Multidrug-resistant tuberculosis patients' views of interventions to reduce treatment loss to follow-up.

SETTING: Patients who initiated treatment for multidrug-resistant tuberculosis (MDR-TB) at 15 Programmatic Management of Drug-resistant Tuberculosis (PMDT) health facilities in the Philippines between July and December 2012. OBJECTIVES: To describe patients' views of current interventions, and suggest changes likely to reduce MDR-TB loss to follow-up. METHODS: In-depth interviews were conducted between April and July 2014 with MDR-TB patients who were undergoing treatment, had finished treatment at the time of the interview (controls), or had been lost to follow-up (LTFU). Responses were thematically analyzed. RESULTS: Interviews were conducted with 182 patients who were undergoing or had completed treatment and 91 LTFU patients. Views and suggestions could be thematically categorized as approaches to facilitate adherence or address barriers to adherence. The top themes were the need for transportation assistance or improvements to the current transportation assistance program, food assistance, and difficulties patients encountered related to their medications. These themes were addressed by respectively 63%, 60%, and 32% of the participants. CONCLUSIONS: A more patient-centered approach is needed to improve MDR-TB treatment adherence. Programs should strive to provide assistance that considers patient preferences, is adequate to cover actual costs or needs, and is delivered in a timely, uninterrupted manner.

A Validated Tropical-Extratropical Flood Hazard Assessment for New York Harbor.

Recent studies of flood risk at New York Harbor (NYH) have shown disparate results for the 100-year storm tide, providing an uncertain foundation for the flood mitigation response after Hurricane Sandy. Here, we present a flood hazard assessment that improves confidence in our understanding of the region's present-day potential for flooding, by separately including the contribution of tropical cyclones (TCs) and extratropical cyclones (ETCs), and validating our modeling study at multiple stages against historical observations. The TC assessment is based on a climatology of 606 synthetic storms developed from a statistical-stochastic model of North Atlantic TCs. The ETC assessment is based on simulations of historical storms with many random tide scenarios. Synthetic TC landfall rates and the final TC and ETC flood exceedance curves are all shown to be consistent with curves computed using historical data, within 95% confidence ranges. Combining the ETC and TC results together, the 100-year return period storm tide at NYH is 2.70 m (2.51-2.92 at 95% confidence), and Hurricane Sandy's storm tide of 3.38 m was a 260-year (170-420) storm tide. Deeper analyses of historical flood reports from estimated Category-3 hurricanes in 1788 and 1821 lead to new estimates and reduced uncertainties for their floods, and show that Sandy's storm tide was the largest at NYH back to at least 1700. The flood exceedance curves for ETCs and TCs have sharply different slopes due to their differing meteorology and frequency, warranting separate treatment in hazard assessments.

[Drug safety: challenge in an aging society]. / Arzneimittelsicherheit : Herausforderung in einer alternden Gesellschaft.

BACKGROUND: Within the context of the demographic change the proportion of the elderly in the overall population is steadily increasing. At the same time elderly patients are prescribed a disproportionately high number of medicines in comparison to younger patients. In the light of multimorbidity and polypharmacy which affect a relevant portion of the older population, drug safety is of particular importance. RESULTS AND DISCUSSION: In recent years, the prescription of psychiatric drugs to elderly patients was repeatedly subjected to regulatory assessment and recommendations, for example the safety of antipsychotics in patients with dementia. As only limited information is often available with respect to the risks of medicines in the elderly population, additional efforts are necessary for improvement of the database. In this context, the system of spontaneous reporting, e.g. the reporting of cases of suspected adverse drug reactions to the responsible authorities, plays an important role with respect to the additional knowledge to be gathered. By reporting observed adverse drug reactions as well as by the quality of the reported information, physicians are able to significantly influence the effectiveness of this system in a positive way. OUTLOOK: As medical care for the majority of the elderly population is provided by general practitioners, adequate longitudinal studies are of special interest for investigating drug safety in the elderly. This aim is being pursued by the AgeCoDe study (German study on aging, cognition and dementia in primary care patients), a prospective, multicentre observational study, which is being carried out within the German competence network of degenerative dementia (Kompetenznetz Degenerative Demenzen).

Moderate physical exercise: a simplified approach for ventricular rate control in older patients with atrial fibrillation.

AIMS: This prospective pilot-study was performed to assess whether regular moderate physical activity elevates the parasympathetic tone to the atrio-ventricular node and decreases VR during permanent AF. BACKGROUND: Adequate ventricular rate (VR) control in patients with permanent atrial fibrillation (AF) is not easy to accomplish. METHODS: 10 patients (mean age 59 +/- 10 years) with permanent AF (duration: 10 +/- 8 years) underwent moderate physical exercise adjusted to their individual physical capability (45 min walking/jogging twice a week). To analyze VR control physical exercise tests and Holter-ECG recordings were performed before and after 4 months. In addition, stepwise lactate tests and psycho-pathometric examinations were obtained. RESULTS: After 4 months of training, there was a trend toward a decrease of mean VR in 24 h Holter-ECGs by 12% from 76 +/- 20 to 67 +/- 12 bpm (P = 0.05) while there was no significant decrease of the minimal VR (38 +/- 8 vs. 36.3 +/- 4.5 bpm, P = 0.54). At a lactate threshold of 2 mmol/l there was a trend towards an increase of the running speed from 105 +/- 11 to 116 +/- 12 m/min (P = 0.05). A significant VR decrease of 8% (range 5-10%) was observed at almost all exercise levels during exercise treadmill testing. Increases of exercise capacity and decreases of VR were accompanied by subjective improvements of health perception. CONCLUSION: Regular moderate physical activity decreases VR at rest and during exercise while increasing exercise capacity. Physical training should be taken into account for ventricular rate control during AF.

The influence of hypoalbuminemia on maximal flow rates and transmembrane pressure during plasmapheresis--an in vitro study.

BACKGROUND: Plasmapheresis has been used for the treatment of acute liver failure (ALF). In these patients, hypoalbuminemia is often observed. Since albumin improves the disaggregability of erythrocytes, hypoalbuminemia might deteriorate rheology and thus influence the overall performance of plasmapheresis. METHODS: Hypoalbuminemia was mimicked by using porcine blood because of its physiologically low albumin/globulin ratio (AGR). Filters (n = 16) were integrated in a closed extracorporeal in vitro system. In the control group (n = 8), native porcine blood (AGR 0.8) was used. In the study group (n = 8), we used porcine blood supplemented with human albumin to obtain the human AGR value of 1.2. Two different heparinization protocols were compared in each group (2.5 IU/ml: n = 4 with albumin and n = 4 without albumin versus 5 IU/ml: n = 4 with and n = 4 without albumin). RESULTS: In both heparinization protocols the higher AGR led to lower transmembrane pressure (TMP) levels compared to the lower AGR. The reduced TMPs enabled higher blood flow and filtration rates. CONCLUSION: Maintenance of a physiological AGR in ALF patients might improve the performance of plasmapheresis and--as opposed to raised heparinization--contribute to a safer application.

Assessment of renal function in renal transplant patients using cystatin C. A comparison to other renal function markers and estimates.

To date, little evidence is available to define the role of cystatin C in patients with renal transplants. Thus, to assess, whether cystatin C (CysC) provides better information on renal function than other markers, CysC, creatinine clearance (CrCl), serum creatinine (SCr), beta2-microglobulin (beta2-M), and 125I-Iothalamate clearance were determined in 30 patients. Correlation and ROC curves were obtained and characteristics like sensitivity and specificity were calculated. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation for CysC and SCr measurements were compared in 85 renal transplant patients. CysC correlated best with GFR, whereas SCr, CrCl and beta2-M all had lower correlation coefficients. CysC was superior to SCr, even when renal function equations of were used. The diagnostic accuracy of CysC was significantly better than SCr. but did not differ significantly from CrCl and beta2-M. Together, our data show that in patients with renal transplants, CysC has a similar diagnostic value as CrCl. However, it is superior to determinations of SCr. The intraindividual variation of CysC is significantly greater than that of SCr. This might be due to better ability of CysC to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. In conclusion, CysC allows for easy and accurate assessment of renal function (GFR) in steady state renal transplant patients and is clearly superior to the commonly used serum creatinine.

Rapid and accurate assessment of glomerular filtration rate in patients with renal transplants using serum cystatin C.

BACKGROUND: Assessment of renal function in patients with renal transplants is of great importance. Various studies have reported cystatin C as an easily and rapidly assessable marker that can be used for accurate information on renal function impairment. To date, no study is available to define the role of cystatin C in patients with renal transplants. METHODS: Thirty steady-state patients (50% male/50% female) with status post-kidney transplantation were studied. To assess renal function, cystatin C, creatinine clearance, serum creatinine, beta2-microglobulin (beta2M), and [125I]iothalamate clearance were determined. Correlations and non-parametric ROC curves for accuracy, using a cut-off glomerular filtration rate (GFR) of 60 ml/min, were obtained for the different markers allowing for calculations of positive predictive values (PPV), positive likelihood ratios (PLR), specificity and sensitivity, respectively. Further, to evaluate the usefulness of these markers for monitoring, intraindividual coefficients of variation (CVs) for cystatin C and creatinine measurements were compared in 85 renal transplant patients. Measurements consisted of at least six pairs of results, which were obtained at different time points during routine follow-up. RESULTS: Cystatin C correlated best with GFR (r=0.83), whereas serum creatinine (r=0.67), creatinine clearance (r=0.57) and beta2M (r=0.58) all had lower correlation coefficients. The diagnostic accuracy of cystatin C was significantly better than serum creatinine (P=0.025), but did not differ significantly from creatinine clearance (P=0.76) and beta2M (P=0.43). At a cut-off of 1.64 mg/l, cystatin C has a PPV of 93%, PLR of 6.4, specificity 89% and sensitivity 70%, respectively. For beta2M, PPV 83%, PLR 1.7, specificity 67% and sensitivity 75% was seen at a cut-off of 3.57 mg/l. Accordingly, at a cut-off of 125 micromol/l for serum creatinine, a PPV 76%, PLR 1.4, specificity 44% and sensitivity 80% was revealed. Finally, at a cut-off of 66 ml/min/1.73 m2 for creatinine clearance, the following characteristics were found: PPV 94%, PLR 7.7, specificity 89% and sensitivity 85%. The intraindividual variation of creatinine was significantly lower than that of cystatin C (P<0.001). With increasing concentrations, their ratios of CV tended towards a value of 1, demonstrating identical variability at low GFR. CONCLUSION: Together, our data show that in patients with renal transplants, cystatin C, in terms of PPV and PLR, has a similar diagnostic value as creatinine clearance. However, it is superior to serum determinations of creatinine and beta2M. The intraindividual variation of cystatin C is greater than that of creatinine. This might be due to the better ability of cystatin C to reflect temporary changes especially in mildly impaired GFR, most critical for early detection of rejection and other function impairment. Thus, cystatin C allows for rapid and accurate assessment of renal function (GFR) in renal transplants and is clearly superior to the commonly used serum creatinine.

[Febrile convulsions: assessment of current status]. / Fieberkrämpfe: eine Standortbestimmung.

Febrile seizures are the most frequent neurologic disorders during childhood. The pathogenesis is not clear even today. Viral infections of the upper airways, exanthema subitum, acute otitis media, infection of the urinary tract and febrile reactions after vaccination are the most frequent precipitating factors. Predictors in identifying children with very high risk of recurrence are young age at onset, family history of febrile seizures in a first-degree relative, a history of recurrent febrile seizures and a lower degree of fever at the onset of febrile seizures. A family history of epilepsy, neurodevelopmental abnormalities and a lower degree of fever at the onset of febrile convulsion are predictors of later epilepsy in children who have febrile seizures. The prognosis of febrile seizures is very good. In the acute situation, rectal diazepam should be given in the event of prolonged febrile seizures (> 3 minutes) only. Intermittent diazepam therapy and long-term antiepileptics are not recommended. The best prophylactic treatment is education and reassurance for parents and children.

Surgical treatment of "steal syndrome" induced by arteriovenous grafts for hemodialysis.

OBJECTIVE: A rare but serious complication of angioaccess surgery for hemodialysis is the so called steal syndrome presenting as ischemia distal to an arteriovenous fistula. The main problem of various surgical techniques to correct steal is subsequent thrombosis of the fistula or persistence of distal ischemia. INTERVENTIONS: This paper describes an unknown technique for correction of ischemic steal consisting of ligation of the artery just distal to the take-off of the fistula and arterial bypass from the artery proximal to the take-off of the fistula to the artery distal to ligation. PATIENTS: Six patients with chronic renal insufficiency (3 male, 3 female) with patent upper arm cephalic fistulas presented with severe hand ischemia. RESULTS: Symptoms improved in all 6 patients immediately after operation. Successful hemodialysis could be maintained using the original fistula. CONCLUSIONS: The described technique is maybe the procedure of choice for the correction of fistula induced ischemic steal.

Symmetric and asymmetric left ventricular hypertrophy in patients with end-stage renal failure on long-term hemodialysis.

BACKGROUND: Patients with end-stage renal disease on regular hemodialysis have an increased prevalence of left ventricular (LV) hypertrophy that is associated with morbidity and mortality. Asymmetric septal hypertrophy and impairment of LV outflow can occur in these patients and may contribute to adverse outcomes. More insight into the prevalence, extent, geometry, and promoting factors of LV hypertrophy is important. METHODS: An unselected group of 62 patients (31 women), aged 55 +/- 14 years, on maintenance hemodialysis was investigated by Doppler echocardiography. Eight patients with valvular heart disease were excluded from further analysis. We assessed prevalence of LV hypertrophy and asymmetric septal hypertrophy, as well as parameters of LV geometry and LV filling and outflow dynamics. RESULTS: Prevalence of LV hypertrophy was 65%. Patients were analyzed according to LV mass and geometry. Mean LV mass index was normal (105 +/- 17 g/m2) in Group 1 without LV hypertrophy (n = 19); it was markedly elevated in Group 2 (symmetric hypertrophy, n = 22) and Group 3 (asymmetric hypertrophy with systolic anterior movement of mitral valve, n = 7), and highest (191 +/- 54 g/m2) in Group 4 (asymmetric hypertrophy without systolic anterior movement of mitral valve, n = 6, p < 0.001). Age, body mass index, and duration of hypertension were associated with LV hypertrophy and asymmetric septal hypertrophy (p = 0.01). Group 3 with systolic anterior motion of mitral valve had the smallest end-diastolic LV diameters (p = 0.02); increased heart rates, and increased ejection velocities in the LV outflow tract (p = 0.03, and p = 0.005, respectively, vs. Groups 1, 2, and 4) which pointed to an impairment of LV outflow. CONCLUSIONS: Symmetric LV hypertrophy and asymmetric septal hypertrophy are frequent in patients on maintenance hemodialysis. Predictors for LV hypertrophy were age and body mass index, and, particularly for asymmetric septal hypertrophy, age and hypertension duration. Volume withdrawal during hemodialysis may lead to symptomatic hypotension due to dynamic obstruction in some patients with severe asymmetric septal hypertrophy.

Plasma potassium in patients with terminal renal failure during and after haemodialysis; relationship with dialytic potassium removal and total body potassium.

BACKGROUND: Chronic haemodialysis (HD) patients may present with severe predialysis hyperkalaemia which is improved by dialytic treatment. However, factors influencing the behaviour of postdialysis plasma potassium (plasma K) are not well known. METHODS: In this prospective study 14 patients (7 female, 7 male) on chronic HD were investigated during a standardized 4-h HD with a 2 m2 high-flux dialyser and up to 6 h postdialysis. Dialytic potassium removal was measured by dialysate collection. Total body potassium (TBK) was measured by whole-body counting of 40K. RESULTS: Plasma K declined from 5.65 to 3.62 mmol/l on HD. In spite of a total dialytic removal of 107 mmol of potassium plasma K rose to 5.01 mmol/16 h postdialysis. TBK, as adjusted for age, was 38.2 and 49.0 mmol/kg BW in female and male patients respectively, i.e. in the normal range. Of a total potassium removal of 107 mmol on HD only 42% originated from the extracellular space. Dialytic potassium removal was best correlated with removal of intracellular potassium but also with extracellular potassium content and with the product of plasma K x TBK. The 6-h postdialysis plasma K was correlated with the predialysis value but not with TBK or dialytic potassium removal. CONCLUSION: A rather high dialytic removal of potassium (which is correlated with plasma K x TBK) does not necessarily prevent a rapid postdialysis rebound of plasma K. Therefore patients with marked hyperkalaemia should be monitored closely postdialysis. TBK can be normal in haemodialysis patients who are well nourished.

[Chronic hepatitis B infection and liver failure following kidney transplantation]. / Chronische HBV-Infektion und Leberversagen nach Nierentransplantation.

Chronic liver diseases, especially due to chronic hepatitis B virus infection, are among the leading causes of late mortality in renal transplant recipients. We report on 4 HBsAg-positive patients observed over a period of 8 years, who were free of symptomatic liver disease for 7-19 years after renal transplantation and died within a few days of acute hepatic failure. The cases presented document the prognostic relevance of chronic hepatitis B virus infection in renal transplant recipients and illustrate that an asymptomatic HBsAg carrier state can evolve within a very short time to fatal liver disease.

Prevention of hepatitis C infection in haemodialysis units. A prospective study.

A prospective study was begun in our haemodialysis unit after four previously negative patients were found to be anti-HCV positive. A dedicated area and dedicated dialysis equipment (but not a separate room) were assigned to anti-HCV-positive patients and testing for HCV antibodies was performed every 3 months. A total of 131 patients were treated during the study period of 18 months. Of these, 50 patients were dialysed during the entire 18 months, and 21 were available to be tested six or more months after having left the centre. During the first 6 weeks after implementing the precautions two more anti-HCV-positive patients were detected. However, during the rest of the study period no further newly infected patients were found. It is concluded that the spread of HCV infection in a haemodialysis environment can be prevented by limited isolation procedures.

Influence of dialyser clearance measurement accuracy on haemodialysis prescription based on Kt/V.

Kt/V urea (u) has been used as a measure of adequacy of haemodialysis (HD). However, the accurate assessment of its components is difficult and subject to error in a clinical setting. This study was designed to evaluate different forms of dialyser clearance (K) measurements and their influence on Kt/V. Sixteen patients on high-flux HD were studied at blood flow (Qb) rates of 250 and 350 ml/min and at constant dialysate flow rates. K of urea was measured by the arteriovenous blood sampling technique (Kbu), corrected for access recirculation (Kbru) and compared with K as determined by dialysate collection (Kdu) using a new sampling device. At Qb 250 and 350 ml/min, Kbu as based on dialysate collection was significantly lower than Kbru and Kbu as based on arteriovenous blood sampling: at Qb 250, Kdu 169.0 +/- 13.3, Kbru 191.2 +/- 11.5, and Kbu 203.0 +/- 9.3 ml/min (P < 0.0005); at Qb 350, Kdu 196.5 +/- 17.3, Kbru 227.7 +/- 15.5, and Kbu 243.6 +/- 12.7 ml/min (P < 0.0005). At Qb 250 ml/min Kbu t/V (1.33 +/- 0.17) overestimated Kdu t/V (1.11 +/- 0.13) by 16:8%, at Qb 350 ml/min by 19.3% (1.58 +/- 0.19 versus 1.27 +/- 0.15). Dialyser clearances based on arteriovenous differences in blood overestimate true clearances (and therefore Kt/V) as measured by dialysate collection. This overestimation is more marked with higher blood flow rates.

Dexamethasone therapy for bacterial meningitis in children. Swiss Meningitis Study Group.

Routine use of steroids as adjunctive treatment of bacterial meningitis remains controversial. We have carried out a prospective, placebo-controlled, double-blind study of dexamethasone in 115 children with acute bacterial meningitis in Switzerland. The patients were randomly assigned to receive either placebo (n = 55) or dexamethasone (n = 60) in addition to optimum antibiotic treatment (100 mg/kg daily ceftriaxone). Dexamethasone therapy (0.4 mg/kg) was started 10 min before the first dose of ceftriaxone and given every 12 h for 2 days. Baseline demographic, clinical, and laboratory features of the two groups were similar. After 24 h treatment meningeal inflammation as shown by cerebrospinal fluid (CSF) glucose concentration was significantly less with dexamethasone than with placebo (mean increase in glucose 63 [76] vs 40 [75]%, p = 0.008). However, other indices of inflammation showed similar changes in both groups. Addition of dexamethasone did not affect the rate at which CSF became sterile. Both groups showed prompt clinical responses and similar frequencies of complications (15 vs 12%). Monitoring for possible adverse effects of dexamethasone revealed no abnormalities. At follow-up examinations 3, 9, and 15 months after hospital discharge, 9 (16%) of 55 placebo recipients and 3 (5%) of 60 dexamethasone recipients had one or more neurological or audiological sequelae (p = 0.066); the relative risk of sequelae was 3.27 (95% CI 0.93-11.47). Our results and those of similarly designed studies lead us to believe that adjunctive dexamethasone therapy improves outcome from bacterial meningitis in infants and children. We recommend its use, preferably in the dose regimen used in this study.

Immune-mediated type A gastritis and glomerulonephritis.

The first two cases reported in the literature of patients with immune-mediated type A gastritis with microcarcinoids (as part of a polyglandular syndrome type II in one) in combination with chronic glomerulonephritis are presented. Immune-mediated type A gastritis appears to be another immunologic disorder that can be associated with chronic glomerulonephritis.

Aortic and mitral valve disease in patients with end stage renal failure on long-term haemodialysis.

OBJECTIVE: To identify valvar heart disease in patients with chronic uraemia by conventional and colour coded Doppler echocardiography. DESIGN: Case series of an unselected group of 62 patients with end stage renal failure. SETTING: Centre for haemodialysis in a referral hospital in Switzerland. PATIENTS: 62 patients on chronic haemodialysis. MAIN OUTCOME MEASURES: Frequency of structural and functional valve abnormalities and their relation to clinical findings. RESULTS: Structural changes were seen in 40 (64%) of 62 patients after 50 months (range 3-178 months) on haemodialysis. The mitral annulus and aortic cusps were thickened in 25 (40%) and in 34 (55%) patients respectively. Aortic stenosis was present in eight (mean (SD) age 60.5 (8.5) years), with a maximal instantaneous pressure gradient of 41 (14) mm Hg. Aortic regurgitation was seen in eight, mitral regurgitation in seven, and mitral stenosis in three patients. Patients with aortic stenosis had been on haemodialysis for significantly longer than the remaining patients (101 (43) v 46 (43) months, p = 0.01) and had significantly higher concentrations of serum alkaline phosphatase (176 (89) v 117 (47) IU/l, p less than 0.01) and of parathyroid hormone (54 (66) v 19 (29) ng/ml, p less than 0.02). CONCLUSIONS: Patients on long-term haemodialysis had an increased frequency of haemodynamically relevant changes in the aortic and mitral valves. The degenerative valve disease may be related in part to the duration of haemodialysis and to alterations in calcium metabolism as indicated by increased plasma concentrations of alkaline phosphatase and parathyroid hormone.