Background: There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. Methods: We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. Results: The CSHA Clinical Frailty Scale was highly correlated ( r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%–30.6%) and entry into an institution (23.9%, 95% CI 8.8%–41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). Interpretation: Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.

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A global clinical measure of fitness and frailty in elderly people

This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.

These guidelines from the Infectious Diseases Society of America (IDSA), the American College of Critical Care Medicine (for the Society of Critical Care Medicine), and the Society for Healthcare Epidemiology of America contain recommendations for the management of adults and children with, and diagnosis of infections related to, peripheral and nontunneled central venous catheters (CVCs), pulmonary artery catheters, tunneled central catheters, and implantable devices. The guidelines, written for clinicians, contain IDSA evidence-based recommendations for assessment of the quality and strength of the data. Recommendations are presented according to the type of catheter, the infecting organism, and the associated complications. Intravascular catheter-related infections are a major cause of morbidity and mortality in the United States. Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and Candida albicans most commonly cause catheter-related bloodstream infection. Management of catheter-related infection varies according to the type of catheter involved. After appropriate cultures of blood and catheter samples are done, empirical i.v. antimicrobial therapy should be initiated on the basis of clinical clues, the severity of the patient's acute illness, underlying disease, and the potential pathogen(s) involved. In most cases of nontunneled CVC-related bacteremia and fungemia, the CVC should be removed. For management of bacteremia and fungemia from a tunneled catheter or implantable device, such as a port, the decision to remove the catheter or device should be based on the severity of the patient's illness, documentation that the vascular-access device is infected, assessment of the specific pathogen involved, and presence of complications, such as endocarditis, septic thrombosis, tunnel infection, or metastatic seeding. When a catheter-related infection is documented and a specific pathogen is identified, systemic antimicrobial therapy should be narrowed and consideration given for antibiotic lock therapy, if the CVC or implantable device is not removed. These guidelines address the issues related to the management of catheter-related bacteremia and associated complications. Separate guidelines will address specific issues related to the prevention of catheter-related infections. Performance indicators for the management of catheter-related infection are included at the end of the document. Because the pathogenesis of catheter-related infections is complicated, the virulence of the pathogens is variable, and the host factors have not been well defined, there is a notable absence of compelling clinical data to make firm recommendations for an individual patient. Therefore, the recommendations in these guidelines are intended to support, and not replace, good clinical judgment. Also, a section on selected, unresolved clinical issues that require further study and research has been included. There is an urgent need for large, well-designed clinical studies to delineate management strategies more effectively, which will improve clinical outcomes and save precious health care resources.

https://gavecelt.it/nuovo/sites/default/files/uploads/guidelines_idsa.pdf

Guidelines for the management of intravascular catheter-related infections

Statistical Methods in Medical Research.

The recent explosion of newly described species of Nocardia results from the impact in the last decade of newer molecular technology, including PCR restriction enzyme analysis and 16S rRNA sequencing. These molecular techniques have revolutionized the identification of the nocardiae by providing rapid and accurate identification of recognized nocardiae and, at the same time, revealing new species and a number of yet-to-be-described species. There are currently more than 30 species of nocardiae of human clinical significance, with the majority of isolates being N. nova complex, N. abscessus, N. transvalensis complex, N. farcinica, N. asteroides type VI (N. cyriacigeorgica), and N. brasiliensis. These species cause a wide variety of diseases and have variable drug susceptibilities. Accurate identification often requires referral to a reference laboratory with molecular capabilities, as many newer species are genetically distinct from established species yet have few or no distinguishing phenotypic characteristics. Correct identification is important in deciding the clinical relevance of a species and in the clinical management and treatment of patients with nocardial disease. This review characterizes the currently known pathogenic species of Nocardia, including clinical disease, drug susceptibility, and methods of identification.

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Clinical and Laboratory Features of the Nocardia spp. Based on Current Molecular Taxonomy

Background: Inhibitors of HIV-1 protease produce a rapid decrease in plasma HIV-1 RNA, with concomitant immune reconstitution. However, severe metabolic side effects together with a previously unseen form of lipodystrophy have been associated with long-term use of protease-inhibitor therapy. The pathogenic mechanisms underlying HIV-1 protease inhibitor-associated lipodystrophy are still largely unknown. Methods: Fourteen HIV-infected patients with HIV-1 protease inhibitor-associated lipodystrophy had a biopsy of subcutaneous fat performed in the antero-lateral aspect of the right leg. The samples were submitted for standard pathologic study together with a careful search for adipocyte apoptosis. Apoptosis was assessed by the terminal deoxynucleotidyl transferase dUTP-digoxigenin nick end labelling (TUNEL) method, using the ApopTag kit (Oncor, Gaithersburg, Maryland, USA). The procedure was performed between three and five times for each sample. Appropriate positive and negative controls were used. Controls which were subcutaneous fat biopsies from patients with untreated melanoma were also examined for the presence of apoptosis. Results: Fourteen HIV-infected patients with a mean exposure to HIV-1 protease inhibitors of 12.6 ± 3.7 months (range: 6-21 months), developed the characteristic features of HIV-1 protease inhibitor-associated lipodystrophy. All but one patient had an abnormal waist : hip ratio, and they all exhibited an abnormal serum lipid profile. Pathologically, subcutaneous fat atrophy was a constant feature, along with focal lipogranuloma formation and vascular proliferation. One of the eleven assessable biopsy samples was negative for the presence of apoptosis, six showed focally positive apoptotic cells, and the remaining four biopsies demonstrated moderate positivity. Apoptotic changes were also detected in endothelial cells. Apoptotic changes were more pronounced in patients with higher increases in CD4 and CD8 counts, and in those with a greater decay in plasma viral load. Conclusions: Subcutaneous adipocyte apoptosis occurs in lipoatrophic areas of patients with HIV-1 protease inhibitor-associated lipodystrophy.

Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy.

Objectives: To evaluate the outcome of elderly patients with community-acquired pneumonia (CAP) seen at an acute-care hospital, analyzing the importance of CAP severity, functional status, comorbidity, and frailty.

Design: Prospective observational study.

Setting: Emergency department and geriatric medical day hospital of a university teaching hospital.

Participants: Ninety-nine patients aged 65 and older seen for CAP over a 6-month recruitment period.

Measurements: Clinical data were used to calculate Pneumonia Severity Index (PSI), Barthel Index (BI), Charlson Comorbidity Index, and Hospital Admission Risk Profile (HARP). Patients were then assessed 15 days later to determine functional decline and 30 days and 18 months later for mortality and readmission. Multiple logistic regression was used to analyze outcomes.

Results: Functional decline was observed in 23% of the 93 survivors. Within the 30-day period, case-fatality rate was 6% and readmission rate 11%; 18-month rates were 24% and 59%, respectively. Higher BI was a protective factor for 30-day and 18-month mortality (odds ratio (OR)=0.96, 95% confidence interval (CI)=0.94–0.98 and OR=0.97, 95% CI=0.95–0.99, respectively; P<.01), and PSI was the only predictor for functional decline (OR=1.03, 95% CI=1.01–1.05; P=.01). Indices did not predict readmission. Analyses were repeated for the 74 inpatients and indicated similar results except for 18-month mortality, which HARP predicted (OR=1.73; 95% CI=1.16–2.57; P<.01).

Conclusion: Functional status was an independent predictor for short- and long-term mortality in hospitalized patients whereas CAP severity predicted functional decline. Severity indices for CAP should possibly thus be adjusted in the elderly population, taking functional status assessment into account.

Outcome predictors of pneumonia in elderly patients: importance of functional assessment.

Nocardia farcinica is a rare Nocardia species causing localised and disseminated infections. A case of Nocardia farcinica infection is presented, and 52 cases previously reported in the literature are reviewed. The hosts usually had predisposing conditions (85%), and acquired the infection through the respiratory tract or skin; the infection then often spread to the brain, kidney, joints, bones and eyes. Pulmonary or pleural infections (43%), brain abscesses (30%) and wound infections (15%) which failed to respond to conventional antimicrobial therapy were the more frequent forms of infection. Nocardia farcinica was frequently isolated from pus (100% of samples), bronchial secretions (41%) and biopsy specimens (63%), but isolation from blood and urine, as in the case presented here, is rare. Antibiotic therapy was adequate in 61% of the patients in whom it was specified, the agents most frequently given being trimethoprim-sulfamethoxazole (54%), amikacin combined with imipenem (7%) and amoxicillin-clavulanate (7%). The high mortality (31%) can be attributed to the severe underlying diseases present, difficulties encountered in identifying the pathogen, inappropriate therapy and late initiation of therapy. Although an infrequent pathogen, Nocardia farcinica should be kept in mind as a cause of infection especially in immunosuppressed patients with indolent infections not responding to third-generation cephalosporins.

Infection caused by Nocardia farcinica: case report and review.

https://www.amjmed.com/article/S0002-9343(01)00703-3/pdf

Herpes zoster as an immune reconstitution disease after initiation of combination antiretroviral therapy in patients with human immunodeficiency virus type-1 infection

https://www.amjmed.com/article/S0002-9343(01)01047-6/pdf

Guillermo Vázquez

Papers

Subcutaneous adipocyte apoptosis in HIV-1 protease inhibitor-associated lipodystrophy.

Outcome predictors of pneumonia in elderly patients: importance of functional assessment.

Infection caused by Nocardia farcinica: case report and review.

Herpes zoster as an immune reconstitution disease after initiation of combination antiretroviral therapy in patients with human immunodeficiency virus type-1 infection

Associations between Fc gamma receptor IIA polymorphisms and the risk and prognosis of meningococcal disease.