Toward Sustainable Adoption of Integrated Care for Prevention of Unplanned Hospitalizations: A Qualitative Analysis.

Introduction: Complex chronic patients are prone to unplanned hospitalizations leading to a high burden on healthcare systems. To date, interventions to prevent unplanned admissions show inconclusive results. We report a qualitative analysis performed into the EU initiative JADECARE (2020-2023) to design a digitally enabled integrated care program aiming at preventing unplanned hospitalizations. Methods: A two-phase process with four design thinking (DT) sessions was conducted to analyse the management of complex chronic patients in the region of Catalonia (ES). In Phase I, Discovery, two DT sessions, October 2021 and February 2022, were done using as background information: i) the results of twenty structured interviews (five patients and fifteen professionals), ii) two governmental documents on regional deployment of integrated care and on the Catalan digital health strategy, respectively, and iii) the results of a cluster analysis of 761 hospitalizations. In Phase II, Confirmation, we examined the 30- and 90-day post-discharge periods of 49,604 hospitalizations as input for two additional DT sessions conducted in November and December 2022. Discussion: The qualitative analysis identified poor personalization of the interventions, the need for organizational changes, immature digitalization, and suboptimal services evaluation as main explanatory factors of the observed efficacy-effectiveness gap. Additionally, a program for prevention of unplanned hospitalizations, to be evaluated during the period 2024-2025, was generated. Conclusions: A digitally enabled adaptive case management approach to foster collaborative work and personalization of care, as well as organizational re-engineering, are endorsed for value-based prevention of unplanned hospitalizations.

Toward Adoption of Health Risk Assessment in Population-Based and Clinical Scenarios: Lessons From JADECARE.

Introduction: Health risk assessment (HRA) strategies are cornerstone for health systems transformation toward value-based patient-centred care. However, steps for HRA adoption are undefined. This article analyses the process of transference of the Adjusted Morbidity Groups (AMG) algorithm from the Catalan Good Practice to the Marche region (IT) and to Viljandi Hospital (EE), within the JADECARE initiative (2020-2023). Description: The implementation research approach involved a twelve-month pre-implementation period to assess feasibility and define the local action plans, followed by a sixteen-month implementation phase. During the two periods, a well-defined combination of experience-based co-design and quality improvement methodologies were applied. Discussion: The evolution of the Catalan HRA strategy (2010-2023) illustrates its potential for health systems transformation, as well as its transferability. The main barriers and facilitators for HRA adoption were identified. The report proposes a set of key steps to facilitate site customized deployment of HRA contributing to define a roadmap to foster large-scale adoption across Europe. Conclusions: Successful adoption of the AMG algorithm was achieved in the two sites confirming transferability. Marche identified the key requirements for a population-based HRA strategy, whereas Viljandi Hospital proved its potential for clinical use paving the way toward value-based healthcare strategies.

Multicentric Assessment of a Multimorbidity-Adjusted Disability Score to Stratify Depression-Related Risks Using Temporal Disease Maps: Instrument Validation Study.

BACKGROUND: Comprehensive management of multimorbidity can significantly benefit from advanced health risk assessment tools that facilitate value-based interventions, allowing for the assessment and prediction of disease progression. Our study proposes a novel methodology, the Multimorbidity-Adjusted Disability Score (MADS), which integrates disease trajectory methodologies with advanced techniques for assessing interdependencies among concurrent diseases. This approach is designed to better assess the clinical burden of clusters of interrelated diseases and enhance our ability to anticipate disease progression, thereby potentially informing targeted preventive care interventions. OBJECTIVE: This study aims to evaluate the effectiveness of the MADS in stratifying patients into clinically relevant risk groups based on their multimorbidity profiles, which accurately reflect their clinical complexity and the probabilities of developing new associated disease conditions. METHODS: In a retrospective multicentric cohort study, we developed the MADS by analyzing disease trajectories and applying Bayesian statistics to determine disease-disease probabilities combined with well-established disability weights. We used major depressive disorder (MDD) as a primary case study for this evaluation. We stratified patients into different risk levels corresponding to different percentiles of MADS distribution. We statistically assessed the association of MADS risk strata with mortality, health care resource use, and disease progression across 1 million individuals from Spain, the United Kingdom, and Finland. RESULTS: The results revealed significantly different distributions of the assessed outcomes across the MADS risk tiers, including mortality rates; primary care visits; specialized care outpatient consultations; visits in mental health specialized centers; emergency room visits; hospitalizations; pharmacological and nonpharmacological expenditures; and dispensation of antipsychotics, anxiolytics, sedatives, and antidepressants (P<.001 in all cases). Moreover, the results of the pairwise comparisons between adjacent risk tiers illustrate a substantial and gradual pattern of increased mortality rate, heightened health care use, increased health care expenditures, and a raised pharmacological burden as individuals progress from lower MADS risk tiers to higher-risk tiers. The analysis also revealed an augmented risk of multimorbidity progression within the high-risk groups, aligned with a higher incidence of new onsets of MDD-related diseases. CONCLUSIONS: The MADS seems to be a promising approach for predicting health risks associated with multimorbidity. It might complement current risk assessment state-of-the-art tools by providing valuable insights for tailored epidemiological impact analyses of clusters of interrelated diseases and by accurately assessing multimorbidity progression risks. This study paves the way for innovative digital developments to support advanced health risk assessment strategies. Further validation is required to generalize its use beyond the initial case study of MDD.

Aerobic capacity and mitochondrial function in bipolar disorder: a longitudinal study during acute phases and after clinical remission.

Background: Aerobic capacity has shown to predict physical and mental health-related quality of life in bipolar disorder (BD). However, the correlation between exercise respiratory capacity and mitochondrial function remains understudied. We aimed to assess longitudinally intra-individual differences in these factors during mood episodes and remission in BD. Methods: This study included eight BD patients admitted to an acute psychiatric unit. Incremental cardiopulmonary exercise test (CPET) was conducted during acute episodes (T0), followed by constant work rate cycle ergometry (CWRCE) to evaluate endurance time, oxygen uptake at peak exercise (VO2peak) and at the anaerobic threshold. The second test was repeated during remission (T1). Mitochondrial respiration rates were assessed at T0 and T1 in peripheral blood mononuclear cells. Results: Endurance time, VO2peak, and anaerobic threshold oxygen consumption showed no significant variations between T0 and T1. Basal oxygen consumption at T1 tended to inversely correlate with maximal mitochondrial respiratory capacity (r=-0.690, p=0.058), and VO2peak during exercise at T1 inversely correlated with basal and minimum mitochondrial respiration (r=-0.810, p=0.015; r=-0.786, p=0.021, respectively). Conclusions: Our preliminary data showed that lower basal oxygen consumption may be linked to greater mitochondrial respiratory capacity, and maximum oxygen uptake during the exercise task was associated with lower basal mitochondrial respiration, suggesting that lower oxygen requirements could be associated with greater mitochondrial capacity. These findings should be replicated in larger samples stratified for manic and depressive states.

The value of admission avoidance: cost-consequence analysis of one-year activity in a consolidated service.

BACKGROUND: Many advantages of hospital at home (HaH), as a modality of acute care, have been highlighted, but controversies exist regarding the cost-benefit trade-offs. The objective is to assess health outcomes and analytical costs of hospital avoidance (HaH-HA) in a consolidated service with over ten years of delivery of HaH in Barcelona (Spain). METHODS: A retrospective cost-consequence analysis of all first episodes of HaH-HA, directly admitted from the emergency room (ER) in 2017-2018, was carried out with a health system perspective. HaH-HA was compared with a propensity-score-matched group of contemporary patients admitted to conventional hospitalization (Controls). Mortality, re-admissions, ER visits, and direct healthcare costs were evaluated. RESULTS: HaH-HA and Controls (n = 441 each) were comparable in terms of age (73 [SD16] vs. 74 [SD16]), gender (male, 57% vs. 59%), multimorbidity, healthcare expenditure during the previous year, case mix index of the acute episode, and main diagnosis at discharge. HaH-HA presented lower mortality during the episode (0 vs. 19 (4.3%); p < 0.001). At 30 days post-discharge, HaH-HA and Controls showed similar re-admission rates; however, ER visits were lower in HaH-HA than in Controls (28 (6.3%) vs. 34 (8.1%); p = 0.044). Average costs per patient during the episode were lower in the HaH-HA group (€ 1,078) than in Controls (€ 2,171). Likewise, healthcare costs within the 30 days post-discharge were also lower in HaH-Ha than in Controls (p < 0.001). CONCLUSIONS: The study showed higher performance and cost reductions of HaH-HA in a real-world setting. The identification of sources of savings facilitates scaling of hospital avoidance. REGISTRATION: ClinicalTrials.gov (26/04/2017; NCT03130283).

Five years of Hospital at Home adoption in Catalonia: impact, challenges, and proposals for quality assurance.

BACKGROUND: Hospital at home (HaH) was increasingly implemented in Catalonia (7.7 M citizens, Spain) achieving regional adoption within the 2011-2015 Health Plan. This study aimed to assess population-wide HaH outcomes over five years (2015-2019) in a consolidated regional program and provide context-independent recommendations for continuous quality improvement of the service. METHODS: A mixed-methods approach was adopted, combining population-based retrospective analyses of registry information with qualitative research. HaH (admission avoidance modality) was compared with a conventional hospitalization group using propensity score matching techniques. We evaluated the 12-month period before the admission, the hospitalization, and use of healthcare resources at 30 days after discharge. A panel of experts discussed the results and provided recommendations for monitoring HaH services. RESULTS: The adoption of HaH steadily increased from 5,185 episodes/year in 2015 to 8,086 episodes/year in 2019 (total episodes 31,901; mean age 73 (SD 17) years; 79% high-risk patients. Mortality rates were similar between HaH and conventional hospitalization within the episode [76 (0.31%) vs. 112 (0.45%)] and at 30-days after discharge [973(3.94%) vs. 1112(3.24%)]. Likewise, the rates of hospital re-admissions at 30 days after discharge were also similar between groups: 2,00 (8.08%) vs. 1,63 (6.58%)] or ER visits [4,11 (16.62%) vs. 3,97 (16.03%). The 27 hospitals assessed showed high variability in patients' age, multimorbidity, severity of episodes, recurrences, and length of stay of HaH episodes. Recommendations aiming at enhancing service delivery were produced. CONCLUSIONS: Besides confirming safety and value generation of HaH for selected patients, we found that this service is delivered in a case-mix of different scenarios, encouraging hospital-profiled monitoring of the service.

Reduced mitochondrial respiratory capacity in patients with acute episodes of bipolar disorder: Could bipolar disorder be a state-dependent mitochondrial disease?

BACKGROUND: Bipolar disorder (BD) is a chronic and recurrent disease characterized by acute mood episodes and periods of euthymia. The available literature postulates that a biphasic dysregulation of mitochondrial bioenergetics might underpin the neurobiology of BD. However, most studies focused on inter-subject differences rather than intra-subject variations between different mood states. To test this hypothesis, in this preliminary proof-of-concept study, we measured in vivo mitochondrial respiration in patients with BD during a mood episode and investigated differences compared to healthy controls (HC) and to the same patients upon clinical remission. METHODS: This longitudinal study recruited 20 patients with BD admitted to our acute psychiatric ward with a manic (n = 15) or depressive (n = 5) episode, and 10 matched HC. We assessed manic and depressive symptoms using standardized psychometric scales. Different mitochondrial oxygen consumption rates (OCRs: Routine, Leak, electron transport chain [ETC], Rox) were assessed during the acute episode (T0) and after clinical remission (T1) using high-resolution respirometry at 37°C by polarographic oxygen sensors in a two-chamber Oxygraph-2k system in one million of peripheral blood mononuclear cells (PMBC). Specific OCRs were expressed as mean ± SD in picomoles of oxygen per million cells. Significant results were adjusted for age, sex, and body mass index. RESULTS: The longitudinal analysis showed a significant increase in the maximal oxygen consumption capacity (ETC) in clinical remission (25.7 ± 16.7) compared to the acute episodes (19.1 ± 11.8, p = 0.025), and was observed separately for patients admitted with a manic episode (29.2 ± 18.9 in T1, 22.3 ± 11.9 in T0, p = 0.076), and at a trend-level for patients admitted with a depressive episode (15.4 ± 3.9 in T1 compared to 9.4 ± 3.2 in T0, p = 0.107). Compared to HC, significant differences were observed in ETC in patients with a bipolar mood episode (H = 11.7; p = 0.003). Individuals with bipolar depression showed lower ETC than those with a manic episode (t = -3.7, p = 0.001). Also, significant differences were observed in ETC rates between HC and bipolar depression (Z = 1.000, p = 0.005). CONCLUSIONS: Bioenergetic and mitochondrial dysregulation could be present in both manic and depressive phases in BD and, importantly, they may restore after clinical remission. These preliminary results suggest that mitochondrial respiratory capacity could be a biomarker of illness activity and clinical response in BD. Further studies with larger samples and similar approaches are needed to confirm these results and identify potential biomarkers in different phases of the disease.

A Practice-Proven Adaptive Case Management Approach for Innovative Health Care Services (Health Circuit): Cluster Randomized Clinical Pilot and Descriptive Observational Study.

BACKGROUND: Digital health tools may facilitate the continuity of care. Enhancement of digital aid is imperative to prevent information gaps or redundancies, as well as to facilitate support of flexible care plans. OBJECTIVE: The study presents Health Circuit, an adaptive case management approach that empowers health care professionals and patients to implement personalized evidence-based interventions, thanks to dynamic communication channels and patient-centered service workflows; analyze the health care impact; and determine its usability and acceptability among health care professionals and patients. METHODS: From September 2019 to March 2020, the health impact, usability (measured with the system usability scale; SUS), and acceptability (measured with the net promoter score; NPS) of an initial prototype of Health Circuit were tested in a cluster randomized clinical pilot (n=100) in patients with high risk for hospitalization (study 1). From July 2020 to July 2021, a premarket pilot study of usability (with the SUS) and acceptability (with the NPS) was conducted among 104 high-risk patients undergoing prehabilitation before major surgery (study 2). RESULTS: In study 1, Health Circuit resulted in a reduction of emergency room visits (4/7, 13% vs 7/16, 44%), enhanced patients' empowerment (P<.001) and showed good acceptability and usability scores (NPS: 31; SUS: 54/100). In study 2, the NPS was 40 and the SUS was 85/100. The acceptance rate was also high (mean score of 8.4/10). CONCLUSIONS: Health Circuit showed potential for health care value generation and good acceptability and usability despite being a prototype system, prompting the need for testing a completed system in real-world scenarios. TRIAL REGISTRATION: ClinicalTrials.gov NCT04056663; https://clinicaltrials.gov/ct2/show/NCT04056663.

Prevention of Unplanned Hospital Admissions in Multimorbid Patients Using Computational Modeling: Observational Retrospective Cohort Study.

BACKGROUND: Enhanced management of multimorbidity constitutes a major clinical challenge. Multimorbidity shows well-established causal relationships with the high use of health care resources and, specifically, with unplanned hospital admissions. Enhanced patient stratification is vital for achieving effectiveness through personalized postdischarge service selection. OBJECTIVE: The study has a 2-fold aim: (1) generation and assessment of predictive models of mortality and readmission at 90 days after discharge; and (2) characterization of patients' profiles for personalized service selection purposes. METHODS: Gradient boosting techniques were used to generate predictive models based on multisource data (registries, clinical/functional and social support) from 761 nonsurgical patients admitted in a tertiary hospital over 12 months (October 2017 to November 2018). K-means clustering was used to characterize patient profiles. RESULTS: Performance (area under the receiver operating characteristic curve, sensitivity, and specificity) of the predictive models was 0.82, 0.78, and 0.70 and 0.72, 0.70, and 0.63 for mortality and readmissions, respectively. A total of 4 patients' profiles were identified. In brief, the reference patients (cluster 1; 281/761, 36.9%), 53.7% (151/281) men and mean age of 71 (SD 16) years, showed 3.6% (10/281) mortality and 15.7% (44/281) readmissions at 90 days following discharge. The unhealthy lifestyle habit profile (cluster 2; 179/761, 23.5%) predominantly comprised males (137/179, 76.5%) with similar age, mean 70 (SD 13) years, but showed slightly higher mortality (10/179, 5.6%) and markedly higher readmission rate (49/179, 27.4%). Patients in the frailty profile (cluster 3; 152/761, 19.9%) were older (mean 81 years, SD 13 years) and predominantly female (63/152, 41.4%, males). They showed medical complexity with a high level of social vulnerability and the highest mortality rate (23/152, 15.1%), but with a similar hospitalization rate (39/152, 25.7%) compared with cluster 2. Finally, the medical complexity profile (cluster 4; 149/761, 19.6%), mean age 83 (SD 9) years, 55.7% (83/149) males, showed the highest clinical complexity resulting in 12.8% (19/149) mortality and the highest readmission rate (56/149, 37.6%). CONCLUSIONS: The results indicated the potential to predict mortality and morbidity-related adverse events leading to unplanned hospital readmissions. The resulting patient profiles fostered recommendations for personalized service selection with the capacity for value generation.

The Assessment of Medical Device Software Supporting Health Care Services for Chronic Patients in a Tertiary Hospital: Overarching Study.

BACKGROUND: Innovative digital health tools are increasingly being evaluated and, in some instances, integrated at scale into health systems. However, the applicability of assessment methodologies in real-life scenarios to demonstrate value generation and consequently foster sustainable adoption of digitally enabled health interventions has some bottlenecks. OBJECTIVE: We aimed to build on the process of premarket assessment of 4 digital health interventions piloted at the Hospital Clinic de Barcelona (HCB), as well as on the analysis of current medical device software regulations and postmarket surveillance in the European Union and United States in order to generate recommendations and lessons learnt for the sustainable adoption of digitally enabled health interventions. METHODS: Four digital health interventions involving prototypes were piloted at the HCB (studies 1-4). Cocreation and quality improvement methodologies were used to consolidate a pragmatic evaluation method to assess the perceived usability and satisfaction of end users (both patients and health care professionals) by means of the System Usability Scale and the Net Promoter Score, including general questions about satisfaction. Analyses of both medical software device regulations and postmarket surveillance in the European Union and United States (2017-2021) were performed. Finally, an overarching analysis on lessons learnt was conducted considering 4 domains (technical, clinical, usability, and cost), as well as differentiating among 3 different eHealth strategies (telehealth, integrated care, and digital therapeutics). RESULTS: Among the participant stakeholders, the System Usability Scale score was consistently higher in patients (studies 1, 2, 3, and 4: 78, 67, 56, and 76, respectively) than in health professionals (studies 2, 3, and 4: 52, 43, and 54, respectively). In general, use of the supporting digital health tools was recommended more by patients (studies 1, 2, 3, and 4: Net Promoter Scores of -3%, 31%, -21%, and 31%, respectively) than by professionals (studies 2, 3, and 4: Net Promoter Scores of -67%, 1%, and -80%, respectively). The overarching analysis resulted in pragmatic recommendations for the digital health evaluation domains and the eHealth strategies considered. CONCLUSIONS: Lessons learnt on the digitalization of health resulted in practical recommendations that could contribute to future deployment experiences.

Actionable Factors Fostering Health Value Generation and Scalability of Prehabilitation: A Prospective Cohort Study.

IMPORTANCE: Prehabilitation has potential for improving surgical outcomes as shown in previous randomized controlled trials. However, a marked efficacy-effectiveness gap is limiting its scalability. Comprehensive analyses of deployment of the intervention in real-life scenarios are required. OBJECTIVE: To assess health outcomes and cost of prehabilitation. DESIGN: Prospective cohort study with a control group built using propensity score-matching techniques. SETTING: Prehabilitation Unit in a tertiary-care university hospital. PARTICIPANTS: Candidates for major digestive, cardiac, thoracic, gynecologic, or urologic surgeries. INTERVENTION: Prehabilitation program, including supervised exercise training, promotion of physical activity, nutritional optimization, and psychological support. MAIN OUTCOMES AND MEASURES: The comprehensive complication index, hospital and intensive care unit length of stay, and hospital costs per patient until 30 days after surgery. Patients were classified by the degree of program completion and level of surgical aggression for sensitivity analysis. RESULTS: The analysis of the entire study group did not show differences in study outcomes between prehabilitation and control groups (n=328 each). The per-protocol analysis, including only patients completing the program (n=112, 34%), showed a reduction in mean hospital stay [9.9 (7.2) vs 12.8 (12.4) days; P =0.035]. Completers undergoing highly aggressive surgeries (n=60) additionally showed reduction in mean intensive care unit stay [2.3 (2.7) vs 3.8 (4.2) days; P =0.021] and generated mean cost savings per patient of €3092 (32% cost reduction) ( P =0.007). Five priority areas for action to enhance service efficiencies were identified. CONCLUSIONS AND RELEVANCE: The study indicates a low rate of completion of the intervention and identifies priority areas for re-design of service delivery to enhance the effectiveness of prehabilitation.

Role of Co-creation for Large-Scale Sustainable Adoption of Digitally Supported Integrated Care: Prehabilitation as Use Case.

Introduction: The efficacy-effectiveness gap constitutes a well-known limitation for adoption of digitally enabled integrated care services. The current report describes the co-creation process undertaken (2016-2021) to deploy a prehabilitation service at Hospital Clínic de Barcelona with the final aim of achieving sustainable adoption and facilitate site transferability. Methods: An implementation research approach with a population-based orientation, combining experience-based co-design and quality improvement methodologies, was applied. We undertook several design-thinking sessions (Oct-Nov 2017, June 2021 and December 2021) to generate and follow-up a work plan fostering service scalability. The implementation process was assessed using the Comprehensive Framework for Implementation Research, leading to the identification of key performance indicators. Discussion: Personalization and modularity of the intervention according to patients' surgical risk were identified as core traits to enhance patients' adherence and value generation. A digitally enabled service workflow, with an adaptive and collaborative case management approach, should combine face-to-face and remotely supervised sessions with intelligent systems for patients' and professionals' decision support. The business model envisages operational costs financed by savings generated by the service. Conclusions: Evidence-based co-creation, combining appropriate methodologies and a structured evaluation framework, was key to address challenges associated with sustainable prehabilitation service adoption, scalability and transferability.

Prospective cohort study for assessment of integrated care with a triple aim approach: hospital at home as use case.

BACKGROUND: Applicability of comprehensive assessment of integrated care services in real world settings is an unmet need. To this end, a Triple Aim evaluation of Hospital at Home (HaH), as use case, was done. As ancillary aim, we explored use of the approach for monitoring the impact of adoption of integrated care at health system level in Catalonia (Spain). METHODS: Prospective cohort study over one year period, 2017-2018, comparing hospital avoidance (HaH-HA) with conventional hospitalization (UC) using propensity score matching. Participants were after the first episode directly admitted to HaH-HA or the corresponding control group. Triple Aim assessment using multiple criteria decision analysis (MCDA) was done. Moreover, applicability of a Triple Aim approach at health system level was explored using registry data. RESULTS: HaH-HA depicted lower: i) Emergency Room Department (ER) visits (p < .001), ii) Unplanned re-admissions (p = .012); and iii) costs (p < .001) than UC. The weighted aggregation of the standardized values of each of the eight outcomes, weighted by the opinions of the stakeholder groups considered in the MCDA: i) enjoyment of life; ii) resilience; iii) physical functioning; iv) continuity of care; v) psychological wellbeing; (vi) social relationships & participation; (vii) person-centeredness; and (viii) costs, indicated better performance of HaH-HA than UC (p < .05). Actionable factors for Triple Aim assessment of the health system with a population-health approach were identified. CONCLUSIONS: We confirmed health value generation of HaH-HA. The study identified actionable factors to enhance applicability of Triple Aim assessment at health system level for monitoring the impact of adoption of integrated care. REGISTRATION: ClinicalTrials.gov (26/04/2017; NCT03130283).

Safety of Short-Term Treatments with Oral Chloroquine and Hydroxychloroquine in Patients with and without COVID-19: A Systematic Review.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have recently become the focus of global attention as possible treatments for Coronavirus Disease 2019 (COVID-19). The current systematic review aims to assess their safety in short treatments (≤14 days), whether used alone or in combination with other drugs. Following the PRISMA and SWiM recommendations, a search was conducted using four health databases for all relevant English-, Chinese-, and Spanish-language studies from inception through 30 July 2021. Patients treated for any condition and with any comparator were included. The outcomes of interest were early drug adverse effects and their frequency. A total of 254 articles met the inclusion criteria, including case and case-control reports as well as cross-sectional, cohort, and randomised studies. The results were summarised either qualitatively in table or narrative form or, when possible (99 studies), quantitatively in terms of adverse event frequencies. Quality evaluation was conducted using the CARE, STROBE, and JADAD tools. This systematic review showed that safety depended on drug indication. In COVID-19 patients, cardiac adverse effects, such as corrected QT interval prolongation, were relatively frequent (0-27.3% and up to 33% if combined with azithromycin), though the risk of torsade de pointes was low. Compared to non-COVID-19 patients, COVID-19 patients experienced a higher frequency of cardiac adverse effects regardless of the regimen used. Dermatological adverse effects affected 0-10% of patients with autoimmune diseases and COVID-19. A broad spectrum of neuropsychiatric adverse effects affected patients treated with CQ for malaria with variable frequencies and some cases were reported in COVID-19 patients. Gastrointestinal adverse effects occurred regardless of drug indication affecting 0-50% of patients. In conclusion, CQ and HCQ are two safe drugs widely used in the treatment of malaria and autoimmune diseases. However, recent findings on their cardiac and neuropsychiatric adverse effects should be considered if these drugs were to be proposed as antivirals again.

Repeatability and learning effect in the 6MWT in preoperative cancer patients undergoing a prehabilitation program.

OBJECTIVE: The main objective was to assess repeatability and learning effect of the 6-min walk test (6MWT) in a cohort of preoperative cancer patients referred to a prehabilitation program. As a secondary objective, we aimed to identify determinants of improvement in the second test. MATERIALS AND METHODS: Secondary analysis from a large prospective study on the implementation of a multimodal prehabilitation program in a real-life scenario. Eligible patients were assessed at baseline before starting the prehabilitation program. The 6MWT was conducted according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines with two tests being performed under identical conditions separated by 30 min. The distance covered (in meters) and the physiological responses (heart rate, oxygen saturation, fatigue, and dyspnea) to each test were recorded and compared. RESULTS: A total of 170 patients (60.9%) were analyzed. Repeatability of the distance covered with the 6MWT was excellent (ICC = 0.98; 95% CI: 0.92-0.99), but a mean increase of + 19.5 m (95% CI: 15.6-23.5 m; p = < .001) in the second test was found, showing a learning effect with limits of agreement between - 31.3 and 70.4 m. Coefficient of variation was 4%. No clinical factor was found to be associated with an improvement in the second test. CONCLUSIONS: The 6MWT showed excellent repeatability in preoperative cancer patients, but a significant learning effect is present. No associated factors with a clinically meaningful improvement in the second test were identified. In light of these findings, two attempts of the 6MWT should be encouraged in this population.

Correlation of ultrasound, cytological, and histological features of 110 benign BI-RADS categories 4C and 5 nonpalpable breast lesions. The Institut Curie's experience.

BACKGROUND: The purpose of this study was to determine the pathological and ultrasound (US) features of benign nonpalpable breast lesions (NPBLs) classified as Breast Imaging Reporting and Data System (BI-RADS) category 4C or 5. METHODS: Between 2003 and 2007, 849 consecutive NPBLs detected at US and classified as BI-RADS category 4C (505) or 5 (344) initially underwent US-guided fine needle aspiration (FNA) at our institution. Benign diagnoses were established according to surgical excision findings or during a minimal 6-month imaging follow-up (mean, 3.7 years [SD, 2.6 years]). US BI-RADS features were reviewed and compared retrospectively using a chi-square test for the following pathological categories: epithelial and fibrous proliferation (EFP), cystic and papillary lesion (C&P), inflammatory lesion (IL), benign tumor (BT), intramammary lymph node (ILN), intraepithelial proliferative lesion (IPL), and nonspecific morphological alteration (NMA). The performance of FNA in the diagnosis of benignity was assessed. RESULTS: Of 849 NPBLs, 110 (12.9%) NPBLs were benign: 88 (17.4%) were BI-RADS category 4C, and 22 (6.4%) were BI-RADS category 5. Forty-four (40%) were EFPs, 21 (19%) were C&Ps, 13 (12%) were NMAs, 11 (10%) were ILs, 11 (10%) were BTs, 8 (7%) were IPLs, and 2 (2%) were ILNs. Lesion shape, US pattern distribution, and posterior features showed statistically significant differences between these categories (P < .05): 33 (75%) EFPs exhibited posterior shadowing, 18 (86%) C&Ps were homogenous, 9 (82%) ILs were heterogeneous, 11 (100%) BTs were homogeneous, 9 (82%) BTs were oval, and 6 (75%) IPLs were irregularly shaped. Of the 110 benign NPBLs, FNA diagnosis was falsely positive in 7 (6%), suspicious in 10 (9%), and benign in 90 (82%), and 3 (3%) were inadequate for diagnosis. CONCLUSION: A diverse array of benign NPBLs can be classified as BI-RADS category 4C or 5 on US, each showing specific imaging presentations.

The patient at the centre: evidence from 17 European integrated care programmes for persons with complex needs.

BACKGROUND: As the prevalence of multi-morbidity increases in ageing societies, health and social care systems face the challenge of providing adequate care to persons with complex needs. Approaches that integrate care across sectors and disciplines have been increasingly developed and implemented in European countries in order to tackle this challenge. The aim of the article is to identify success factors and crucial elements in the process of integrated care delivery for persons with complex needs as seen from the practical perspective of the involved stakeholders (patients, professionals, informal caregivers, managers, initiators, payers). METHODS: Seventeen integrated care programmes for persons with complex needs in 8 European countries were investigated using a qualitative approach, namely thick description, based on semi-structured interviews and document analysis. In total, 233 face-to-face interviews were conducted with stakeholders of the programmes between March and September 2016. Meta-analysis of the individual thick description reports was performed with a focus on the process of care delivery. RESULTS: Four categories that emerged from the overarching analysis are discussed in the article: (1) a holistic view of the patient, considering both mental health and the social situation in addition to physical health, (2) continuity of care in the form of single contact points, alignment of services and good relationships between patients and professionals, (3) relationships between professionals built on trust and facilitated by continuous communication, and (4) patient involvement in goal-setting and decision-making, allowing patients to adapt to reorganised service delivery. CONCLUSIONS: We were able to identify several key aspects for a well-functioning integrated care process for complex patients and how these are put into actual practice. The article sets itself apart from the existing literature by specifically focussing on the growing share of the population with complex care needs and by providing an analysis of actual processes and interpersonal relationships that shape integrated care in practice, incorporating evidence from a variety of programmes in several countries.