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Objective: This study aims to describe time trends in and patterns of use of hormonal contraception and postmenopausal hormone therapy and to identify factors associated with their use among Spanish women., Methods: We performed a cross-sectional analysis using data from 1,954 population controls (aged 24-85 y) in 12 provinces of Spain who were enrolled in the Multi Case-Control Spain study (2007-2013). Data were collected from a questionnaire conducted face-to-face by trained personnel. We collected information on sociodemographic factors, lifestyle, sleep patterns, reproductive history, and occupational history., Results: Overall, 48.5% of Spanish women reported ever use of hormonal contraception, and 9.8% of women in the postmenopausal group reported use of postmenopausal hormone therapy. Younger cohorts used hormonal contraception for a longer period, whereas postmenopausal hormone therapy use dramatically dropped in the 2000s. Women with higher education levels (including education of partners) and smoking history were the most probable users of hormonal contraception, whereas inverse associations were observed among housewives, obese women, and nulliparous women. Postmenopausal hormone therapy use was associated with a surgical or therapeutic cause of menopause and with occupational history of rotating shifts., Conclusions: In this Spanish population, several demographic, lifestyle, occupational, and reproductive factors are associated with use of hormonal compounds. Characterizing hormonal users and monitoring trends in the use of these hormonal compounds are essential from a public health perspective.

We compared the incidence of and factors associated with hepatocellular carcinoma (HCC) among hepatitis C virus (HCV)-monoinfected subjects and human immunodeficiency virus (HIV)/HCV-coinfected individuals, both with decompensated cirrhosis. In a retrospective study, a cohort of 180 individuals with HIV coinfection and 1037 HCV-monoinfected patients with decompensated HCV-related cirrhosis from eight centres in Spain were analyzed. HCC was found in 234 (23%) HCV-monoinfected subjects and in four (2%) HIV-coinfected subjects (p<0.001). At the time of the first hepatic decompensation, 188 (17%) and 4 (2%) (p<0.001) patients in the former and in the latter group, respectively, showed HCC. Fifty-four (11%) patients without HCC at baseline developed such a disease during follow-up. There were no incident cases among the HIV-coinfected population. The density of incidence (95% IC) of HCC in HIV/HCV-coinfected and HCV-monoinfected patients was 0 (0-1.70) and 3.31 (2.70-4.64) cases per 100 person-years (p<0.001), respectively. Lack of HIV infection [adjusted odds risk (AOR) (95% IC)=16.7 (3.9-71.1)] and high alanine aminotransferase levels [AOR (95% IC)=2.5 (1.1-5)] were the only two independent predictors of the emergence of HCC. In the group of patients in whom the date of HCV infection could be estimated, the time elapsed until HCC diagnosis was shorter among HIV-coinfected subjects. The incidence of HCC in patients with HCV-related cirrhosis after the first hepatic decompensation is lower in HIV-coinfected patients. This is probably due to the fact that HIV infection shortens the survival of HCV-coinfected patients with end-stage liver disease to such an extent that HCC not had a chance to emerge.

Objectives: To determine the incidence of and risk factors for severe hepatotoxicity of nelfinavir-containing regimens among human immunodeficiency virus/hepatitis C virus (HIV/HCV)-coinfected patients with known stage of liver fibrosis., Methods: All HIV/HCV-coinfected patients were monitored for a period of 12 months after starting nelfinavir-containing regimens and, with an available liver biopsy, were included in a retrospective study., Results: A total of 82 patients were included in the study. Nine (10.9%) HIV/HCV-coinfected patients showed an episode of severe hepatotoxicity during the study period. Eight (9.8%) individuals showed grade 3 or 4 change in levels of serum alanine aminotransferase and one subject presented with an event of decompensated liver cirrhosis. Six (18.2%) of 33 patients with advanced liver fibrosis and three (6%) of 49 individuals without advanced liver fibrosis showed an episode of severe hepatotoxicity (P = 0.1). In the multivariate analysis, only nevirapine use during nelfinavir therapy [adjusted odds ratio (AOR) 8.9; 95% confidence interval (CI), 1.4-54.1; P = 0.01] was independently associated with risk of development of severe liver toxicity., Conclusions: The incidence of severe hepatotoxicity of nelfinavir-containing regimens is low among HIV/HCV-coinfected patients with known stage of liver fibrosis. In addition, our findings show that concomitant nevirapine use is associated with an increased risk of severe hepatotoxicity in these subjects. Likewise, the proportion of severe liver toxicity tended to be higher in individuals with advanced liver fibrosis.

Objectives: To compare the in vitro and in vivo activity of penicillin, cefotaxime and ceftriaxone, using three strains of Streptococcus pneumoniae with different susceptibilities to penicillin (MICs of 0.015, 0.25 and 2 mg/L, respectively)., Methods: Time-kill curves and an experimental model of endocarditis in rabbits., Results: Penicillin was efficacious in clearing bacteria from vegetations and blood irrespective of whether infections were caused by penicillin-susceptible or penicillin-resistant strains (P < 0.01 with respect to control groups). The same efficacy was shown with cefotaxime and ceftriaxone. Comparing the results of the in vivo model with those obtained in time-kill curves, penicillin showed the best results., Conclusions: These results confirm that penicillin is efficacious in the treatment of pneumococcal infections, including those produced by strains with MICs < or = 2 mg/L (with the exception of pneumococcal meningitis). These results also suggest that the breakpoints to define susceptibility and resistance of S. pneumoniae to penicillin must be reviewed, as has been done with amoxicillin and third-generation cephalosporins.

The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.

A multicenter, comparative study was performed to determine the epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium tuberculosis and Mycobacterium kansasii in human immunodeficiency virus (HIV)-infected patients. From 1 January 1995 through 31 December 1999, 25 HIV-infected patients received diagnoses of M. kansasii infection, and another 75 were selected as control subjects from among patients who had M. tuberculosis infection. Variables associated with M. tuberculosis disease in the multivariate analysis were previous intravenous drug use (odds ratio [OR], 8; 95% confidence interval [CI], 1.5-41.4) and interstitial radiologic pattern (OR, 12.7; 95% CI, 1.7-94.3). Variables associated with M. kansasii were previous diagnosis of acquired immunodeficiency syndrome (OR, 15.8; 95% CI, 4.2-59.6) and concomitant opportunistic infections (OR, 14.2; 95% CI, 2-105.7). Clinical and radiologic features were similar for both groups, but epidemiological characteristics and prognosis were different. M. kansasii disease was associated more closely with level of immunosuppression and progression of HIV infection than was disease caused by M. tuberculosis.

In order to assess whether complete inactivation of retinitis at the end of induction therapy leads to delayed progression during maintenance therapy with weekly intravitreal ganciclovir, the time to the first progression to retinitis was evaluated in 27 AIDS patients (34 eyes) with stable cytomegalovirus retinitis. Data were censored before the introduction of protease inhibitors. Overall, retinitis progressed in 22 of 34 eyes in a median time of 12 weeks (mean +/- SD, 33 +/- 9 weeks). However, retinitis progressed in 15 of 19 eyes in which only partial inactivation was achieved following induction therapy (median time, 10 weeks; mean +/- SD, 17 +/- 4 weeks) but in only 7 of 15 eyes when complete inactivation was obtained (median time, 59 weeks; mean +/- SD, 56 +/- 19 weeks) (P= 0.02). There were no differences between the groups in CD4+ cell counts, drugs, route of induction treatment, or length of induction therapy. Induction therapy should be prolonged until complete inactivation of retinitis is obtained, since achieving only a partial response appears to be a factor in earlier progression when patients are switched to maintenance therapy with intravitreal ganciclovir.

The mortality rate of patients with cases of enterococcal bacteremia is high, although it has often been related to the patients' underlying conditions rather than to the infection itself. To analyze the attributable prognosis of enterococcal bacteremia (assessed by its attributable mortality rate and duration of hospital stay), a prospective, matched case-control study was done. All adults with an episode of enterococcal bacteremia without endocarditis were included. A control patient was randomly selected for every case patient and matched by sex, age and hospital ward. Univariate and multivariate analyses were performed. A total of 122 pairs were included, and incidence of enterococcal bacteremia was 2.3 episodes/1000 discharges. Crude 30-day mortality rates for case patients and control patients were 23% and 17%, respectively (P=.29); thus, the estimated attributable mortality rate was 6% (95% confidence interval, -4% to 16%). The mean duration of hospital stay of case patients and control patients were 38 and 17 days, respectively (P<.001); thus, the estimated attributable duration of hospital stay was 21 days (95% CI, 7-32 days). Enterococcal bacteremia without endocarditis does not increase risk of death by itself but extends the duration of hospital stay of patients who develop it.

To determine the risk factors involved in the development of enterococcal bacteremia, a prospective, observational, case-control study was carried out over 18 months. All episodes of enterococcal bacteremia with clinical significance detected in adults were included. A control matched by sex, age and hospitalization ward (medical, surgical or intensive care unit) was selected randomly for each patient with enterococcal bacteremia. Uni- and multivariate analyses of the epidemiological characteristics of both groups were performed. Etiologic fractions of every risk factor were also determined. One hundred twenty-two pairs were included. The severity of the chronic underlying diseases was similar in both groups. Neutropenia, cirrhosis, organ transplantation, intravascular catheter, urinary catheter, nasogastric tube, parenteral nutrition and previous administration of cephalosporins and imipenem were the factors associated with enterococcal bacteremia in the univariate analysis. The factors independently associated with enterococcal bacteremia in the multivariate analysis were neutropenia (odds ratio [OR] = 8), urinary catheter (OR = 3) and previous administration of cephalosporins (OR = 4) and imipenem (OR = 10). Their respective etiologic fractions were 9%, 44%, 11% and 29%. Efforts to reduce the occurrence of enterococcal bacteremia should be focused on appropriate use of cephalosporins, imipenem and external devices.

Objective: To evaluate whether cerebrospinal fluid concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-8 may be used as diagnostic markers for the differential diagnosis of aseptic vs. bacterial meningitis and/or ventriculitis in neurosurgical patients., Design: Prospective, observational study., Setting: University teaching hospital., Subjects: A total of 112 cerebrospinal fluid samples from 14 asymptomatic patients with normal cerebrospinal fluid after neurosurgery, 27 asymptomatic and 19 symptomatic patients with postneurosurgical aseptic meningitis, 32 patients with postneurosurgical cerebrospinal fluid infection, and 20 with severe subarachnoid and/or cerebral hemorrhage., Measurements and Main Results: Specific ELISA kits were used to analyze TNF-alpha, IL-1beta, IL-6, and IL-8 concentrations on cerebrospinal fluid samples. Elevations in cerebrospinal fluid concentrations of TNF-alpha, IL-1beta, IL-6, and IL-8 were induced by different diseases or neurosurgical procedures, but cerebrospinal fluid bacterial infection induced the highest concentrations. To discriminate between aseptic cerebrospinal fluid pleocytosis and cerebrospinal fluid infection with a specificity of 95%, cerebrospinal fluid leukocyte count >1700/mL, TNF-alpha >150 pg/mL, and IL-1beta >90 pg/mL showed sensitivities of 51%, 74%, and 90%, respectively. Sufficiently sensitive and specific cutoff points could not be found for cerebrospinal fluid IL-6 or IL-8., Conclusion: Cerebrospinal fluid IL-1beta appears to be the best biochemical marker of cerebrospinal fluid infection in neurosurgical patients.

Background: Fever of intermediate duration (FID), characterized by a febrile syndrome lasting from 7 to 28 days, is a frequent condition in clinical practice, but its epidemiological and etiologic features are not well described. Murine typhus (MT) is a worldwide illness; nevertheless, to our knowledge, no studies describing its epidemiological and clinical characteristics have been performed in the south of Spain. Also, its significance as a cause of FID is unknown., Objective: To determine the epidemiological features, clinical characteristics, and prognosis of MT and, prospectively, its incidence as a cause of FID., Design: Prospective study of cases of MT over 17 years (1979-1995) and of all cases of FID treated in a tertiary teaching hospital in Seville, Spain., Results: One hundred and four cases of MT were included, and MT was the cause in 6.7% of 926 cases of FID. Insect bites were reported in only 3.8% of the cases of MT previous to the onset of illness. Most cases (62.5%) occurred in the summer and fall. A high frequency of rash (62.5%) was noted. Arthromyalgia (77%), headache (71%), and respiratory (25%) and gastrointestinal (23%) symptoms were also frequent. Laboratory findings were unspecific. Organ complications were uncommon (8.6%), but they were severe in 4 cases. The mean duration of fever was 12.5 days. Cure was achieved in all cases, although only 44 patients received specific treatment., Conclusions: Murine typhus is prevalent in the south of Spain and is a significant cause of FID. Clinical signs are benign, but some patients may develop severe complications. A high degree of clinical suspicion is required for diagnosis.

A prospective, multicenter study was carried out over a period of 10 months. All patients with clinically significant bacteremia caused by Enterococcus spp. were included. The epidemiological, microbiological, clinical, and prognostic features and the relationship of these features to the presence of high-level resistance to gentamicin (HLRG) were studied. Ninety-three patients with enterococcal bacteremia were included, and 31 of these cases were caused by HLRG (33%). The multivariate analysis selected chronic renal failure, intensive care unit stay, previous use of antimicrobial agents, and Enterococcus faecalis species as the independent risk factors that influenced the development of HLRG. The strains with HLRG showed lower levels of susceptibility to penicillin and ciprofloxacin. Clinical features (except for chronic renal failure) were similar in both groups of patients. HLRG did not influence the prognosis for patients with enterococcal bacteremia in terms of either the crude mortality rate (29% for patients with bacteremia caused by enterococci with HLRG and 28% for patients not infected with strains with HLRG) or the hospital stay after the acquisition of enterococcal bacteremia. Hemodynamic compromise, inappropriate antimicrobial therapy, and mechanical ventilation were revealed in the multivariate analysis to be the independent risk factors for mortality. Prolonged hospitalization was associated with the nosocomial acquisition of bacteremia and polymicrobial infections.

Pneumocystis carinii is a common opportunistic pathogen in patients infected with the human immunodeficiency virus (HIV). Pneumocystis carinii pneumonia is common, while extrapulmonary infections with Pneumocystis carinii have been reported sparingly. The clinical features are frequently nonspecific. The detection of Pneumocystis carinii in cerebrospinal fluid (CSF) has not been reported thus far. In this report, an unusual case of Pneumocystis carinii meningoradiculitis in an HIV-infected patient who had previously received primary prophylaxis with trimethoprim-sulfamethoxazole is presented.