Development of the Parental Experience with Care for Children with Serious Illnesses (PRECIOUS) quality of care measure.

BACKGROUND: Parent-reported experience measures are part of pediatric Quality of Care (QoC) assessments. However, existing measures were not developed for use across multiple healthcare settings or throughout the illness trajectory of seriously ill children. Formative work involving in-depth interviews with parents of children with serious illnesses generated 66 draft items describing key QoC processes. Our present aim is to develop a comprehensive parent-reported experience measure of QoC for children with serious illnesses and evaluate its content validity and feasibility. METHODS: For evaluating content validity, we conducted a three-round Delphi expert panel review with 24 multi-disciplinary experts. Next, we pre-tested the items and instructions with 12 parents via cognitive interviews to refine clarity and understandability. Finally, we pilot-tested the full measure with 30 parents using self-administered online surveys to finalize the structure and content. RESULTS: The Delphi expert panel review reached consensus on 68 items. Pre-testing with parents of seriously ill children led to consolidation of some items. Pilot-testing supported feasibility of the measure, resulting in a comprehensive measure comprising 56 process assessment items, categorized under ten subthemes and four themes: (1) Professional qualities of healthcare workers, (2) Supporting parent-caregivers, (3) Collaborative and holistic care, and (4) Efficient healthcare structures and standards. We named this measure the PaRental Experience with care for Children with serIOUS illnesses (PRECIOUS). CONCLUSIONS: PRECIOUS is the first comprehensive measure and has the potential to standardize assessment of QoC for seriously ill children from parental perspectives. PRECIOUS allows for QoC process evaluation across contexts (such as geographic location or care setting), different healthcare workers, and over the illness trajectory for children suffering from a range of serious illnesses.

Protein supplementation versus standard feeds in underweight critically ill children: a pilot dual-centre randomised controlled trial protocol.

INTRODUCTION: Protein-energy malnutrition, increased catabolism and inadequate nutritional support leads to loss of lean body mass with muscle wasting and delayed recovery in critical illness. However, there remains clinical equipoise regarding the risks and benefits of protein supplementation. This pilot trial will determine the feasibility of performing a larger multicentre trial to determine if a strategy of protein supplementation in critically ill children with body mass index (BMI) z-score ≤-2 is superior to standard enteral nutrition in reducing the length of stay in the paediatric intensive care unit (PICU). METHODS AND ANALYSIS: This is a randomised controlled trial of 70 children in two PICUs in Singapore. Children with BMI z-score ≤-2 on PICU admission, who are expected to require invasive mechanical ventilation for more than 48 hours, will be randomised (1:1 allocation) to protein supplementation of ≥1.5 g/kg/day in addition to standard nutrition, or standard nutrition alone for 7 days after enrolment or until PICU discharge, whichever is earlier. Feasibility outcomes for the trial include effective screening, satisfactory enrolment rate, timely protocol implementation (within first 72 hours) and protocol adherence. Secondary outcomes include mortality, PICU length of stay, muscle mass, anthropometric measurements and functional outcomes. ETHICS AND DISSEMINATION: The trial protocol was approved by the institutional review board of both participating centres (Singhealth Centralised Institutional Review Board and National Healthcare Group Domain Specific Review Board) under the reference number 2020/2742. Findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT04565613.

NEMESIS: Noninferiority, Individual-Patient Metaanalysis of Selective Internal Radiation Therapy with 90Y Resin Microspheres Versus Sorafenib in Advanced Hepatocellular Carcinoma.

In randomized clinical trials, no survival benefit has been observed for selective internal radiation therapy (SIRT) over sorafenib in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess, through a metaanalysis, whether overall survival (OS) with SIRT, as monotherapy or followed by sorafenib, is noninferior to sorafenib and to compare safety profiles for patients with advanced HCC. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library up to February 2019 to identify randomized clinical trials comparing SIRT, as monotherapy or followed by sorafenib, with sorafenib monotherapy among patients with advanced HCC. The main outcomes were OS and frequency of treatment-related severe adverse events (≥grade 3). The per-protocol population was the primary analysis population. A noninferiority margin of 1.08 in terms of hazard ratio was prespecified for the upper boundary of 95% confidence interval for OS. Prespecified subgroup analyses were performed. Results: Three randomized clinical trials, involving 1,243 patients, comparing sorafenib with SIRT (SIRveNIB and SARAH) or SIRT followed by sorafenib (SORAMIC), were included. After randomization, 411 of 635 (64.7%) patients allocated to SIRT and 522 of 608 (85.8%) allocated to sorafenib completed the studies without major protocol deviations. Median OS with SIRT, whether or not followed by sorafenib, was noninferior to sorafenib (10.2 and 9.2 mo [hazard ratio, 0.91; 95% confidence interval, 0.78-1.05]). Treatment-related severe adverse events were reported in 149 of 515 patients (28.9%) who received SIRT and 249 of 575 (43.3%) who received sorafenib only (P < 0.01). Conclusion: SIRT as initial therapy for advanced HCC is noninferior to sorafenib in terms of OS and offers a better safety profile.

Prevalence of Shukra vega dharana in an Indian population: A cross sectional survey protocol.

BACKGROUND: Despite being an important aspect of health and quality of life, individuals tend to suppress natural sexual urge ('Shukra vega') due to a variety of factors. Unless managed appropriately through self-regulatory mechanisms, suppressed sexual urge ('Shukra vega dharana', SVD) not only causes psychological suffering but may also put other basic needs at risk. Adult, married, males who are either living away from their spouse for long durations or separated or divorced are at a considerably higher risk of developing SVD as compared to others. Considering the recent rise of sexual diseases and sexual violence, it is critical to understand the extent and epidemiology of SVD in this sub-population of India. OBJECTIVE: The study was attempted to understand the extent and epidemiology of SVD in this sub-population of India. MATERIALS AND METHODS: To determine the prevalence of SVD in adult married, male individuals located in Nashik, Ahmadnagar and Thane cities of India who are either living away from their spouse or separated or divorced, a crosssectional, anonymous survey will be conducted among a sample of male individuals meeting eligibility criteria. A multi-stage sampling approach will be used to identify cities/organizations (where the study will be conducted) and participants for the study. Post informed consent, eligible individuals will respond to a survey questionnaire. Responses will be populated in a spreadsheet, analyzed and reported. Understanding extent and epidemiology of SVD in an Indian sub-population will not only facilitate design of future research studies but will also inform health, social and educational policy associated with sex education (training individuals in the appropriate management of sexual urge).

Information sources and online information seeking behaviours of cancer patients in Singapore.

The aim of this study was to investigate the prevalence of Internet usage among cancer patients in seeking health-related information and the type of information sought. Sources of information received from, preferences for information sources and the perceived usefulness of information from these sources were also examined in this study. A self-administered questionnaire was used to evaluate the information needs of patients undergoing cancer treatment. The questionnaire also evaluated the current source and preferred source of information as well as their online information seeking behaviours. A total of 411 patients with cancer were recruited from an ambulatory cancer centre. The patients' physicians and healthcare specialists comprised a large majority of the patients' information sources; they were also the most preferred source of information. 59.1% of the respondents used the Internet to search for cancer-related information, namely diagnosis and treatment options, side effects of treatment and complementary and alternative therapy; demonstrating the importance of the above information. Physicians (60.3%) and healthcare specialists (26.5%) were the largest and most preferred sources of information for cancer patients in our study. It was not uncommon for cancer patients to use the Internet to search for additional information demonstrating the need to integrate this tool more effectively for knowledge transfer for those patients who want it. It is important for healthcare professionals to help cancer patients by directing them to sources of quality information (including websites). In addition, the provision of guidelines on how to evaluate health information on the Internet would be helpful to cancer patients.

Art therapy is associated with sustained improvement in cognitive function in the elderly with mild neurocognitive disorder: findings from a pilot randomized controlled trial for art therapy and music reminiscence activity versus usual care.

BACKGROUND: Mild cognitive impairment (MCI) is a phase in cognitive decline when it is still possible to intervene to reverse the decline. Cognitive stimulation delivered through psychosocial interventions provides both psychological intervention and social stimulation to improve cognition. A pilot open-label parallel-arms randomized controlled trial was undertaken to examine the effects of art therapy (AT) and music reminiscence activity (MRA) compared to the control, on the primary outcome of neurocognitive domain assessments in elderly people with MCI. METHODS: Community-living elderly people with MCI (Petersen's criteria), assessed for study eligibility, were randomized using a web-based system with equal allocation to two intervention arms: AT (guided viewing of art pieces and production of visual arts) and MRA (listening, and recalling memories related to music) and a control arm (standard care without any intervention). Interventions were led by trained therapists weekly for 3 months, then fortnightly for 6 months. Neurocognitive domains (mean of memory, attention, and visuo-spatial abilities standardized scores), psychological wellbeing (subsyndromal depression and anxiety) and telomere length as a biological marker of cellular ageing, were assessed by intervention-blinded assessors at baseline, 3 months and 9 months. RESULTS: In total, 250 people were screened and 68 were randomized and included in the analysis. In the AT arm, neurocognitive domains improved compared to the control arm at 3 months (mean difference (d) = 0.40; 90% CI 0.126, 0.679) and were sustained at 9 months (d = 0.31; 90% CI 0.068, 0.548). There was some improvement in depression and anxiety at 3 and 9 months and in telomere length at 9 months, but this was not significant. Similar improvements were observed in the MRA arm over the control arm, but they were not significant. There were no intervention-related adverse effects. CONCLUSIONS: Art therapy delivered by trained staff as "art as therapy" and "art psychotherapy" may have been the significant contributor to cognitive improvements. The findings support cognitive stimulation for elderly people with cognitive decline and signal the need for larger studies and further investigation of carefully designed psycho-social interventions for this group. TRIAL REGISTRATION: Clinical Trials.gov, NCT02854085 . Registered on 7 July 2016.

SIRveNIB: Selective Internal Radiation Therapy Versus Sorafenib in Asia-Pacific Patients With Hepatocellular Carcinoma.

Purpose Selective internal radiation therapy or radioembolization (RE) shows efficacy in unresectable hepatocellular carcinoma (HCC) limited to the liver. This study compared the safety and efficacy of RE and sorafenib in patients with locally advanced HCC. Patients and Methods SIRveNIB (selective internal radiation therapy v sorafenib), an open-label, investigator-initiated, phase III trial, compared yttrium-90 (90Y) resin microspheres RE with sorafenib 800 mg/d in patients with locally advanced HCC in a two-tailed study designed for superiority/detriment. Patients were randomly assigned 1:1 and stratified by center and presence of portal vein thrombosis. Primary end point was overall survival (OS). Efficacy analyses were performed in the intention-to-treat population and safety analyses in the treated population. Results A total of 360 patients were randomly assigned (RE, 182; sorafenib, 178) from 11 countries in the Asia-Pacific region. In the RE and sorafenib groups, 28.6% and 9.0%, respectively, failed to receive assigned therapy without significant cross-over to either group. Median OS was 8.8 and 10.0 months with RE and sorafenib, respectively (hazard ratio, 1.1; 95% CI, 0.9 to 1.4; P = .36). A total of 1,468 treatment-emergent adverse events (AEs) were reported (RE, 437; sorafenib, 1,031). Significantly fewer patients in the RE than sorafenib group had grade ≥ 3 AEs (36 of 130 [27.7%]) v 82 of 162 [50.6%]; P < .001). The most common grade ≥ 3 AEs were ascites (five of 130 [3.8%] v four of 162 [2.5%] patients), abdominal pain (three [2.3%] v two [1.2%] patients), anemia (zero v four [2.5%] patients), and radiation hepatitis (two [1.5%] v zero [0%] patients). Fewer patients in the RE group (27 of 130 [20.8%]) than in the sorafenib group (57 of 162 [35.2%]) had serious AEs. Conclusion In patients with locally advanced HCC, OS did not differ significantly between RE and sorafenib. The improved toxicity profile of RE may inform treatment choice in selected patients.

Art therapy and music reminiscence activity in the prevention of cognitive decline: study protocol for a randomized controlled trial.

BACKGROUND: Attention has shifted to the use of non-pharmacological interventions to prevent cognitive decline as a preventive strategy, as well as for those at risk and those with mild cognitive impairment. Early introduction of psycho-social interventions can address cognitive decline and significantly impact quality of life and the wellbeing of elderly individuals. This pilot study explores the feasibility of using art therapy and music reminiscence activity to improve the cognition of community living elderly with mild cognitive impairment. METHODS/DESIGN: This open-label, interventional study involves a parallel randomized controlled trial design with three arms (two intervention arms and a control group) over a nine-month period. Participants will be community-living elderly individuals aged 60-85 years, both genders, who meet predefined inclusion and exclusion criteria. In the initial three months, interventions will be provided weekly and for the remaining six months fortnightly. A sample size of 90 participants is targeted based on expected neuropsychological test performance, a primary outcome measure, and drop-out rates. The randomization procedure will be carried out via a web-based randomization system. Interventions will be provided by trained staff with a control group not receiving any intervention but continuing life as usual. Assessments will be done at baseline, three months, and nine months, and include neuroimaging to measure cerebral changes and neuropsychological tests to measure for changes in cognition. Secondary outcome measures will include mood changes in anxiety and depression and telomere lengths. Statistical analysis will be undertaken by statisticians; all efficacy analysis will be carried out on an intention-to-treat basis. Primary and secondary outcomes will be modeled using the linear mixed model for repeated measurements and further analysis may be undertaken to adjust for potential confounders. DISCUSSION: This will be the first study to compare the effectiveness of art therapy and music reminiscence activity in a randomized controlled trial. We expect that the trial will provide useful evidence for developing psychosocial interventions for the elderly with mild cognitive impairment. TRIAL REGISTRATION: The study was registered on 7 July 2016 at Clinical Trials.gov, a service of the US National Institute of Health ( NCT02854085 ), retrospectively.

Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial.

BACKGROUND: Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients. METHODS: This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy. DISCUSSION: Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010.

On developing a pragmatic strategy for clinical trials: A case study of hepatocellular carcinoma.

Randomised controlled trials (RCTs) with sufficiently high statistical power are not always feasible for patients when the administration of the treatment is burdensome. Nevertheless, useful information concerning the relative effectiveness of the Test and Standard therapies, may be gleaned from under powered trials, non-randomised comparative studies and/or clinician's beliefs: the latter possibly additionally providing some suggestion of the strength of evidence required in order to adopt the Test therapy into clinical practice. In such circumstances, a Bayesian synthesis may be useful in quantifying the evidence of treatment effectiveness. In this article, we aim to present a Bayesian approach for synthesizing the cumulative evidence of the use of adjuvant hepatic intra-arterial iodine-131-lipiodol (I131L) following curative resection in hepatocellular carcinoma (HCC) patients. We constructed a posterior distribution using the information from two small RCTs, three non-randomised comparative studies, three single arm studies and the views of investigators on the use of I131L. This distribution enables calculation of the probability that the Test therapy is more effective than the Standard by a pre-stipulated amount. If this is very high, then for example, one may conclude the Test may replace the Standard therapy. If it is not, then the Standard would be retained for clinical use. Despite a strong early indication of the effectiveness of I131L, the evolving evidence over a 10-year period became more sceptical of its value. Although highly recommended, difficulties of implementing a Bayesian approach in this context are highlighted.

Vancomycin versus daptomycin for the treatment of methicillin-resistant Staphylococcus aureus bacteremia due to isolates with high vancomycin minimum inhibitory concentrations: study protocol for a phase IIB randomized controlled trial.

BACKGROUND: Vancomycin is the standard first-line treatment for methicillin-resistant Staphylococcus aureus bacteremia. However, recent consensus guidelines recommend that clinicians consider using alternative agents such as daptomycin when the vancomycin minimum inhibitory concentration is greater than 1 ug/ml. To date however, there have been no head-to-head randomized trials comparing the safety and efficacy of daptomycin and vancomycin in the treatment of such infections. The primary aim of our study is to compare the efficacy of daptomycin versus vancomycin in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations (greater than or equal to 1.5 ug/ml) in terms of reducing all-cause 60-day mortality. METHODS/DESIGN: The study is designed as a multicenter prospective open label phase IIB pilot randomized controlled trial. Eligible participants will be inpatients over 21-years-old with a positive blood culture for methicillin-resistant Staphylococcus aureus with vancomycin minimum inhibitory concentration of greater than or equal to 1.5 ug/ml. Randomization into intervention or active control arms will be performed with a 1:1 allocation ratio. We aim to recruit 50 participants over a period of two years. Participants randomized to the active control arm will receive vancomycin dose-while those randomized to the intervention arm will receive daptomycin. Participants will receive a minimum of 14 days study treatment.The primary analysis will be conducted on the intention-to-treat principle. The Fisher's exact test will be used to compare the 60-day mortality rate from index blood cultures (primary endpoint) between the two treatment arms, and the exact two-sided 95% confidence interval will be calculated using the Clopper and Pearson method. Primary analysis will be conducted using a two sided alpha of 0.05. DISCUSSION: If results from this pilot study suggest that daptomycin shows significant efficacy in the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus isolates with high vancomycin minimum inhibitory concentrations, we aim to proceed with a larger scale confirmatory study. This would help guide clinicians and inform practice guidelines on the optimal treatment for such infections. TRIAL REGISTRATION: The trial is listed on clinicaltrials.gov (NCT01975662, date of registration: 29 October 2013).

Multicenter phase II study of sequential radioembolization-sorafenib therapy for inoperable hepatocellular carcinoma.

BACKGROUND: The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. METHODS: Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). RESULTS: Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. CONCLUSIONS: This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. TRIAL REGISTRATION: ClinicalTrials.gov NCT00712790.

Hyperbaric oxygen therapy in necrotising soft tissue infections: a study of patients in the United States Nationwide Inpatient Sample.

PURPOSE: Necrotising soft tissue infection (NSTI) is a deadly disease associated with a significant risk of mortality and long-term disability from limb and tissue loss. The aim of this study was to determine the effect of hyperbaric oxygen (HBO(2)) therapy on mortality, complication rate, discharge status/location, hospital length of stay and inflation-adjusted hospitalisation cost in patients with NSTI. METHODS: This was a retrospective study of 45,913 patients in the Nationwide Inpatient Sample (NIS) from 1988 to 2009. RESULTS: A total of 405 patients received HBO(2) therapy. The patients with NSTI who received HBO(2) therapy had a lower mortality (4.5 vs. 9.4 %, p = 0.001). After adjusting for predictors and confounders, patients who received HBO(2) therapy had a statistically significantly lower risk of dying (odds ratio (OR) 0.49, 95 % confidence interval (CI) 0.29-0.83), higher hospitalisation cost (US$52,205 vs. US$45,464, p = 0.02) and longer length of stay (LOS) (14.3 days vs. 10.7 days, p < 0.001). CONCLUSIONS: This retrospective analysis of HBO(2) therapy in NSTI showed that despite the higher hospitalisation cost and longer length of stay, the statistically significant reduction in mortality supports the use of HBO(2) therapy in NSTI.