Die Behandlung der Tuberkulose Degen, Thomas; Bregenzer, Thomas
Praxis (Bern. 1994),
04/2016, Letnik:
105, Številka:
8
Journal Article
Recenzirano
Zusammenfassung. Die Tuberkulose wird seltener. Sie wirft aber immer wieder Fragen auf, wenn sie verzögert diagnostiziert wurde und mögliche Ansteckungen in der Umgebung des Patienten berücksichtigt ...werden müssen oder weil wir zunehmend mit Resistenzen rechnen müssen. Als Standard wird mit einer Viererkombination aus Rifampicin, Isoniazid, Ethambutol und Pyrazinamid empirisch die Therapie angefangen. Dieses initiale Regime dient der Reduktion der Keimzahl. Die Konsolidierungsphase der Therapie mit zwei Substanzen dient der Elimination verbleibender Keime. Therapiedauer und Adherence sind die kritischen Grössen, um eine Heilung zu erreichen. Die preemptive Therapie der latenten Tuberkulose besteht weiterhin aus einer Isoniazid-Monotherapie über sechs bis neun Monate. Für komplexere Situationen wie die Therapie von immunsupprimierten Patienten oder im Fall von Resistenzen sollte Rücksprache mit Experten genommen werden.
The treatment of tuberculosis Degen, Thomas; Bregenzer, Thomas
Praxis (Bern. 1994),
2016-Apr-13, 20160413, Letnik:
105, Številka:
8
Journal Article
Recenzirano
The incidence of tuberculosis decreases. However, clinical cases frequently raise questions, mainly in the context of contact tracing or when antimicrobial resistance is suspected. Empiric standard ...treatment consists of rifampin, isoniazid, ethambutol and pyrazinamide. This initial regimen aims to reduce the number of pathogenic germs while the consolidation therapy should eradicate the remaining pathogens. Treatment duration and adherence are crucial for cure. For the treatment of latent tuberculosis the traditional 6 to 9 months isoniazid regimen is still the treatment of choice. In complex cases such as tuberculosis in immunocompromised patients or if resistant tuberculosis is suspected, patients should be referred to a specialized center.
Among medical inpatients at risk of malnutrition, the use of individualized nutritional support during the hospital stay was found to reduce complications and improve mortality at short-term. We ...evaluated clinical outcomes at 6-months follow-up.
We randomly assigned 2028 patients to receive protocol-guided individualized nutritional support to reach protein and energy goals (intervention group) or hospital food as usual (control group) during the hospital stay. The intervention was discontinued at hospital discharge and further nutritional support was based on the discretion of the treating team. We had complete follow-up information of 1995 patients (98%), which were included in the final analysis. The primary endpoint was all-cause mortality at 6-months. Prespecified secondary end points included non-elective hospital readmissions, functional outcome and quality of life.
At 6-month, 231 of 994 (23.2%) intervention group patients had died compared to 246 of 999 (24.6%) control group patients, resulting in a hazard ratio for death of 0.90 (95%CI 0.76 to 1.08, p = 0.277). Compared to control patients, intervention group patients had similar rates of hospital readmission (27.3% vs. 27.6%, HR 1.00 (95%CI 0.84 to 1.18), p = 0.974), falls (11.2% vs. 10.9%, HR 0.96 (95%CI 0.72 to 1.27), p = 0.773) and similar quality of life and activities of daily living scores.
While individualized nutritional support during the hospital stay significantly reduced short-term mortality, there was no legacy effect on longer term outcomes. Future trials should investigate whether continuation of nutritional support after hospital discharge reduces the high malnutrition-associated mortality rates in this vulnerable patient population.
ClinicalTrials.gov number, NCT02517476.
Objectives In 2002, the UK's National Institute for Health and Care Excellence concluded that the multiple sclerosis (MS) disease modifying therapies; interferon-β and glatiramer acetate, were not ...cost effective over the short term but recognised that reducing disability over the longer term might dramatically improve the cost effectiveness. The UK Risk-sharing Scheme (RSS) was established to ensure cost-effective provision by prospectively collecting disability-related data from UK-treated patients with MS and comparing findings to a natural history (untreated) cohort. However, deficiencies were found in the originally selected untreated cohort and the resulting analytical approach. This study aims to identify a more suitable natural history cohort and to develop a robust analytical approach using the new cohort. Design The Scientific Advisory Group, recommended the British Columbia Multiple Sclerosis (BCMS) database, Canada, as providing a more suitable natural history comparator cohort. Transition probabilities were derived and different Markov models (discrete and continuous) with and without baseline covariates were applied. Setting MS clinics in Canada and the UK. Participants From the BCMS database, 898 ‘untreated’ patients with MS considered eligible for drug treatment based on the UK's Association of British Neurologists criteria. Outcome measure The predicted Expanded Disability Status Scale (EDSS) score was collected and assessed for goodness of fit when compared with actual outcome. Results The BCMS untreated cohort contributed 7335 EDSS scores over a median 6.4 years (6357 EDSS ‘transitions’ recorded at consecutive visits) during the period 1980–1995. A continuous Markov model with ‘onset age’ as a binary covariate was deemed the most suitable model for future RSS analysis. Conclusions A new untreated MS cohort from British Columbia has been selected and will be modelled using a continuous Markov model with onset age as a baseline covariate. This approach will now be applied to the treated UK RSS MS cohort for future price adjustment calculations.
The nutritional risk screening (NRS 2002) is a validated screening tool for malnutrition. This study aims to investigate the prognostic value of the NRS 2002 and its individual components regarding ...long-term mortality and adverse outcomes in a well-characterized cohort of medical inpatients.
We performed a 5-year follow-up investigation of patients included in the investigator-initiated, prospective, randomized controlled multicenter EFFORT trial that evaluated the effects of individualized nutritional intervention vs. standard hospital food. We used multivariable cox regression analyses adjusted for randomisation arm, study centre, comorbidities and main admission diagnosis to investigate associations between NRS 2002 total scores at time of hospital admission and several long-term outcomes.
We had confirmed mortality data over the mean follow-up time of 3.2 years in 1874 from the initial cohort of 2028 EFFORT patients. Mortality showed a step-wise increase in patients with NRS 3 (289/565 51.2%) and NRS 4 (355/717 49.6%) to 59.5% (353/593) in patient with NRS≥5 corresponding to an adjusted Hazard Ratio (HR) of 1.28 (95%CI 1.15 to 1.42, p ≤ 0.001) for mortality after one year and 1.13 (95%CI 1.05 to 1.23, p = 0.002) for the overall time period. All individual components of NRS including disease severity, food intake, weight loss and BMI provided prognostic information regarding long-term mortality risk.
Nutritional risk mirrored by a NRS 2002 total score is a strong and independent predictor of long-term mortality and morbidity in polymorbid medical inpatients particularly in patients with high nutritional risk with an NRS ≥5 points.
We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to ...clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre® YeastOne™ test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.
Objective To generate evidence on the longer term cost effectiveness of disease modifying treatments in patients with relapsing-remitting multiple sclerosis.Design Prospective cohort study with ...historical comparator.Setting Specialist multiple sclerosis clinics in 70 centres in the United Kingdom.Participants Patients with relapsing-remitting multiple sclerosis who started treatment from May 2002 to April 2005 under the UK risk sharing scheme.Interventions Treatment with interferon beta or glatiramer acetate in accordance with guidelines of the UK Association of British Neurologists.Main outcome measures Observed utility weighted progression in disability at two years’ follow-up assessed on the expanded disability status scale (EDSS) compared with that expected by applying the progression rates in a comparator dataset, modified for patients receiving treatment by multiplying by the hazard ratio derived separately for each disease modifying treatment from the randomised trials.Results In the primary per protocol analysis, progression in disability was worse than that predicted and worse than that in the untreated comparator dataset (“deviation score” of 113%; excess in mean disability status scale 0.28). In sensitivity analyses, however, the deviation score varied from −72% (using raw baseline disability status scale scores, rather than applying a “no improvement” algorithm) to 156% (imputing missing data for year two from progression rates for year one).Conclusions It is too early to reach any conclusion about the cost effectiveness of disease modifying treatments from this first interim analysis. Important methodological issues, including the need for additional comparator datasets, the potential bias from missing data, and the impact of the “no improvement” rule, will need to be addressed and long term follow-up of all patients is essential to secure meaningful results. Future analyses of the cohort are likely to be more informative, not least because they will be less sensitive to short term fluctuations in disability.
To assess perinatal outcome in monochorionic twin pregnancies according to different stages of severe mid-trimester twin-twin transfusion syndrome managed by fetoscopic laser coagulation of the ...placental vascular anastomoses.
In a prospective study fetoscopic laser therapy was performed in 200 consecutive pregnancies with severe mid-trimester twin-twin transfusion syndrome at a median gestational age of 20.7 weeks (range 15.9-25.3 weeks). Outcome data were analyzed for the whole group and separately for each stage according to the Quintero staging system.
The overall survival rate was 71.5% (286/400), with survival of both twins in 59.5% (119/200) and survival of at least one of the twins in 83.5% (167/200). The median gestational age at delivery of liveborn neonates was 34.3 weeks (range 23.1-40.4 weeks). There was a significant trend toward reduced survival rates with increasing stage (P=.038). The percentage of pregnancies with survival of both fetuses was 75.9% (22/29) for stage I, 60.5% (49/81) for stage II, 53.8% (43/80) for stage III, and 50% (5/10) for stage IV. At least one of the twins survived in 93.1% (27/29) at stage I, 82.7% (67/81) at stage II, 82.5% (66/80) at stage III, and 70% (7/10) at stage IV. The overall survival rate for donor fetuses was 70.5% (141/200) and for recipient fetuses, 72.5% (145/200).
These data show that laser therapy is an effective therapeutic option for all stages of severe twin-twin transfusion syndrome and provide information to counsel patients according to the stage of the syndrome.
Measurement of prohormones representing different pathophysiological pathways could enhance risk stratification in patients with community-acquired pneumonia (CAP) and other lower respiratory tract ...infections (LRTI).
We assessed clinical parameters and five biomarkers, the precursor levels of adrenomedullin (ADM), endothelin-1 (ET1), atrial-natriuretic peptide (ANP), anti-diuretic hormone (copeptin), and procalcitonin in patients with LRTI and CAP enrolled in the multicenter ProHOSP study. We compared the prognostic accuracy of these biomarkers with the pneumonia severity index (PSI) and CURB65 (Confusion, Urea, Respiratory rate, Blood pressure, Age 65) score to predict serious complications defined as death, ICU admission and disease-specific complications using receiver operating curves (ROC) and reclassification methods.
During the 30 days of follow-up, 134 serious complications occurred in 925 (14.5%) patients with CAP. Both PSI and CURB65 overestimated the observed mortality (X2 goodness of fit test: P = 0.003 and 0.01). ProADM or proET1 alone had stronger discriminatory powers than the PSI or CURB65 score or any of either score components to predict serious complications. Adding proADM alone (or all five biomarkers jointly) to the PSI and CURB65 scores, significantly increased the area under the curve (AUC) for PSI from 0.69 to 0.75, and for CURB65 from 0.66 to 0.73 (P < 0.001, for both scores). Reclassification methods also established highly significant improvement (P < 0.001) for models with biomarkers if clinical covariates were more flexibly adjusted for. The developed prediction models with biomarkers extrapolated well if evaluated in 434 patients with non-CAP LRTIs.
Five biomarkers from distinct biologic pathways were strong and specific predictors for short-term adverse outcome and improved clinical risk scores in CAP and non-pneumonic LRTI. Intervention studies are warranted to show whether an improved risk prognostication with biomarkers translates into a better clinical management and superior allocation of health care resources.
NCT00350987.
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