Maruschka P. Merkus

Predictors of poor outcome in chronic dialysis patients: The Netherlands cooperative study on the adequacy of dialysis

In a prospective cohort study, we constructed a composite index of poor outcome that incorporates survival, morbidity, and quality of life (QL). We identified baseline patient and treatment characteristics that predicted poor outcome 1 year after the start of chronic dialysis. Outcome was classified as poor if a patient had died or if at least two of the following criteria were present: (1) 30 days or greater of hospitalization per year, (2) serum albumin level of 30 g/L or less or a malnutrition index score of 11 or greater, (3) a 36-item Medical Outcomes Study (MOS)-Short Form Health Survey Questionnaire (SF-36) physical summary QL score of 2 or more SDs less than the general population mean score, and (4) an SF-36 mental summary QL score of 2 or more SDs less than the general population mean score. Multivariate logistic regression analysis was used to identify independent predictors of poor outcome. Of 250 included patients, 189 were assessable with respect to poor outcome. Of these patients, 47 (25%) were classified as poor. A baseline presence of comorbidity, serum albumin level of 30 g/L or less, physical or mental QL score 2 or more SDs less than the general population mean score, and, to a lesser extent, residual glomerular filtration rate of 2.5 mL/min/1.73 m(2) or less were independently associated with a greater risk for poor outcome. A post hoc analysis indicated a mean arterial blood pressure greater than 107 mm Hg was predictive of poor outcome in patients undergoing peritoneal dialysis. In conclusion, our prognostic model provides a useful tool to identify chronic dialysis patients at risk for poor health status. Strategies aimed at preserving residual renal function, controlling blood pressure, monitoring QL, and consequently giving psychosocial support may reduce the risk for poor outcome.

Prognostic factors for the progression of Parkinson's disease: a systematic review.

The purpose of this systematic review is to summarize studies that describe the course of Parkinsons disease (PD) and to identify factors that predict change in motor impairment, disability, and quality of life. A literature search was conducted in MEDLINE, EMBASE, CINAHL, and Web of Science limited to the English, French, German, Spanish, and Dutch language. Reports were selected if the study involved subjects with PD, the outcome measures described impairment, disability, or quality of life and follow‐up was at least 6 months. All included studies were scored for methodological quality. Data were extracted and summarized in a best evidence synthesis. We screened 1,535 titles and abstracts, of which 27 fulfilled our inclusion criteria. A meta‐analysis to quantitatively aggregate progression scores of motor impairment and disability was not possible because of the wide variety of outcome measures used and the heterogeneous study populations. Limited evidence is found for lower UPDRS‐ME at baseline, dementia and SE < 70% as prognostic factors for future motor impairment. There is strong evidence for higher age at onset and higher PIGD‐score; and limited evidence for higher bradykinesia‐score, non‐tremor dominant subtype, symmetrical disease at baseline, and depression as prognostic factors for progression of disability. Prognostic factors were identified for impairment and disability. The literature on prognosis in PD is not fulfilling the high methodological standards applied nowadays. There is a need for prospective cohorts of PD patients assembled at a common early point in the disease with long time follow‐up.

Validation of the KDQOL-SFTM: A dialysis-targeted health measure

Background: In evaluations of dialysis therapy, an assessment of health-related quality of life (HRQOL) is often important. The aim of this study was to determine the basic psychometric properties, reliability and validity of the short form of the KDQOLTM i.e. the KDQOL-SFTM, a dialysis-targeted instrument, and to assess its ability to detect changes over time. Methods: In a prospective cohort study (Netherlands Cooperative Study on the Adequacy of Dialysis, NECOSAD), all new adult ESRD patients in 32 different Dutch centers were consecutively enrolled. Demographic, clinical and HRQOL data were obtained 3 and 12 months after the start of chronic dialysis therapy. Results: The reliability of the KDQOL-SFTM was supported by test results that were above the recommended minimal values. Validity of KDQOL-SFTM was confirmed by the hypothesized positive correlations of the overall health rating and renal function, and by the negative correlations between the number of comorbidities and dialysis dose. Moreover, dialysis-targeted dimensions were more sensitive in detecting relevant differences pertaining to kidney diseases than generic dimensions. The KDQOL-SFTM was able to detect clinical changes over time. Conclusions: The psychometric properties of the KDQOL-SFTM were good, and the different dialysis-targeted dimensions were informative with a high reliability and validity. These results support the application of the KDQOL-SFTM in studies evaluating dialysis therapy.

Percutaneous endoscopic gastrostomy in patients with amyotrophic lateral sclerosis and impaired pulmonary function

Amyotrophic lateral sclerosis is a rapidly progressive disease of unknown etiology resulting in tetraparalysis, dysarthria, dysphagia, and ultimately death from respiratory insufficiency. In the course of the disease, recurrent episodes of aspiration, pneumonia, dehydration, and malnutrition may necessitate nasoenteral tube placement, an inconvenient and unattractive arrangement in patients with dribbling and impaired swallowing. A percutaneous endoscopic gastrostomy seemed a better, though potentially hazardous, alternative in view of the often severely restricted pulmonary function of these patients. Therefore, we prospectively investigated the use of percutaneous endoscopic gastrostomy in 68 consecutive patients with amyotrophic lateral sclerosis. Minimum required pulmonary function was defined as forced vital capacity (FVC) of 1 L or more and CO2 gas exchange capability as pCO2 of 45 mm Hg or less. The methodology of insertion was adapted to facilitate the early removal of gastric air. Fifty-five patients (median FVC, 1.7 L; pCO2, 40 mm Hg) were eligible for the gastrostomy procedure, and 13 patients (median FVC, 0.8 L; pCO2, 47 mm Hg) were not. Despite the fact that modification of the method of insertion rendered the procedure more difficult, the success rate was 89% (49/55); it was 96% (49/51) when failures related to distorted anatomy were excluded. The procedure-related mortality rate was 1.8% and the 24-hour in-hospital mortality rate was 3.6%, mainly related to respiratory insufficiency. The 30-day out-of-hospital mortality rate was 11.5%. Major complications (3.6%) consisted of a spontaneously draining cutaneous abscess in 2 cases. Peristomal redness was present in 6 cases, and 5 patients required analgesics for wound pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Unified Parkinson's disease rating scale motor examination: are ratings of nurses, residents in neurology, and movement disorders specialists interchangeable?

The Unified Parkinsons Disease Rating Scale (UPDRS) is widely used for the clinical evaluation of Parkinsons disease (PD). We assessed the rater variability of the UPDRS Motor examination (UPDRS‐ME) of nurse practitioners, residents in neurology, and a movement disorders specialist (MDS) compared to a senior MDS. We assessed the videotaped UPDRS‐ME of 50 PD patients. Inter‐rater and intra‐rater variability were estimated using weighted kappa (κw) and intraclass correlation coefficients (ICC). Additionally, inter‐rater agreement was quantified by calculation of the mean difference between 2 raters and its 95% limits of agreement. Intra‐rater agreement was also estimated by calculation of a 95% repeatability limits. The κw and ICC statistics indicated good to very good inter‐rater and intra‐rater reliability for the majority of individual UPDRS items and the sum score of the UPDRS‐ME in all raters. However, for inter‐rater agreement, it appeared that both nurses, residents, and the MDS consistently assigned higher scores than the senior MDS. Mean differences ranged between 1.7 and 5.4 (all differences P < 0.05), with rather wide 95% limits of agreement. The intra‐rater 95% repeatability limits were rather wide. We found considerable rater difference for the whole range of UPDRS‐ME scores between a senior MDS and nurse practitioners, residents in neurology, and the MDS. This finding suggests that the amount by which raters may disagree should be quantified before starting longitudinal studies of disease progression or clinical trials. Finally, evaluation of rater agreement should always include the assessment of the extent of bias between different raters.

Low mannose‐binding lectin (MBL) levels in neonates with pneumonia and sepsis

We investigated whether deficiency of mannose‐binding lectin (MBL), a component of innate immunity, is associated with neonatal pneumonia and sepsis during the first 72 h, i.e. early onset, and during the first month after birth. In 88 neonatal intensive care patients (71 premature), MBL2 genotype and MBL plasma levels at birth were determined prospectively by Taqman analysis and enzyme‐linked immunosorbent assay, respectively. Thirty‐five neonates (40%) had low, i.e. ≤ 0·7 µg/ml, MBL plasma levels at birth. Median (interquartile range) MBL plasma levels in 32 no early‐onset sepsis (EOS) cases, 44 possible EOS cases and 11 EOS cases were 1·57 (0·57–2·67) µg/ml, 1·05 (0·41–1·70) µg/ml and 0·20 (0·10–0·77) µg/ml, respectively (P < 0·01). During the first month, 28 neonates (32%) had no infection, 49 (55%) had suspected infection, five (6%) had pneumonia and six (7%) had culture‐proven sepsis. Low MBL levels at birth were associated both with an increased risk of developing pneumonia (OR: 12·0; 95% CI: 1·1–126·1; P = 0·04) and culture‐proven sepsis (OR: 15·0; 95% CI: 1·5–151·3; P = 0·02). These results were confirmed by genetic analysis of MBL deficiency. Low MBL levels at birth are associated with an increased risk of early‐onset sepsis, culture‐proven sepsis and pneumonia during the first month of life.

High prevalence of mannose-binding lectin (MBL) deficiency in premature neonates

Mannose‐binding lectin (MBL) is a component of innate immunity and thus particularly important in neonates in whom adaptive immunity is not yet completely developed. Promoter polymorphisms and structural exon‐1 mutations in the MBL2 gene cause reduced or deficient MBL plasma concentrations. The aim of our study was to determine the prevalence of MBL deficiency in neonates admitted to the neonatal intensive care unit (NICU). Eighty‐five NICU patients (69 premature) were included in the study. We measured MBL concentrations in umbilical cord and neonatal blood within 24 h after birth by ELISA technique. MBL2 genotypes (n = 67) were determined by Taqman analysis. MBL concentrations were measured longitudinally during three weeks in 26 premature neonates. The association between pre‐ and intra‐partum clinical data and MBL concentrations was investigated. At birth, 29 (42%) premature and six (38%) term neonates had MBL plasma concentrations ≤  0·7 µg/ml which was regarded as deficient. Twenty‐one (38%) premature and four (36%) term neonates had variant MBL2 haplotypes, corresponding to exon‐1 mutations and the LXPA haplotype. MBL concentrations increased over time in neonates with wild‐type MBL2 haplotypes, but not in neonates with variant haplotypes. Low MBL plasma concentrations were related to lower gestational age and variant MBL2 haplotypes. Umbilical cord and neonatal MBL plasma concentrations appeared to be similar. In conclusion, almost half of our NICU patients, especially the premature ones, were MBL‐deficient at birth. These infants may be at increased risk of neonatal infections. MBL concentration can reliably be measured in umbilical cord blood and it is positively correlated with gestational and postnatal age.

The prognosis of esophageal carcinoma staged irresectable (T4) by endosonography.

BACKGROUND Endosonography is an accurate preoperative staging technique for esophageal carcinoma. We retrospectively investigated a cohort of patients with carcinoma of the esophagus or gastric cardia that was endosonographically staged to be irresectable and studied whether their survival was influenced by the treatment received. STUDY DESIGN Between April 1992 and July 1995, 654 patients were referred for endosonographic staging. We retrospectively searched our database for patients staged T4 and collected followup. Kaplan-Meier survival and Cox proportional hazards model were used to study the effect of treatment and various other factors on survival. RESULTS Fifty-one patients (median age, 62 years; range, 44-87; 37 male) were staged T4 by endosonography. Followup was collected of all patients. Explorative surgery was chosen in 24 patients (47%), and the tumor was resected in 13 patients. Median survival in the surgical group was 9.67 months (95% confidence interval [CI] 6.03, 13.31) and 7.06 months (95% CI: 5.68, 8.44) in the nonsurgical group (not significant). Patients with infiltration in the respiratory tract had a 2.5 times higher risk of death than patients without (adjusted hazard ratio: 2.54; 95% CI: 1.30, 4.96). CONCLUSIONS Patients staged irresectable by endosonography (T4 stage) have a very poor prognosis, regardless of further therapy. Survival of this group of patients was not influenced by surgery.

Feeding tubes in endoscopic and clinical practice: the longer the better?

In an attempt to combine successful distal feeding tube positioning and a more prolonged stay without interfering with tube patency and feeding regimens, commercially available 105-cm polyurethane feeding tubes were compared with experimental tubes 125 cm and 145 cm long. The technique for endoscopic positioning at the bedside of the patient was standardized. Forty-five patients who required intraduodenal or intrajejunal enteral feeding in the intensive care unit were randomly assigned to one of the three tube-length groups. Even the 105-cm short feeding tubes were able to be introduced beyond the duodenojejunal junction, although insufficient tube length remained for tube fixation at the nose. The longer variants, however, were positioned significantly (p < 0.01) deeper in the intestine, with enough spare tube length for slack formation in the stomach and fixation at the nose. Tubes were electively removed in 29% of the patients. Irrespective of tube length, premature removal by the patient (in 36%) or by the nurse (in 11%) was rather high. Tube blockage was irremediable in 9%. Feeding tubes survived on average 10.6 days in all three tube-length groups, despite the fact that many drugs were administered by tube as well. The successful, easy, and fast endoscopic positioning of feeding tubes far into the intestine and at the patients bedside may further expand the possibility for enteral feeding. Moreover, polyurethane materials are well tolerated, and increasing the tube length does not interfere with tube patency or feeding plans.

The involvement of Fc gamma receptor gene polymorphisms in Kawasaki disease.

Kawasaki disease is an acute febrile syndrome in infancy, characterized by vasculitis of medium‐sized arteries. Without treatment the disease can lead to coronary artery lesions (CAL) in approximately 25% of the children. Therapy consists of intravenous immunoglobulins (IVIG), leading to a decrease of complications to 5–16%. Little is known about the working mechanisms of IVIG. In this study we evaluated the involvement of Fcγ receptors (FcγRs) in Kawasaki disease by the determination of the frequency of known single nucleotide polymorphisms (SNPs) in the genes coding for the FcγRs and compared this with frequencies in a cohort of healthy controls. There was no difference in the distribution of the functionally relevant genotypes for FcγRIIa‐131H/R, FcγRIIb‐232I/T, FcγRIIIa‐158 V/F and FcγRIIIb‐NA1/NA2 between the patient group and the healthy controls. Furthermore, there were no polymorphisms linked to the disease severity as indicated by the absence or development of CAL during the disease. Altered transcription or expression of FcγR on specific cell types of the immune system may still play a role in susceptibility and treatment success, but at a level different from the functional SNPs in FcγR genes tested in this study.