A novel multistep approach to standardize the reported risk factors for in-hospital falls: a proof-of-concept study.

Background: Uncertainty and inconsistency in terminology regarding the risk factors (RFs) for in-hospital falls are present in the literature. Objective: (1) To perform a literature review to identify the fall RFs among hospitalized adults; (2) to link the found RFs to the corresponding categories of international health classifications to reduce the heterogeneity of their definitions; (3) to perform a meta-analysis on the risk categories to identify the significant RFs; (4) to refine the final list of significant categories to avoid redundancies. Methods: Four databases were investigated. We included observational studies assessing patients who had experienced in-hospital falls. Two independent reviewers performed the inclusion and extrapolation process and evaluated the methodological quality of the included studies. RFs were grouped into categories according to three health classifications (ICF, ICD-10, and ATC). Meta-analyses were performed to obtain an overall pooled odds ratio for each RF. Finally, protective RFs or redundant RFs across different classifications were excluded. Results: Thirty-six articles were included in the meta-analysis. One thousand one hundred and eleven RFs were identified; 616 were linked to ICF classification, 450 to ICD-10, and 260 to ATC. The meta-analyses and subsequent refinement of the categories yielded 53 significant RFs. Overall, the initial number of RFs was reduced by about 21 times. Conclusion: We identified 53 significant RF categories for in-hospital falls. These results provide proof of concept of the feasibility and validity of the proposed methodology. The list of significant RFs can be used as a template to build more accurate measurement instruments to predict in-hospital falls.

Real-World Data and Budget Impact Analysis (BIA): Evaluation of a Targeted Next-Generation Sequencing Diagnostic Approach in Two Orthopedic Rare Diseases.

Objective: Next-generation sequencing (NGS) technology, changing the diagnostic approach, has become essential in clinical settings, and its adoption by public health laboratories is now the practice. Despite this, as technological innovations, its intake requires an evaluation of both the clinical utility and the economic investment, especially considering the rare disease scenario. This study evaluated the analytical validity and the budget impact of an NGS-Ion Torrent™ approach for the molecular germline diagnosis of two musculoskeletal rare diseases. Methods: Two cohorts of 200 and 199 patients with suspect or clinical diagnosis of multiple osteochondromas (MO) and osteogenesis imperfecta (OI) previously evaluated with a single-gene diagnostic protocol were re-analyzed using a targeted NGS assay. Analytical validity was assessed by comparing NGS and single-gene protocol. A budget impact analysis using real-world cost data-considering the healthcare perspective- was performed by applying activity-based costing (ABC). The cost considered consumables, personnel, and equipment. Additional costs not related to NGS activities were not considered. Sensitivity analysis was performed. Results: The NGS method showed a higher (for MO) and comparable (for OI) diagnostic sensitivity than the traditional techniques, apart from always reducing the time and costs of diagnosis. Overall, the cost saving per patient is € 765 for OI and € 74 for MO. Materials represented the highest cost driver of the NGS process. A time saving-proportional to the panel size-has been assessed in both cases. Conclusions: Our targeted NGS diagnostic approach decreases time to diagnosis and costs, appearing to be beneficial and recommended both for patients and from a healthcare perspective in routine diagnosis also considering very small gene panels and a low patient flow. The adequate analytical sensitivity always required the additional Sanger sequencing step of the low- and non-covered regions. A more accurate strategy evaluation is suggested in the case of ultra-rare/complex diseases, large gene-panel, or non-reference diagnostic centers.

Estimate false-negative RT-PCR rates for SARS-CoV-2. A systematic review and meta-analysis.

BACKGROUND: Molecular-based tests used to identify symptomatic or asymptomatic patients infected by SARS-CoV-2 are characterized by high specificity but scarce sensitivity, generating false-negative results. We aimed to estimate, through a systematic review of the literature, the rate of RT-PCR false negatives at initial testing for COVID-19. METHODS: We systematically searched Pubmed, Embase and CENTRAL as well as a list of reference literature. We included observational studies that collected samples from respiratory tract to detect SARS-CoV-2 RNA using RT-PCR, reporting the number of false-negative subjects and the number of final patients with a COVID-19 diagnosis. Reported rates of false negatives were pooled in a meta-analysis as appropriate. We assessed the risk of bias of included studies and graded the quality of evidence according to the GRADE method. All information in this article is current up to February 2021. RESULTS: We included 32 studies, enrolling more than 18,000 patients infected by SARS-CoV-2. The overall false-negative rate was 0.12 (95%CI from 0.10 to 0.14) with very low certainty of evidence. The impact of misdiagnoses was estimated according to disease prevalence; a range between 2 and 58/1,000 subjects could be misdiagnosed with a disease prevalence of 10%, increasing to 290/1,000 misdiagnosed subjects with a disease prevalence of 50%. CONCLUSIONS: This systematic review showed that up to 58% of COVID-19 patients may have initial false-negative RT-PCR results, suggesting the need to implement a correct diagnostic strategy to correctly identify suspected cases, thereby reducing false-negative results and decreasing the disease burden among the population.

[Temporary percutaneous ventricular assist devices for cardiogenic shock and high-risk percutaneous coronary intervention: a systematic literature review]. / Sistemi percutanei di assistenza ventricolare temporanea per lo shock cardiogeno e la rivascolarizzazione coronarica percutanea ad alto rischio: revisione sistematica della letteratura.

BACKGROUND: Percutaneous ventricular assist devices (pVADs) are frequently used for the treatment of patients with cardiogenic shock (CS) due to acute myocardial infarction (AMI) and as a support in percutaneous coronary intervention (PCI) for high-risk patients. CS is a clinical condition characterized by inadequate tissue perfusion due to cardiac dysfunction and for 80% of cases it is caused by AMI with left ventricular insufficiency. CS is responsible for about 50% of deaths in patients with myocardial infarction. Usually, PCIs do not require hemodynamic support, which could be however necessary in patients undergoing high-risk PCI. Presently, available pVADs in Europe are Impella 2.5, Impella CP, HeartMate PHP, TandemHeart, PulseCath iVAC2L. The aim of this review is to evaluate the efficacy and safety of pVADs in patients with refractory CS complicating AMI or undergoing high-risk PCI. METHODS: We systematically searched for randomized controlled trials (RCTs) and controlled observational studies in PubMed, Embase and PubMed CENTRAL databases until September 2018. We included studies comparing pVADs with intra-aortic balloon pumps (IABP) or medical therapy in patients with CS complicating AMI or undergoing high-risk PCI. Researchers independently assessed records' eligibility, inclusion and methodological quality of included studies. If possible, data of included studies was combined in a meta-analysis. Risk ratio (RR) and 95% confidence interval (CI) were calculated using a random effects model. RESULTS: Overall, 8 studies were included. Five studies (3 RCTs and 2 observational studies) evaluated pVADs in patients with SC complicating AMI. Meta-analyses showed that 30-day mortality did not differ between patients treated with pVADs and the control group (RR 1.05, 95% CI 0.84-1.31). However, risk of major bleeding was 2 times higher in patients treated with pVADs compared to controls. Three studies evaluated pVADs in patients undergoing high-risk PCI. Due to the lack of data, it was not possible to combine study results in a meta-analysis. One RCT reported no difference in 30- and 90-day mortality between patients randomized to Impella or IABP. Two non-randomized controlled studies reported no difference in terms of in-hospital all-cause mortality between the two groups. CONCLUSIONS: Our meta-analysis suggests similar results in terms of efficacy and safety between pVADs and control (IABP and medical therapy) for the treatment of patients with CS complicating AMI or undergoing high-risk PCI.

Comparison of cryoballoon and radiofrequency ablation techniques for atrial fibrillation: a meta-analysis.

AIMS: To perform an updated meta-analysis to assess efficacy, safety and technical performance of pulmonary vein isolation using cryoballoon or radiofrequency catheter ablation in patients with paroxysmal or persistent atrial fibrillation. METHODS: In June 2017, databases and websites were systematically searched for systematic reviews, randomized controlled trials and observational studies reporting data on efficacy, safety and technical performance outcomes at follow-up at least 12 months. Researchers independently assessed records' eligibility, inclusion and methodological quality of included studies. RESULTS: Six randomized controlled trials and 25 observational studies - 11 853 patients were included. Studies on paroxysmal atrial fibrillation were 29 and included 11 635 patients. Meta-analysis results showed no difference between cryoballoon and radiofrequency in terms of recurrent atrial fibrillation [risk ratio 1.04, 95% confidence interval (CI) 0.98-1.10] or atrial tachyarrhythmias (risk ratio 1.04, 95% CI 1-1.08) and fluoroscopy time (mean difference -1.92 min, 95% CI -4.89 to 1.05). Cryoballoon ablation was associated with fewer reablations (risk ratio 0.79, 95% CI 0.64-0.98), lower incidence of pericardial effusion (risk ratio 0.52, 95% CI 0.31-0.89) and cardiac tamponade (risk ratio 0.33, 95% CI 0.18-0.62) and shorter total procedural time (mean difference -23.48 min, 95% CI -37.97; -9.02) but with higher incidence of phrenic nerve palsy (risk ratio 5.43, 95% CI 2.67-11.04). Prespecified subgroup analysis confirmed overall results as for freedom from atrial fibrillation and atrial tachyarrhythmias. Only two observational studies included patients with persistent atrial fibrillation, thus hindering any conclusion in this population. CONCLUSION: In patients with paroxysmal atrial fibrillation, cryoballoon and radiofrequency ablation produce similar results in terms of freedom from recurrent atrial fibrillation or atrial tachyarrhythmias but with a different safety profile, being cryoballoon ablation less associated with cardiac complications but more likely to cause phrenic nerve palsy.

Interventions to reduce waiting times for elective procedures.

BACKGROUND: Long waiting times for elective healthcare procedures may cause distress among patients, may have adverse health consequences and may be perceived as inappropriate delivery and planning of health care. OBJECTIVES: To assess the effectiveness of interventions aimed at reducing waiting times for elective care, both diagnostic and therapeutic. SEARCH METHODS: We searched the following electronic databases: Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1946-), EMBASE (1947-), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), ABI Inform, the Canadian Research Index, the Science, Social Sciences and Humanities Citation Indexes, a series of databases via Proquest: Dissertations & Theses (including UK & Ireland), EconLit, PAIS (Public Affairs International), Political Science Collection, Nursing Collection, Sociological Abstracts, Social Services Abstracts and Worldwide Political Science Abstracts. We sought related reviews by searching the Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness (DARE). We searched trial registries, as well as grey literature sites and reference lists of relevant articles. SELECTION CRITERIA: We considered randomised controlled trials (RCTs), controlled before-after studies (CBAs) and interrupted time series (ITS) designs that met EPOC minimum criteria and evaluated the effectiveness of any intervention aimed at reducing waiting times for any type of elective procedure. We considered studies reporting one or more of the following outcomes: number or proportion of participants whose waiting times were above or below a specific time threshold, or participants' mean or median waiting times. Comparators could include any type of active intervention or standard practice. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from, and assessed risk of bias of, each included study, using a standardised form and the EPOC 'Risk of bias' tool. They classified interventions as follows: interventions aimed at (1) rationing and/or prioritising demand, (2) expanding capacity, or (3) restructuring the intake assessment/referral process.For RCTs when available, we reported preintervention and postintervention values of outcome for intervention and control groups, and we calculated the absolute change from baseline or the effect size with 95% confidence interval (CI). We reanalysed ITS studies that had been inappropriately analysed using segmented time-series regression, and obtained estimates for regression coefficients corresponding to two standardised effect sizes: change in level and change in slope. MAIN RESULTS: Eight studies met our inclusion criteria: three RCTs and five ITS studies involving a total of 135 general practices/primary care clinics, seven hospitals and one outpatient clinic. The studies were heterogeneous in terms of types of interventions, elective procedures and clinical conditions; this made meta-analysis unfeasible.One ITS study evaluating prioritisation of demand through a system for streamlining elective surgery services reduced the number of semi-urgent participants waiting longer than the recommended time (< 90 days) by 28 participants/mo, while no effects were found for urgent (< 30 days) versus non-urgent participants (< 365 days).Interventions aimed at restructuring the intake assessment/referral process were evaluated in seven studies. Four studies (two RCTs and two ITSs) evaluated open access, or direct booking/referral: One RCT, which showed that open access to laparoscopic sterilisation reduced waiting times, had very high attrition (87%); the other RCT showed that open access to investigative services reduced waiting times (30%) for participants with lower urinary tract syndrome (LUTS) but had no effect on waiting times for participants with microscopic haematuria. In one ITS study, same-day scheduling for paediatric health clinic appointments reduced waiting times (direct reduction of 25.2 days, and thereafter a decrease of 3.03 days per month), while another ITS study showed no effect of a direct booking system on proportions of participants receiving a colposcopy appointment within the recommended time. One RCT and one ITS showed no effect of distant consultancy (instant photography for dermatological conditions and telemedicine for ear nose throat (ENT) conditions) on waiting times; another ITS study showed no effect of a pooled waiting list on the number of participants waiting for uncomplicated spinal surgery.Overall quality of the evidence for all outcomes, assessed using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) tool, ranged from low to very low.We found no studies evaluating interventions to increase capacity or to ration demand. AUTHORS' CONCLUSIONS: As only a handful of low-quality studies are presently available, we cannot draw any firm conclusions about the effectiveness of the evaluated interventions in reducing waiting times. However, interventions involving the provision of more accessible services (open access or direct booking/referral) show some promise.

A method for addressing research gaps in HTA, developed whilst evaluating robotic-assisted surgery: a proposal.

BACKGROUND: When evaluating health technologies with insufficient scientific evidence, only innovative potentials can be assessed. A Regional policy initiative linking the governance of health innovations to the development of clinical research has been launched by the Region of Emilia Romagna Healthcare Authority. This program, aimed at enhancing the research capacity of health organizations, encourages the development of adoption plans that combine use in clinical practice along with experimental use producing better knowledge. Following the launch of this program we developed and propose a method that, by evaluating and ranking scientific uncertainty, identifies the moment (during the stages of the technology's development) where it would be sensible to invest in research resources and capacity to further its evaluation. The method was developed and tested during a research project evaluating robotic surgery. METHODS: A multidisciplinary panel carried out a 5-step evaluation process: 1) definition of the technology's evidence profile and of all relevant clinical outcomes; 2) systematic review of scientific literature and outline of the uncertainty profile differentiating research results into steady, plausible, uncertain and unknown results; 3) definition of the acceptable level of uncertainty for investing research resources; 4) analysis of local context; 5) identification of clinical indications with promising clinical return. RESULTS: Outputs for each step of the evaluation process are: 1) evidence profile of the technology and systematic review; 2) uncertainty profile for each clinical indication; 3) exclusion of clinical indications not fulfilling the criteria of maximum acceptable risk; 4) mapping of local context; 5) recommendations for research.Outputs of the evaluation process for robotic surgery are described in the paper. CONCLUSIONS: This method attempts to rank levels of uncertainty in order to distinguish promising from hazardous clinical use and to outline a research course of action. Decision makers wishing to tie coverage policies to the development of scientific evidence could find this method a useful aid to the governance of innovations.

The changing face of mild head injury: temporal trends and patterns in adolescents and adults from 1997 to 2008.

OBJECTIVE: To explore the temporal trend of incidence, causes of injury and main characteristics of adolescent and adult subjects with mild head injury (MHI). DESIGN: This study had a retrospective design. SETTING: The study was conducted in a longitudinal database of an Italian Emergency Department (ED). PARTICIPANTS: The study comprised 19124 consecutive subjects who visited and were managed within 24 h from the event, according to a predefined protocol for MHI from 1997 to 2008. MAIN OUTCOME MEASURES: Incidence, demography, cause of injury and characteristics of any post-traumatic intracranial lesion within 7 days from MHI. RESULTS: The number of subjects with MHI decreased from 2019 per year (1997-1999) to 1232 per year (2006-2008; P for linear trend <0.001), without differences in the total number of subjects visited in the ED. The decrease was observed in all age-decades, in particular, in subjects in the age ranges of 20-29 and 30-39 years. Over time, the age of subjects with MHI lost a bimodal distribution, and the mean age increased from 43 (25-69) years (median (interquartile range)) in 1997-1999 to 56 (33-78) years in 2006-2008 (P<0.001). The prevalence of falls increased from 36.5% to 55.0%, whereas crashes fell from 53.2% to 31.9%. The incidence of subdural haematoma (SDH) and epidural haematoma (EDH) did not change over time, whereas traumatic subarachnoid haemorrhage (t-SAH) and intra-cerebral haematoma/brain contusion (ICH) increased (from 0.7% to 1.9% and from 2.5% to 3.2%; P for trend: <0.001 for both. CONCLUSIONS: The incidence and the clinical characteristics of MHI subjects are rapidly changing in our setting. These data need to be considered in defining the effectiveness of preventive measures and deciding resource allocation.

[Determinants of clinical priority and of actual waiting times for surgical interventions]. / Determinanti della priorità clinicà e dei tempi effettivi di attesa per interventi di chirurgia generale.

OBJECTIVES: To explore determinants of clinical priority and of actual waiting times for elective surgical interventions. DESIGN, SETTING PARTECIPANTS: 405 patients cared for at two general surgery wards, receiving an explicit judgement of clinical priority and whose actual waiting times to surgery were assessed. Clinicalpriority was assessed through 0 (no priority) to 10 (maximum priority). MAIN OUTCOME MEASURE: Identification through multivariate regression techniques of the clinical characteristics associated with high clinical priority (score 28) and with shorter actual waiting times. RESULTS: Patients with cancer, severe pain, relevant impairment in functional status and relevant expert improvement on quality and duration of survival were more frequently attributed a high clinical priority. As for waiting times, presence of cancer was the only factor associated with shorter waitings. Only for cancer patients high priority judgement was associated with shorter waiting times (median 21 vs. 69 days; p < 0.008). CONCLUSIONS: These findings suggest that actual waiting times are not influenced by the same clinical characteristics that clinicians value when assigning clinical priority. That may have some relevant implications on how waiting lists are managed, if consideration of relevant aspects of patients' needs are missed.

Development and assessment of a priority score for cataract surgery.

BACKGROUND: Point-count measures of clinical priority are increasingly put forward for managing waiting lists. However, their development does not consider explicitly the appropriateness of the indications. Furthermore, an estimate of their effect in clinical practice is needed, assessing the amount of gains and losses in terms of time waited for patients with different priority scores. METHODS: We developed appropriateness criteria for cataract surgery using the RAND method and applied them to a sample of 567 patients consecutively placed on a waiting list for cataract surgery. In addition, clinicians were asked to express the priority attributed to each patient using a 10-cm visual analogue scale, where 0 = minimal priority and 10 = maximum priority. We developed a priority score, using regression analysis to identify the set of clinical characteristics that best predicted clinicians' priority rating and to estimate their individual weight. We used a computer simulation model to compare mean waiting times with management of the waiting list using the priority score and using the "first-come, first-served" approach. RESULTS: Overall, 332 patients (60.8%) were referred for cataract surgery for indications deemed appropriate, and their mean priority rating was 5.9 (95% confidence interval [CI] 5.7-6.1). The corresponding figures for the 201 (36.8%) uncertain indications and the 13 (2.4%) inappropriate indications were 4.5 (95% CI 4.1-4.7) and 2.6 (95% CI 1.3-3.9) respectively. The clinical characteristics included in the priority score (visual acuity in the operated eye and in the contralateral eye, visual function and ability to live or work independently) accounted for 35% of the variance in clinicians' ratings of priority. In the computer simulation model, patients with the highest priority experienced a variable reduction in mean waiting time (9% to 27%) depending to how time spent waiting was integrated into the clinical score. INTERPRETATION: We conclude that the use of priority ratings in the management of a waiting list for cataract surgery leads to results that maintain the desirable coherence between priority and appropriateness of indication. The results also suggest that the implementation in clinical practice of priority scores may be worth the effort, given the potential reduction in waiting time for patients at high priority.