The capability set for work - correlates of sustainable employability in workers with multiple sclerosis.

BACKGROUND: The aim of this study was to examine whether work capabilities differ between workers with Multiple Sclerosis (MS) and workers from the general population. The second aim was to investigate whether the capability set was related to work and health outcomes. METHODS: A total of 163 workers with MS from the MS@Work study and 163 workers from the general population were matched for gender, age, educational level and working hours. All participants completed online questionnaires on demographics, health and work functioning. The Capability Set for Work Questionnaire was used to explore whether a set of seven work values is considered valuable (A), is enabled in the work context (B), and can be achieved by the individual (C). When all three criteria are met a work value can be considered part of the individual's 'capability set'. RESULTS: Group differences and relationships with work and health outcomes were examined. Despite lower physical work functioning (U = 4250, p = 0.001), lower work ability (U = 10591, p = 0.006) and worse self-reported health (U = 9091, p ≤ 0.001) workers with MS had a larger capability set (U = 9649, p ≤ 0.001) than the general population. In workers with MS, a larger capability set was associated with better flexible work functioning (r = 0.30), work ability (r = 0.25), self-rated health (r = 0.25); and with less absenteeism (r = - 0.26), presenteeism (r = - 0.31), cognitive/neuropsychiatric impairment (r = - 0.35), depression (r = - 0.43), anxiety (r = - 0.31) and fatigue (r = - 0.34). CONCLUSIONS: Workers with MS have a larger capability set than workers from the general population. In workers with MS a larger capability set was associated with better work and health outcomes. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. The study is registered at the Dutch CCMO register ( https://www.toetsingonline.nl ). This study is approved by the METC Brabant, 12 February 2014. First participants are enrolled 1st of March 2014.

Diffuse alveolar hemorrhage as an early complication of alemtuzumab treatment: A case report of a multiple sclerosis patient and an overview of 14 cases.

Alemtuzumab is effective in relapsing remitting multiple sclerosis (RRMS). Serious adverse events have led to a renewed safety reassessment by the European Medicines Agency (EMA), leading to an approval under strict conditions. We report a RRMS patient experiencing diffuse alveolar hemorrhage (DAH) on day 4 of her first alemtuzumab cycle. In addition, we present an overview of the cases of alemtuzumab-induced DAH that were included in EMA's review procedure, additional well documented cases reported to the EMA and those cases reported in the literature. Combining these cases revealed striking similarities. Importantly, DAH was an early complication. All RRMS patients with known outcome showed complete recovery.

Caregiver strain among life partners of persons with mild disability due to relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic disorder of the central nervous system with an unpredictable disease course. Life partners often become caregivers, which can be both rewarding and challenging, as the caregiver's physical and mental health is often negatively affected. Previous studies on caregiver strain focused on caregivers of persons with MS with relatively high disability levels, while caregiver strain may already be experienced by life partners living with mildly disabled persons with MS. OBJECTIVE: The current study examines factors associated with caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS. METHODS: We included 173 persons with relapsing-remitting MS (79% female; mean age 42.8 years; 90% employed; median EDSS 2.0) and their life partners. The life partners completed questionnaires on caregiver strain and neuropsychiatric and cognitive functioning of the person with MS. The persons with MS completed questionnaires about demographics, fatigue, personality, physical, cognitive and neuropsychiatric functioning, and underwent neuropsychological and neurological examinations. A linear regression analysis was conducted to examine predictors of caregiver strain. RESULTS: 24% of the life partners experienced above average levels of caregiver strain. A multivariate linear regression analysis revealed that a higher age of the person with MS (ß = 0.16, p = 0.04), more physical disability (ß = 0.17 p = 0.04), more cognitive and neuropsychiatric problems of the person with MS as reported by the life partner (ß = 0.33, p = 0.001) and higher severity of neuropsychiatric symptoms as reported by the life partner (ß = 0.32, p = 0.001) were associated with higher caregiver strain (R2 = 0.49). CONCLUSION: Higher caregiver strain in life partners of persons with mild disability due to relapsing-remitting MS was primarily associated with cognitive and neuropsychiatric problems of the person with MS.

Coping strategies in relation to negative work events and accommodations in employed multiple sclerosis patients.

BACKGROUND: Job loss is common in multiple sclerosis (MS) and is known to exert a negative effect on quality of life. The process leading up to job loss typically includes negative work events, productivity losses and a need for accommodations. By using active coping strategies job loss may be prevented or delayed. OBJECTIVE: Our goal was to examine negative work events and accommodations in relation to coping strategies in employed relapsing-remitting MS patients. METHODS: Ninety-seven MS patients (77% females; 21-59 years old) completed questionnaires concerning the patient's work situation, coping strategies, demographics, physical, psychological and cognitive functioning. Forward binary logistic regression analyses were conducted to examine coping strategies and other (disease) characteristics predictive of reported negative work events and accommodations. RESULTS: Nineteen per cent of the employed MS patients reported one or more negative work events, associated with a higher use of emotion-oriented coping and more absenteeism. Seventy-three per cent reported using one or more work accommodations, associated with a higher educational level and more presenteeism. MS patients reporting physical changes to the workplace employed more emotion-oriented coping, while flexible scheduling was associated with task-oriented coping. CONCLUSION: Emotion-oriented and task-oriented coping strategies are associated with negative work events and the use of accommodations.

Interleukin-6 in CAPD patients without peritonitis: relationship to the intrinsic permeability of the peritoneal membrane.

We investigated whether day to day changes in the transport characteristics of the peritoneal membrane to macromolecules in patients treated with CAPD, were related to the levels of interleukin-6 (IL-6) in the effluent of an overnight dwell. Four stable CAPD patients without peritonitis collected all "nightbags" on consecutive days during 2 months for the determination of peritoneal IgG clearance. Serum samples were obtained weekly. IL-6 was determined in the effluent on all occasions where the IgG clearance was less than mean - SD or greater than mean + SD. On these days clearances of beta 2-microglobulin, albumin and alpha 2-macroglobulin were determined as well, to calculate the peritoneal restriction coefficient, i.e. the slope of the power relationship between protein clearances and their free diffusion coefficient in water. This coefficient was used as a parameter of the intrinsic permeability of the membrane. IL-6 was measured by a sensitive and specific bioassay, using the B13.29, subclone 9.9 hybridoma cell assay. Dialysate IL-6 was measured on 43 occasions when IgG clearance was high and on 37 occasions when IgG clearance was low. In all 4 patients indirect evidence was found for local production of IL-6 within the peritoneal cavity: mean dialysate/serum ratios were 15 to 452 times higher than could be expected when IL-6 would enter the dialysate by diffusion only. The patient with the highest dialysate/serum ratio showed higher clearances of albumin, IgG and alpha 2-macroglobulin than the other 3 patients (p less than 0.001) and a lower restriction coefficient (p less than 0.001), indicating a high intrinsic permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

Day-to-day variability of protein transport used as a method for analyzing peritoneal permeability in CAPD.

The transperitoneal transport of macromolecules is dependent on both effective peritoneal surface area and intrinsic permeability of the peritoneum. For passage of small solutes, the effective surface area is the main determinant. We hypothesized that day-to-day variations in peritoneal clearances are caused by changes in the effective surface area and not in the intrinsic permeability. Four CAPD (continuous ambulatory peritoneal dialysis) patients without peritonitis were investigated on 28 consecutive days. Concentrations of beta-2-microglobulin, albumin, IgG, and alpha-2-macroglobulin were determined daily in dialysate (night bags) and weekly in serum. Clearances and their coefficients of variation were calculated. Mean coefficients of the intraindividual variation of protein clearances increased, the higher the molecular weight: they ranged from 12% for beta-2-microglobulin clearance to 22% for alpha-2-macroglobulin clearance. Correlations were present between the clearances of albumin, IgG, and alpha-2-macroglobulin, but not between any of these and beta-2-microglobulin clearance. In all patients, protein clearance (C) was a power function of the free diffusion coefficient in water (D) according to the equation: C = a. Db in which b represents the restriction coefficient of the peritoneum, and thus intrinsic permeability. The coefficient of variation of the restriction coefficient was low (range 4-6%). This supports our assumption that the intrinsic permeability is fairly constant on the short term. Day-to-day variations in protein clearances are thus mainly caused by alterations in the effective peritoneal surface area. Long-term follow-up of the restriction coefficient in individual patients might identify those at risk for the development of structural changes in the peritoneal membrane.

Analysis of inflammatory mediators and peritoneal permeability to macromolecules shortly before the onset of overt peritonitis in patients treated with CAPD.

OBJECTIVE: To investigate whether changes in peritoneal membrane characteristics and inflammatory mediators in dialysate precede the onset of overt infection during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients with a high peritonitis incidence stored every night bag at 4 degrees C. Routinely, each bag was thrown away after two days. Only if patients developed peritonitis, all bags were delivered for study. Thus, two night bags immediately prior to the first peritonitis bag were available for analysis. A control study was done 14 days after recovery. Dialysate samples were measured for TNF alpha, IL-6, PGE2, 6-keto-PGF1 alpha, TxB2, and serum proteins. The clearance of beta 2-microglobulin was used as an indicator of the effective peritoneal surface area. The intrinsic peritoneal permeability was characterized by the restriction coefficient. RESULTS: Eight episodes occurred in 5 patients. The night dwells available prior to the first peritonitis effluent were drained maximally nine dwells and minimally one dwell before the first peritonitis bag. Dialysate leukocyte counts exceeded 100 x 10(6)/L only on the day of manifest infection. However, bacterial cultures were already positive at least one day before overt infection in four episodes and in three of these cases two days before. No changes were observed prior to peritonitis for the clearance of beta 2-microglobulin or the restriction coefficient. In contrast to these permeability characteristics, the cytokines, TNF alpha and, though less significant, also IL-6, were increased in dialysate one day prior to overt infection, when compared to the values obtained at the control investigation. This was especially evident in effluents drained no longer than two dwells before the first peritonitis bag. Prostaglandin concentrations in dialysate were not different before the onset of manifest peritonitis from the values measured after recovery. CONCLUSION: In this study, the increased effective peritoneal surface area and intrinsic peritoneal permeability during acute infection appeared to be preceded by elevations in the cytokines TNF alpha and, to a lesser extent, IL-6. These increments occurred only very shortly before the onset of clinical symptoms.

Cancer antigen 125 is locally produced in the peritoneal cavity during continuous ambulatory peritoneal dialysis.

The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10-23), dialysate CA 125 18 U/mL (range 5.2-76), dialysate/plasma ratio 1.9 (range 0.61-5.4), and number of mesothelial cells 400/mL (range 10-5000). Peritoneal concentrations of mesothelial cells and CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/10(6) cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125.

Dialysate markers of peritoneal tissue during peritonitis and in stable CAPD.

OBJECTIVE: To investigate whether dialysate concentrations of substances that are locally produced within the peritoneal cavity can be used to study the effects of inflammation on peritoneal tissue. DESIGN: We followed the appearance rates (AR) of concentrations of cancer antigen (CA) 125, phospholipids (PHL), hyaluronan (HA), and the procollagen peptides PICP (procollagen 1 C-terminal) and PIIINP (procollagen 3 N-terminal) in dialysate during peritonitis (8 consecutive days) and after recovery. Data were compared with the stable situation. SETTING: CAPD (continuous ambulatory peritoneal dialysis) unit in the Academic Medical Center in Amsterdam. PATIENTS: Twelve CAPD patients with a total of 16 episodes of peritonitis and 10 clinically stable CAPD patients were studied. RESULTS: All substances showed temporal increments in dialysate during peritonitis compared to control. No difference was found between the control day of peritonitis and the stable patients. Maximum AR were reached in the acute phase of peritonitis for CA125, PHL, and HA and on day 4 for both PICP and PIIINP. A second increment in CA125 occurred on days 4 to 6. These findings indicate acute damage to the mesothelium (CA125) and other cells (PHL) by the infection. HA may reflect stromal changes. Subsequently, peritoneal healing (PICP,PIIINP) and remesothelialization (second peak CA125) are likely to occur. CONCLUSIONS: Dialysate concentrations of these substances can be used as markers for the effects of peritonitis on the peritoneum of CAPD patients in vivo. The similarity between the marker concentrations in the effluent after recovery from peritonitis and those in stable CAPD patients implies that complete peritoneal healing is likely to occur after uncomplicated peritonitis.

Intraperitoneal interleukin-8 and neutrophil influx in the initial phase of a CAPD peritonitis.

OBJECTIVE: To investigate whether or not a change in dialysate interleukin-8 (IL-8) concentration precedes the onset of clinically overt peritonitis and is significant in the recruitment of granulocytes during continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. DESIGN: CAPD patients stored their overnight effluent at 4 degrees C, which was routinely thrown away after 2 days. If peritonitis developed, patients delivered their effluent of the preceding two nights and the peritonitis effluent for analysis. A control study was performed 1 to 3 months after recovery. Dialysate samples were analyzed for number of cells, differential cell count, IL-8 and elastase concentrations, and their neutrophil chemoattractive capacity. In addition, serum samples during peritonitis were analyzed for IL-8 concentrations. RESULTS: Ten peritonitis episodes in 7 patients were analyzed. Numbers of neutrophils and levels of dialysate IL-8 and elastase started to increase 4 to 12 hours before the first peritonitis effluent. The dialysate/serum IL-8 ratio was 423.5 during peritonitis and 7.0 in the postperitonitis controls. There was a significant correlation between the number of neutrophils and IL-8 concentration in the dialysate. The in vitro neutrophil chemotaxis was increased toward the peritonitis effluents, as compared to control effluents. Incubation of the peritonitis effluents with anti-IL-8 monoclonal antibody blocked the increase in neutrophil chemotaxis above control levels by an average of 26.7%. CONCLUSION: IL-8 is produced in the peritoneal cavity during CAPD treatment and may mediate part of the neutrophil recruitment and degranulation in the initial phase of a CAPD peritonitis.

Impaired initial cell reaction in CAPD-related peritonitis.

Our objective was to determine the incidence of peritonitis episodes with an impaired initial cell reaction (IICR:neutrophil number < 100 x 10(6)/L) over a period of ten years, and to find possible explanations for this unusual presentation of peritonitis. A retrospective review of the files of continuous ambulatory peritoneal dialysis (CAPD) patients included in the CAPD program 1984 and 1993 was done. Analysis of cytokine and prostanoid patterns during four peritonitis episodes with an IICR was compared to 12 episodes with a normal initial cell reaction (NICR). Dialysate cell numbers and immunoeffector characteristics of peritoneal cells were compared in 7 IICR patients in a stable situation and a control group of 70 stable CAPD patients. The setting was a CAPD unit in the Academic Medical Center in Amsterdam. Thirty-five CAPD patients who had one or more peritonitis episodes with an IICR and a control group of 249 CAPD patients were included in the study. The incidence of peritonitis with an IICR was 6%. These episodes occurred more than once in 51% of the patients who presented with IICR. In 72% the cell reaction was only delayed: a cell number exceeding 100 x 10(6)/L was reached later. Staphylococcus aureus was significantly more frequently the causative microorganism compared to all peritonitis episodes (PE) that occurred during the study period. Patients with IICR had lower dialysate cell counts in a stable situation, compared to a control group (p < 0.01). This was caused by a lower number of macrophages and CD4 positive lymphocytes. The phagocytosis capacity of the macrophages appeared to be normal. In a comparison of four PE with an IICR and 12 episodes with an NICR, the tumor necrosis factor-alpha (TNF-alpha) response was similar and occurred on day 1, also pointing to normally functioning macrophages. However, the maximal appearance rates of interleukin-6 (IL-6) and IL-8 occurred later in the episodes with IICR compared to NICR (day 2 vs day 1, p < 0.05). No differences were found in vasodilating prostaglandins, mesothelial cell markers (cancer antigen 125, phospholipids, hyaluronan), and mesothelial cell numbers in the stable situation nor during peritonitis. Peritonitis can present as abdominal pain in the absence of a cloudy dialysate. In some of the patients this presentation occurred more than once. This impaired, most often delayed, cell reaction was associated with a delayed secondary cytokine response. As IL-6 and IL-8 can be synthesized by mesothelial cells, this suggests an impaired functioning mesothelium. This could not be confirmed, however, by a lower number of mesothelial cells in effluent or lower dialysate levels of mesothelial cell markers.

Individual characterization of the peritoneal restriction barrier to macromolecules.

The transport of macromolecules such as proteins and dextrans during CAPD is restricted by the permeability of the peritoneum. When its degree is determined by diffusion characteristics of macromolecules, the intrinsic permeability of the peritoneal membrane can be expressed as the relation between clearance of macromolecules and parameters of diffusion velocity. In order to characterize the peritoneal restriction barrier in individual patients, such a relationship has to meet the following conditions: (a) a good fit to linearity, (b) a low inter- and intra individual variability and (c) similarity for proteins and equal sized dextran fractions. In the present study a comparison is made between the reciprocal plot (RP): C-1 = s (esr) + A and the diffusion plot (DP): C = A'. Ds20,w. In these equations C is clearance, esr is Einstein Stokes radius, D20,w is the free diffusion coefficient in water, A and A' are constants, while s is the slope of the regression line and therefore represents intrinsic peritoneal permeability to macromolecules. The 95% confidence interval of the correlation coefficient r was above 0.95 in all studies for the RP and the DP. In general it was somewhat higher for the DP. The inter-individual coefficient of variation was lower in the DP than in the RP. This was also the case for the intra-individual coefficient of variation of the slope for proteins (DP 4% vs RP 27%, p less than 0.01) and for dextrans (DP 18% vs RP 47%, p less than 0.05). The correlation coefficient between dextran slopes and protein slopes was higher for DP (r = 0.68) than for RP (r = 0.50).(ABSTRACT TRUNCATED AT 250 WORDS)

Nitrate in stable CAPD patients and during peritonitis.

During continuous ambulatory peritoneal dialysis (CAPD) peritoneal vessels are dilated. Nitric oxide (NO) causes vasodilation in many organs. Nitrate, a stable metabolite of NO, was measured in plasma and dialysate. In 6 stable CAPD patients standard peritoneal analyses were performed. The mass transfer area coefficient (MTAC) of nitrate was 11.5 mL/min (10.0-17.0 mL/min) (median and range). The MTAC of creatinine was of the same order of magnitude: 10.7 mL/min (8.0-14.2 mL/min), although the molecular weight of nitrate is lower (62 vs 113 dalton). The correlation between the MTAC of nitrate and the MTAC of creatinine indicated diffusion from the circulation and not local production of NO (r = 0.71; p = 0.11). Peritoneal permeability is increased in the acute phase of peritonitis, partly caused by extensive vasodilation. The potential role of NO during peritonitis was investigated in 8 CAPD patients with 11 peritonitis episodes in the acute phase and after recovery. The median dialysate/plasma (D/P) ratio of nitrate in the acute phase was 1.47 (range 0.96-2.55), which was higher than after recovery: 1.07 (0.99-1.75), p < 0.05. No relation was found between the D/P ratio of nitrate and the D/P ratio of TNF alpha (tumor necrosis factor). In conclusion, dialysate nitrate levels in stable CAPD patients are likely to be determined by diffusion from the circulation. D/P ratios exceeding 1.0 during the acute phase of peritonitis are probably the result of local NO production. This may contribute to the marked vasodilation during peritonitis.

[Improvement of vision in nursing home patients through eyeglasses]. / Visusverbetering door brilcorrectie bij verpleeghuispatiënten.

Adequate refraction correction may contribute to the quality of life of elderly persons who will be less dependent on care in daily life and will be less prone to fall. In nearly 20% of 102 nursing home residents binocular visual acuity improved with at least one line on the Snellen Chart by adjustment of refractive correction.

Cytokine patterns in the effluent of continuous ambulatory peritoneal dialysis: relationship to peritoneal permeability.

Cytokines are pluripotent pleiotropic agents that have received widespread attention over the last few years. Not surprisingly, the have also been studied in the context of continuous ambulatory peritoneal dialysis. Cytokines play a central role in this treatment modality for uremic patients, because these inflammatory mediators act upon the biological dialysis membrane, i.e. the peritoneum, while simultaneously they participate in host defense mechanisms. This review describes which cytokines are present in dialysate, whether there is support for intraperitoneal release, and under which circumstances. If focuses particularly on the relationship between cytokines in peritoneal effluent and peritoneal permeability to macromolecules. In addition, the presence of prostanoids in dialysate and their role in the local regulation of peritoneal permeability are discussed, because cyclooxygenase products are tightly linked to cytokine networks.

Clinical significance and detection of individual differences and changes in transperitoneal transport.

A review is given on the pathophysiology of the transport of solutes and fluid during continuous ambulatory peritoneal dialysis. Special attention is paid to the assessment of peritoneal permeability in individual patients, its inter- and intraindividual variability, the effect of systemic disease, some regulatory mechanisms, and alterations observed during long-term continuous ambulatory peritoneal dialysis.