Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalised adults with severe COVID-19 pneumonia: An open-label randomised trial.

BACKGROUND: The efficacy and safety of high versus medium doses of glucocorticoids for the treatment of patients with COVID-19 has shown mixed outcomes in controlled trials and observational studies. We aimed to evaluate the effectiveness of methylprednisolone 250 mg bolus versus dexamethasone 6 mg in patients with severe COVID-19. METHODS: A randomised, open-label, controlled trial was conducted between February and August 2021 at four hospitals in Spain. The trial was suspended after the first interim analysis since the investigators considered that continuing the trial would be futile. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 mg once daily for up to 10 days or methylprednisolone 250 mg once daily for 3 days. RESULTS: Of the 128 randomised patients, 125 were analysed (mean age 60 ± 17 years; 82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group versus 4.8% in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, -8.8 to 9.1%]; p = 0.98). None of the secondary outcomes (admission to the intensive care unit, non-invasive respiratory or high-flow oxygen support, additional immunosuppressive drugs, or length of stay), or prespecified sensitivity analyses were statistically significant. Hyperglycaemia was more frequent in the methylprednisolone group at 27.0 versus 8.1% (absolute risk difference, -18.9% [95% CI, -31.8 to - 5.6%]; p = 0.007). CONCLUSIONS: Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.

Development and validation of a questionnaire for assessing patients´ perceptions of interprofessional integration in health care.

The integration of care between primary, secondary, tertiary health care and social care needs to be interprofessional and patient-centered. The aim of this study was to develop and validate a questionnaire for measuring patients' perception of integration across health care teams and social services. Data for psychometric assessment of our questionnaire were collected from patients who attended at eleven Primary Care Centers and one tertiary referral Hospital in Spain from March to October 2018. The questionnaire was tested in a pilot study with 40 patients before being administered in a sample of 279 patients. The questionnaires were distributed in urban Health Centers, peri-urban or rural Health Centers (67%) and a tertiary referral hospital (33%). The questionnaire included 9 items that measured patient perceived experiences about care coordination, data accessibility and delivery of clinical information. The model explained 51% of the variation in the data and Cronbach's alpha was 0.8. Two factors comprising perception of coordination and assessment of patient-centered care were identified. The overall perception for integration was low. The reliability and validation of our questionnaire showed its potential as a valuable instrument for assessing patients' perception of the integration of care and can be used within the quality metrics to assess the success of integrated health care management programs.

The complexity of classifying ANCA-associated small-vessel vasculitis in actual clinical practice: data from a multicenter retrospective survey.

The different sets of criteria for diagnosis or classification of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) lead to numerous overlapping and reclassified diagnoses in clinical practice. We designed this study to assess the difficulties in classifying patients with AAV. As a secondary objective, different variables were tested to predict prognosis. We conducted a retrospective chart review in a Western Spain multicentre survey. A total of 115 adult patients diagnosed with AAV from 2002 to 2013 and followed for at least 3 years were included. They were classified according to (1) Chapel Hill Consensus Conference (CHCC), (2) European Medicines Agency algorithm and (3) French Vasculitis Study Group/European Vasculitis Society phenotypes. Fifty-three patients (46%) had neither distinctive histopathological data of a single AAV definition nor any surrogate markers for granulomatous inflammation and thus did not fulfill any diagnostic criteria. Ocular, ear, nose, throat, skin, and lung involvement were more frequent with proteinase 3 (PR3) antibodies, whereas peripheral neuropathy was more frequent with myeloperoxidase (MPO) antibodies. When the disease was severe at diagnosis, the HR for mortality was 10.44. When induction treatment was not given in accordance with the guidelines, the HR for mortality was 4.00. For maintenance treatment, the HR was 5.49 for mortality and 2.48 for relapse. AAV classification is difficult because many patients had neither specific clinical data nor distinctive histological features of a single CHCC definition. A structured clinical assessment of patient severity is the best tool to guide the management of AAV.

Bisphosphonates for Paget's disease of bone in adults.

BACKGROUND: Bisphosphonates are considered to be the treatment of choice for people with Paget's disease of bone. However, the effects of bisphosphonates on patient-centred outcomes have not been extensively studied. There are insufficient data to determine whether reducing and maintaining biochemical markers of bone turnover to within the normal range improves quality of life and reduces the risk of complications. OBJECTIVES: To assess the benefits and harms of bisphosphonates for adult patients with Paget's disease of bone. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ISI Web of Knowledge and trials registers up to March 2017. We searched regulatory agency published information for rare adverse events. SELECTION CRITERIA: Randomised controlled trials (RCTs) of bisphosphonates as treatment for Paget's disease in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently screened search results, extracted data and assessed studies for risk of bias. We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 20 trials (25 reports, 3168 participants). Of these, 10 trials (801 participants) compared bisphosphonates (etidronate, tiludronate, ibandronate, pamidronate, olpadronate, alendronate, risedronate, zoledronate) versus placebo, seven compared two bisphosphonates (992 participants), one trial compared a bisphosphonates with a bisphosphonate plus calcitonin (44 participants), and two studies, the largest trial (1331 participants) and its interventional extension study (502 participants), compared symptomatic treatment and intensive treatment where the goal was to normalise alkaline phosphatase.Most studies were assessed at low or unclear risk of bias. Six of 10 studies comparing bisphosphonates versus placebo were assessed at high risk of bias, mainly around incomplete outcome data and selective outcome reporting.Participant populations were reasonably homogeneous in terms of age (mean age 66 to 74 years) and sex (51% to 74% male). Most studies included participants who had elevated alkaline phosphatase levels whether or not bone pain was present. Mean follow-up was six months.Bisphosphonates versus placeboBisphosphonates tripled the proportion (31% versus 9%) of participants whose bone pain disappeared (RR 3.42, 95% confidence interval (CI) 1.31 to 8.90; 2 studies, 205 participants; NNT 5, 95% CI 1 to 31; moderate-quality evidence). This result is clinically important. Data were consistent when pain change was measured as any reduction (RR 1.97, 95% CI 1.29 to 3.01; 7 studies, 481 participants).There was uncertainty about differences in incident fractures: 1.4% fractures occurred in the bisphosphonates group and none in the placebo group (RR 0.89, 95% CI 0.18 to 4.31; 4 studies, 356 participants; very low-quality evidence).None of the studies reported data on orthopaedic surgery, quality of life or hearing thresholds.Results regarding adverse effects and treatment discontinuation were uncertain. There was a 64% risk of mild gastrointestinal adverse events in intervention group participants and 48% in the control group (RR 1.32, 95% CI 0.91 to 1.92; 6 studies, 376 participants; low-quality evidence). The likelihood of study participants discontinuing due to adverse effects was slightly higher in intervention group participants (4.4%) than the control group (4.1%) (RR 1.01, 95% CI 0.41 to 2.52; 6 studies, 517 participants; low-quality evidence). Zoledronate was associated with an increased risk of transient fever or fatigue (RR 2.57, 95% CI 1.21 to 5.44; 1 study, 176 participants; moderate-quality evidence).Bisphosphonates versus active comparatorMore participants reported pain relief with zoledronate than pamidronate (RR 1.30, 95% CI 1.10 to 1.53; 1 study, 89 participants; NNT 5, 95% CI 3 to 11) or risedronate (RR 1.36, 95% CI 1.06 to 1.74; 1 study, 347 participants; NNT 7, 95% CI 4 to 24; very low quality evidence). This result is clinically important.There was insufficient evidence to confirm or exclude differences in adverse effects of bisphosphonates (RR 1.05, 95% CI 0.95 to 1.76; 2 studies, 437 participants; low-quality evidence) and treatment discontinuation (2 studies, 437 participants) (RR 2.04, 95% CI 0.43 to 9.59; 2 studies, 437 participants; very low-quality evidence).Intensive versus symptomatic treatmentThere was no consistent evidence of difference to response in bone pain, bodily pain or quality of life in participants who received intensive versus symptomatic treatment.Inconclusive results were observed regarding fractures and orthopaedic procedures for intensive versus symptomatic treatment (intensive treatment for fracture: RR 1.84, 95% CI 0.76 to 4.44; absolute risk 8.1% versus 5.2%; orthopaedic procedures: RR 1.58, 95% CI 0.80 to 3.11; absolute risk 5.6% versus 3.0%; 1 study, 502 participants; low-quality evidence).There was insufficient evidence to confirm or exclude an important difference in adverse effects between intensive and symptomatic treatment (RR 1.05, 95% CI 0.79 to 1.41; low-quality evidence).There was insufficient evidence to confirm or exclude an important difference of risk of rare adverse events (including osteonecrosis of the jaw) from the regulatory agencies databases. AUTHORS' CONCLUSIONS: We found moderate-quality evidence that bisphosphonates improved pain in people with Paget's disease of bone when compared with placebo. We are uncertain about the results of head-to-head studies investigating bisphosphonates. We found insufficient evidence of benefit in terms of pain or quality of life from intensive treatment. Information about adverse effects was limited, but serious side effects were rare, and rate of withdrawals due to side effects was low.

Development and Validation of the COMPLES Score for Differentiating Between Tuberculous Effusions with Low Pleural pH or Glucose and Complicated Parapneumonic Effusions.

BACKGROUND: The frequency of "complicated" pleural effusions (CPE) (i.e., pleural fluid pH ≤ 7.2 and/or glucose ≤60 mg/dL) of tuberculous origin (CTPE) is not well reported. This study aims to quantify their prevalence, and develop a score to differentiate CTPE from complicated parapneumonic effusions (CPPE). METHODS: Retrospective analysis of databases from three Spanish hospitals which included patients with CTPE and CPPE. Forty percent of the study population served to generate a scoring system (COMPLES, COMplicated PLeural Effusion Score) that was further validated in the remaining 60 %. RESULTS: During the study period (1992-2015) 549 patients were diagnosed with tuberculous effusions and 434 parapneumonic effusions, of whom 25 and 64 %, respectively, had CPE. COMPLES was based on the combination of pleural fluid adenosine deaminase (ADA), the percentage of mononuclear cells (MNC %), pH, and age. The cutoff values and assigned scores were: ADA (<46 IU/L [0 points], 46-100 IU/L [4 points], ≥100 IU/L [6 points]), MNC % (<10 % [0 points], 10-50 [3 points], >50 [8 points]), pH (<7.07 [0 points], 7.07-7.20 [3 points], >7.20 [5 points]), and age (≥30 [0 points], <30 years [3 points]). A sum of 12 or more points had 97 % sensitivity, 92 % specificity, likelihood ratio positive 12.3, likelihood ratio negative 0.03, and area under the curve of 0.947 for identifying CTPE versus CPPE in the validation set. CONCLUSIONS: CPE is not an unusual presentation of tuberculosis. A simple new scoring system provides a reliable tool for differentiating between CTPE and CPPE.

Randomized Controlled Trial to Assess the Feasibility of a Novel Clinical Decision Support System Based on the Automatic Generation of Alerts through Remote Patient Monitoring.

Background/Objectives: Early identification of complications in chronic and infectious diseases can reduce clinical deterioration, lead to early therapeutic interventions and lower morbidity and mortality rates. Here, we aimed to assess the feasibility of a novel clinical decision support system (CDSS) based on the automatic generation of alerts through remote patient monitoring and to identify the patient profile associated with the likelihood of severe medical alerts. Methods: A prospective, multicenter, open-label, randomized controlled trial was conducted. Patients with COVID-19 in home isolation were randomly assigned in a 1:1 ratio to receive either conventional primary care telephone follow-up plus access to a mobile app for self-reporting of symptoms (control group) or conventional primary care telephone follow-up plus access to the mobile app for self-reporting of symptoms and wearable devices for real-time telemonitoring of vital signs (case group). Results: A total of 342 patients were randomized, of whom 247 were included in the per-protocol analysis (103 cases and 144 controls). The case group received a more exhaustive follow-up, with a higher number of alerts (61,827 vs. 1825; p < 0.05) but without overloading healthcare professionals thanks to automatic alert management through artificial intelligence. Baseline factors independently associated with the likelihood of a severe alert were having asthma (OR: 1.74, 95% CI: 1.22-2.48, p = 0.002) and taking corticosteroids (OR: 2.28, 95% CI: 1.24-4.2, p = 0.008). Conclusions: The CDSS could be successfully implemented and enabled real-time telemonitoring of patients' clinical status, providing valuable information to physicians and public health agencies.

Impact of age on the transmission of SARS-CoV-2 in healthcare workers : Influence of nonoccupational risk factors.

BACKGROUND: The incidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV­2) infection was highest among older adults early in the COVID-19 pandemic; however, this pattern was later reversed with young adults showing the highest incidence. The aim of this study was to identify risk factors in healthcare workers (HCWs) associated with this evolution. METHODS: We conducted a survey nested within a prospective cohort study of 680 HCWs from a tertiary referral public hospital who received 2 doses of SARS-CoV­2 vaccine in January and February 2021 (VACCICO-VAO cohort). In October 2022 all participants were invited to participate in a survey. Risk factors were tested for association with COVID-19 ever, the number of COVID-19 episodes, and the time to the first episode. RESULTS: Among 350 respondents (51% response rate, 90% female, mean age 48.1 years), 323 COVID-19 episodes were diagnosed during the study period. Multivariable analysis revealed that age < 35 years vs. > 50 years (odds ratio, OR 2.12, 95% confidence interval, CI 1.27-3.51; P = 0.004) and not maintaining social distance at social events (OR: 1.82, 95% CI: 1.16-3.19; P = 0.011) were associated with a higher risk of COVID-19. Age < 35 years (hazard ratio, HR 1.70, 95% CI 1.14-2.54; P = 0.010), and not maintaining social distance (HR 1.34, 95% CI 1.05-1.72; P = 0.020) were also associated with the time to the first episode. CONCLUSIONS: The youngest HCWs had the highest incidence rate of COVID-19, which was not explained by occupational risk factors or health conditions. The increase in nonoccupational exposure since the end of the lockdowns in summer 2020 could by a key factor.

Should Physicians Be Aware of Rhythm Disturbances in Adults with Systemic Autoimmune Diseases and Anti-Ro52 Antibodies? A Cross-Sectional Study.

Objectives: The association between anti-Ro/SSA antibodies and the appearance of cardiac rhythm disorders in adults is discussed. We aim to study this relationship, together with active treatments and comorbidities, and its impact on daily clinical practice in adults with systemic autoimmune diseases (SADs). Methods: This cross-sectional single-center study was conducted in a tertiary hospital between January 2021 and March 2022. A sample of adult patients followed up in the SAD Unit with a diagnosis of a SAD and previously tested for anti-Ro/SSA and anti-La/SSB were recruited. All of them underwent a 12-lead electrocardiogram. Results: 167 patients were included. 90 (53.9%) were positive for anti-Ro60, 101 (60.5%) for anti-Ro52, and 45 (26.9%) for anti-La/SSB; 52 (31.3%) were triple-negative. 84% were women, and the mean age was 59 years (standard deviation 12.8). The most common SAD was primary Sjögren's syndrome (34.8%), followed by systemic lupus erythematosus (24.6%) and rheumatoid arthritis (22.8%). A statistically significant relationship was found between anti-Ro52 positivity and cardiac rhythm disorders (relative risk = 2.007 [1.197-3.366]), specifically QTc prolongation (relative risk = 4.248 [1.553-11.615]). Multivariate regressions showed a significant association, with diabetes mellitus being the most related comorbidity. The association between anti-Ro52 antibodies and atrioventricular conduction disorders was not significant. Conclusions: The presence of anti-Ro52 antibodies in adult patients with SADs is associated with an increased risk of QTc prolongation. Electrocardiographic screening of patients with SAD, anti-Ro52 antibodies, and other risk factors, like diabetes mellitus or QT-prolonging drugs, seems advisable. Those with baseline electrocardiogram abnormalities or additional risk factors should undergo electrocardiographic monitoring.

[Paget's disease of bone: 1877-2023. Etiology, and management of a disease on epidemiologic transition]. / Enfermedad ósea de Paget: 1877-2023. Etiología y abordaje de una enfermedad en transición epidemiológica.

Paget's disease of bone is characterized by the alteration, in one or several bone locations, of the equilibrium between bone formation and bone resorption. This imbalance results in a disorganized, widened bone, in many cases with increased bone density, although more fragile. A genetic predisposition for Paget's disease of bone could explain between 5% and 40% of the cases. Different environmental factors should explain the rest of the cases. Paget's disease of bone was classically considered the second most common metabolic bone disease. However, in recent decades there has been a marked decrease in both incidence and clinical severity. These changes have led to believe that the influence of some environmental factor may have diminished or even disappeared. This decrease in incidence should not be an excuse for abandoning Paget's disease of bone research, but rather it should be the reason to remain searching to try to understand better its pathogenesis.

Tools to Reduce Low-Value Care: Lessons From COVID-19 Pandemic Comment on "Key Factors that Promote Low-Value Care: Views of Experts From the United States, Canada, and the Netherlands".

Based on a summary of interviews with 18 experts, Verkerk et al defined the seven key factors that promoted low-value care, which included system, social, and knowledge factors. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, these key factors have been influential due to the uncertainty of the disease at the beginning of the pandemic. Globally, several measures have been implemented to reduce low-value care practices and promote high-value care for COVID-19 patients. From huge multicenter, non-industry sponsored or multiplatform trials, to the use of social networks sites is an indispensable and effective way to disseminate medical information. Thanks to these measures, we have transformed a scenario of ignorance into an evidence-based medical scenario in less than a year. Verkerk and colleagues' proposed key factors are an excellent framework for characterizing and highlighting the lessons that can be learnt from how we have fought against the pandemic and low-value practices.

Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19.

OBJECTIVE: To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. METHODS: Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. RESULTS: Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59-79] vs 73 years [IQR 61-83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91-2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75-0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32-1.80; p < .001). There is no difference between megadoses and low-dose (p .298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71-0.95; p < .001 and OR 0.80 95% CI 0.65-0.97; p < .001) respectively. CONCLUSION: There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses.

Overall survival, renal survival and relapse in patients with microscopic polyangiitis: a systematic review of current evidence.

OBJECTIVE: There are limited data on the long-term prognosis of microscopic polyangiitis (MPA). A systematic review was performed to estimate the survival, renal survival and relapse rates in patients with MPA. METHODS: Articles included in MEDLINE and EMBASE databases were reviewed. Randomized or non-randomized trials, cohort, case-control and cases-series studies of patients with MPA diagnosed according to Chapel Hill Consensus Conference definitions, a high rate of biopsy-confirmed diagnosis, follow-up >1 year and follow-up losses <10%. Two independent authors using a predefined questionnaire for evaluating the quality and risk of bias for each study extracted data. RESULTS: Eighteen studies for MPA prognosis (n = 940) and six for MPA outcomes after transplantation (n = 65) were included. Survival rates were 77-100% at 1 year, 46-80% at 5 years and 60-80% at 10 years. Higher mortality density occurred within the first months after diagnosis. Vasculitis was the cause of death in 32-50% of patients. Relapses were detected in 19-39% of cases (median time to relapse 15-43 months). Renal graft survival was 85-94% at 1 year and 51-87% at 5 years. Age, renal involvement and immunosuppressive treatment were related to mortality. Lower relapse rate was achieved with 12 vs 6 CYC pulses. CONCLUSION: Evidence regarding MPA prognosis is weak. MPA mortality is mainly concentrated in the first months after diagnosis. Fewer than 50% of deaths are related to MPA activity. MPA long-term prognosis is less severe, although relapses are frequent. End-stage renal failure is a frequent complication of MPA, and renal transplantation could be an effective therapy in these patients. Early diagnosis, early initiation of a tailored therapy according to risk factors and a longer follow-up of the patients are needed.

Use of noninvasive ventilation on internal wards for elderly patients with limitations to respiratory care: a cohort study.

BACKGROUND: The use of noninvasive positive pressure ventilation (NPPV) outside the intensive wards has been evaluated in patients with no limitation on life-sustaining support. Our aim was to evaluate its usefulness in general wards for patients with NPPV as the ceiling of ventilator care when admission to the intensive care unit (ICU) has been withheld. MATERIALS AND METHODS: Noninvasive positive pressure ventilation was used in 44 patients with acute respiratory failure (ARF) and limitations to respiratory care- 22 with chronic obstructive pulmonary disease (COPD) exacerbations and 22 with acute cardiogenic pulmonary oedema (CPE). Survival at hospital discharge, and survival and readmission rate at 12 months were assessed. RESULTS: Sixty-three per cent of COPD and 55% of CPE patients survived hospital discharge; and 50% and 37% respectively, were alive after 1 year. The cause of the in-hospital mortality was related to the admission diagnosis in 88% of cases. Cancer in COPD patients [P = 0·040, odds ratio (OR) = 15, 95% CI = 1·14-198] and the completion of NPPV treatment in both diseases (P = 0·008, OR = 0·03, 95% CI = 0·00-0·39 for COPD and P = 0·010, OR = 0·04, 95% CI = 0·00-0·45 for CPE) were related to in-hospital mortality. Fifty-six per cent of COPD and 33% of CPE patients that survived hospital admission were readmitted. CONCLUSIONS: Our study suggests that the use of NPPV in general wards could be a safe and effective option, as a last choice treatment, in patients with NPPV as the ceiling of ventilator care when admission to ICU has been withheld.

Methylprednisolone in adults hospitalized with COVID-19 pneumonia : An open-label randomized trial (GLUCOCOVID).

PURPOSE: To determine whether a 6-day course of methylprednisolone (MP) improves outcome in patients with severe SARS-CoV­2 (Corona Virus Disease 2019 [COVID-19]). METHODS: The study was a multicentric open-label trial of COVID-19 patients who were aged ≥ 18 years, receiving oxygen without mechanical ventilation, and with evidence of systemic inflammatory response who were assigned to standard of care (SOC) or SOC plus intravenous MP (40 mg bid for 3 days followed by 20 mg bid for 3 days). The primary outcome was a composite of death, admission to the intensive care unit, or requirement for noninvasive ventilation. Both intention-to-treat (ITT) and per protocol (PP) analyses were performed. RESULTS: A total of 91 patients were screened, and 64 were randomized (mean age70 ± 12 years). In the ITT analysis, 14 of 29 patients (48%) in the SOC group and 14 of 35 (40%) in the MP group suffered the composite endpoint (40% versus 20% in patients under 72 years and 67% versus 48% in those over 72 years; p = 0.25). In the PP analysis, patients on MP had a significantly lower risk of experiencing the composite endpoint (age-adjusted risk ratio 0.42; 95% confidence interval, CI 0.20-0.89; p = 0.043). CONCLUSION: The planned sample size was not achieved, and our results should therefore be interpreted with caution. The use of MP had no significant effect on the primary endpoint in ITT analysis; however, the PP analysis showed a beneficial effect due to MP, which consistent with other published trials support the use of glucocorticoids in severe cases of COVID-19.

Cardiometabolic Therapy and Mortality in Very Old Patients With Diabetes Hospitalized due to COVID-19.

BACKGROUND: The effects of cardiometabolic drugs on the prognosis of diabetic patients with COVID-19, especially very old patients, are not well known. This work was aimed to analyze the association between preadmission cardiometabolic therapy (antidiabetic, antiaggregant, antihypertensive, and lipid-lowering drugs) and in-hospital mortality among patients ≥80 years with type 2 diabetes mellitus (T2DM) hospitalized for COVID-19. METHOD: We conducted a nationwide, multicenter, observational study in patients ≥80 years with T2DM hospitalized for COVID-19 between March 1 and May 29, 2020. The primary outcome measure was in-hospital mortality. A multivariate logistic regression analysis was performed to assess the association between preadmission cardiometabolic therapy and in-hospital mortality. RESULTS: Of the 2 763 patients ≥80 years old hospitalized due to COVID-19, 790 (28.6%) had T2DM. Of these patients, 385 (48.7%) died during admission. On the multivariate analysis, the use of dipeptidyl peptidase-4 inhibitors (adjusted odds ratio [AOR] 0.502, 95% confidence interval [CI]: 0.309-0.815, p = .005) and angiotensin receptor blockers (AOR 0.454, 95% CI: 0.274-0.759, p = .003) were independent protectors against in-hospital mortality, whereas the use of acetylsalicylic acid was associated with higher in-hospital mortality (AOR 1.761, 95% CI: 1.092-2.842, p = .020). Other antidiabetic drugs, angiotensin-converting enzyme inhibitors, and statins showed neutral association with in-hospital mortality. CONCLUSIONS: We found important differences between cardiometabolic drugs and in-hospital mortality in older patients with T2DM hospitalized for COVID-19. Preadmission treatment with dipeptidyl peptidase-4 inhibitors and angiotensin receptor blockers could reduce in-hospital mortality; other antidiabetic drugs, angiotensin-converting enzyme inhibitors, and statins seem to have a neutral effect; and acetylsalicylic acid could be associated with excess mortality.

Evolution of the Use of Corticosteroids for the Treatment of Hospitalised COVID-19 Patients in Spain between March and November 2020: SEMI-COVID National Registry.

OBJECTIVES: Since the results of the RECOVERY trial, WHO recommendations about the use of corticosteroids (CTs) in COVID-19 have changed. The aim of the study is to analyse the evolutive use of CTs in Spain during the pandemic to assess the potential influence of new recommendations. MATERIAL AND METHODS: A retrospective, descriptive, and observational study was conducted on adults hospitalised due to COVID-19 in Spain who were included in the SEMI-COVID-19 Registry from March to November 2020. RESULTS: CTs were used in 6053 (36.21%) of the included patients. The patients were older (mean (SD)) (69.6 (14.6) vs. 66.0 (16.8) years; p < 0.001), with hypertension (57.0% vs. 47.7%; p < 0.001), obesity (26.4% vs. 19.3%; p < 0.0001), and multimorbidity prevalence (20.6% vs. 16.1%; p < 0.001). These patients had higher values (mean (95% CI)) of C-reactive protein (CRP) (86 (32.7-160) vs. 49.3 (16-109) mg/dL; p < 0.001), ferritin (791 (393-1534) vs. 470 (236-996) µg/dL; p < 0.001), D dimer (750 (430-1400) vs. 617 (345-1180) µg/dL; p < 0.001), and lower Sp02/Fi02 (266 (91.1) vs. 301 (101); p < 0.001). Since June 2020, there was an increment in the use of CTs (March vs. September; p < 0.001). Overall, 20% did not receive steroids, and 40% received less than 200 mg accumulated prednisone equivalent dose (APED). Severe patients are treated with higher doses. The mortality benefit was observed in patients with oxygen saturation

The nutritional status of the elderly patient infected with COVID-19: the forgotten risk factor?

BACKGROUND: Since the first cases of COVID-19 were reported in Wuhan, the nutritional status of individuals infected with the virus has not been included in the risk profiles prepared. However, nutritional status, along with other factors, is decisive in the evolution of patients with other infectious diseases. The nutritional status of individuals is considered an indicator of health status. Furthermore, optimal nutritional status transcends the individual, and poor diet in a population can be considered a group risk factor. Evidence exists on the influence that diet has on the immune system and susceptibility to disease. OBJECTIVE: To evaluate the nutritional status of patients older than 65 years who were admitted due to COVID-19 and how this has influenced the evolution of patients. DESIGN: This prospective and observational study was performed in patients with COVID-19 infection confirmed by real-time polymerase chain reaction. Data were collected from the first 24 h of admission. All patients admitted during one month to the wards assigned to COVID-19 infection were included. RESULTS: A total of 83 patients were studied. The statistical study of mortality showed associations with age (p = .005), living in a nursing home (p = .022), a high Charlson Comorbidity Index (p = .039), hypertension (p = .032), comorbidities of dementia (p = .019) and cerebral vascular disease (p = .041), and Barthel Index (p = .010). The analysis of the influence of the nutritional state on mortality revealed a statistical association between malnutrition and mortality in the pooled data analysis (p = .005) and analysis by degrees of malnutrition (p = .27). CONCLUSIONS: Malnutrition was a risk factor as powerful as others such as hypertension, age, and different comorbidities. We must evaluate and treat the nutritional status of elderly patients with COVID-19 infection since it directly affects their evolution.

Paget's disease of bone is not associated with common polymorphisms in interleukin-6, interleukin-8 and tumor necrosis factor alpha genes.

BACKGROUND: Cytokines, specially interleukin (IL)-6, play an important role in the differentiation and activation of osteoclasts and might be involved in osteoblast stimulation in Paget's disease of bone (PDB). OBJECTIVES: The aim of this study was to investigate the association of polymorphisms in IL-6, IL-8 and tumor necrosis factors-alpha (TNFA) genes among Spanish patients with PDB. METHODS: We studied four single nucleotide polymorphisms (-174 G>C IL-6, -251 T>A IL-8, -238 G>A TNFA and -308 G>A TNFA) in 172 PDB patients and 150 healthy controls. Distribution of alleles and pro-inflammatory genotypes were studied for association with the presence of the disease and with clinical and laboratory data, as well as the response to bisphosphonate treatment in PDB patients. RESULTS: We found no statistically significant association between genotype and allele distribution of any of the cytokines polymorphism studied and PDB. No association between the clinical and therapeutic characteristics of PDB and the investigated polymorphism were found. CONCLUSIONS: This study does not support the hypothesis that the analyzed IL6, IL8 and TNFA polymorphism are associated with PDB.

Cause-specific death in hospitalized individuals infected with SARS-CoV-2: more than just acute respiratory failure or thromboembolic events.

Infection with SARS-CoV-2 is becoming the leading cause of death in most countries during the 2020 pandemic. The objective of this study is to assess the association between COVID-19 and cause-specific death. The design is retrospective cohort study. We included data from inpatients diagnosed with COVID-19 between March 18 and April 21, 2020, who died during their hospital stay. Demographic, clinical and management data were collected. Causes of death were ascertained by review of medical records. The sample included 128 individuals. The median age was 84 (IQR 75-89), 57% were men. In 109 patients, the death was caused by SARS-CoV-2 infection, whereas in 19 (14.8%, 95 CI 10-22%), the infection acted only as a precipitating factor to decompensate other pathologies. This second group of patients was older (88y vs 82, p < 0.001). In age-adjusted analysis, they had a greater likelihood of heart failure (OR 3.61 95% CI 1.15-11.32), dependency in activities of daily living (OR 12.07 95% CI 1.40-103.86), frailty (OR 8.73 95% CI 1.37-55.46). The presence of X-ray infiltrates was uncommon (OR 0.07, 95% CI 0.02-0.25). A higher percentage of patient deaths from causes unrelated to COVID-19 complications occurred during the two first weeks of the pandemic. Fifteen percent of patients with COVID-19 infection died from decompensation of other pathologies and the cause of death was unrelated to COVID-19 severe complications. Most of these patients had more comorbidities and were frail and elderly. These findings can partially explain the excess mortality in older people.