¿Es la enfermedad pulmonar obstructiva crónica un factor protector en la infección por SARS-CoV-2? La importancia del tratamiento broncodilatador / Is chronic obstructive pulmonary disease a protective factor in SARS-CoV-2 infection? The importance of bronchodilator treatment

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Neoadjuvant chemoradiation versus adjuvant chemotherapy for locally advanced adenocarcinoma of the rectosigmoid junction.

AIM: The optimal treatment approach for adenocarcinoma of the rectosigmoid junction remains unclear. The aim of this work was to compare outcomes of neoadjuvant chemoradiation (NCR) and adjuvant chemotherapy (AC) treatment for cancer of the rectosigmoid junction. METHOD: This was a nationwide, retrospective cohort study (2004-2015) using hospital-based cancer outcomes data (National Cancer Database). All patients who underwent resection with curative intent for locally advanced [American Joint Committee on Cancer (AJCC) Stages II and III] adenocarcinoma of the rectosigmoid junction were included. Exclusion criteria were age less than 18 or over 75 years, Charlson-Deyo score > 2, AJCC Stages I and IV and unstaged tumours. Treatment with NCR was compared with treatment with AC, the primary outcome being overall survival. Other end-points were resection margin status, the presence of lymphovascular invasion and postoperative length of stay. RESULTS: A total of 2828 patients were included in this study, of whom 1701 (59.7%) received NCR. NCR was more frequently utilized in patients who were black (10.3% vs 7.6%, P < 0.05) and underwent treatment at academic institutions (37.9% vs 22.5%, P < 0.05). Treatment with NCR did not differentially influence survival following risk adjustment (hazard ratio 1.17, CI 0.98-1.40; P = 0.085). NCR was independently associated with a decreased likelihood of a positive resection margin (OR 0.44, CI 0.33-0.58; P < 0.001) and lymphovascular invasion (OR 0.51, CI 0.40-0.67; P < 0.001). However, treatment with NCR was associated with the need for prolonged hospitalization compared with AC (7.3 days vs 6.5 days; P = 0.015). The study was limited by its retrospective design, external validity and risk of tumour misclassification. CONCLUSION: NCR currently seems to be favoured over AC for the management of locally advanced adenocarcinoma of the rectosigmoid junction. This approach may not be justified as NCR is associated with prolonged hospitalization needs without a clear survival benefit when compared with AC. Prospective studies are warranted to definitively compare outcomes of NCR and AC in this patient population.

Discontinuation of dolutegravir, elvitegravir/cobicistat and raltegravir because of toxicity in a prospective cohort.

OBJECTIVES: The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. METHODS: A population-based, prospective, multicentre cohort study was carried out. Treatment-naïve subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA < 50 HIV-1 RNA copies/mL in 14 hospitals in Catalonia or the Balearic Islands (Spain) were included in the study. Every discontinuation because of adverse events (AEs) was double-checked directly with treating physicians. Multivariable Cox models identified factors correlated with discontinuation. RESULTS: A total of 4165 subjects (37% treatment-naïve) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. CONCLUSIONS: In this large prospective cohort study, patients receiving dolutegravir, raltegravir or elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.

Adaptation of antibiotic treatment to clinical practice guidelines in patients aged ⩾65 years hospitalised due to community-acquired pneumonia.

Early, conforming antibiotic treatment in elderly patients hospitalised for community-acquired pneumonia (CAP) is a key factor in the prognosis and mortality. The objective was to examine whether empirical antibiotic treatment was conforming according to the Spanish Society of Pulmonology and Thoracic Surgery guidelines in these patients. Multicentre study in patients aged ⩾65 years hospitalised due to CAP in the 2013-14 and 2014-15 influenza seasons. We collected socio-demographic information, comorbidities, influenza/pneumococcal vaccination history and antibiotics administered using a questionnaire and medical records. Bivariate analyses and multilevel logistic regression were made. In total, 1857 hospitalised patients were included, 82 of whom required intensive care unit (ICU) admission. Treatment was conforming in 51.4% (95% confidence interval (CI) 49.1-53.8%) of patients without ICU admission and was associated with absence of renal failure without haemodialysis (odds ratio (OR) 1.49, 95% CI 1.15-1.95) and no cognitive dysfunction (OR 1.71, 95% CI 1.25-2.35), when the effect of the autonomous community was controlled for. In patients with ICU admission, treatment was conforming in 45.1% (95% CI 34.1-56.1%) of patients and was associated with the hospital visits in the last year (<3 vs. ⩾3, OR 2.70, 95% CI 1.03-7.12) and there was some evidence that this was associated with season. Although the reference guidelines are national, wide variability between autonomous communities was found. In patients hospitalised due to CAP, health services should guarantee the administration of antibiotics in a consensual manner that is conforming according to clinical practice guidelines.

Mortality among methicillin-resistant Staphylococcus aureus carriers in long-term care facilities.

INTRODUCTION: Little is known about the natural course of patients with chronic stable illnesses colonized with methicillin-resistant Staphylococcus aureus (MRSA). The aim is to determine the impact of MRSA colonization in mortality among long-term health care facility (LTHCF) residents. METHOD: A multicenter, prospective, observational study was designed. Residents in 4 LTHCFs were classified according to MRSA carriage status and followed for 12 months. Treatment consisted of 5 days of nasal mupirocin in MRSA carriers. RESULTS: Ninety-three MRSA-carriers among 413 residents were identified. Thirty-one MRSA-colonized patients died during the study period, 11 of whom from an infectious disease. Independent predictors of their higher mortality rates included heart failure, current neoplasm, MRSA carriage and COPD at 3 months and these same factors plus stroke, Bar-thel index <40, pressure ulcers, and older age at 12 months. MRSA-persistence was 35% and 62.5% at 3 and 12 months, respectively. CONCLUSIONS: MRSA colonization among frail LTHCFs residents is highly prevalent, and is associated with higher mortality. Despite treatment of MRSA carriers, many remained colonized. Factors that promote persistence of MRSA colonization, and the impact of their modification on mortality rates in these patients, need further investigation.

Prevalence and risk factors for meticillin-resistant Staphylococcus aureus in an acute care hospital and long-term care facilities located in the same geographic area.

UNLABELLED: To determine the prevalence and risk factors (RF) for methicillin-resistant Staphylococcus aureus (MRSA) during stay in 1 acute care hospital (ACH) and 4 long-term care facilities (LTCF). After obtaining the informed consent, nasal and skin ulcer swabs were taken and a survey was conducted to determine RF for MRSA. Six hundred and ninety nine patients were included, 413 LTCF and 286 ACH patients and MRSA prevalence were 22.5% and 7.3% respectively. MRSA was located in the nares, skin ulcers, and in both in 61.4%, 21.1%, and 17.5%. Among MRSA carriers, 81% of the ACH and 66.7% of the LTCF patients were only colonized. The multivariate analysis for the ACH revealed the following factors to be associated with MRSA: referral from an LTCF (OR 4.84), pressure ulcers (OR 4.32), a Barthel score < 60 (OR 2.60), and being male (OR 5.21). For the LTCF: urinary catheterisation (OR 3.53), pressure ulcers (OR 2.44), other skin lesions (OR 2.64), antibiotic treatment in ≤ 6 months, (OR 2.23), previous MRSA colonization (OR 2.15), and a Barthel score <20 (OR 1.28). Molecular typing identified 2 predominant clones Q, P, present in all centres. No relationship was found between clones and antibiotic susceptibility. IN CONCLUSION: MRSA prevalence is high in all centres but is 3 times greater in LTCF. The risk factors most strongly associated with MRSA were pressure ulcers and a stay in an LTCF. We propose preventive isolation in these cases.

Abacavir/lamivudine plus darunavir/ritonavir in routine clinical practice: a multicentre experience in antiretroviral therapy-naive and -experienced patients.

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudine + darunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudine + darunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.

Optimal timing for initiation of highly active antiretroviral therapy in treatment-naïve human immunodeficiency virus-1-infected individuals presenting with AIDS-defining diseases: the experience of the PISCIS Cohort.

In this prospective, multicentre cohort study, we analysed specific prognostic factors and the impact of timing of highly active antiretroviral therapy (HAART) on disease progression and death among 625 human immunodeficiency virus (HIV)-1-infected, treatment-naïve patients diagnosed with an AIDS-defining disease. HAART was classified as early (<30 days) or late (30-270 days). Deferring HAART was significantly associated with faster progression to a new AIDS-defining event/death overall (p 0.009) and in patients with Pneumocystis jiroveci pneumonia (p 0.017). In the multivariate analysis, deferring HAART was associated with a higher risk of a new AIDS-defining event/death (p 0.002; hazard ratio 1.83; 95% CI 1.25-2.68). Other independent risk factors for poorer outcome were baseline diagnosis of AIDS-defining lymphoma, age >35 years, and low CD4(+) count (<50 cells/µL).

Long-term benefits of nevirapine-containing regimens: multicenter study with 506 patients, followed-up a median of 9 years.

OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/µL, 19% CD4 < 200/µL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/µL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.

HIV-1 infected patients older than 50 years. PISCIS cohort study.

OBJECTIVE: The aim of this study is to characterize the ways in which older HIV-infected people differ from younger HIV-infected people. METHODS: Prospective cohort study. PISCIS cohort includes newly attended HIV-infected subjects since January 1, 1998. Naive patients were selected. Two groups were defined: G1 (>or=50 years at time of diagnosis, n=493) and G2 (18-49 years, n=4511). Statistical analysis was performed using chi(2), Student's t test, Cox regression and linear mixed models. RESULTS: G1 had different features: males (G1: 84% vs. G2: 75%, p<0.001), sexual transmission (52% vs. 32%, p<0.001), AIDS at first visit (38% vs. 22%, p<0.001). The follow-up was 6 years. Ninety-five percent of patients in G1 and 92% in G2 presented a detectable viral load (>or=500 copies/mm(3)) at the first visit (p=0.016). G1 presented lower CD4 levels with respect to G2 throughout the period but the increase of CD4 in G1 at the end of the study period was 254 cells/mm(3) whereas for G2 it was 196 cells/mm(3) (p<0.001). Mortality was 9% for G1 and 4% for G2 (p<0.001). CONCLUSIONS: HIV-infected people diagnosed at the age of 50 years or older showed different features. They showed good viral and immunological response to HAART.

Sporadic and epidemic community legionellosis: two faces of the same illness.

The present study compares the risk factors, presentation and outcome of community-acquired Legionella pneumophila pneumonia in 138 sporadic-case patients (1994-2004) and 113 outbreak-case patients (2002) treated in two hospitals in Catalonia (Spain) since urinary antigen assays were adopted. Univariate and multivariate analysis were performed to compare epidemiological and clinical features, blood chemistry values, radiological findings and outcome of sporadic and epidemic legionnaires' disease. Univariate analysis showed that male sex, chronic lung disease, HIV infection and immunosuppressive therapy prevailed in sporadic cases. Presentation with respiratory symptoms, confusion and blood chemistry alterations, such as hyponatraemia, aspartate aminotransferase and blood urea nitrogen elevation, and partial pressure of oxygen P(O)(2) <7.98 KPa (60 mmHg) were also more frequent in sporadic cases, while headache prevailed in outbreak cases. Sporadic cases had a greater delay in treatment, were more severe and had a worse outcome than epidemic cases. Multivariate analysis showed significant differences in sex, chronic lung disease, HIV infection and headache. The clinical and outcome differences between the two groups may be explained by the detection of milder forms of legionnaires' disease, the earlier treatment and the lower severity of underlying disease in the outbreak cases.

A measure of subjective burden for dementia care: the Caregiving Difficulty Scale--Intellectual Disability.

BACKGROUND: It has been suggested in the literature on family caregiving for persons with Alzheimer's dementia (AD) that levels of objective and subjective burden among carers often predict institutionalization of the persons with AD. There is a paucity of measures to assess whether perceived burden among formal caregivers may also predict movement to more restrictive settings for persons with intellectual disabilities (ID) and AD. This study focused upon the development of a measure of subjective burden, The Caregiving Difficulty Scale - Intellectual Disability (CDS-ID) as a first step in addressing this measurement deficit. METHODS: An existing caregiver subjective burden scale, the Caregiving Hassles Scale (CHS) was adapted for use with 203 staff caregivers of persons with ID and AD. Preliminary testing of existing CHS items and proposed new items was carried out in two countries, Ireland and the USA. Confirmatory factor analysis with the existing items and exploratory factor analysis with existing and proposed new items for the scale was used to establish the content and test the psychometric properties of a revised scale, the CDS-ID. RESULTS: On the existing CHS items, staff carers appeared to experience greater subjective burden than has been reported for family caregivers. However, the psychometric properties of the CHS found with this population were poor. Factor analysis produced a revised scale, the CDS-ID with three subscales with Cronbach alphas ranging from 0.75 to 0.93 and 38 items overall. CONCLUSIONS: This new scale when used with objective burden and other scales offers an opportunity to more systematically measure the difficulties staff experience when caring for persons with ID who present with symptoms of AD.

Health characteristics and health services utilization in older adults with intellectual disability living in community residences.

BACKGROUND: The health status and health needs of adults with intellectual disability (ID) change with advancing age, and are often accompanied by difficulties with vision, hearing, mobility, stamina and some mental processes. AIM: The present study collected health status information on a large cohort of adults with ID aged > or = 40 years living in small group, community-based residences in two representative areas of New York State, USA. METHOD: Adult group home residents with ID aged between 40 and 79 years (n = 1371) were surveyed to determine their health status and patterns of morbidity. RESULTS: Most subjects were characterized as being in good health. The frequency of cardiovascular, musculoskeletal and respiratory conditions, and sensory impairments increased with age, while neurological, endocrine and dermatological diseases did not. Psychiatric and behavioural disorders declined with increasing age, at least through 70 years of age. Although most conditions increased with age, their frequency varied by sex and level of ID. Frequencies of age-related organ system morbidity were compared to data from the National Health and Nutrition Evaluation Survey III. It was found that adults with ID had a lower overall reported frequency of cardiovascular risk factors, including hypertension and hyperlipidaemia, and adult-onset diabetes. Inconsistencies with mortality data among older adults with ID were observed (which showed equal if not greater prevalence of deaths as a result of cardiovascular disease and cancer). CONCLUSION: These results suggest that either a cohort effect is operating (i.e. contemporary populations are healthier than previous populations), or that there may be under-recognition of select risk factors and diseases.

Failure of a short-term prednisone regimen to prevent nevirapine-associated rash: a double-blind placebo-controlled trial: the GESIDA 09/99 study.

OBJECTIVES: Rash is the most frequent adverse event associated with nevirapine. The use of prednisone has been controversial in this setting. A double-blind placebo-controlled study was performed to evaluate its efficacy in nevirapine-induced rash prevention. DESIGN: Multicentered, randomized, double-blind, placebo-controlled clinical trial with prednisone (30 mg/day x 2 weeks). INCLUSION CRITERIA: HIV-1 infection; CD4 count >200 cells/mm3; plasma viral load (PVL) <5 log10 copies/ml; nevirapine (200 mg/day x 2 weeks, followed by 200 mg twice daily) plus stavudine and didanosine. Clinical follow-up was performed at 15, 30, and 60 days and thereafter every 2 months. RESULTS: In all, 75 evaluable patients were enrolled (39 prednisone/36 placebo). Median baseline CD4 + cell count was 390 cells/mm3 and PVL, 20,200 copies/ml. Overall, nine cases of rash (12.5%) were detected, seven (18%) in the prednisone group and two (5.5%) in the placebo group (odds ratio [OR], 3.85; 95% confidence interval [CI], 0.65-29.3; p =.11). Incidence of moderate-to-severe rashes leading to nevirapine withdrawal was 13.5% (5 of 37) in the prednisone group and 3% (1 of 35) in the placebo group ( p =.2). Median time to rash in both groups was 16 days. Adverse events that motivated withdrawal of therapy appeared in 6 patients from the prednisone group (15.4%) and 3 from the placebo group (8.3%) ( p =.3). CONCLUSION: Short-term prednisone administration does not prevent nevirapine rash, but might even increase its incidence.