Intermittent hemodialysis is widely used as renal-replacement therapy in patients with acute renal failure, but an adequate dose has not been defined. We performed a prospective study to determine ...the effect of daily intermittent hemodialysis, as compared with conventional (alternate-day) intermittent hemodialysis, on survival among patients with acute renal failure.
A total of 160 patients with acute renal failure were assigned to receive daily or conventional intermittent hemodialysis. Survival was the primary end point of the study. The duration of acute renal failure and the frequency of therapy-related complications were secondary end points.
The two study groups were similar with respect to age, sex, cause and severity of acute renal failure, medical or surgical intensive care setting, and the score on the Acute Physiology, Age, and Chronic Health Evaluation. Daily hemodialysis resulted in better control of uremia, fewer hypotensive episodes during hemodialysis, and more rapid resolution of acute renal failure (mean +/-SD, 9+/-2 vs. 16+/-6 days; P=0.001) than did conventional hemodialysis. The mortality rate, according to the intention-to-treat analysis, was 28 percent for daily dialysis and 46 percent for alternate-day dialysis (P=0.01). In a multiple regression analysis, less frequent hemodialysis (on alternate days, as opposed to daily) was an independent risk factor for death.
The high mortality rate among critically ill patients with acute renal failure who require renal-replacement therapy is related to both coexisting conditions and uremic damage to other organ systems. Intensive hemodialysis reduces mortality without increasing hemodynamically induced morbidity.
An increasing rate of respiratory colonization and infection in cystic fibrosis (CF) is caused by fungi of the Scedosporium apiospermum species complex or Lomentospora prolificans (Sac-Lp). These ...fungi rank second among the filamentous fungi colonizing the CF airways, after Aspergillus fumigatus. However, the epidemiology, clinical relevance and risk of pulmonary colonization with Sac-Lp are rarely understood in CF. The objective of the present prospective multicenter study was to study pathogen distribution and determine association factors of pulmonary Sac-Lp colonization in patients with CF.
Clinical, microbiological and laboratory data of 161 patients aged 6-59 years with CF in Germany were analyzed for Sac-Lp distribution and association factors. The free statistical software R was utilized to investigate adjusted logistic regression models for association factors.
Of the 161 patients included in the study, 74 (56%) were male. The median age of the study cohort was 23 years (interquartile range 13-32 years). 58 patients of the total cohort (36%) were < 18 years old. Adjusted multivariate regression analysis revealed that Sac-Lp colonization was associated with younger age (OR 0.8684, 95%CI: 0.7955-0.9480, p<0.005) and less colonization with H. influenzae (OR 0.0118, 95%CI: 0.0009-0.1585, p<0.001). In addition, Sac-Lp-colonized patients had more often allergic bronchopulmonary aspergillosis (ABPA) (OR 14.6663, 95%CI: 2.1873-98.3403, p<0.01) and have been colonized more often with the mucoid phenotype of Pseudomonas aeruginosa (OR 9.8941, 95%CI: 1.0518-93.0705, p<0.05).
Newly found association of ABPA and Pseudomonas revealed new probable risk factors for Sac-Lp colonization. Allergy might play a role in inducing immunologic host reactions which lead to a less effective response to species of Sac-Lp.
The reason for weight loss at high altitudes is largely unknown. To date, studies have been unable to differentiate between weight loss due to hypobaric hypoxia and that related to increased physical ...exercise. The aim of our study was to examine the effect of hypobaric hypoxia on body weight at high altitude in obese subjects. We investigated 20 male obese subjects (age 55.7 ± 4.1 years, BMI 33.7 ± 1.0 kg/m2). Body weight, waist circumference, basal metabolic rate (BMR), nutrition protocols, and objective activity parameters as well as metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at the end of a 1-week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after returning to LA (D42). Although daily pace counting remained stable at high altitude, at D14 and D42, participants weighed significantly less and had higher BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased significantly at high altitude despite the reduction in body weight. Diastolic blood pressure was significantly lower at D7, D14, and D42 compared to D1. This study shows that obese subjects lose weight at high altitudes. This may be due to a higher metabolic rate and reduced food intake. Interestingly, leptin levels rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to play a major role, although the physiological mechanisms remain unclear. Weight loss at high altitudes was associated with clinically relevant improvements in diastolic blood pressure.
The extend of lung disease remains the most important prognostic factor for survival in patients with cystic fibrosis (CF), and lack of adherence is the main reason for treatment failure. Early ...detection of deterioration in lung function and optimising adherence are therefore crucial in CF care. We implement a randomized controlled trial to evaluate efficacy of telemonitoring of adherence, lung function, and health condition in combination with behavior change interventions using innovative digital technologies.
This is a multi-centre, randomized, controlled, non-blinded trial aiming to include 402 patients ≥ 12 years-of-age with CF. A standard-of-care arm is compared to an arm receiving objective, continuous monitoring of adherence to inhalation therapies, weekly home spirometry using electronic devices with data transmission to patients and caring physicians combined with video-conferencing, a self-management app and professional telephone coaching. The duration of the intervention phase is 18 months. The primary endpoint is time to the first protocol-defined pulmonary exacerbation. Secondary outcome measures include number of and time between pulmonary exacerbations, adherence to inhalation therapy, changes in forced expiratory volume in 1 s from baseline, number of hospital admissions, and changes in health-related quality of life. CF-associated medical treatment and care, and health care related costs will be assessed by explorative analysis in both arms.
This study offers the opportunity to evaluate the effect of adherence interventions using telemedicine capable devices on adherence and lung health, possibly paving the way for implementation of telemedicine in routine care for patients with CF.
This study has been registered with the German Clinical Trials Register (Identifier: DRKS00024642, date of registration 01 Mar 2021, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00024642 ).
High-altitude (HA) exposure affects cognitive functions, but studies have found inconsistent results. The aim of this systematic review was to evaluate the effects of HA exposure on cognitive ...functions in healthy subjects. A structural overview of the applied neuropsychological tests was provided with a classification of superordinate cognitive domains. A literature search was performed using PubMed up to October 2021 according to PRISMA guidelines. Eligibility criteria included a healthy human cohort exposed to altitude in the field (at minimum 2440 m 8000 ft) or in a hypoxic environment in a laboratory, and an assessment of cognitive domains. The literature search identified 52 studies (29 of these were field studies; altitude range: 2440 m-8848 m 8000-29,029 ft). Researchers applied 112 different neuropsychological tests. Attentional capacity, concentration, and executive functions were the most frequently studied. In the laboratory, the ratio of altitude-induced impairments (64.7%) was twice as high compared to results showing no change or improved results (35.3%), but altitudes studied were similar in the chamber compared to field studies. In the field, the opposite results were found (66.4 % no change or improvements, 33.6% impairments). Since better acclimatization can be assumed in the field studies, the findings support the hypothesis that sufficient acclimatization has beneficial effects on cognitive functions at HA. However, it also becomes apparent that research in this area would benefit most if a consensus could be reached on a standardized framework of freely available neurocognitive tests.
Purpose
Residual renal function (RRF) contributes to dialysis adequacy, quality of life and survival of hemodialysis patients. There is an ongoing debate whether better preservation of residual renal ...function is the result of chronic fluid volume overload. Our prospective investigation analyzed the effects of different dialytic therapies on RRF and left ventricular hypertrophy, which may be considered—at least in part—a surrogate marker of chronic fluid overload.
Methods
Two cohorts of end-stage renal disease patients initiating renal replacement therapy (high efficiency post-dilution on-line hemodiafiltration (HDF) in 58 patients, conventional hemodialysis (HD) in 60 patients) were prospectively followed up. RRF was determined at baseline, 12 and 24 months, left ventricular mass index (LVMI) at baseline and after 24 months.
Results
Demographic and renal characteristics, medication or exposure to nephrotoxins were comparable among the two cohorts of patients. RRF declined in all patients throughout the 2-year study period. In HDF patients, the decline was less pronounced (28 %) than in conventional HD patients (68 %). More patients undergoing HD received cardio- and renoprotective antihypertensive drugs. CRP levels were significantly higher in conventional HD. Hypotensive episodes were fewer in HDF. LVMI decreased in 90 % of HDF compared to only 25 %of HD patients.
Conclusions
Our data clearly indicate that better preservation of RRF by high efficiency hemodiafiltration is not associated with left ventricular hypertrophy.
Chronic obstructive pulmonary disease (COPD) is one of the most important causes of morbidity and mortality in the world. The disease is often aggravated by periods of increased symptoms requiring ...medical attention. Among the possible triggers for these exacerbations, meteorological factors are under consideration. The objective of this study was to assess the influence of various meteorological factors on the health status of patients with COPD. For this purpose, the daily number of ambulatory care visits due to COPD was analysed in Bavaria, Germany, for the years 2006 and 2007. The meteorological factors were provided by the model at the European Centre for Medium Range Weather Forecast (ECMWF). For the multivariate analysis, a generalised linear model was used. In Bavaria, an increase of 1% of daily consultations (about 103 visits per day) was found to be associated with a change of 0.72 K temperature, 209.55 of log air surface pressure in Pa, and a decrease of 1% of daily consultations with 1,453,763 Ws m2 of solar radiation. There also seem to be regional differences between north and south Bavaria; for instance, the effect of wind speed and specific humidity with a lag of 1 day were only significant in the north. This study could contribute to a tool for the prevention of exacerbations. It also serves as a model for the further evaluation of the impact of meteorological factors on health, and could easily be applied to other diseases or other regions.
Respiratory drugs are widely used in children to treat labeled and non-labeled indications but only some data are available quantifying comprehensively off-label usage. Thus, we aim to analyse drug ...utilisation and off-label prescribing of respiratory drugs focusing on age- and indication-related off-label use. Patients aged ≤18 years documented in the Bavarian Association of Statutory Health Insurance Physicians database (approx. 2 million children) between 2004 and 2008 were included in our study. Annual period prevalence rates (PPRs) per 10,000 children and the proportion of age- and indication-related off-label prescriptions were calculated and stratified by age and gender. Within the study period, highest PPRs were found for the fixed combination of clenbuterol/ambroxol (between 374-575 per 10,000 children) and the inhaled short acting beta-2-agonist salbutamol (between 378-527 per 10,000 children). Highest relative PPR increase was found for oral salbutamol (approx. 39-fold) whereas the most distinct decrease was found for oral long-acting beta-2-agonist clenbuterol (-97%). Compound classes most frequently involved in off-label prescribing were inhaled bronchodilative compounds (91,402; 37.3%) and oral beta-2-agonists (26,850; 22.5%). The highest absolute number of off-label prescriptions were found for inhaled salbutamol (n = 67,084; 42.0%) and oral clenbuterol/ambroxol (fixed combination, n = 18,897; 20.7%). Off-label prescribing due to indication was of much greater relevance than age-related off-label use. Most frequently, bronchodilative compounds were used off-label to treat respiratory tract infections. Highest off-label prescription rates were found in the youngest patients without relevant gender-related differences. Off-label prescribing of respiratory drugs is common especially in young children. Bronchodilative drugs were most frequently used off-label for treating acute bronchitis or upper respiratory tract infections underlining the essential need for a more rational prescribing in this area.
Acute mountain sickness (AMS) is characterized by headache often accompanied by gastrointestinal complaints that vary from anorexia through nausea to vomiting. The aim of this study was to ...investigate the influence of high altitude on plasma levels of gastroenteropancreatic (GEP) peptides and their association to AMS symptoms. Plasma levels of 6 GEP peptides were measured by radioimmunoassay in 11 subjects at 490 m (Munich, Germany) and, after rapid passive ascent to 3454 m (Jungfraujoch, Switzerland), over the course of three days. In a second study (n = 5), the same peptides and ghrelin were measured in subjects who consumed standardized liquid meals at these two elevations. AMS symptoms and oxygen saturation were monitored. In the first study, both fasting (morning 8 a.m.) and stimulated (evening 8 p.m.) plasma levels of pancreatic polypeptide (PP) and cholecystokinin (CCK) were significantly lower at high altitude as compared to baseline, whereas gastrin and motilin concentrations were significantly increased. Fasting plasma neurotensin was significantly enhanced whereas stimulated levels were reduced. Both fasting and stimulated plasma motilin levels correlated with gastrointestinal symptom severity (r = 0.294, p = 0.05, and r = 0.41, p = 0.006, respectively). Mean O(2)-saturation dropped from 96% to 88% at high altitude. In the second study, meal-stimulated integrated (= area under curve) plasma CCK, PP, and neurotensin values were significantly suppressed at high altitude, whereas integrated levels of gastrin were increased and integrated VIP and ghrelin levels were unchanged. In summary, our data show that acute exposure to a hypobaric hypoxic environment causes significant changes in fasting and stimulated plasma levels of GEP peptides over consecutive days and after a standardized meal. The changes of peptide levels were not uniform. Based on the inhibition of PP and neurotensin release a reduction of the cholinergic tone can be postulated.
We studied HLA class II molecules on blood monocyte subsets, blood dendritic cells, sputum macrophages, and monocyte-derived macrophages at the protein (flow cytometry) and mRNA level (RT-PCR) in ...adult patients with cystic fibrosis (CF) and healthy control subjects as putative contributors to the CF phenotype. In healthy donors, we found a high average HLA-DQ expression of 4.35 mean specific fluorescence intensity units (ΔMnI) on classical blood monocytes. In F508del homozygous CF patients, the average ΔMnI was low (1.80). Patients were divided into two groups, in which 14 of these patients had HLA-DQ expression above 2 ΔMnI (average 3.25 ΔMnI, CF-DQ
group1
) and 36 below (average 1.24 ΔMnI, CF-DQ
group2
). Also, the CD16-positive monocyte subset and blood dendritic cells showed much lower levels of HLA-DQ for the CF-DQ
group2
patients compared with healthy controls. In macrophages from sputum and derived from monocytes, in vitro HLA-DQ expression was dramatically decreased to background levels in CF-DQ
group2
. MHC class II transcripts were reduced in CF with a sevenfold decrease in HLA-DQβ1 for CF-DQ
group2
patients. Higher levels of the inflammation marker CRP were associated with low HLA-DQ protein expression, and in vitro treatment with the inflammatory molecule lipopolysaccharide reduced HLA-DQ expression. Interferon γ (IFNγ) could overcome this effect in healthy donor cells while, in CF, the IFNγ-induced activation was impaired. Our data demonstrate a pronounced reduction of HLA-DQ expression in CF, which is associated with inflammation and a reduced response to IFNγ.
Key message
• CF patients show a reduced expression of MHCII molecules in monocytes and macrophages.
• HLA-DQ and HLA-DR transcript levels are also reduced in CF patients.
• CF patient C-reactive protein levels correlate with low HLA-DQ expression.
• Reduced expression of MHC class II molecules appears to be linked to inflammation.
• CF patients exhibit an impaired response to IFNgamma.
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