Association of glucagon-like peptide-1 receptor agonists with suicidal ideation and self-injury in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study.

AIMS/HYPOTHESIS: Regulators worldwide are reviewing safety data on glucagon-like peptide-1 receptor agonists (GLP-1RA), following reports by the Icelandic Medicines Agency in July 2023 of suicidal ideation and self-injury (SIS) in individuals taking liraglutide and semaglutide. We aimed to assess the risk of SIS in new users of GLP-1RA when compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i) users, prescribed to treat type 2 diabetes in individuals with obesity. METHODS: This is a cohort study combining several population-wide databases and covering a Spanish population of five million inhabitants, including all adults with obesity who initiated treatment with either GLP-1RA or SGLT-2i for type 2 diabetes from 2015 to 2021. To estimate the comparative effect of GLP-1RA on the risk of SIS, we employed a new user, active comparator design and we carried out multivariable Cox regression modelling with inverse probability of treatment weighting (IPTW) based on propensity scores. We performed several stratified and sensitivity analyses. RESULTS: We included 3040 patients initiating treatment with GLP-1RA and 11,627 with SGLT-2i. When compared with patients treated with SGLT-2i, those in the GLP-1RA group were younger (55 vs 60 years old, p<0.001), had more anxiety (49.4% vs 41.5%, p<0.001), sleep disorders (43.2% vs 34.1%, p<0.001) and depression (24.4% vs 19.0%, p<0.001), and were more obese (35.1% of individuals with BMI ≥40 vs 15.1%, p<0.001). After propensity score weighting, standardised mean differences between groups were <0.1 for all covariates, showing adequate balance between groups at baseline after adjustment. In the main per-protocol analyses we found no evidence that GLP-1RA increased the incidence of SIS (HR 1.04; 95% CI 0.35, 3.14). Intention-to-treat analyses resulted in an HR of 1.36 (95% CI 0.51, 3.61). In analyses excluding individuals with no BMI information and using imputation for BMI missing values, respective HRs were 0.89 (95% CI 0.26, 3.14) and 1.29 (95% CI 0.42, 3.92). Stratified analyses showed no differences between subgroups. CONCLUSIONS/INTERPRETATION: Our findings do not support an increased risk of SIS when taking GLP-1RA in individuals with type 2 diabetes and obesity; however, the rarity of SIS events and the wide uncertainty of effect size (although null, effect may be compatible with a risk as high as threefold) calls for a cautious interpretation of our results. Further studies, including final evaluations from regulatory bodies, are called for to discard a causal link between GLP-1RA and suicidality.

A machine learning model for predicting serum neutralizing activity against Omicron SARS-CoV-2 BA.2 and BA.4/5 sublineages in the general population.

Supervised machine learning (ML) methods have been used to predict antibody responses elicited by COVID-19 vaccines in a variety of clinical settings. Here, we explored the reliability of a ML approach to predict the presence of detectable neutralizing antibody responses (NtAb) against Omicron BA.2 and BA.4/5 sublineages in the general population. Anti-SARS-CoV-2 receptor-binding domain (RBD) total antibodies were measured by the Elecsys® Anti-SARS-CoV-2 S assay (Roche Diagnostics) in all participants. NtAbs against Omicron BA.2 and BA4/5 were measured using a SARS-CoV-2 S pseudotyped neutralization assay in 100 randomly selected sera. A ML model was built using the variables of age, vaccination (number of doses) and SARS-CoV-2 infection status. The model was trained in a cohort (TC) comprising 931 participants and validated in an external cohort (VC) including 787 individuals. Receiver operating characteristics analysis indicated that an anti-SARS-CoV-2 RBD total antibody threshold of 2300 BAU/mL best discriminated between participants either exhibiting or not detectable Omicron BA.2 and Omicron BA.4/5-Spike targeted NtAb responses (87% and 84% precision, respectively). The ML model correctly classified 88% (793/901) of participants in the TC: 717/749 (95.7%) of those displaying ≥2300 BAU/mL and 76/152 (50%) of those exhibiting antibody levels <2300 BAU/mL. The model performed better in vaccinated participants, either with or without prior SARS-CoV-2 infection. The overall accuracy of the ML model in the VC was comparable. Our ML model, based upon a few easily collected parameters for predicting neutralizing activity against Omicron BA.2 and BA.4/5 (sub)variants circumvents the need to perform not only neutralization assays, but also anti-S serological tests, thus potentially saving costs in the setting of large seroprevalence studies.

Cumulative incidence of SARS-CoV-2 infection in the general population of the Valencian Community (Spain) after the surge of the Omicron BA.1 variant.

Studies investigating the cumulative incidence of and immune status against SARS-CoV-2 infection provide valuable information for shaping public health decision-making. A cross-sectional study on 935 participants, conducted in the Valencian Community (VC), measuring anti-SARS-CoV-2-receptor binding domain-RBD-total antibodies and anti-Nucleocapsid (N)-IgGs via electrochemiluminescence assays. Quantitation of neutralizing antibodies (NtAb) against ancestral and Omicron BA.1 and BA.2 variants and enumeration of SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells was performed in 100 and 137 participants, respectively. The weighted cumulative incidence was 51.9% (95% confidence interval [CI]: 48.7-55.1) and was inversely related to age. Anti-RBD total antibodies were detected in 97% of participants; vaccinated and SARS-CoV-2-experienced (VAC-ex; n = 442) presented higher levels (p < 0.001) than vaccinated/naïve (VAC-n; n = 472) and nonvaccinated/experienced (UNVAC-ex; n = 63) subjects. Antibody levels correlated inversely with time elapsed since last vaccine dose in VAC-n (Rho, -0.52; p < 0.001) but not in VAC-ex (rho -0.02; p = 0.57). Heterologous booster shots resulted in increased anti-RBD antibody levels compared with homologous schedules in VAC-n, but not in VAC-ex. NtAbs against Omicron BA.1 were detected in 94%, 75%, and 50% of VAC-ex, VAC-n and UNVAC-ex groups, respectively. For Omicron BA.2, the figures were 97%, 84%, and 40%, respectively. SARS-CoV-2-S-reactive IFN-γ T cells were detected in 73%, 75%, and 64% of VAC-ex, VAC-n and UNVAC-ex, respectively. Median frequencies for both T-cell subsets were comparable across groups. In summary, by April 2022, around half of the VC population had been infected with SARS-CoV-2 and, due to extensive vaccination, displayed hybrid immunity.

Home Blood Pressure Self-monitoring plus Self-titration of Antihypertensive Medication for Poorly Controlled Hypertension in Primary Care: the ADAMPA Randomized Clinical Trial.

BACKGROUND: Patient empowerment through pharmacological self-management is a common strategy in some chronic diseases such as diabetes, but it is rarely used for controlling blood pressure. OBJECTIVE: This study aimed to assess self-monitoring plus self-titration of antihypertensive medication versus usual care for reducing systolic blood pressure (SBP) at 12 months in poorly controlled hypertensive patients. DESIGN: The ADAMPA study was a pragmatic, controlled, randomized, non-masked clinical trial with two parallel arms in Valencia, Spain. PARTICIPANTS: Hypertensive patients older than 40 years, with SBP over 145 mmHg and/or diastolic blood pressure (DBP) over 90 mmHg, were recruited from July 2017 to June 2018. INTERVENTION: Participants were randomized 1:1 to usual care versus an individualized, pre-arranged plan based on self-monitoring plus self-titration. MAIN MEASURE: The primary outcome was the adjusted mean difference (AMD) in SBP between groups at 12 months. KEY RESULTS: Primary outcome data were available for 312 patients (intervention n=156, control n=156) of the 366 who were initially recruited. The AMD in SBP at 12 months (main analysis) was -2.9 mmHg (95% CI, -5.9 to 0.1, p=0.061), while the AMD in DBP was -1.9 mmHg (95% CI, -3.7 to 0.0, p=0.052). The results of the subgroup analysis were consistent with these for the main outcome measures. More patients in the intervention group achieved good blood pressure control (<140/90 mmHg) at 12 months than in the control group (55.8% vs 42.3%, difference 13.5%, 95% CI, 2.5 to 24.5%, p=0.017). At 12 months, no differences were observed in behavior, quality of life, use of health services, or adverse events. CONCLUSION: Self-monitoring plus self-titration of antihypertensive medication based on an individualized pre-arranged plan used in primary care may be a promising strategy for reducing blood pressure at 12 months compared to usual care, without increasing healthcare utilization or adverse events. TRIAL REGISTRATION: EudraCT, number 2016-003986-25 (registered 17 March 2017) and clinicaltrials.gov , NCT03242785.

Has Arthroscopic Meniscectomy Use Changed in Response to the Evidence? A Large-database Study From Spain.

BACKGROUND: Several randomized clinical trials on the treatment of meniscal tears have shown that surgery is not superior to nonoperative treatment in middle-aged and older adults. However, clinical practice has not changed consistently worldwide in response to this evidence, and arthroscopic meniscectomy remains one of the most frequently performed operations. QUESTIONS/PURPOSES: (1) How has the use of arthroscopic meniscectomy changed in Spain between 2003 and 2018, particularly in middle-aged (35 to 59 years) and older patients (over 60 years) relative to younger patients? (2) How have surgical volumes changed across different healthcare areas in the same health system? (3) How has the proportion of outpatient versus inpatient arthroscopic procedures changed over time? METHODS: Data on all 420,228 arthroscopic meniscectomies performed in Spain between 2003 and 2018 were obtained through the Atlas of Variations in Medical Practice project (these years were chosen because data in that atlas for 2002 and 2019 were incomplete). This database has been promoted by the Spanish Health Ministry since 2002, and it collects basic information on all admissions to public and public-private partnership hospitals. The Spanish population of 2003 was used to calculate age- and sex-standardized rates of interventions per 10,000 inhabitants and year. To assess the change in standardized rates among the age groups over the study period, a linear regression analysis was used. Standard small-area variation statistics were used to analyze variation among healthcare areas. Data on outpatient surgery and length of stay for inpatient procedures were also included. RESULTS: The standardized rate of arthroscopic meniscectomy in Spain in 2003 was 4.8 procedures per 10,000 population (95% CI 3.9 to 5.6), while in 2018, there were 6.3 procedures per 10,000 population (95% CI 5.4 to 7.3), which represents an increase of 33%. Standardized rates increased slightly in the age group < 35 years (0.06 interventions per 10,000 inhabitants per year [95% CI 0.05 to 0.08]), whereas they increased more markedly in the age groups of 35 to 59 years (0.14 interventions per 10,000 inhabitants per year [95% CI 0.11 to 0.17]) and in those 60 years and older (0.13 interventions per 10,000 inhabitants per year [95% CI 0.09 to 0.17]). The variability among healthcare areas in the meniscectomy rate progressively decreased from 2003 to 2018. In 2003, 32% (6544 of 20,384) of knee arthroscopies were performed on an outpatient basis, while in 2018, these accounted for 67% (19,573 of 29,430). CONCLUSION: We observed a progressive increase in arthroscopic meniscectomies in Spain; this procedure was more prevalent in older patients presumed to have degenerative pathologic findings. This increase occurred despite increasing high-level evidence of a lack of the additional benefit of meniscectomy over other less-invasive treatments in middle-aged and older people. Our study highlights the need for action in health systems with the use of financial, regulatory, or incentive strategies to reduce the use of low-value procedures, as well as interventions to disseminate the available evidence to clinicians and patients. Research is needed to identify the barriers that are preventing the reversal of interventions that high-quality evidence shows are ineffective. LEVEL OF EVIDENCE: Level III, therapeutic study.

Severe Acute Respiratory Syndrome Coronavirus 2 Adaptive Immunity in Nursing Home Residents Following a Third Dose of the Comirnaty Coronavirus Disease 2019 Vaccine.

A third Comirnaty vaccine dose increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain antibody levels (median, 93-fold) and neutralizing antibody titers against Wuhan-Hu-1 (median, 57-fold), Beta (me 22-fold), Delta, (median, 43-fold), and Omicron (median, 8-fold) variants, but had less impact on S-reactive T-cell immunity in nursing home residents.

SARS-CoV-2 Delta-variant breakthrough infections in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant breakthrough infections in nursing home residents following vaccination with Comirnaty® COVID-19 vaccine were characterized. In total, 201 participants (median age, 87 years; range, 64-100; 133 female) from two nursing homes in the Valencian community (Spain) were included. SARS-CoV-2-Spike (S) antibody responses were determined by a lateral flow immunocromatography (LFIC) assay and by quantitative electrochemiluminescent assay in LFIC-negative participants. SARS-CoV-2-S-IFNγ T cells were enumerated by flow cytometry in 10 participants. Nasopharyngeal SARS-CoV-2 RNA loads were quantified by real-time polymerase chain reaction assays. Vaccine breakthrough COVID-19 due to the Delta variant occurred in 39 residents (median age, 87 years; range, 69-96; 31 female) at a median of 6.5 months after vaccination (nine requiring hospitalization). Breakthrough infections occurred at a higher rate (p < 0.0001) in residents who had not been previously infected with SARS-CoV-2 (naïve) (33/108; 18%) than in those with prior diagnosis of SARS-CoV-2 infection (experienced) (6/93; 6.4%), and were more likely (p < 0.0001) to develop in residents who tested negative by LFIC (20/49) at 3 months after vaccination as compared to their LFIC-positive counterparts (19/142). Among LFIC-negative residents, a trend towards lower plasma anti-RBD antibody levels was noticed in those developing breakthrough infection (p = 0.16). SARS-CoV-2 RNA loads in nasopharyngeal specimens were lower in SARS-CoV-2-experienced residents (p < 0.001) and in those testing positive by LFIC (p = 0.13). The frequency of SARS-CoV-2-S-reactive T cells at 3 months was similar in LFIC-negative residents with (n = 7) or without (n = 3) breakthrough infection. Prior history of SARS-CoV-2 infection and detection of S-reactive antibodies by LFIC at 3 months is associated with a lower risk of Delta-variant breakthrough infection in nursing home residents at midterm after Comirnaty® COVID-19 vaccination.

SARS-CoV-2 Omicron BA.1 variant breakthrough infections in nursing home residents after an homologous third dose of the Comirnaty® COVID-19 vaccine: Looking for correlates of protection.

We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4+ and CD8+ T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4+ (p = 0.82) and CD8+ (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4+ or CD8+ T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents.

Few-cycle all-fiber supercontinuum laser for ultrabroadband multimodal nonlinear microscopy.

Temporally coherent supercontinuum sources constitute an attractive alternative to bulk crystal-based sources of few-cycle light pulses. We present a monolithic fiber-optic configuration for generating transform-limited temporally coherent supercontinuum pulses with central wavelength at 1.06 µm and duration as short as 13.0 fs (3.7 optical cycles). The supercontinuum is generated by the action of self-phase modulation and optical wave breaking when pumping an all-normal dispersion photonic crystal fiber with pulses of hundreds of fs duration produced by all-fiber chirped pulsed amplification. Avoidance of free-space propagation between stages confers unequalled robustness, efficiency and cost-effectiveness to this novel configuration. Collectively, the features of all-fiber few-cycle pulsed sources make them powerful tools for applications benefitting from the ultrabroadband spectra and ultrashort pulse durations. Here we exploit these features and the deep penetration of light in biological tissues at the spectral region of 1 µm, to demonstrate their successful performance in ultrabroadband multispectral and multimodal nonlinear microscopy.

The effectiveness of mRNA vaccines to prevent SARS-CoV-2 infection and hospitalisation for COVID-19 according to the time elapsed since their administration in health professionals in the Valencian Autonomous Community (Spain).

The objective was to understand the effectiveness of the BNT162b2 and mRNA-1273 vaccines against SARS-CoV-2 in health professionals(HPs) in the Valencian Autonomous Community(Spain) who had completed a full vaccination regimen, both in terms of preventing infections and avoiding hospitalisations, according to the time elapsed since the vaccine administration. Case-controlled study with negative test results. HPs who had undergone at least one PCR or antigen(Ag) active infection diagnostic test(AIDT) to rule out SARS-CoV-2 infection between 25 January and 18 July 2021 were included. HPs with positive AIDT result were considered as cases and those with a negative result controls. Adjusted vaccine effectiveness(VEa) to prevent SARS-CoV-2 infection and its 95% confidence interval(95% CI) were calculated using the formula VEa = (1 - OR) × 100. The VEa for the prevention of SARS-CoV-2 infection 12 to 120 days after completing the full two-dose vaccine regimen was 91.6%(95%CI[89.6%,93.2%]) for the BNT162b2 vaccine and 95.2%(95%CI[88.3%,98.1%]) for the mRNA-1273 vaccine. After 120 days the VEa was 71.5%(95%CI[67.0%,75.5%]) for the BNT162b2 vaccine and 88.3%(95%CI[75.7,94.4%]) for the mRNA-1273 vaccine. The VEa for prevention of hospitalisation for COVID-19 for the complete two-dose regimen of mRNA vaccines (BNT162b2 and mRNA-1273) was 96.8%(95%CI[76.1%,99.6%]). The administration of the complete regimen of the BNT162b2 and mRNA-1273 vaccine against SARS-CoV-2 was highly effective for the prevention of COVID-19 cases in HPs when 12 to 120 days had elapsed since the second dose. However, said effectiveness decreased as time from the vaccine administration elapsed, although it was maintained for the prevention of hospitalisation of HPs.

Clinical outcomes of nonvitamin K oral anticoagulants and acenocoumarol for stroke prevention in contemporary practice: A population-based propensity-weighted cohort study.

AIMS: Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of non-VKA oral anticoagulants (NOAC), unlike warfarin, and this could affect comparative effectiveness and safety (CES). However, data on CES for NOAC come almost exclusively from studies using warfarin as the comparator. We aimed to assess outcomes of NOAC and acenocoumarol in people with non-valvular atrial fibrillation (NVAF) in real-world clinical practice. METHODS: This is a population-based retrospective cohort study. All new users of oral anticoagulants from November 2011 to December 2015 with NVAF were included (n = 41,560). Data were obtained by linking several health electronic records of the Valencia region, Spain. Incidence rates were estimated. We used the inverse probability of treatment weighted Cox analysis to control for indication bias when assessing the risk of effectiveness and safety outcomes for each NOAC compared with acenocoumarol. Several sensitivity analyses were performed. RESULTS: We did not find differences in the risk of mortality, ischaemic stroke or any gastrointestinal bleeding. However, we did find a decreased risk of intracranial haemorrhage for dabigatran (HR: 0.34, 95% CI 0.20-0.56) and rivaroxaban (HR: 0.55, 95% CI 0.35-0.85) as compared to acenocoumarol. In subanalyses, apixaban showed a higher risk of ischaemic stroke in high-risk persons (≥75 years and CHA2DS2-VASC score ≥ 2). CONCLUSIONS: No differences in clinical outcomes were found between NOAC and acenocoumarol overall, although dabigatran and rivaroxaban showed a lower risk of intracranial haemorrhage. Findings on the potential inferiority of specific NOAC in high-risk subgroups should be studied further.

Laparoscopic Versus Open Incisional Hernia Repair: Long-Term Follow-up Results of a Randomized Clinical Trial.

PURPOSE: Long-term extension of a previous randomized controlled clinical trial comparing open (OVHR) vs. laparoscopic (LVHR) ventral hernia repair, assessing recurrence, reoperation, mesh-related complications and self-reported quality of life with 10 years of follow-up. METHODS: Eighty-five patients were followed up to assess recurrence (main endpoint), reoperation, mesh complications and death, from the date of index until recurrence, death or study completion, whichever was first. Recurrence, reoperation rates and death were estimated by intention to treat. Mesh-related complications were only assessed in the LVHR group, excluding conversions (intraperitoneal onlay; n = 40). Quality of life, using the European Hernia Society Quality of Life score, was assessed in surviving non-reoperated patients (n = 47). RESULTS: The incidence rates with 10 person-years of follow-up were 21.01% (CI 13.24-33.36) for recurrence, 11.92% (CI: 6.60-21.53) for reoperation and 24.88% (CI 16.81-36.82) for death. Sixty-two percent of recurrences occurred within the first 2 years of follow-up. No significant differences between arms were found in any of the outcomes analyzed. Incidence rate of intraperitoneal mesh complications with 10 person-years of follow-up was 6.15% (CI 1.99-19.09). The mean EuraHS-QoL score with 13.8 years of mean follow-up for living non-reoperated patients was 6.63 (CI 4.50-8.78) over 90 possible points with no significant differences between arms. CONCLUSION: In incisional ventral hernias with wall defects up to 15 cm wide, laparoscopic repair seems to be as safe and effective as open techniques, with no long-term differences in recurrence and reoperation rates or global quality of life, although lack of statistical power does not allow definitive conclusions on equivalence between alternatives. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov (NCT04192838).

Group-based Trajectory Models to Assess Quality of INR Control and Its Association With Clinical Outcomes.

BACKGROUND: The Time in Therapeutic Range (TTR) is the gold-standard measure used to assess the quality of oral anticoagulation with vitamin K antagonists. However, TTR is a static measure, and International Normalized Ratio (INR) control is a dynamic process. Group-based Trajectory Models (GBTM) can address this dynamic nature by classifying patients into different trajectories of INR control over time. OBJECTIVES: The objective of this study was to assess the quality of INR control in a population-based cohort of new users of vitamin K antagonist with a diagnosis of atrial fibrillation using GBTM. METHODS: We classified patients into different trajectories according to their propensity for being adequately anticoagulated over their first year of treatment using GBTM, and we evaluated the association between trajectories and relevant clinical outcomes over the following year. RESULTS: We included 8024 patients in the cohort who fulfilled the inclusion criteria; the mean number of INR determinations over the first year of treatment was 13.9. We identified 4 differential trajectories of INR control: Optimal (9.7% of patients, TTR: 83.8%), Improving (27.4% of patients, TTR: 61.2%), Worsening (28%; TTR: 69.1%), and Poor control (34.9%; TTR: 41.5%). In adjusted analysis, Poor and Worsening control patients had a higher risk of death than Optimal control patients (hazard ratio: 1.79; IC 95%, 1.36-2.36 and hazard ratio: 1.36; IC 95%, 1.02-1.81, respectively). Differences in other outcomes did not achieve statistical significance, except for a reduced risk of transient ischemic attack in the Improving Control group. CONCLUSIONS: GBTM may contribute to a better understanding and assessment of the quality of oral anticoagulation and may be used in addition to traditional, well-established measures such as TTR.

Effects of oxygen on post-surgical infections during an individualised perioperative open-lung ventilatory strategy: a randomised controlled trial.

BACKGROUND: We aimed to examine whether using a high fraction of inspired oxygen (FIO2) in the context of an individualised intra- and postoperative open-lung ventilation approach could decrease surgical site infection (SSI) in patients scheduled for abdominal surgery. METHODS: We performed a multicentre, randomised controlled clinical trial in a network of 21 university hospitals from June 6, 2017 to July 19, 2018. Patients undergoing abdominal surgery were randomly assigned to receive a high (0.80) or conventional (0.3) FIO2 during the intraoperative period and during the first 3 postoperative hours. All patients were mechanically ventilated with an open-lung strategy, which included recruitment manoeuvres and individualised positive end-expiratory pressure for the best respiratory-system compliance, and individualised continuous postoperative airway pressure for adequate peripheral oxyhaemoglobin saturation. The primary outcome was the prevalence of SSI within the first 7 postoperative days. The secondary outcomes were composites of systemic complications, length of intensive care and hospital stay, and 6-month mortality. RESULTS: We enrolled 740 subjects: 371 in the high FIO2 group and 369 in the low FIO2 group. Data from 717 subjects were available for final analysis. The rate of SSI during the first postoperative week did not differ between high (8.9%) and low (9.4%) FIO2 groups (relative risk [RR]: 0.94; 95% confidence interval [CI]: 0.59-1.50; P=0.90]). Secondary outcomes, such as atelectasis (7.7% vs 9.8%; RR: 0.77; 95% CI: 0.48-1.25; P=0.38) and myocardial ischaemia (0.6% [n=2] vs 0% [n=0]; P=0.47) did not differ between groups. CONCLUSIONS: An oxygenation strategy using high FIO2 compared with conventional FIO2 did not reduce postoperative SSIs in abdominal surgery. No differences in secondary outcomes or adverse events were found. CLINICAL TRIAL REGISTRATION: NCT02776046.

Long-term cost-utility analysis of remote monitoring of older patients with pacemakers: the PONIENTE study.

BACKGROUND: Cost-effectiveness studies on pacemakers have increased in the last years. However the number of long-term cost-utility studies is limited. The objective of this study was to perform a cost-utility analysis comparing remote monitoring (RM) versus conventional monitoring (CM) in hospital of older patients with pacemakers, 5 years after implant. METHODS: Under a controlled, not randomized, nor masked clinical trial, 83 patients with pacemakers were initially selected. After five years of follow-up, a total of 55 patients (CM = 34; RM = 21) completed the study. A cost-utility analysis of RM in terms of costs per gained quality-adjusted life years (QALYs) was conducted. The costs from the Public Health System (PHS) as well as patients and their relatives were taken into account for the study. The robustness of the results was verified by the probabilistic analyses through Monte-Carlo simulations. RESULTS: After a five-year follow-up period, total costs were lower in the RM group by 23.02% than in the CM group (€274.52 versus €356.62; p = 0.033) because of a cost saving from patients' perspective (€59.05 versus €102.98; p = 0.002). However, the reduction of in-hospital visits derived from RM exhibited insignificant impact on the costs from the PHS perspective, with a cost saving of 15.04% (€215.48 vs. €253.64; p = 0.144). Costs/QALYs obtained by the RM group were higher as compared to the CM group, although there were no significant differences. The incremental cost-effectiveness ratio of CM in comparison to RM became positive (€301.16). CONCLUSIONS: This study confirms RM of older patients with pacemakers appears still as a cost-utility alternative to CM in hospital after 5 years of follow-up. TRIAL REGISTRATION: ClinicalTrials.gov: (Identifier: NCT02234245 ). Registered 09 September 2014 - Prospectively registered.

Rationale and design of a pragmatic clinical trial to assess the impact of self-monitoring blood pressure at home and self-titration of antihypertensive medication in poorly controlled hypertension: the ADAMPA study protocol.

BACKGROUND: Lack of control of hypertension is one of the most prevalent problems encountered by general practitioners (GPs). Self-measured blood pressure monitoring at home (SMBP) and self-titration of medication could be a good strategy to improve hypertension management, however, evidence is limited and not conclusive. We aimed to assess the effectiveness, in the primary care setting, of an intervention that includes educational components, SMBP and self-titration of antihypertensive medication to decrease systolic blood pressure compared to usual care, in a population with poorly controlled hypertension, during a 12-month period. METHODS: Pragmatic, controlled, randomized, unblinded clinical trial with two parallel groups assigned in a ratio of 1:1 to self-management (which includes educational components, SBMP and self-titration of antihypertensive medication based on a patient's GP's pre-established adjustment plan) or to usual care (with educational components too). DISCUSSION: If the data from this trial show positive results, the study may contribute to a change of strategy in the treatment of hypertension, focusing on the patient as the main actor to achieve blood pressure control. Furthermore, this approach might contribute to the financial sustainability of the National Health Service. TRIAL REGISTRATION: This trial has been registered in the database with reference number EudraCT: 2016-003986-25. Registered 05 May 2017, https://www.clinicaltrialsregister.eu/ctr-search/search?query=2016-003986-25.

Antibiotic Use in Children - A Cross-National Analysis of 6 Countries.

OBJECTIVES: To describe the rates of pediatric antibiotic use across 6 countries on 3 continents. STUDY DESIGN: Cross-national analysis of 7 pediatric cohorts in 6 countries (Germany, Italy, South Korea, Norway, Spain, and the US) was performed for 2008-2012. Antibiotic dispensings were identified and grouped into subclasses. We calculated the rates of antimicrobial prescriptions per person-year specific to each age group, comparing the rates across different countries. RESULTS: A total of 74 744 302 person-years from all participating centers were included in this analysis. Infants in South Korea had the highest rate of antimicrobial consumption, with 3.41 prescribed courses per child-year during the first 2 years of life. This compares with 1.6 in Lazio, Italy; 1.4 in Pedianet, Italy; 1.5 in Spain; 1.1 in the US; 1.0 in Germany; and 0.5 courses per child-year in Norway. Of antimicrobial prescriptions written in Norway, 64.8% were for first-line penicillins, compared with 38.2% in Germany, 31.8% in the US, 27.7% in Spain, 25.1% in the Italian Pedianet population, 9.8% in South Korea, and 8% in the Italian Lazio population. CONCLUSIONS: We found substantial differences of up to 7.5-fold in pediatric antimicrobial use across several industrialized countries from Europe, Asia, and North America. These data reinforce the need to develop strategies to decrease the unnecessary use of antimicrobial agents.

Simulations of the gain profile and performance of a diode side-pumped QCW Nd:YAG laser.

A design of a diode side-pumped Nd:YAG laser module and simulations of the gain distribution inside the active medium are presented in this paper. The code is based on a nonsequential ray-tracing Monte Carlo method for the light generated by the laser diodes. The fluorescence image of the active medium was analyzed in order to compare it with the simulations, which were found to be in good agreement with experimental data. The laser was tested in QCW mode and provided a maximum average power of 220 W while maintaining constant energy per pulse in the 100-1000 Hz range.

Trends and area variations in Potentially Preventable Admissions for COPD in Spain (2002-2013): a significant decline and convergence between areas.

BACKGROUND: Potentially Preventable Hospitalizations (PPH) are hospital admissions for conditions which are preventable with timely and appropriate outpatient care being Chronic Obstructive Pulmonary Disease (COPD) admissions one of the most relevant PPH. We estimate the population age-sex standardized relative risk of admission for COPD-PPH by year and area of residence in the Spanish National Health System (sNHS) during the period 2002-2013. METHODS: The study was conducted in the 203 Hospital Service Areas of the sNHS, using the 2002 to 2013 hospital admissions for a COPD-PPH condition of patients aged 20 and over. We use conventional small area variation statistics and a Bayesian hierarchical approach to model the different risk structures of dependence in both space and time. RESULTS: COPD-PPH admissions declined from 24.5 to 15.5 per 10,000 persons-year (Men: from 40.6 to 25.1; Women: from 9.1 to 6.4). The relative risk declined from 1.19 (19 % above 2002-2013 average) in 2002 to 0.77 (30 % below average) in 2013. Both the starting point and the slope were different for the different regions. Variation among admission rates between extreme areas dropped from 6.7 times higher in 2002 to 4.6 times higher in 2013. CONCLUSIONS: COPD-PPH conditions in Spain have undergone a strong decline and a reduction in geographical variation in the last 12 years, suggesting a general improvement in health policies and health care over time. Variability among areas still remains, with a substantial room for improvement.

Joint spatial modeling to identify shared patterns among chronic related potentially preventable hospitalizations.

BACKGROUND: Rates of Potentially Preventable Hospitalizations (PPH) are used to evaluate access of territorially delimited populations to high quality ambulatory care. A common geographic pattern of several PPH would reflect the performance of healthcare providers. This study is aimed at modeling jointly the geographical variation in six chronic PPH conditions in one Spanish Autonomous Community for describing common and discrepant patterns, and to assess the relative weight of the common pattern on each condition. METHODS: Data on the 39,970 PPH hospital admissions for diabetes short term complications, chronic obstructive pulmonary disease (COPD), congestive heart failure, dehydration, angina admission and adult asthma, between 2007 and 2009 were extracted from the Hospital Discharge Administrative Databases and assigned to one of the 240 Basic Health Zones. Rates and Standardized Hospitalization Ratios per geographic unit were estimated. The spatial analysis was carried out jointly for PPH conditions using Shared Component Models (SCM). RESULTS: The component shared by the six PPH conditions explained about the 36% of the variability of each PPH condition, ranging from the 25.9 for dehydration to 58.7 for COPD. The geographical pattern found in the latent common component identifies territorial clusters with particularly high risk. The specific risk pattern that each isolated PPH does not share with the common pattern for all six conditions show many non-significant areas for most PPH, but with some exceptions. CONCLUSIONS: The geographical distribution of the risk of the PPH conditions is captured in a 36% by a unique latent pattern. The SCM modeling may be useful to evaluate healthcare system performance.