The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study.

BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.

Outcome of Minimally Invasive and Open Pancreatoduodenectomy in Patients with Intestinal- and Pancreatobiliary Subtype Ampullary Cancer: An International Multicenter Cohort Study.

OBJECTIVE: To compare minimally invasive and open pancreatoduodenectomy in different subtypes of ampullary adenocarcinoma. SUMMARY BACKGROUND DATA: Ampullary adenocarcinoma (AAC) is widely seen as the best indication for minimally invasive pancreatoduodenectomy (MIPD) due to the lack of vascular involvement and dilated bile and pancreatic duct. However, it is unknown whether outcomes of MIPD for AAC differ between the pancreatobiliary (AAC-PB) and intestinal (AAC-IT) subtypes as large studies are lacking. METHODS: This is an international cohort study, encompassing 27 centers from 12 countries. Outcome of MIPD and open pancreatoduodenectomy (OPD) were compared in patients with AAC-IT and AAC-PB. Primary end points were R1 rate, lymph node yield, and 5-year overall survival (5yOS). RESULTS: Overall, 1187 patients after MIPD for AAC were included, of whom 572 with AAC-IT (62 MIPD, 510 OPD) and 615 with AAC-PB (41 MIPD and 574 OPD). The rate of R1 resection was not significantly different between MIPD and OPD for both AAC-IT (3.4% vs 6.9%, P=0,425) and AAC-PB (9.8% vs 14.9%, P=0,625). AAC-IT, more lymph nodes were resected with MIPD group (19 vs 16, P=0.007), compared to OPD. The 5y-OS did not differ after MIPD and OPD for both AAC-IT (56.8% vs 59.5%, P=0.827 and AAC-PB (52.5% vs 44.4%, P=0.357). The rates of surgical complication between MIPD and OPD did not differ between AmpIT and AmpPB. DISCUSSION: This international multicenter study found no differences in outcomes between MIPD and OPD for AAC-IT and AAC-PB. MIPD and OPD demonstrated comparable outcomes in oncological resection, survival and surgical outcomes for both subtypes of AAC.

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.

BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.

The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study.

BACKGROUND: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.

Steatotic hepatocellular adenoma: an unusual cause of a hypermetabolic liver lesion.

A 22-year-old woman with a history of surgically treated pelvic teratoma and solid liver lesion in the extension study. Radiological follow-up was decided. This liver lesion experienced a progressive increase in size, reaching 6 cm. Contrast-enhanced liver MRI was performed, revealing a heterogeneous mass in the right hepatic lobe with non-hepatocyte-like behaviour. With this information, the following entities were ruled out: haemangioma, adenoma, hepatocarcinoma and focal nodular hyperplasia. Given that it could be a teratoma metastasis, a tumour of any other origin or a non-tumoral lesion with no hepatocyte component, it was decided to perform a 2-[18F]FDG PET/CT scan. It showed the liver mass with notable glycolytic hypermetabolism, suggestive of malignancy. In a multidisciplinary committee, it was decided to perform a laparoscopic right hepatectomy. Pathological examination revealed a benign hepatocytic lesion compatible with a steatotic adenoma.

Long-Term Outcomes of Perioperative Versus Neoadjuvant Chemotherapy for Resectable Colorectal Liver Metastases: An International Multicentre Propensity-Score Matched Analysis with Stratification by Contemporary Risk-Scoring.

BACKGROUND: There is still debate regarding the principal role and ideal timing of perioperative chemotherapy (CTx) for patients with upfront resectable colorectal liver metastases (CRLM). This study assesses long-term oncological outcomes in patients receiving neoadjuvant CTx only versus those receiving neoadjuvant combined with adjuvant therapy (perioperative CTx). METHODS: International multicentre retrospective analysis of patients with CRLM undergoing liver resection between 2010 and 2015. Characteristics and outcomes were compared before and after propensity score matching (PSM). Primary endpoints were long-term oncological outcomes, such as recurrence-free survival (RFS) and overall survival (OS). Furthermore, stratification by the tumour burden score (TBS) was applied. RESULTS: Of 967 patients undergoing hepatectomy, 252 were analysed, with a median follow-up of 45 months. The unmatched comparison revealed a bias towards patients with neoadjuvant CTx presenting with more high-risk patients (p = 0.045) and experiencing increased postoperative complications ≥Clavien-Dindo III (20.9% vs. 8%, p = 0.003). Multivariable analysis showed that perioperative CTx was associated with significantly improved RFS (hazard ratio [HR] 0.579, 95% confidence interval [CI] 0.420-0.800, p = 0.001) and OS (HR 0.579, 95% CI 0.403-0.834, p = 0.003). After PSM (n = 180 patients), the two groups were comparable regarding baseline characteristics. The perioperative CTx group presented with a significantly prolonged RFS (HR 0.53, 95% CI 0.37-0.76, p = 0.007) and OS (HR 0.58, 95% CI 0.38-0.87, p = 0.010) in both low and high TBS patients. CONCLUSIONS: When patients after resection of CRLM are able to tolerate additional postoperative CTx, a perioperative strategy demonstrates increased RFS and OS in comparison with neoadjuvant CTx only in both low and high-risk situations.

Burden of heart failure in primary healthcare.

OBJECTIVES: To determine the epidemiology of heart failure registered in primary healthcare clinical records in Catalunya, Spain, between 2010 and 2014, focusing on incidence, mortality, and resource utilization. DESIGN: Retrospective observational cohort study. SETTING: Study was carried out in primary care setting. PARTICIPANTS AND INTERVENTIONS: Patients registered as presenting a new heart failure diagnosis. The inclusion period ran from 1st January 2010 to 31st December 2013, but patients were followed until 31st December 2013 in order to analyze mortality. MAIN MEASURES: Information came from electronic medical records. RESULTS: A total of 64441 patients were registered with a new diagnosis of heart failure (2.76 new cases per 1000 persons-year). Among them, 85.8% were ≥65 years. The number of cases/1000 persons-year was higher in men in all age groups. Incidence ranged from 0.04 in women <45 years to 27.61 in the oldest group, and from 0.08 in men <45 years to 28.52 in the oldest group. Mortality occurred in 16305 (25.3%) patients. Primary healthcare resource utilization increased after the occurrence of heart failure, especially the number of visits made by nurses to the patients' homes. CONCLUSION: Heart failure incidence increases with age, is greater in men, and remains stable. Mortality continues to be high in newly diagnosed patients in spite of the current improvements in treatment. Home visits represent the greatest cost for the management of this disease in primary care setting.

Predictive model for atrial fibrillation in hypertensive diabetic patients.

BACKGROUND: Several scores to identify patients at high risk of suffering atrial fibrillation have been developed. Their applicability in hypertensive diabetic patients, however, remains uncertain. Our aim is to develop and validate a diagnostic predictive model to calculate the risk of developing atrial fibrillation at five years in a hypertensive diabetic population. METHODS: The derivation cohort consisted of patients with both hypertension and diabetes attended in any of the 52 primary healthcare centres of Barcelona; the validation cohort came from the 11 primary healthcare centres of Terres de l'Ebre (Catalonia South) from January 2013 to December 2017. Multivariable Cox regression identified clinical risk factors associated with the development of atrial fibrillation. The overall performance, discrimination and calibration of the model were carried out. RESULTS: The derivation data set comprised 54 575 patients. The atrial fibrillation rate incidence was 15.3 per 1000 person/year. A 5-year predictive model included age, male gender, overweight, heart failure, valvular heart disease, peripheral vascular disease, chronic kidney disease, number of antihypertensive drugs, systolic and diastolic blood pressure, heart rate, thromboembolism, stroke and previous history of myocardial infarction. The discrimination of the model was good (c-index = 0.692; 95% confidence interval, 0.684-0.700), and calibration was adequate. In the validation cohort, the discrimination was lower (c-index = 0.670). CONCLUSIONS: The model accurately predicts future atrial fibrillation in a population with both diabetes and hypertension. Early detection allows the prevention of possible complications arising from this disease.

Effect of an Intensive Weight-Loss Lifestyle Intervention on Kidney Function: A Randomized Controlled Trial.

INTRODUCTION: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. METHODS: Randomized controlled "PREvención con DIeta MEDiterránea-Plus" (PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDiet, PA promotion, and behavioral support (intervention) or usual-care advice to adhere to an energy-unrestricted MedDiet (control) between September 2013 and December 2016. The primary outcome was 1-year change in estimated glomerular filtration rate (eGFR). Secondary outcomes were changes in urine albumin-to-creatinine ratio (UACR), incidence of moderately/severely impaired eGFR (<60 mL/min/1.73 m2) and micro- to macroalbuminuria (UACR ≥30 mg/g), and reversion of moderately (45 to <60 mL/min/1.73 m2) to mildly impaired GFR (60 to <90 mL/min/1.73 m2) or micro- to macroalbuminuria. RESULTS: After 1 year, eGFR declined by 0.66 and 1.25 mL/min/1.73 m2 in the intervention and control groups, respectively (mean difference, 0.58 mL/min/1.73 m2; 95% CI: 0.15-1.02). There were no between-group differences in mean UACR or micro- to macroalbuminuria changes. Moderately/severely impaired eGFR incidence and reversion of moderately to mildly impaired GFR were 40% lower (HR 0.60; 0.44-0.82) and 92% higher (HR 1.92; 1.35-2.73), respectively, in the intervention group. CONCLUSIONS: The PREDIMED-Plus lifestyle intervention approach may preserve renal function and delay CKD progression in overweight/obese adults.

Impact of isolating COVID-19 patients in a supervised community facility on transmission reduction among household members.

BACKGROUND: Isolation of COVID-19 patients has been universally implemented to control transmission of the outbreak. Hotels and other facilities have been adapted to help appropriate isolation be achieved. Our study tested the efficacy of isolating patients in a reconditioned hotel versus isolation in their domiciles to reduce infection transmission. METHODS: Observational cohort study based on a survey to COVID-19 patients between April and June 2020. One cohort had been isolated in a hotel and the other in their domiciles. Multivariate regression models analyzed the factors related to the occurrence of COVID-19 infection among the household members. RESULTS: A total of 229 household members of COVID-19 patients were analyzed, 139 of them belonging to the group of hotel-isolated patients and 90 in the group of domicile-isolated ones. More than half of the household members became infected (53.7%). Higher risk of infection was found in the household members of domicile-isolated patients isolated and in those reporting overcrowding at home, (odds ratio [OR] 1.67, 95% confidence interval [CI] 0.89-3.12) and (OR 1.44, 95% CI 0.81; 2.56), respectively. CONCLUSIONS: The isolation of COVID-19 patients in community-supervised facilities may protect their household members from transmission of the disease. Overcrowded homes may contribute to the transmission of the infection.

Persistence of repeated self-reported illusion of control as a product of action and outcome association in productive and preventive scenarios.

Individuals interpret themselves as causal agents when executing an action to achieve an outcome, even when action and outcome are independent. How can illusion of control be managed? Once established, does it decay? This study aimed to analyze the effects of valence, probability of the outcome [p(O)] and probability of the actions performed by the participant [p(A)], on the magnitude of judgments of control and corresponding associative measures (including Rescorla-Wagner's, Probabilistic Contrast, and Cheng's Power Probabilistic Contrast models). A traffic light was presented on a computer screen to 81 participants who tried to control the green or red lights by pressing the spacebar, after instructions describing a productive or a preventive scenario. There were 4 blocks of 50 trials under all of 4 different p(O)s in random order (0.10, 0.30, 0.70, and 0.90). Judgments were assessed in a bidimensional scale. The 2 × 4 × 4 mixed experimental design was analyzed through General Linear Models, including factor group (between-subject valence), and block and p(O) (within subjects). There was a small effect of group and a large and direct effect of p(O) on judgments. Illusion was reported by 66% of the sample and was positive in the productive group. The oscillation of p(O) produced stronger illusions; decreasing p(O)s produced nil or negative illusions. Only Rescorla-Wagner's could model causality properly. The reasons why p(A) and the other models could not generate significant results are discussed. The results help to comprehend the importance of keeping moderate illusions in productive and preventive scenarios.

Comprehensive Geriatric Assessment in Cardiovascular Disease.

Frailty and cardiovascular disease (CVD) are both highly prevalent in older adults. Cardiovascular disease has been identified as the most frequent cause of death, while frailty has been identified as one of geriatric giants characterized by decreased physiological reserves and increased vulnerability. However, the exact pathobiological links between the two conditions have not been fully elucidated. Consequently, we observe a relevant difficulty not only in accurately defining cardiovascular risk in vulnerable elderly patients (and the other way around), but also a lack of consensus regarding CVD management in the very old. Nowadays, considering the enormous technical innovation, many elderly patients, if appropriately selected, could be eligible even for the most complex treatments, including invasive cardiological procedures. Identification of frail patients at risk of negative outcomes can allow the customization of therapeutic interventions in elderly patients with CVD, allowing the elderly who can benefit from them to undergo even invasive procedures and avoiding futile or dangerous treatments for the most vulnerable patients. A large number of tools and definitions for assessing frailty have been proposed; different scales and assessment tools can be useful for different purposes, but at present there is no clear indication for their use in CVD. In this chapter, we will describe the main geriatric approach to ascertain frailty, the assessment tools used in patients with cardiovascular diseases, and propose an operational strategy to evaluate frailty and identify patients eligible for pharmacologic or surgical interventions.

Relationship between the place of living and mortality in patients with advanced heart failure.

BACKGROUND: Social and environmental factors in advanced heart failure (HF) patients may be crucial to cope with the end stages of the disease. This study analyzes health inequalities and mortality according to place of residence (rural vs urban) in HF patients at advanced stages of the disease. METHODS: Population-based cohort study including 1148 adult patients with HF attended in 279 primary care centers. Patients were followed for at least 1 year after reaching New York Heart Association IV functional class, between 2010 and 2014. Data came from primary care electronic medical records. Cox regression models were applied to determine the hazard ratios (HR) of mortality. RESULTS: Mean age was 81.6 (SD 8.9) years, and 62% were women. Patients in rural areas were older, particularly women aged > 74 years (p = 0.036), and presented lower comorbidity. Mortality percentages were 59 and 51% among rural and urban patients, respectively (p = 0.030). Urban patients living in the most socio-economically deprived neighborhoods presented the highest rate of health service utilization, particularly with primary care nurses (p-trend < 0.001). Multivariate analyses confirmed that men (HR 1.60, 95% confidence interval (CI) 1.34-1.90), older patients (HR 1.05, 95% CI 1.04-1.06), Charlson comorbidity index (HR 1.16, 95% CI 1.11-1.22), and residing in rural areas (HR 1.35, 95% CI 1.09 to 1.67) was associated with higher mortality risk. CONCLUSIONS: Living in rural areas determines an increased risk of mortality in patients at final stages of heart failure.

Precipitating factors of heart failure decompensation, short-term morbidity and mortality in patients attended in primary care.

OBJECTIVE: To evaluate the precipitating factors for heart failure decompensation in primary care and associations with short-term prognosis. Design Prospective cohort study with a 30-d follow-up from an index consultation. Regression models to determine independent factors associated with hospitalisation or death. SETTING: Primary care in ten European countries. Patients Patients with diagnosis of heart failure attended in primary care for a heart failure decompensation (increase of dyspnoea, unexplained weight gain or peripheral oedema). MAIN OUTCOME MEASURES: Potential precipitating factors for decompensation of heart failure and their association with the event of hospitalisation or mortality 30 d after a decompensation. RESULTS: Of 692 patients 54% were women, mean age 81 (standard deviation [SD] 8.9) years; mean left ventricular ejection fraction (LVEF) 55% (SD 12%). Most frequently identified heart failure precipitation factors were respiratory infections in 194 patients (28%), non-compliance of dietary recommendations in 184 (27%) and non-compliance with pharmacological treatment in 157 (23%). The two strongest precipitating factors to predict 30 d hospitalisation or death were respiratory infections (odds ratio [OR] 2.8, 95% confidence interval [CI] (2.4-3.4)) and atrial fibrillation (AF) > 110 beats/min (OR 2.2, CI 1.5-3.2). Multivariate analysis confirmed the association between the following variables and hospitalisation/death: In relation to precipitating factors: respiratory infection (OR 1.19, 95% CI 1.14-1.25) and AF with heart rate > 110 beats/min (OR 1.22, 95% CI 1.10-1.35); and regarding patient characteristics: New York Heart Association (NYHA) III or IV (OR 1.22, 95% CI 1.15-1.29); previous hospitalisation (OR 1.15, 95% CI 1.11-1.19); and LVEF < 40% (OR 1.14, 95% CI 1.09-1.19). CONCLUSIONS: In primary care, respiratory infections and rapid AF are the most important precipitating factors for hospitalisation and death within 30 d following an episode of heart failure decompensation. Key points Hospitalisation due to heart failure decompensation represents the highest share of healthcare costs for this disease. So far, no primary care studies have analysed the relationship between precipitating factors and short term prognosis of heart failure decompensation episodes. We found that in 692 patients with heart failure decompensation in primary care, the respiratory infection and rapid atrial fibrillation (AF) increased the risk of short-term hospital admission or death. Patients with a hospital admission the previous year and a decompensation episode caused by respiratory infection were even more likely to be hospitalized or die within 30 d.

Short-term mortality in end-stage heart failure patients.

OBJECTIVES: This study is aimed at analyzing the impact of the main factors contributing to short and long-term mortality in patients at final stages of heart failure (HF). SETTING: Patients attended at any of the 279 primary health care centers belonging to the Institut Català de la Salut, in Catalonia (Spain). PARTICIPANTS: Patients with Advanced HF. DESIGN: Multicenter cohort study including 1148 HF patients followed for one-year after reaching New York Heart Association (NYHA) IV. MAIN MEASUREMENTS: The primary outcome was all-cause mortality. Multivariate logistic regression models were performed to assess the outcomes at 1, 3, 6, and 12 months. RESULTS: Mean age of patients was 82 (SD 9) years and women represented 61.7%. A total of 135 (11.8%) and 397 (34.6%) patients died three months and one year after inclusion, respectively. Male gender, age, and decreased body mass index were associated with higher mortality at three, six and twelve months. In addition, low systolic blood pressure levels, severe reduction in glomerular filtration, malignancy, and higher doses of loop diuretics were related to higher mortality from 6 to 12 months. The most important risk factor over the whole period was presenting a body mass index lower than 20kg/m2 (three months OR 3.06, 95% CI: 1.58-5.92; six months OR 4.42, 95% CI: 2.08-9.38; and 12 months OR 3.68, 95% CI: 1.76-7.69). CONCLUSIONS: We may conclude that male, age, and decreased body mass index determined higher short-term mortality in NYHA IV. In addition, low systolic blood pressure, reduced glomerular filtration, malignancy, and higher doses of loop diuretics contribute to increasing the risk of mortality at medium and long-term. Such variables are easily measurable and can help to decide the best way to face the most advances stages of the disease.

Effectiveness of a multidisciplinary BIOPSYCHOSOCIAL intervention for non-specific SUBACUTE low back pain in a working population: a cluster randomized clinical trial.

BACKGROUND: Low back pain (LBP) is a multifactorial condition with individual and societal impact that affects populations globally. Current guidelines for the treatment of LBP recommend pharmacological and non-pharmacological strategies. The aim of this study was to compare usual clinical practice with the effectiveness of a biopsychosocial multidisciplinary intervention in reducing disability, severity of pain and improving quality of life in a working population of patients with subacute (2-12 weeks), non-specific LBP. METHODS: Longitudinal cluster randomized clinical trial conducted in 39 Primary Health Care Centres (PHCC) of Barcelona, with patients aged 18-65 years (n = 501; control group = 239; 26 PHCC, intervention group = 262; 13 PHCC). The control group received usual clinical care. The intervention group received usual clinical care plus a biopsychosocial multidisciplinary intervention, which consisted of physiotherapy, cognitive-behavioural therapy and medication. The main outcomes were changes in the Roland Morris Disability Questionnaire (RMDQ), and the minimal clinically important differences. Secondary outcomes were changes in the McGill Pain (MGPQ) and Quality of Life (SF-12) questionnaires. Assessment was conducted at baseline, 3 and 12 months. Analysis was by intention-to-treat and analyst-blinded. Multiple imputations were used. RESULTS: Of the 501 enrolled patients, 421 (84%) provided data at 3 months, and 387 (77.2%) at 12 months. Mean age was 46.8 years (SD: 11.5) and 64.7% were women. In the adjusted analysis of the RMDQ outcome, only the intervention group showed significant changes at 3 months (- 1.33 points, p = 0.005) and at 12 months (- 1.11 points, p = 0.027), but minimal clinically important difference were detected in both groups. In the adjusted analysis of the RMDQ outcome, the intervention group improvement more than the control group at 3 months (- 1.33 points, p = 0.005) and at 12 months (- 1.11 points, p = 0.027). The intervention group presented a significant difference. Both groups presented a minimal clinically important difference, but more difference in the intervention group. The intervention group presented significant differences in the MGPQ scales of current pain intensity and VAS scores at 3 months. No statistically significant differences were found in the physical and mental domains of the SF-12. CONCLUSIONS: A multidisciplinary biopsychosocial intervention in a working population with non-specific subacute LBP has a small positive impact on disability, and on the level of pain, mainly at short-term, but no difference on quality of life. TRIAL REGISTRATION: ISRCTN21392091 (17 oct 2018) (Prospectively registred).

Medication patterns in older adults with multimorbidity: a cluster analysis of primary care patients.

BACKGROUND: Older adults suffer from various chronic conditions which make them particularly vulnerable. The proper management of multiple drug use is therefore crucial. The aim of our study was to describe drug prescription and medication patterns in this population. METHODS: A cross-sectional study in Barcelona (Spain) using electronic health records from 50 primary healthcare centres. Participants were aged 65 to 94 years, presenting multimorbidity (≥2 chronic diseases), and had been prescribed at least 1 drug for 6 months or longer during 2009. We calculated the prevalence of prescribed drugs and identified medication patterns using multiple correspondence analysis and k-means clustering. Analyses were stratified by sex and age (65-79, 80-94 years). RESULTS: We studied 164,513 patients (66.8% women) prescribed a median of 4 drugs (interquartile range [IQR] = 3-7) in the 65-79 age-group and 6 drugs (IQR = 4-8) in the 80-94 age-group. A minimum of 45.9% of patients aged 65-79 years, and 61.8% of those aged 80-94 years, were prescribed 5 or more drugs. We identified 6 medication patterns, a non-specific one and 5 encompassing 8 anatomical groups (alimentary tract and metabolism, blood, cardiovascular, dermatological, musculo-skeletal, neurological, respiratory, and sensory organ). CONCLUSIONS: Drug prescription is widespread among the elderly. Six medication patterns were identified, 5 of which were related to one or more anatomical group, with associations among drugs from different systems. Overall, guidelines do not accurately reflect the situation of the elderly multimorbid, new strategies for managing multiple drug uses are needed to optimize prescribing in these patients.

Dextranase production by recombinant Pichia pastoris under operational volumetric mass transfer coefficient (kLa) and volumetric gassed power input (Pg/V) attainable at commercial large scale.

Most of the reported bioprocesses carried out by the methylotrophic yeast Pichia pastoris have been performed at laboratory scale using high power inputs and pure oxygen, such conditions are not feasible for industrial large-scale processes. In this study, volumetric mass transfer (kLa) and volumetric gassed power input (Pg/V) were evaluated within values attainable in large-scale production as scale-up criteria for recombinant dextranase production by MutS P. pastoris strain. Cultures were oxygen limited when the volumetric gassed power supply was limited to 2 kW m-3. Specific growth rate, and then dextranase production, increased as kLa and Pg/V did. Meanwhile, specific production and methanol consumption rates were constant, due to the limited methanol condition also achieved at 2 L bioprocesses. The specific dextranase production rate was two times higher than the values previously reported for a Mut+ strain. After a scale-up process, at constant kLa, the specific growth rate was kept at 30 L bioprocess, whereas dextranase production decreased, due to the effect of methanol accumulation. Results obtained at 30 L bioprocesses suggest that even under oxygen-limited conditions, methanol saturated conditions are not adequate to express dextranase with the promoter alcohol oxidase. Bioprocesses developed within feasible and scalable operational conditions are of high interest for the commercial production of recombinant proteins from Pichia pastoris.

Mortality in heart failure with atrial fibrillation: Role of digoxin and diuretics.

BACKGROUND: The impact of atrial fibrillation (AF) on mortality of patients with heart failure (HF) has been established. Nevertheless, the effect of some factors in mortality, such as digoxin or diuretic use, remains controversial. This study aims at assessing mortality in community-dwelling patients with stable HF related to AF and determines the relation of these drugs with prognosis. MATERIALS AND METHODS: Community-based cohort study of HF patients diagnosed between January 2010 and December 2014 attended at any one of the 279 primary healthcare centres of the Catalan Institute of Health (Spain). Follow-up ended on December 31, 2015, and the main outcome was mortality for all causes. The effect of clinical and demographic characteristics on survival was assessed by Cox proportional hazards model. RESULTS: A total of 13 334 HF patients were included. Mean age was 78.7 years (SD 10.1), and 36.8% had AF. Mean follow-up was 26.9 months (SD 14.0). At the end of the study, 25.8% patients had died, and mortality was higher when AF was present (28.8% vs 24.1%, P < 0.001, respectively). Multivariate model confirmed the higher risk of death for AF patients (HR 1.10 95%, CI 1.02-1.19). Digoxin and diuretics were not associated with higher mortality in AF patients (HR 1.04 95% CI 0.92-1.18 and HR 1.04 95% CI 0.85-1.26, respectively). CONCLUSIONS: An excess of mortality in HF patients with AF was found in a large retrospective community-based cohort. Digoxin and diuretics did not affect mortality in HF patients with AF.

Multimorbidity patterns in the elderly: a prospective cohort study with cluster analysis.

BACKGROUND: Multimorbidity is the coexistence of more than two chronic diseases in the same individual; however, there is no consensus about the best definition. In addition, few studies have described the variability of multimorbidity patterns over time. The aim of this study was to identify multimorbidity patterns and their variability over a 6-year period in patients older than 65 years attended in primary health care. METHODS: A cohort study with yearly cross-sectional analysis of electronic health records from 50 primary health care centres in Barcelona. Selected patients had multimorbidity and were 65 years of age or older in 2009. Diagnoses (International Classification of Primary Care, second edition) were extracted using O'Halloran criteria for chronic diseases. Multimorbidity patterns were identified using two steps: 1) multiple correspondence analysis and 2) k-means clustering. Analysis was stratified by sex and age group (65-79 and ≥80 years) at the beginning of the study period. RESULTS: Analysis of 2009 electronic health records from 190,108 patients with multimorbidity (59.8% women) found a mean age of 71.8 for the 65-79 age group and 84.16 years for those over 80 (Standard Deviation [SD] 4.35 and 3.46, respectively); the median number of chronic diseases was seven (Interquartil range [IQR] 5-10). We obtained 6 clusters of multimorbidity patterns (1 nonspecific and 5 specifics) in each group, being the specific ones: Musculoskeletal, Endocrine-metabolic, Digestive/Digestive-respiratory, Neurological, and Cardiovascular patterns. A minimum of 42.5% of the sample remained in the same pattern at the end of the study, reflecting the stability of these patterns. CONCLUSIONS: This study identified six multimorbidity patterns per each group, one nonnspecific pattern and five of them with a specific pattern related to an organic system. The multimorbidity patterns obtained had similar characteristics throughout the study period. These data are useful to improve clinical management of each specific subgroup of patients showing a particular multimorbidity pattern.