achieve a weight gain of 30 g or more per day compared with infants in SCG. Nutrition interventions, therefore, must aim not only on mere promotion of EBF for up to 6 months but stress on ensuring EBF is 'effective' for optimum transfer of breastmilk through adoption of appropriate techniques, including cross-cradle hold, by mothers.

Topical Esmolol Hydrochloride as a Novel Treatment Modality for Diabetic Foot Ulcers

Preclinical and phase 1/2 studies with esmolol hydrochloride suggest its potential role in treatment of diabetic foot ulcers (DFUs). To study the efficacy of topical esmolol for healing of uninfected DFUs. A randomized, double-blind, multicenter, phase 3 clinical trial was conducted from December 26, 2018, to August 19, 2020, at 27 referral centers across India. Participants included adults with DFUs. Participants were randomized after a run-in phase (1 week) to receive esmolol, 14%, gel with standard of care (SoC), SoC only, or vehicle with SoC (3:3:1 proportion) for 12 weeks (treatment phase) and followed up subsequently until week 24. The primary outcome was the proportion of wound closure within the 12-week treatment phase in the esmolol with SoC and SoC only groups. Analysis was conducted using an intention-to-treat safety evaluable population, full analysis set or efficacy-evaluable population, and per-protocol population comparing the esmolol plus SoC and SoC only treatment groups. In the study, 176 participants (122 men [69.3%]; mean [SD] age, 56.4 [9.0] years; mean [SD] hemoglobin A1c level, 8.6% [1.6%]) with DFUs classified as University of Texas Diabetic Wound Classification system grade IA and IC (mean [SD] ulcer area, 4.7 [2.9] cm2) were randomized to the 3 groups. A total of 140 participants were analyzed for efficacy. The proportion of participants in the esmolol with SoC group who achieved target ulcer closure within 12 weeks was 41 of 68 (60.3%) compared with 30 of 72 (41.7%) participants in the SoC only group (odds ratio [OR], 2.13; 95% CI, 1.08-4.17; P = .03). A total of 120 participants completed the end of study visit which were analyzed. Target ulcer closure by the end of the study (week 24) was achieved in 44 of 57 (77.2%) participants in the esmolol with SoC group and 35 of 63 (55.6%) participants in the SoC only group (OR, 2.71; 95% CI, 1.22-5.99; P = .01). The median time for ulcer closure was 85 days for the esmolol with SoC group and was not estimable for SoC only group. Significant benefits of Esmolol with SoC were seen in patients with factors that impede the healing of DFU. Treatment-emergent adverse events were noted in 18.8% of the participants, but most (87.3%) of these events were not attributable to the study drug. In this multicenter, randomized, double-blind clinical trial, the addition of esmolol to SoC was shown to significantly improve the healing of DFUs. With these results, topical esmolol may be an appropriate addition to SoC for treating DFUs. ClinicalTrials.gov Identifier: NCT03998436; Clinical Trial Registry, India CRI Number: CTRI/2018/11/016295.

66 Key Features of Virtual Reality Impact Effectiveness of Pain Reduction in Pediatric Burn Patients

Abstract Introduction Virtual reality (VR) is a safe and effective pain management during burn dressing. However, key features of VR that impact the effectiveness of pain reduction remains unknown. Methods Our randomized clinical trial included 90 children aged 6 to 17 years who were treated in the outpatient clinic of an American Burn Association–verified pediatric burn center. Active VR participants (n=31) played a VR game while passive VR participants (n=30) were immersed in the same VR environment without interactions. VR groups were also compared with a standard care group (n=29). The primary outcome was self-reported overall pain and worst pain during burn dressing using a visual analog scale (VAS; range, 0-100). Participants in the active and passive VR groups reported 3 key features of the VR game (engaging, fun, realistic) and all participants (VR and standard care group) reported how much time he/she thought about pain during the burn dressing. Key features of the VR game and time thinking about pain were reported using a scale ranging from 0 (not at all) to 100 (very much). A composite score was created by ranking scores of the 3 key features of the VR game and then summarizing them into one final composite score. Our study hypothesis was that the key features of the VR game significantly impact the effectiveness of VR in reducing pain during burn dressing care. Results Nonparametric Spearman correlation analysis indicated the active VR group reported statistically significant higher average scores for all 3 key features of VR (engaging: 78.9, 95% confidence interval (CI)=68.5-89.3; fun: 85.7, 95%CI=76.6-94.7; realistic: 73.1, 95% CI=62.3-83.8) in comparison with the passive VR group (engaging: 72.7, 95% CI=59.9-85.5; fun: 77.3, 95%CI=65.6-89.0; realistic: 59.1, 95% CI=44.7-73.5) (all p-value &amp;lt; 0.01). The composite VR score was also significantly correlated with how much time the participant thought about pain during the burn dressing (coefficient= -0.344, p=0.007). The final multivariate logistic regression model of reporting moderate-to-severe pain found that key features of the VR game were statistically significant factors for overall pain and worst pain after adjusting for age, race/ethnicity, healing degree, pain medication use within 6 hours, and anxiety score (p&amp;lt; 0.01). Conclusions This study provides evidence that key features of VR significantly impact its effectiveness in pain management among pediatric burn patients. Applicability of Research to Practice Active VR game is more effective and should be used for pediatric pain management.

Negative pressure wound therapy versus standard care for incisional laparotomy subcutaneous wounds in gastrointestinal perforations: A randomized controlled study

BackgroundSurgical site infections after gastrointestinal perforation with peritonitis have significant morbidity, increased hospital stays, and cost of treatment. The appropriate management of these wounds is still debatable. MethodsPatients undergoing surgery for gastrointestinal perforation with peritonitis via midline incision were screened for inclusion. After the closure of the midline fascia, patients were randomized into an open negative pressure wound therapy group (application of negative pressure wound therapy and attempted delayed closure at day 4) or a standard care group (no negative pressure wound therapy and attempted delayed closure at day 4). Postoperative outcomes, including surgical site infection till 30 days, were compared between the groups. This was assessed by an independent assessor not involved in the study for delayed closure. Although a priori sample size was calculated, an interim analysis was performed due to slow recruitment during the COVID pandemic. After interim analysis, a continuation of the trial was deemed unethical and terminated. ResultsNinety-six patients were assessed, and 69 were randomized (34 in the negative pressure wound therapy group and 31 in the standard care group). The age, body mass index, comorbidities, blood loss, operative time, and stoma formation were comparable. The surgical site infection was significantly lower in the negative pressure wound therapy group compared to the standard care group (6 [18%] vs 19 [61%], P < .01). The number needed to prevent 1 surgical site infection was 2.3. In a subgroup analysis, the use of negative pressure wound therapy also significantly decreased the rate of surgical site infection in stoma patients (4 [30.7%] vs 9 [69.3%], P = .03). ConclusionOpen negative pressure wound therapy significantly decreases the incisional surgical site infection rate in patients with a dirty wound secondary to gastrointestinal perforation with peritonitis.

The effect and mechanisms of music therapy on the autonomic nervous system and brain networks of patients of minimal conscious states: a randomized controlled trial.

Music therapy has been employed as an alternative treatment modality for the arousal therapy of patients with disorders of consciousness (DOC) in clinical settings. However, due to the absence of continuous quantitative measurements and the lack of a non-musical sound control group in most studies, the identification of the specific impact of music on DOC patients remains challenging. In this study, 20 patients diagnosed with minimally consciousness state (MCS) were selected, and a total of 15 patients completed the experiment. All patients were randomly assigned to three groups: an intervention group (music therapy group, n = 5), a control group (familial auditory stimulation group, n = 5), and a standard care group (no sound stimulation group, n = 5). All three groups received 30 min of therapy five times a week for a total of 4 weeks (20 times per group, 60 times in total). Autonomic nervous system (ANS) measurements, Glasgow Coma Scale (GCS), and functional magnetic resonance-diffusion tensor imaging (fMRI-DTI) were used to measure the peripheral nervous system indicators and brain networks, and to evaluate patients' behavior levels. The results reveal that PNN50 (p = 0.0004**), TP (p = 0.0003**), VLF (p = 0.0428**), and LF/HF (p = 0.0001**) in the music group were significantly improved compared with the other two groups. Such findings suggest that the ANS of patients with MCS exhibits higher activity levels during music exposure compared to those exposed to family conversation or no auditory stimulation. In fMRI-DTI detection, due to the relative activity of ANS in the music group, the ascending reticular activation system (ARAS) in the brain network also exhibited significant nerve fiber bundle reconstruction, superior temporal gyrus (STG), transverse temporal gyrus (TTG), inferior temporal gyrus (ITG), limbic system, corpus callosum, subcorticospinal trace, thalamus and brainstem regions. In the music group, the reconstructed network topology was directed rostrally to the diencephalon's dorsal nucleus, with the brainstem's medial region serving as the hub. This network was found to be linked with the caudal corticospinal tract and the ascending lateral branch of the sensory nerve within the medulla. Music therapy, as an emerging treatment for DOC, appears to be integral to the awakening of the peripheral nervous system-central nervous system based on the hypothalamic-brainstem-autonomic nervous system (HBA) axis, and is worthy of clinical promotion. The research was supported by the Beijing Science and Technology Project Foundation of China, No. Z181100001718066, and the National Key R&D Program of China No. 2022YFC3600300, No. 2022YFC3600305.

Autologous platelet-rich fibrin promotes wound healing in cats.

Street cats commonly present large skin wounds that pose significant challenges in veterinary practice. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate increasingly used in humans to promote wound healing. Ease of use and clinical success in humans has prompted interest in using PRF in veterinary practice. However, until now, there is no reported study on the use of autologous PRF in feline wound management. This study evaluated the effect of application of autologous PRF in cats with naturally occurring cutaneous wounds. 16 cats with full-thickness cutaneous acute/subacute wounds were randomly allocated to PRF or Control (standard care) groups. Each cat was enrolled for 2 weeks. PRF was prepared according to previously described procedures. PRF was applied on Days 1 and 4 in addition to standard wound care. Wound size was measured using tracing planimetry. Wound surface area was calculated using SketchAndCalc™ software on scanned tracing images. Average wound sizes at enrolment were 8.39 cm2 (Control) (standard deviation (SD) 5.08 cm2) and 9.18 cm2 (PRF) (SD 3.71 cm2) (range 2.42-15.97 cm2). By Day 14, the mean wound size for the Control group was 2.17 cm2 (SD 1.52 cm2) and for the PRF was 0.62 cm2 (SD 0.44 cm2) (p = 0.015). At Day 14, the PRF group showed mean 93.85% wound contraction with SD 3.66, while the control group showed mean 76.23% wound contraction with SD 5.30 (p = <0.0001). Based on the results, PRF could be further investigated to promote wound healing in cats as a low-risk and convenient adjunctive therapy.

Extracorporeal Shockwave Therapy (ESWT) in the Management of Diabetic Foot Ulcer: A Prospective Randomized Clinical Trial

Diabetic foot ulcer (DFU) is the most common cause of prolonged hospitalization with a high cost of care due to unsatisfactory outcomes with the current mode of therapy. Extracorporeal shockwave therapy (ESWT) is a new technology in the care of non-healing wounds. The study's main objective was to compare the healing parameters of DFUs between patients undergoing the standard of care (SOC) alone and ESWT + SOC. The secondary objective was to assess inflammatory markers in both study groups. The study was designed as a single-centre, randomised trial to provide evidence on the effects of ESWT on DFU healing. Informed consent was obtained from all participants before enrolment. Forty-eight participants were recruited, enrolled, and randomly allocated into the two study groups. Twenty-five patients were allocated to the ESWT + SOC group, and 23 patients were allocated into the SOC-only group for a treatment period of six weeks. The univariate binary analysis showed more patients with healed DFU in the ESWT+SOC group than the SOC-only group at six weeks, though the difference did not reach statistical significance (OR=3.2, p=0.07). The adjusted multivariate binary analysis confirmed this finding; however, the effect size did not reach statistical significance at six weeks (OR=3.9, p=0.08). The level of circulating inflammatory markers was similar in both groups of patients. It is the author's opinion that there is a potential benefit of ESWT on diabetic wound healing with further research warranted to determine its role in treatment of DFU. A larger trial with a more extended treatment period is, however, needed to substantiate our findings.

Dalbavancin vs standard of care for Staphylococcus aureus bacteraemia in patients unable to receive outpatient parenteral antimicrobial therapy

This study compared dalbavancin with standard of care (SOC) for patients with Staphylococcus aureus bacteraemia (SAB) who were unable to receive outpatient parenteral antimicrobial therapy (OPAT). This retrospective cohort compared re-admission rates related to the index infection between patients treated with dalbavancin or SOC for SAB. Patients aged ≥18 years seen by the infectious diseases consult service who had received at least one dose of dalbavancin or at least 1 week of SOC parenteral antibacterials as directed therapy for SAB at the time of discharge were included. The SOC group consisted of patients transferred from the main hospital to one of the post-acute care facilities to complete parenteral antibacterials. The primary outcome was re-admission rate within 30 days of completion of therapy. Secondary outcomes included re-admission rate within 90 days of completion of therapy and adherence to the antibacterial regimen. Twenty-seven patients received dalbavancin and 27 patients received SOC. Baseline demographics were comparable between groups, although more patients in the SOC group had indwelling prostheses or hardware (4% vs 22%). The majority of SAB was caused by methicillin-susceptible S. aureus (56% vs 59%). Re-admission rates for the dalbavancin group were similar to those for the SOC group within 30 days (15% vs 22%; P=0.484) and 90 days (19% vs 22%; P=0.735) of completion of therapy. Adherence to the antibacterial regimen was significantly higher among patients treated with dalbavancin compared with SOC (85% vs 44%; P<0.001). Dalbavancin offers similar clinical outcomes to SOC for patients with SAB who are unable to receive OPAT.