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In the current document, we introduce the numerous emerging areas and frontiers in the use of point-of-care clinical ultrasonography. Of these, we review the following 3: 1) the use of clinical ultrasonography in infectious and tropical diseases (we address it's usefulness in the diagnosis and follow-up of the main syndromes, tropical diseases and in areas with scarce resources); 2) the usefulness of clinical ultrasonography in the assessment of response to volume infusion in severely ill patients (we review basic concepts and the main static and dynamic variables employed for this evaluation); and 3) the use of clinical ultrasonography in the assessment of muscle mass in elderly patients with primary sarcopenia (we review the main muscles and measurements employed for them it.
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The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
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Transtornos Respiratórios/terapia , Envelhecimento , Asma/terapia , Tomada de Decisões , Europa (Continente) , União Europeia , Guias como Assunto , Humanos , Cooperação Internacional , Área Carente de Assistência Médica , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Rinite/terapia , Fatores de Risco , Organização Mundial da SaúdeRESUMO
The management of patients with comorbidity and polypathology represents a challenge for all healthcare systems. Clinical practice guidelines (CPGs) have limitations when applied to this population. The aim of this study is to propose the terminology and methodology for optimally approach comorbidity and polypathology in the CPGs. Based on a literature review, we suggest a number of proposals for the approach in different phases of CPG preparation, with special attention to the inclusion of clusters of comorbidity in the initial questions the implementation of indirect evidence, the burden of disease management for patients and their environment, when establishing recommendations, as well as the strategies of dissemination and implementation. These proposals should be developed in greater depth with the implication of more agents in order to have valid and useful tools for this population.
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Doença Crônica , Guias de Prática Clínica como Assunto , Doença Crônica/epidemiologia , Doença Crônica/terapia , Comorbidade , HumanosRESUMO
Patients with multimorbidity increasingly impact healthcare systems, both in primary care and in hospitals. This is particularly true in Internal Medicine. This population associates with higher mortality rates, polypharmacy, hospital readmissions, post-discharge syndrome, anxiety, depression, accelerated age-related functional decline, and development of geriatric syndromes, amongst others. Internists and Hospitalists, in one of their roles as Generalists, are increasingly asked to attend to these patients, both in their own Departments as well as in surgical areas. The management of polypathology and multimorbidity, however, is often complex, and requires specific clinical skills and corresponding experience. In addition, patients' needs, health-care environment, and routines have changed, so emerging and re-emerging specific competences and approaches are required to offer the best coordinated, continuous, and comprehensive integrated care to these populations, to achieve optimal health outcomes and satisfaction of patients, their relatives, and staff. This position paper proposes a set of emerging and re-emerging competences for internal medicine specialists, which are needed to optimally address multimorbidity now and in the future.
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Multimorbidade , Médicos , Humanos , Idoso , Assistência ao Convalescente , Alta do Paciente , Atenção à Saúde , PolimedicaçãoRESUMO
AIMS: To determine the association between different comorbidities and other clinical conditions with mortality in patients with multiple diseases (PMD) suffering from chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: Patients with COPD and PMD criteria were included in an observational, prospective and multicentrer study. Data on age, gender, Charlson index, Barthel index, Lawton-Brody index, Pfeiffer test, sociofamilial Gijon scale, education level, hospitalizations during the previous 3 and 12 months and survival at one year were collected. The relationship between the variables and mortality were established by means of a univariate analysis and logistic regression model. RESULTS: A total of 688 PMD with COPD and mean age of 77.9 years were included. The mean score one the Charlson index was 3.99 (2.07). The most frequent comorbidities were heart failure (59%), diabetes (48%), myocardial infarction (29%), moderate kidney failure (22%), cerebrovascular disease (19%), hypertension (71%), anemia (62%), atrial fibrillation (34%), dyslipidemia (28%) and obesity (21%). A total of 26% of patients were dependent for activities of daily living, 47% needed a caregiver and 54% were at risk of having social problems. At one year, 258 patients (37%) had died. The Charlson index, dependency for activities of daily living and anemia were associated with mortality and hypertension and capacity for reading and writing were associated with survival. CONCLUSIONS: Comorbidity and discapacity are two prognostic factors in COPD patients.
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Doença Pulmonar Obstrutiva Crônica/mortalidade , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Indicadores Básicos de Saúde , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Prognóstico , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Espanha/epidemiologiaRESUMO
In this work, we introduce the numerous emerging areas and frontiers in the use of point-of-care ultrasonography. Of these, we review the following three: 1) the use of clinical ultrasonography in infectious and tropical diseases (we address its usefulness in the diagnosis and follow-up of the main syndromes, in tropical diseases, and in areas with scarce resources); 2) the usefulness of clinical ultrasonography in the assessment of response to volume infusion in severely ill patients (we review basic concepts and the main static and dynamic variables used for this evaluation); and 3) the use of clinical ultrasonography in the assessment of muscle mass in elderly patients with primary sarcopenia (we review the main muscles and measurements used for it).
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Testes Imediatos/tendências , Ultrassonografia/tendências , Idoso , Doenças Transmissíveis Importadas/diagnóstico por imagem , Estado Terminal , Hidratação , Humanos , Infecções/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Pneumonia/diagnóstico por imagem , Áreas de Pobreza , Sarcopenia/diagnóstico por imagem , Medicina TropicalRESUMO
BACKGROUND: Nursing homes are highly vulnerable to the occurrence of COVID-19 outbreaks, which result in high lethality rates. Most of them are not prepared to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHOD: A coordinated on-site medicalization program (MP) in response to a sizeable COVID-19 outbreak in 4 nursing homes was organized, with the objectives of improving survival, offering humanistic palliative care to residents in their natural environment, and reducing hospital referrals. Ten key processes and interventions were established (provision of informatics infrastructure, medical equipment, and human resources, universal testing, separation of "clean" and "contaminated" areas, epidemiological surveys, and unified protocols stratifying for active or palliative care approach, among others). Main outcomes were a composite endpoint of survival or optimal palliative care (SOPC), survival, and referral to hospital. RESULTS: Two hundred and seventy-two of 457 (59.5%) residents and 85 of 320 (26.5%) staff members were affected. The SOPC, survival, and referrals to hospital occurred in 77%, 72.5%, and 29% of patients diagnosed before the start of MP, with respect to 97%, 83.7%, and 17% of those diagnosed during the program, respectively. The SOPC was independently associated to MP (OR = 15 [3-81]); and survival in patients stratified to active approach, to the use of any antiviral treatment (OR = 28 [5-160]). All outbreaks were controlled in 39 [37-42] days. CONCLUSIONS: A coordinated on-site MP of nursing homes with COVID-19 outbreaks achieved a higher SOPC rate, and a reduction in referrals to hospital, thus ensuring rigorous but also humanistic and gentle care to residents.
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COVID-19/epidemiologia , Surtos de Doenças , Medicalização/organização & administração , Casas de Saúde/organização & administração , Pneumonia Viral/epidemiologia , Idoso , Feminino , Humanos , Masculino , Pneumonia Viral/virologia , SARS-CoV-2 , Espanha/epidemiologiaRESUMO
OBJECTIVE: To determine the prevalence of relevant drug-drug interactions (DDIs) and associated predictor factors in a sample of patients with multiple complex chronic diseases (polypathological patients) receiving multiple drug therapy. Our secondary objective was to determine the acceptance of a drug interaction reporting program with recommendations addressed to the prescribing physicians. SUBJECTS AND METHODS: A cross-sectional study performed in three primary care centres assigned to a teaching hospital. All patients with 2 or more chronic diseases and treated simultaneously with 5 or more drugs were recruited in the study. DDIs were detected by using Drug-Reax System((R)) (Micromedex) program, the Drug Data Base (Bot) Spanish General Council of Official Colleges of Pharmacists or literature search when needed. Those DDIs which, according to the opinion of the pharmacist investigators, required any intervention were considered relevant. Acceptance of the reported DDI recommendations was evaluated by means of a survey addressed by primary care physicians ("acceptable," pertinent recommendation to modify treatment). RESULTS: A total of 283 polypathological polymedicated patients were included. Mean age was 74.5 years (range 43-100 years). Mean number of diseases per patient was 2.5 and prescriptions 9.7). Out of a total of 2748 drug prescriptions, 1053 DDIs in 250 patients (96.5%) were identified. Of these, 45% were filtered as relevant DDIs. The presence of ischemic heart disease, two or more hospital admissions and having received 7 or more prescriptions were associated with the presence of DDIs. 177 informs containing 473 recommendations about DDIs were sent to primary care physicians from our Pharmacy Department. 339 recommendations were answered by primary care physicians, and 84% were favourably accepted. CONCLUSIONS: Almost every polypathological polymedicated patient is exposed to at least one DDI and about a 60% would require any intervention. Appropriate filtering and personalising recommendations in a collaborative way may represent an adequate manner to improve the risk-benefit ratio of the drug prescriptions.
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Doença Crônica/tratamento farmacológico , Interações Medicamentosas , Polimedicação , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Serviços de Informação sobre Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como AssuntoRESUMO
INTRODUCTION: Hip fracture in the elderly is one of the most prevalent diagnoses in Orthopedic Surgery Departments. It has a great impact in medical, economic and social terms. Our objective is to analyze clinical impact of a co-management care model between orthopedic surgery and internal medicine departments for elderly patients admitted with hip fracture in a tertiary referral hospital. MATERIAL AND METHODS: Retrospective cohort study of patients older than 65 years old admitted with hip fracture between January 2005-August 2006 (HIST cohort) without a co-management care model, and between January 2008-August 2010 (COFRAC cohort) with a co-manEdadment care model. Analysis of demographic, clinical and surgery characteristics, complications incidence and mortality and re-admissions at 30 days was made. RESULTS: A total of 701 patients were included (471 HIST, 230 COFRAC). There were no differences in sex, gender, time to surgery, type of anesthesia and surgery, length of stay, ambulation at discharge and 30-days emergency room consultation, readmissions or mortality at 30 days. There were differences in identification of polypatological patients (16.8 vs. 24.4%, P=0.02), presence of osteoporosis (3.9 vs. 7.6%, P=0.03), motor deficit (3.5 vs. 8.8%, P=0.03), number of chronic drugs (3.7±2.5 vs. 4.3±3.2, P<0.01), diagnosis of delirium (15.6 vs. 20.9%, P=0.048), constipation (80.3 vs. 74.7%, p<0.001), monitoring of anemia (83.3 vs. 97.1%, P>0.01) and renal failure at discharge (44.5 vs. 97.3%, P<0.01) and hospital mortality (4.6 vs. 1.3%, P=0.02). CONCLUSIONS: Co-management for elderly patients admitted with hip fracture provides a better information about previously chronic conditions, a higher control of hospital complications and decreases hospital mortality.
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Elderly people are more severely affected by COVID-19. Nevertheless scarce information about specific prognostic scores for this population is available. The main objective was to compare the accuracy of recently developed COVID-19 prognostic scores to that of CURB-65, Charlson and PROFUND indices in a cohort of 272 elderly patients from four nursing homes, affected by COVID-19. Accuracy was measured by calibration (calibration curves and Hosmer-Lemeshov (H-L) test), and discriminative power (area under the receiver operation curve (AUC-ROC). Negative and positive predictive values (NPV and PPV) were also obtained. Overall mortality rate was 22.4 %. Only ACP and Shi et al. out of 10 specific COVID-19 indices could be assessed. All indices but CURB-65 showed a good calibration by H-L test, whilst PROFUND, ACP and CURB-65 showed best results in calibration curves. Only CURB-65 (AUC-ROCâ¯=â¯0.81 [0.75-0.87])) and PROFUND (AUC-ROCâ¯=â¯0.67 [0.6-0.75])) showed good discrimination power. The highest NPV was obtained by CURB-65 (95 % [90-98%]), PROFUND (93 % [77-98%]), and their combination (100 % [82-100%]); whereas CURB-65 (74 % [51-88%]), and its combination with PROFUND (80 % [50-94%]) showed highest PPV. PROFUND and CURB-65 indices showed the highest accuracy in predicting death-risk of elderly patients affected by COVID-19, whereas Charlson and recent developed COVID-19 specific tools lacked it, or were not available to assess. A comprehensive clinical stratification on two-level basis (basal death risk due to chronic conditions by PROFUND index, plus current death risk due to COVID-19 by CURB-65), could be an appropriate approach.
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OBJECTIVES: To analyse the sensitivity, specificity and positive predictive (PPV) and negative predictive (NPV) values of each measure of the Barthel index (BI) compared with the full questionnaire for polypathological patients (PPPs). METHODS: Multicentre cross-sectional study. We considered 2 cut-off points for the BI (≥90 points for screening frailty and <60 points for diagnosing severe dependence). For each measure and combination of 2 measures, we calculated the sensitivity, specificity, PPV and NPV with respect to the full BI. RESULTS: The mean BI of the 1,632 included PPPs (mean age, 77.9±9.8years; 53% men) was 69±31 (<90 for 58.7% and <60 for 31.4% of the patients). The "feeding" measure achieved the highest NPV, for a BI ≥60 and ≥90 points (87% and 99.6%, respectively). The "walking" and "going up and down stairs" measures achieved the highest PPV, for a BI ≥60 and ≥90 (99.2%/99.5% and 81%/92%, respectively. The combination of the 2 measures increased the PPV to 95% and 99.6%, respectively. CONCLUSIONS: PPPs in hospital settings have a high rate of functional impairment. The measure for feeding achieved the highest NPV and can therefore be employed for diagnosing severe dependence. The combination of the measures for walking and going up and down stairs achieved the highest PPV and can therefore be employed to propose frailty screening for PPPs.
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AIMS: the aims of the present study were to evaluate the clinical and microbiological characteristics of patients suffering from community-acquired pneumonia attended in the Internal Medical Departments of several Spanish institutions and to analyze those prognostic factors predicting thirty-day mortality in such patients. MATERIAL AND METHODS: Past medical history, symptoms and signs, radiological pattern and blood parameters including albumin and C Reactive Protein, were recorded for each patient. Time from admission to starting antibiotics (in hours) and follow-up (in days) were also recorded. Patients were stratified by the Pneumonia Severity Index in five risk classes. RESULTS: 389 patients were included in the study, most of them in Fine categories III to V. Mortality rate for all patients was 12.1% (48 patients), increasing up to 40% in Fine Class V. Neither age, sex nor time from admission to the start of antibiotic treatment predicted survival rates. Plasmatic levels of PCR or microbiologic diagnosis were not related to clinical outcome. In the Cox regression analysis, oriented patients (OR 0.138, IC95% 0.055-0.324), and those with normal albuminemia (OR 0.207, IC95% 0.103-0.417) showed better survival rates. On the contrary, those with active carcinoma (OR 3.2, IC95% 1.181-8.947) significantly showed a reduced life expectancy. CONCLUSION: Besides the fully accepted Fine scale criteria, albumin measurements should be included in routine evaluation in order to improve patient s prognostic classification.
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Pneumonia/mortalidade , Idoso , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Departamentos Hospitalares , Humanos , Medicina Interna , Masculino , Pneumonia/complicações , Prognóstico , Estudos ProspectivosRESUMO
OBJECTIVES: To analyse the correlation, sensitivity, specificity and positive predictive (PPV) and negative predictive (NPV) values of each question on the Pfeiffer questionnaire (SPMSQ) compared with the full questionnaire for polypathological patients (PPPs). METHODS: Multicentre cross-sectional study. An SPMSQ score is considered pathological if 3 or more errors are recorded. For each question and combination of 2 questions, we calculated the correlation (kappa index), sensitivity, specificity and predictive values compared with the full SPMSQ. RESULTS: Of the 1632 PPPs included (mean age, 77.9±9.8 years, 53% men), 1434 performed the SPMSQ (the remaining presented delirium); 39% of the PPPs were pathological. The question "What day is it today?" and the command "Count backwards by 3s from 20" obtained good correlation and NPV (85 and 89%, respectively); the combination of both increased the NPV to 97%. The question "When were you born?' achieved good correlation and greater PPV (93%). CONCLUSIONS: The combination of the question "What day is it today?" and the command "Count backwards by 3s from 20" achieved a high NPV. The question related to the date of birth achieved the highest PPV.
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Polypathological patients constitute a prevalent, fairly homogeneous population, which is characterised by high clinical complexity, substantial vulnerability and significant resource consumption, in addition to high mortality and the need for comprehensive, coordinated care. It is particularly important to establish a reliable prognosis in these patients. It is also extremely useful for professionals involved in the decision-making process for patients and their families in vital planning and their preferences, for strategic health planning in management fields, and for clinical research, by facilitating their incorporation into clinical trials and other intervention studies. Two prognostic instruments stand out in terms of suitability for polypathological patients: PROFUND and PROFUNCTION. The former faithfully stratifies the risk of dying at 12 months and four years and the latter, the risk of suffering a significant functional deterioration at 12 months. In terms of the healthcare approach in patients with multiple pathologies, creating and executing a consensual, personalised action plan that is adapted to the patient's reality is encouraged. The plan will consider the prognosis, and the evidence and viability of interventions; its ultimate aim will be to ensure the synergy and alignment of the health team's goals and strategies with peoples' values and preferences, in order to achieve a more proactive health model focused on supporting patients in their ability to manage their illnesses. In the personalised action plan, the main areas of intervention are: health promotion and prevention; patient and caregiver activation and self-management; activation of a social support network and social support; optimisation of pharmacotherapy; rehabilitation, functional and cognitive preservation measures; and anticipated decision planning.
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OBJECTIVE: Analysing most relevant clinical features and concordance between different functional scales in patients with advanced medical diseases (PAMD). METHODS: Cross-sectional multicentre study that included PAMD (heart, lung, kidney, liver, and neurological diseases) in hospital settings from February 2009 to October 2010. We analysed clinical, biological and functional features in performing activities of daily living (ADL) by medians of Barthel Index (BI); additionally we assessed their performance status by medians of Eastern Cooperative Oncology Group-Performance Status (ECOG-PS) and Palliative Performance Scale (PPS) scores. We evaluated the concordance of these instruments in assessing functional impairment by κ and intraclass correlation coefficient tests. RESULTS: 1847 patients were included (average age 79â years, 50.1% men). Most common symptoms were dyspnoea (62.31%), asthenia (23%) and delirium (20.14%). Functional assessment showed a high prevalence of severe or total impairment in performing basic ADL by medians of used instruments (BI median=35 (IQR=70), and 52.1% of patients with severe-total impairment; ECOG-PS median=2 (IQR 30), and 44% of patients with severe-total impairment; and PPS median=50 (IQR 30), and 32% of patients with severe-total impairment). Concordance among these instruments was acceptably good (κ indexes ranging from 0.653 to 0.745 (p<0.0001)). CONCLUSIONS: PAMD represent a population with severe functional impairment, which requires a multidisciplinary approach for proper management. Assessment of functional ability in this population by BI, ECOG-PS, and PPS showed good concordance.
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Atividades Cotidianas , Benchmarking , Índice de Gravidade de Doença , Doente Terminal , Idoso , Estudos Transversais , Feminino , Humanos , Avaliação de Estado de Karnofsky , Masculino , Cuidados Paliativos , EspanhaRESUMO
The presence of Rickettsia felis was investigated in three species of pulicid fleas (Ctenocephalides felis, Ctenocephalides canis and Pulex irritans) collected in 38 locales in Andalusia (Spain) over the period 1999-2004. Amplification of a fragment of OmpB gene was positive in 54.17 % of lots of Ct. felis. The identity of the PCR bands was confirmed as R. felis by sequence data obtained directly from the PCR amplicon. No rickettsia was found in Ct. canis nor P. irritans.
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Infecções por Rickettsia/epidemiologia , Rickettsia felis , Sifonápteros/microbiologia , Animais , Geografia , Humanos , Incidência , Infecções por Rickettsia/classificação , Sifonápteros/classificação , Espanha/epidemiologiaRESUMO
BACKGROUND/OBJECTIVES: The PROFUND index stratifies accurately the 12-month mortality risk of polypathological patients (PPs), but its fitness over a longer follow-up period remains unknown. We aimed to explore the calibration and discrimination power of PROFUND index over 4-years, in order to assess its follow-up interval generalizability. DESIGN: Multicenter prospective cohort-study. SETTING: 33 Spanish hospitals. PARTICIPANTS: PPs included after hospital discharge, outpatient clinics, or home hospitalization. MEASUREMENTS: Mortality over a 4-year follow-up period. METHODS: PROFUND index calibration was assessed by risk-quartiles predicted/observed mortality (Hosmer-Lemeshow goodness-of-fit test), and its discrimination power by ROC curves. RESULTS: A total of 768 patients were included (630 [82%] of them completed the 4-year follow-up). Global mortality rate was 63.5%. When assessing individual patient scores, mortality was 52% in the lowest risk group (0-2 points in PROFUND score); 73.5% in the low-intermediate risk group (3-6 points), 85% in the intermediate-high group (7-10 points); and 92% in the highest risk group (≥11 points). Accuracy testing of the PROFUND index showed good calibration (P=.8 in the Hosmer-Lemeshow goodness-of-fit test), and also a good discrimination power (AUC=0.71 [0.67-0.77] in ROC curve). CONCLUSIONS: The PROFUND index maintained its accuracy in predicting mortality of polypathological patients over a 4-year follow-up period. This index may be of potential usefulness in deciding the most appropriate health-care interventions in populations with multimorbidity.
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Delírio/epidemiologia , Demência/epidemiologia , Hospitalização/estatística & dados numéricos , Múltiplas Afecções Crônicas/mortalidade , Neoplasias/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Cuidadores , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Mortalidade , Prognóstico , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Índice de Gravidade de Doença , Espanha/epidemiologiaRESUMO
A guinea-pig pneumonia model involving imipenem-susceptible and imipenem-resistant strains of Acinetobacter baumannii was developed to assess the in-vitro and in-vivo activities of imipenem, alone or in combination with amikacin, and the pharmacokinetic and pharmacodynamic parameters. Serum levels were measured by bioassay (imipenem) or immunoassay (amikacin), followed by calculation of pharmacokinetic and pharmacodynamic parameters (Cmax, AUC, t1/2, Cmax/MIC, AUC/MIC, and Deltat/MIC). In-vivo efficacy was evaluated by comparing bacterial counts in the lungs of treatment groups with end-of-therapy controls by anova and post-hoc tests. Decreases in the Cmax (13.4%), AUC (13%), t1/2 (25%) and Deltat/MIC (11.8-32.2%) of imipenem were observed when it was administered with amikacin, compared with administration of imipenem alone. Similarly, decreases in the Cmax (34.5%), AUC (11.6%), Cmax/MIC (34.5%) and AUC/MIC (11.7%) of amikacin were observed when it was administered with imipenem. Bacterial counts in lungs were reduced by imipenem (p 0.004) with the imipenem-susceptible strain, and by amikacin (p 0.001) with the imipenem-resistant strain. The combination of imipenem plus amikacin was inferior to imipenem alone with the imipenem-susceptible strain (p 0.01), despite their in-vitro synergy, and was inferior to amikacin alone with the imipenem-resistant strain (p < 0.0001). In summary, combined use of imipenem with amikacin was less efficacious than monotherapy, probably because of a drug-drug interaction that resulted in decreased pharmacokinetic and pharmacodynamic parameters for both antimicrobial agents.