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Biomedical subjects

H Knobel

Publications and source records attributed to H Knobel.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Invasive aspergillosis: treatment].

Invasive aspergillosis is a severe disease, affecting essentially congenital or acquired immunodepressed patients, as well as neutropenic or transplanted ones, and those undergoing prolonged chemotherapy or treatment with corticoids. At present, the physician only disposes of the following treatment: amphotericin B desoxycolate, lipidic amphotericins and itraconazole p.o. or intravenously. Very soon, other drugs like voriconazole, posaconazole, liposomal nystatin and echinocandins probably will have a role in the treatment. It is most important to know thoroughly the patients's base disease and its specific treatment and the role of the drugs at present available, their relevant dosage, biodisponibility and pharmacokinetics, as well as adverse effects and evidence-based criterions of application. It is very important indeed to maintain a high suspicion of the disease and a rapid start of treatment. It is equally important to assess the role of coadjuvant treatments. We insist in the importance of surgery in solving of the disease in some cases (progressive pulmonar aspergillosis, sinusitis) combined with appropriate antifungal treatment.

English Abstract↗
PubMed1999

A randomized study comparing triple versus double antiretroviral therapy or no treatment in HIV-1-infected patients in very early stage disease: the Spanish Earth-1 study.

BACKGROUND: Most current guidelines state that antiretroviral therapy should be considered for HIV-infected patients with plasma HIV RNA > 5000-10000 copies/ml and CD4 cells > 500 x 10(6) cells/l. However, there is increasing concern about whether this is the optimal point to begin treatment or whether it is better to delay the initiation to more advanced stages. OBJECTIVE: To study the immunological and virological benefits of starting antiretroviral therapy at these early stages. METHODS: A total of 161 HIV-infected asymptomatic patients with CD4 cell count > 500 x 10(6) cells/l and viral load > 10000 copies/ml were randomly assigned to one of five treatment groups: no treatment, twice daily zidovudine and thrice daily zalcitabine (ZDV-ddC), twice daily zidovudine and didanosine (ZDV-ddI), twice daily stavudine and didanosine (D4T-ddI), or a twice daily three-drug regimen with stavudine and lamivudine and ritonavir. The endpoints were progression to < 350 x 10(6) cells/l CD4 cells, to < 500 x 10(6) cells/l with either two Centers for Disease Control class B symptoms or an increase of viral load > 0.5 log10 copies/ml above baseline, or to AIDS or death. In various substudies, the lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to mitogens and cytomegalovirus, and HIV-1 specific antigens and other immunophenotypic markers were also analysed. RESULTS: Progression rates to study endpoints within 1 year were greater in the control group (31%) than in all groups receiving antiretroviral therapy pooled together (5%; estimated hazard ratio 7.41; 95% confidence interval 5.72-74.55; P < 0.001). The peak mean viral load decrease was greater in the three-drug group when compared with any of the three groups with a two-drug regimen (2.32, 1.65, 1.72 and 1.84, respectively; P < or = 0.001). At 1 year, viral load remained below 20 copies/ml in 30 out of 33 patients in the three-drug group (91%) and in only eight out of 94 patients (9%) in two-drug groups (P = 0.001). The peak mean increase in CD4 cells was also greater in the three-drug group than in the double treatment arms (259 versus 85, 144 and 145 x 10(6) cells/l, respectively; P = 0.001). By comparison, 36% of patients in the three-drug group regimen had to change the therapy as a result of adverse events. Substudies were performed in 60 patients recruited at two sites. Tonsillar tissue HIV RNA was measured in seven patients (two in the two-drug groups and five in the three-drug group) in whom plasma HIV RNA was < 20 copies/ml at 1 year. It was 15151 and 133333 copies/mg tissue in the two patients from the two-drug group, < 40 copies/mg tissue in four patients in the three-drug group, and 485 copies/mg in one patient in the three-drug group. At 1 year there was a mean increase of 4.21+/-2.94% in CD8+CD38+ cells in the control group and a decrease of 9.48+/-3.36% in the two-drug groups (P = 0.01), and 19.87+/-3.64 in the three-drug group (P = 0.001 and P = 0.05, for comparisons with control group and two-drug groups, respectively). Although proliferative responses to cytomegalovirus antigens were significantly greater in those receiving antiretroviral therapy, response to HIV-1 p24 antigen was not detected in any patient in either treatment group. CONCLUSIONS: This study supports the recommendation to start antiretroviral therapy with a three-drug combination during very early stages of HIV-1 disease, at least if viral load is above a cut-off point (10000 copies/ml in our study). The risk of progression was sevenfold higher in non-treated patients at 8 months of follow-up. Some immune system parameters improved toward normal values after 1 year of antiretroviral therapy, but the proliferative response of CD4 T lymphocytes against the p24 HIV-1 antigen was not recovered. Therapeutic approaches with more potent, better-tolerated and more convenient regimens will increasingly favour early intervention with antiretroviral t

Adult↗
PubMed1999

Fatigue. Measures and relation to pain.

Fatigue describes reduced capacity to sustain force or power output, reduced capacity to perform multiple tasks over time and simply a subjective experience of feeling exhausted, tired, weak or having lack of energy. Pain and fatigue have several components in common, such as being subjective, prevalent in most patients with cancer and caused by multiple factors of both a physical and psychological nature. In order to explore the relationship between fatigue and pain, data from five studies were used: two random samples from the Norwegian population (n=2323 and n=1965), Hodgkin's disease survivors (n=459), palliative care patients (n=434) and patients with bone metastases (n=94). All patients had completed one or more of the following instruments: EORTC QLQ-C30, SF-36 and/or Fatigue Questionnaire. The level of fatigue was much higher in the two palliative care populations (54.4 and 63.2) as compared to the normal population samples (25.0). Patients with bone metastases had significantly more pain (72.0) than the patients in the palliative care trial (47.4) and norms (20.5). In the two palliative care and bone metastases populations fatigue was almost unchanged over time, while pain was reduced. In the palliative care population a high level of fatigue (80.3) and pain (57.8) was reported 0-1 month before death. The relationship between pain, fatigue and the health-related quality of life domains should be explored in more detail, especially in follow-up studies in order to assess possible changes over time. In addition, the validity of the existing instruments measuring fatigue should be investigated for use in patients with advanced disease and short life expectancy.

Adult↗
PubMed1999

[Adherence to very active antiretroviral treatment: impact of individualized assessment].

BACKGROUND: To determine if the intervention of individual advice improves adherence and effectiveness to highly active antiretroviral therapy. METHODS: Randomized open trial. Patients treated with zidovudine + lamivudine + indinavir were assigned (2/1) to conventional care or individual advise. Individual advise consists in adaptation to treatment to patient style of live and detailed information of therapy. Adherence were estimated with structured interview and pillo counts and were considered correct when more than 90% of prescribed drugs were taken. RESULTS: Patients 170, conventional care: 110 and IA: 60. FOLLOW-UP: 24 weeks. Baseline characteristics were similar in both groups. Correct adherence were estimated in 52.7% of conventional care and in 76.7% of individual advise (p = 0.002, relative risk: 1.45; CI 95%: 1.16-1.82). Undetectable viral load (NASBA < 50 copies/ml) in 54.5% of conventional care and in 65% of individual advise (p = 0.18, relative risk: 1.19; CI 95%: 0.93-1.53). Reduction of viral load in the conventional care group 1.02 +/- 0.5 log10/ml, and in the individual advise group 1.98 +/- 0.7 log10/ml. CONCLUSION: The individual advice improve adherence with a tendency to improve effectiveness of highly active antiretroviral therapy.

Adult↗
PubMed1998

[Screening for bone disease risk with clinical factors in women after physiologic menopause].

BACKGROUND: Densitometric screening for osteoporosis in postmenopausal women has not been demonstrated cost-effective. We have tried to identify clinical factors for screening previous to densitometry avoiding unnecessary explorations. PATIENTS AND METHODS SETTING: outpatient clinics of a menopausal unit in a 450-bed general hospital. Cross-sectional study, in two steps, of two groups of 140 and 284 women attending for physiological menopause. A clinical questionnaire, physical data and lumbar densitometry (Hologic QDR 1000) were obtained classifying the cases as "normal" or "low bone mass" (osteopenia or osteoporosis) according with the WHO criteria. In the first group a logistic regression analysis was done to identify predictive factors for abnormal densitometry, then validated in the second group. Sensitivity, specificity, predictive values (PV) and classification ability of clinical factors were analyzed. RESULTS: Four factors were independent predictors of abnormal densitometry: age > 51 (odds ratio [OR] = 6.64; 95% CI, 2.36-18.7); body weight < 70 kg (OR = 4.32; 95% CI, 1.71-10.09); years of fertility < 32 (OR = 3.77; 95% CI, 1.36-10.04), and number of live births > 2 (OR = 3.47; 95% CI, 1.27-9.53). Presence of one factor offers: sensitivity 91.9%; specificity 15%; positive PV 66.6%, and negative PV 50%, whereas the presence of two factors offers: sensitivity 62.7%; specificity 70%; positive PV 79.9%, and negative PV 50.3%. Clinical screening allows, when two factors are present, to avoid a 35.5% of densitometries and the false-negative cases represent 18%. CONCLUSIONS: Detection of bone-risk clinical factors (abnormal densitometry) yields a screening, previous to densitometry, that avoids at least one third of explorations in women with physiological menopause, improving the efficiency of the test.

Cross-Sectional Studies↗
PubMed1998

[Prevention of opportunistic infections in the protease inhibitor era].

From the middle of 1996 we are living a striking reduction of incidence of opportunistic infections (Ols) associated to human immunodeficiency virus (HIV). The recovery of the immune system, at least partially, is showing up substantial changes of Ols after the introduction of highly active antiretroviral therapy (HAART): relieves, sometime complete resolutions, of Ols that previously did not give any response to the treatment (cryptosporidiosis, microsporidiosis, progressive multifocal leucoencephalopathy and Kaposi's sarcoma), changes of clinical presentations after HAART (CMV retinitis [CMVR] with vitritis and Mycobacterium avium-intracellulare [MAC] lymphadenitis), related to exuberant inflammatory response; and at last, long periods without reactivation of the Ols after prophylaxis suppression (CMVR and Pneumocystis carinii pneumonia [PCN]). All this sep up the necessity of a change in the prophylaxis recommendations after HAART introduction. This change would have been unthinkable two years ago, the point is to answer the following question: when can Ols prophylaxis to be stopped after HAART? The progress in the therapy of HIV and Ols infections have happened that fast that this recommendations will have to be reconsidered continuously.

AIDS-Related Opportunistic Infections↗
PubMed1998

Hodgkin's disease: quality of life in future trials.

It is of great importance to collect data of objective as well as subjective morbidity in patients cured for Hodgkin's disease. Such information may be used when new treatment strategies are discussed, in patients information and communication, to establish rehabilitation programs and to identify individuals who may benefit from rehabilitation. Measurement of health related quality of life (HRQOL) may give important information on how the cancer and/or the treatment has influenced the patients. There is no gold standard instrument for measurement of HRQOL in cancer. However, it is a consensus to use multidimensional patients rated measures with a standard format and scoring procedure. SF-36, EORTC QLQ-C30 and FACT are widely used in Europe and North America. Domain specific instruments includes a more comprehensive evaluation of a specific domain, for example anxiety or fatigue. Fatigue seems to be a prevalent symptom in Hodgkin's disease survivors and might affect patients' ability to perform normal activities and will often reduce their quality of life. Fatigue is defined as a subjective feeling of tiredness and might be measured by standardised and validated instruments such as the Fatigue Questionnaire (FQ) and the Multi-Dimensional Fatigue Inventory (MFI-20). Clinical significance might be defined as a meaningful difference based on consensus by the patient, the doctor and the society. In oncology there is no agreement of how long a meaningful difference in survival should be. For HRQOL a difference between 7 to 10 on a scale ranking from 0 to 100 has been regarded as clinical significant by some researchers. Another strategy to approach the issue of clinical significance is to use norms-estimates from the normal population- and/or reference estimates as guidelines. The long-term complication of the successful treatment of Hodgkin's disease reinforced the need for continued surveillance of treatment and related morbidities. Fatigue is a prevalent symptom and detailed diagnostic work-up is essential to identify patients with this problem. More knowledge about possible biological causes is required in order to understand fatigue and the impact on quality of life among Hodgkin's disease survivors.

Clinical Trials as Topic↗
PubMed1997

[Acceptance of, compliance with and tolerance to antiretroviral treatment in patients with human immunodeficiency virus infection].

BACKGROUND: The objective of the study is to assess the acceptance, compliance and side effects of antiretroviral therapy in relation to age, gender, risk group, HIV infection stage and type of treatment. METHODS: This is a cohort-observational study. Inclusion criteria were: consecutive non-selected IIV patients in which antiretroviral treatment was indicated on medical grounds. The study was carried out from February 1990 to February 1996. We measured: a) poor compliance, when suspicion (by medical history, analytical data and administered drug control by the hospital pharmacy) more than a 25% of prescribed treatment was not taken; b) adverse events that obliged to discontinued the drug; and c) long-term therapy, when treatment acceptance and compliance and regular follow-up was stated. Statistics methods: Ji-square and Student's t- test. RESULTS: 567 patients were included, with a median follow up of 609 days. Male 413, female 154. Mean age: 32.9 years. Average CD4+ cells: 0.260 x 10(9)/L. There was a history of intravenous drug use (IDU) in 60.4% of cases and CDC classification group C (1993) 34.2%. Antiretroviral treatment was refused by 16.6% of patients, more frequently IDU patients (21.3%, p < 0.0001). There was a drop-out rate of 17.3%, with no differences among different groups. Poor compliance was found in 23% of cases, more frequently in IDU and group-C patients. Adverse events were observed in 22.6% of cases, more frequently in female (33.8%, p < 0.0004) and group C patients (28.6%, p < 0.04). The treatments used (AZT monotherapy, DDI monotherapy, AZT DDI and AZT + DDC) had no influence on compliance or follow-up. Long-term follow-up and compliance was achieved in 47.6% of patients, with a lesser degree in IDU (42.4%, p < 0.002) and group C patients (39.7%, p < 0.006). CONCLUSIONS: HIV-infected patients treated with antiretroviral agents, not enrolled in clinical trials, had similar rates of compliance that patients with other chronic diseases. Treatment refusal and poor compliance were more frequent in IDU patients, while adverse events were more frequent in patients with more advanced HIV infection stage.

Adult↗
PubMed1996

[Clostridium difficile and diarrhea associated with the use of antibiotics in the origin of nosocomial and community-acquired diarrhea].

BACKGROUND: Clostridium difficile is currently recognized as an important nosocomial enteric pathogen. The significance as etiologic agent of community and nosocomial diarrhea is not well known in Spain. METHODS: Retrospective study of all cases of community diarrhea that required admission in the hospital and all nosocomial diarrhea observed in a period of three months in a 450-bed university hospital. We performed conventional coprocultives and detection of toxin-A of C. difficile with the method ELISA Premier. RESULTS: During the period of study were included 66 patients, 19 pediatrics and 47 adults patients (23 males, 24 females, age: 54.5 +/- 21.8 years). Three cases (15.8%) of pediatrics patients were diagnosticated of antibiotic-associated diarrhea, only one case were of nosocomial origin. Toxin A of C. difficile were detected in 6 cases, all were patients under two years old, represented 60% of these patients. The origin of diarrhea were: community in 32 cases and nosocomial in 15 of adults patients, in 18 cases (38.3%) were diagnosticated antibiotic-associated diarrhea, 11 were nosocomial. Toxin A of C. difficile were detected in 12 patients, 25.5% of adults, and 4 cases had criteria of C. difficile associated diarrhea, representing 8.5% of the diarrhea. None of this cases were suspected during admission. CONCLUSIONS: Antibiotic-associated diarrhea and C. difficile associated diarrhea were not infrequent cause of diarrhea of nosocomial and of community origin in our environment. We recommended culture and/or detection of toxins of C. difficile in patients who were treated with antibiotics and diarrhea of more than 72 hours of evolution.

Adolescent↗