International comparison of health spending and utilization among people with complex multimorbidity.

OBJECTIVE: The objective of this study was to explore cross-country differences in spending and utilization across different domains of care for a multimorbid persona with heart failure and diabetes. DATA SOURCES: We used individual-level administrative claims or registry data from inpatient and outpatient health care sectors compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States (US). DATA COLLECTION/EXTRACTION METHODS: Data collected by ICCONIC partners. STUDY DESIGN: We retrospectively analyzed age-sex standardized utilization and spending of an older person (65-90 years) hospitalized with a heart failure exacerbation and a secondary diagnosis of diabetes across five domains of care: hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, and outpatient drugs. PRINCIPAL FINDINGS: Sample sizes ranged from n = 1270 in Spain to n = 21,803 in the United States. Mean age (standard deviation [SD]) ranged from 76.2 (5.6) in the Netherlands to 80.3 (6.8) in Sweden. We observed substantial variation in spending and utilization across care settings. On average, England spent $10,956 per person in hospital care while the United States spent$30,877. The United States had a shorter length of stay over the year (18.9 days) compared to France (32.9) and Germany (33.4). The United States spent more days in facility-based rehabilitative care than other countries. Australia spent $421 per person in primary care, while Spain (Aragon) spent$1557. The United States and Canada had proportionately more visits to specialist providers than primary care providers. Across almost all sectors, the United States spent more than other countries, suggesting higher prices per unit. CONCLUSION: Across 11 countries, there is substantial variation in health care spending and utilization for a complex multimorbid persona with heart failure and diabetes. Drivers of spending vary across countries, with the United States being the most expensive country due to high prices and higher use of facility-based rehabilitative care

Differences in health care spending and utilization among older frail adults in high-income countries: ICCONIC hip fracture persona.

ObjectiveThis study explores differences in spending and utilization of health care services for an older person with frailty before and after a hip fracture.Data sourcesWe used individual-level patient data from five care settings.Study designWe compared utilization and spending of an older person aged older than 65 years for 365 days before and after a hip fracture across 11 countries and five domains of care as follows: acute hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, and outpatient drugs. Utilization and spending were age and sex standardized..Data collection/extraction methodsThe data were compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries as follows: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Principal findingsThe sample ranged from 1859 patients in Spain to 42,849 in France. Mean age ranged from 81.2 in Switzerland to 84.7 in Australia. The majority of patients across countries were female. Relative to other countries, the United States had the lowest inpatient length of stay (11.3), but the highest number of days were spent in post-acute care rehab (100.7) and, on average, had more visits to specialist providers (6.8 per year) than primary care providers (4.0 per year). Across almost all sectors, the United States spent more per person than other countries per unit ($13,622 per hospitalization,$233 per primary care visit, $386 per MD specialist visit). Patients also had high expenditures in the year prior to the hip fracture, mostly concentrated in the inpatient setting.ConclusionAcross 11 high-income countries, there is substantial variation in health care spending and utilization for an older person with frailty, both before and after a hip fracture. The United States is the most expensive country due to high prices and above average utilization of post-acute rehab care

Differences in health outcomes for high-need high-cost patients across high-income countries.

ObjectiveThis study explores variations in outcomes of care for two types of patient personas-an older frail person recovering from a hip fracture and a multimorbid older patient with congestive heart failure (CHF) and diabetes.Data sourcesWe used individual-level patient data from 11 health systems.Study designWe compared inpatient mortality, mortality, and readmission rates at 30, 90, and 365 days. For the hip fracture persona, we also calculated time to surgery. Outcomes were standardized by age and sex.Data collection/extraction methodsData was compiled by the International Collaborative on Costs, Outcomes and Needs in Care across 11 countries for the years 2016-2017 (or nearest): Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Principal findingsThe hip sample across ranged from 1859 patients in Aragon, Spain, to 42,849 in France. Mean age ranged from 81.2 in Switzerland to 84.7 in Australia, and the majority of hip patients across countries were female. The congestive heart failure (CHF) sample ranged from 742 patients in England to 21,803 in the United States. Mean age ranged from 77.2 in the United States to 80.3 in Sweden, and the majority of CHF patients were males. Average in-hospital mortality across countries was 4.1%. for the hip persona and 6.3% for the CHF persona. At the year mark, the mean mortality across all countries was 25.3% for the hip persona and 32.7% for CHF persona. Across both patient types, England reported the highest mortality at 1 year followed by the United States. Readmission rates for all periods were higher for the CHF persona than the hip persona. At 30 days, the average readmission rate for the hip persona was 13.8% and 27.6% for the CHF persona.ConclusionAcross 11 countries, there are meaningful differences in health system outcomes for two types of patients

A methodology for identifying high-need, high-cost patient personas for international comparisons.

ObjectiveTo establish a methodological approach to compare two high-need, high-cost (HNHC) patient personas internationally.Data sourcesLinked individual-level administrative data from the inpatient and outpatient sectors compiled by the International Collaborative on Costs, Outcomes, and Needs in Care (ICCONIC) across 11 countries: Australia, Canada, England, France, Germany, the Netherlands, New Zealand, Spain, Sweden, Switzerland, and the United States.Study designWe outline a methodological approach to identify HNHC patient types for international comparisons that reflect complex, priority populations defined by the National Academy of Medicine. We define two patient profiles using accessible patient-level datasets linked across different domains of care-hospital care, primary care, outpatient specialty care, post-acute rehabilitative care, long-term care, home-health care, and outpatient drugs. The personas include a frail older adult with a hip fracture with subsequent hip replacement and an older person with complex multimorbidity, including heart failure and diabetes. We demonstrate their comparability by examining the characteristics and clinical diagnoses captured across countries.Data collection/extraction methodsData collected by ICCONIC partners.Principal findingsAcross 11 countries, the identification of HNHC patient personas was feasible to examine variations in healthcare utilization, spending, and patient outcomes. The ability of countries to examine linked, individual-level data varied, with the Netherlands, Canada, and Germany able to comprehensively examine care across all seven domains, whereas other countries such as England, Switzerland, and New Zealand were more limited. All countries were able to identify a hip fracture persona and a heart failure persona. Patient characteristics were reassuringly similar across countries.ConclusionAlthough there are cross-country differences in the availability and structure of data sources, countries had the ability to effectively identify comparable HNHC personas for international study. This work serves as the methodological paper for six accompanying papers examining differences in spending, utilization, and outcomes for these personas across countries

Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - Evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: Study protocol for a randomized controlled trial

Background: Gabapentin has shown efficacy in the treatment of chronic neuropathic or mixed pain in adults. Although pediatric pain specialists have extensive experience with gabapentin for the treatment of neuropathic pain, its use is off-label. Its efficacy and safety in this context have never been shown. The aim of this trial is to compare gabapentin with placebo as add-on to morphine for the treatment of severe chronic mixed or neuropathic pain in children. This trial is part of the European Union Seventh Framework Programme project Gabapentin in Paediatric Pain (GAPP) to develop a pediatric use marketing authorization for a new gabapentin suspension. Methods/design: The GAPP-2 study is a randomized, double-blind, placebo-controlled, multicenter superiority phase II study in children with severe chronic neuropathic or mixed pain. Its primary objective is to evaluate the efficacy of a gabapentin liquid formulation as adjunctive therapy to morphine. Sixty-six eligible children 3 months to 18 years of age with severe pain (pain scores ≥ 7), stratified in three age groups, will be randomized to receive gabapentin (to an accumulating dose of 45 to 63 mg/kg/day, dependent on age) or placebo, both in addition to morphine, for 12 weeks. Randomization will be preceded by a short washout period, and treatment will be initiated by a titration period of 3 weeks. After the treatment period, medication will be tapered during 4 weeks. The primary endpoint is the average pain scores in the two treatment groups (average of two measures each day for 3 days before the end-of-study visit [V10] assessed by age-appropriate pain scales (Face, Legs, Activity, Cry, Consolability scale; Faces Pain Scale-Revised; Numeric Rating Scale). Secondary outcomes include percentage responders to treatment (subjects with 30% reduction in pain scale), number of episodes of breakthrough pain, number of rescue interventions, number of pain-free days, participant dropouts, quality of life (Pediatric Quality of Life Inventory), and acceptability of treatment. Outcomes will be measured at the end-of-study visit after 12 weeks of treatment at the optimal gabapentin dose. Groups will be compared on an intention-to-treat basis. Discussion: We hope to provide evidence that the combination of morphine and gabapentin will provide better analgesia than morphine alone and will be safe. We also aim to obtain confirmation of the recommended pediatric dose. Trial registration: EudractCT, 2014-004897-40. Registered on 7 September 2017. ClinicalTrials.gov, NCT03275012. Registered on 7 September 2017

The research gap in chronic paediatric pain: A systematic review of randomised controlled trials

Background and Objective: Chronic pain is associated with significant functional and social impairment. The objective of this review was to assess the characteristics and quality of randomized controlled trials (RCTs) evaluating pain management interventions in children and adolescents with chronic pain. Methods: We performed a systematic search of PubMed, Embase and the Cochrane Library up to July 2017. We included RCTs that involved children and adolescents (3 months-18 years) and evaluated the use of pharmacological or non-pharmacological intervention(s) in the context of pain persisting or re-occurring for more than 3 months. Methodological quality was evaluated using the Cochrane Risk of Bias (ROB) Tool. Results: A total of 58 RCTs were identified and numbers steadily increased over time. The majority were conducted in single hospital institutions, with no information on study funding. Median sample size was 47.5 participants (Q1,Q3: 32, 70). Forty-five percent of RCTs included both adults and children and the median of the mean ages at inclusion was 12.9 years (Q1,Q3: 11, 15). Testing of non-pharmacological interventions was predominant and only 5 RCTs evaluated analgesics or co-analgesics. Abdominal pain, headache/migraine and musculoskeletal pain were the most common types of chronic pain among participants. Methodological quality was poor with 90% of RCTs presenting a high or unclear ROB. Conclusions: Evaluation of analgesics targeting chronic pain relief in children and adolescents through RCTs is marginal. Infants and children with long-lasting painful conditions are insufficiently represented in RCTs. We discuss possible research constraints and challenges as well as methodologies to circumvent them. Significance: There is a substantial research gap regarding analgesic interventions for children and adolescents with chronic pain. Most clinical trials in the field focus on the evaluation of non-pharmacological interventions and are of low methodological quality. There is also a specific lack of trials involving infants and children and adolescents with long-lasting diseases

Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells

As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the US, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain, and osteonecrosis of the jaw. The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence, and lower their osteogenic differentiation potential. Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems. This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability, osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs

Predicting inadequate bowel preparation for colonoscopy in participants receiving split-dose bowel preparation: development and validation of a prediction score

Contains fulltext : 152602.pdf (Publisher’s version ) (Closed access)BACKGROUND: Adequate bowel preparation is important for optimal colonoscopy. It is important to identify patients at risk for inadequate bowel preparation because this allows taking precautions in this specific group. OBJECTIVE: To develop a prediction score to identify patients at risk for inadequate bowel preparation who may benefit from an intensified bowel cleansing regimen. DESIGN: Patient and colonoscopy data were prospectively collected, whereas clinical data were retrospectively collected for a total of 1996 colonoscopies in participants who received split-dose bowel preparation. Multivariate logistic regression analyses were conducted in a random two-thirds of the cohort to develop a prediction model. Validation and evaluation of the discriminative power of the prediction model were performed within the remaining one-third of the cohort. SETTING: Four centers, including one academic and three medium-to-large size nonacademic centers. PATIENTS: Consecutive colonoscopies in November and December 2012. Mean age was 57.3 +/- 15.9 years, 45.8% were male and indications for colonoscopy were screening and/or surveillance (27%), abdominal symptoms and/or blood loss and/or anemia (60%), inflammatory bowel disease (9%), and others (4%). INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Inadequate bowel preparation defined as Boston Bowel Preparation Scale score /=3, use of tricyclic antidepressants, use of opioids, diabetes, chronic constipation, history of abdominal and/or pelvic surgery, history of inadequate bowel preparation, and current hospitalization. The discriminative ability of the scale was good, with an area under the curve of 0.77 in the validation cohort. LIMITATIONS: Study design partially retrospective, no data on patient compliance. CONCLUSION: We developed a validated, easy-to-use prediction scale that can be used to identify subjects with an increased risk of inadequate bowel preparation with good accuracy

Influence of two pedalling rate conditions on mechanical output and physiological responses during all-out intermittent exercise

BACKGROUND AND STUDY AIMS: Cecal intubation rate (CIR) and adenoma detection rate (ADR) have been found to be inversely associated with the occurrence of post-colonoscopy colorectal cancer. Depicting differences in CIR and ADR between hospitals could provide incentives for quality improvement. The aim of this study was to compare quality parameters of routine colonoscopies between seven hospitals in The Netherlands in order to determine the extent to which possible differences were attributable to procedural and institutional factors. PATIENTS AND METHODS: Consecutive patients undergoing colonoscopy were prospectively included between November 2012 and January 2013 at two academic and five nonacademic hospitals. Patients with inflammatory bowel disease or hereditary colorectal cancer syndromes were excluded. Main outcome measures were CIR and ADR. RESULTS: A total of 3129 patients were included (mean age 59 +/- 15 years; 45.5 % male). The majority of patients (86.2 %) had a Boston Bowel Preparation Scale (BBPS) score >/= 6. Overall CIR was 94.8 %, ranging from 89.4 % to 99.2 % between hospitals. After adjustment for case mix (age, sex, American Society of Anesthesiologists score, and indication for colonoscopy), factors associated with CIR were hospital and a BBPS score >/= 6. Overall ADR was 31.8 % and varied between hospitals, ranging from 24.8 % to 46.8 %. Independent predictors for ADR were hospital, BBPS score >/= 6, and cecal intubation. By combining CIR and ADR for each hospital, a colonoscopy quality indicator (CQI) was developed, which can be used by hospitals to stimulate quality improvement. CONCLUSION: Differences in the quality of colonoscopy between hospitals can be demonstrated using CIR and ADR. As both indicators are affected by institution and bowel preparation, a comparison between hospitals based on the newly developed CQI could assist in further improving the quality of colonoscopy

Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: The GABA-1 trial-a study protocol

Introduction Gabapentin is currently used â € off-label' in children and adolescents with chronic neuropathic pain, and reliable evidence of its effects and optimal dosing are lacking. Objectives The GABA-1 trial aims to compare the efficacy and safety of gabapentin liquid formulation relative to tramadol and to explore the pharmacokinetics of both drugs in the treatment of chronic, neuropathic or mixed pain in the paediatric population. Methods and analysis The trial is a multicentre, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial. Participants aged from 3 months to <18 years of age with moderate to severe (≥4/10 in age-appropriate pain scales) chronic neuropathic or mixed pain will be recruited in 14 clinical sites in eight European countries. A total of 94 subjects will be randomised to receive gabapentin and tramadol placebo or tramadol and gabapentin placebo throughout 16-19 weeks (including 3 weeks of titration [optimisation period], 12 weeks of treatment at a stable dose [maintenance period] and 1-4 weeks of tapering [discontinuation period]). The primary objective is to assess the efficacy of gabapentin relative to tramadol for the treatment of moderate to severe chronic neuropathic or mixed pain by comparing the difference in average pain scores (assessed by age-appropriate pain scales) between intervention arms after 15 weeks of treatment. Secondary objectives include the assessment of the safety, quality of life and global satisfaction with treatment and the description of the pharmacokinetic-pharmacodynamic relationship of gabapentin liquid formulation and tramadol oral drops to validate the recommended paediatric doses. Only rescue pain medication by paracetamol and/or ibuprofen is allowed during the trial. Ethics and dissemination Ethic approval was obtained in the eight participating countries. Results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. Trial registration numbers 2014-004851-30 and NCT02722603. Trial status Ongoing research study, currently recruiting