Conversion from Cyclosporine to Tacrolimus Improves Quality-of-Life Indices, Renal Graft Function and Cardiovascular Risk Profile

Long-term use of cyclosporine after renal transplantation results in nephrotoxicity and an increased cardiovascular risk profile. Tacrolimus may be more favorable in this respect. In this randomized controlled study in 124 renal transplant patients, the effects of conversion from cyclosporine to tacrolimus on renal function, cardiovascular risk factors, and perceived side-effects were investigated after a follow-up of 2 years. After conversion from cyclosporine to tacrolimus renal function remained stable, whereas continuation of cyclosporine was accompanied by a rise in serum creatinine from 142 +/- 48 micromol/L to 157 +/- 62 micromol/L (p < 0.05 comparing both groups). Conversion to tacrolimus resulted in a sustained reduction in systolic and diastolic blood pressure, and a sustained improvement in the serum lipid profile, leading to a reduction in the Framingham risk score from 5.7 +/- 4.3 to 4.8 +/- 5.3 (p < 0.05). Finally, conversion to tacrolimus resulted in decreased scores for occurrence of and distress due to side-effects. In conclusion, conversion from cyclosporine to tacrolimus in stable renal transplant patients is beneficial with respect to renal function, cardiovascular risk profile, and side-effects. Therefore, for most renal transplant patients tacrolimus will be the drug of choice when long-term treatment with a calcineurin inhibitor is indicated.     

Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals

Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level <100,000 vs. > or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population.     

Efficacy of oral administration and oral intake of edible vaccines

To evaluate whether vaccine administration via intragastric gavage is indicative for the outcome of edible vaccines, mice were orally immunised with ovalbumin (OVA) mixed with or without Vibrio cholerae toxin (CT) in various compositions via various routes: (1) OVA dissolved in saline and intragastrically (IG) administered ('IG'); (2) OVA mixed with food extract and administered IG ('food IG'); (3) food chow absorbed with OVA dissolved in saline and fed to the animals ('food'); and (4) OVA dissolved in saline and administered via drinking bottles ('drinking'). When given to naive mice, 'IG' and 'food IG' but not 'food' or 'drinking' induced anti-OVA IgG1 responses in serum, but oral boost immunisations were necessary. Serum IgA was not induced. Oral boosting of subcutaneously (SC) primed mice enhanced the IgG1 and IgA response in serum regardless of the route of immunisation or the vaccine composition. CT did not dramatically enhance the immune response. All immunisation routes except 'drinking' induced antigen-specific IgA antibody secreting cells (ASC) in the lamina propria of naive mice. But antigen-specific antibody responses in faeces were not observed. We concluded that oral (i.e. IG) administration is distinct from oral intake. The composition of the vaccine (food or saline) did not influence oral administration. We thus suggested that the route of administration greatly influenced the outcome of oral immunisation. Although oral administration is a well-accepted route to test the potentials of oral vaccines, our study demonstrated that it is merely indicative for the effectiveness of edible vaccines. Studies on the feasibility of edible vaccines should thus be performed by eating the vaccine.     

Predicting health-related quality of life in dialysis patients: Factors related to negative outcome expectancies and social support

ObjectivesDialysis patients report a low health-related quality of life (HRQOL) due to high disease burden and far-reaching consequences of dialysis treatment. This study examined several cognitive-behavioral and social factors, with a focus on negative outcome expectancies, that might be relevant for HRQOL in end-stage kidney disease (ESKD) patients treated with dialysis.MethodsPatients treated with hemodialysis or peritoneal dialysis were recruited from Dutch hospitals and dialysis centers. Patients completed self-report questionnaires at baseline (n = 175) and six months follow-up (n = 130). Multiple regression analyses were performed.ResultsHigher scores on factors related to negative outcome expectancies at baseline, especially helplessness and worrying, and less perceived social support were significantly related to worse HRQOL six months later. When controlling for baseline HRQOL, besides sex and comorbidity, helplessness remained significantly predictive of worse HRQOL six months later, indicating that helplessness is associated with changes in HRQOL over time.ConclusionsNegative outcome expectancies and social support are relevant markers for HRQOL and/or changes in HRQOL over time.Practice implicationsNegative outcome expectancies could be prevented or diminished by enhanced treatment information, an improved patient-clinician relationship, and interventions that promote adaptive and realistic expectations. Additionally, increasing supportive social relationships could be a relevant treatment focus.     

History of ocular straylight measurement: A review

The earliest studies on ‘disability glare’ date from the early 20^th century. The condition was defined as the negative effect on visual function of a bright light located at some distance in the visual field. It was found that for larger angles (>1degree) the functional effect corresponded precisely to the effect of a light with a luminosity equal to that of the light that is perceived spreading around such a bright source. This perceived spreading of light was called straylight and by international standard disability glare was defined as identical to straylight. The phenomenon was recognized in the ophthalmological community as an important aspect of the quality of vision and attempts were made to design instruments to measure it. This must not be confused with instruments that assess light spreading over small distances (<1 degree), as originating from (higher order) aberrations and defocus. In recent years a new instrument has gained acceptance (C-Quant) for objective and controllable assessment of straylight in the clinical setting. This overview provides a sketch of the historical development of straylight measurement, as well as the results of studies on the origins of straylight (or disability glare) in the normal eye, and on findings on cataract (surgery) and corneal conditions.     

A new method to evaluate the effects of shear on the skin

Currently, pressure ulcer preventive strategies focus mainly on pressure redistribution. Little attention is paid to reduce the harmful effects of shear‐force, because little is known about pathophysiological aspects of shear‐force. Even today, no method to measure the effects of shear‐force on the skin is available. Therefore, the aim of this study was to investigate the response to shear‐forces in terms of analyzing a noninvasive biomarker and reactive hyperemic parameter measured at the skin of healthy participants. A physical model was developed to produce a combination of pressure and shear or pressure alone on the skin. Ten healthy male participants were included and pressure (3.9 kPa) and a combined loading of pressure and shear (2.4 kPa + 14.5 N) was applied at the volar aspect of the forearms for 15 and 30 minutes. A Sebutape sample was used to collect IL‐1α and total protein (TP) noninvasively. The reactive hyperemic parameter was derived from a laser Doppler flowmeter. The increase in IL‐1α/TP‐ratio after a combined loading of pressure and shear for 30 minutes of 6.2 ± 2.5 was significantly higher compared with all other test conditions (p < 0.05). The increase in cutaneous blood cell flux was already significantly higher when a combined loading of pressure and shear was applied for 15 minutes compared with pressure alone. These results shows that the IL‐1α/TP‐ratio and cutaneous blood cell flux can be used as robust measures of the effect of shear‐force on skin in humans. Therefore, this model can be used to evaluate materials aimed at the reduction of shear.     

The 5-Year Course of Obsessive-Compulsive Symptoms and Obsessive-Compulsive Disorder in First-Episode Schizophrenia and Related Disorders

Objective: To determine the course of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) in first-episode schizophrenia and related disorders and their relationship with clinical characteristics. Methods: Consecutively, admitted patients with a first-episode of schizophrenia, schizophreniform disorder, or schizoaffective disorder were screened for OCS, and these were measured with the Yale-Brown Obsessive-Compulsive Scale. Positive and Negative Syndrome Scale and Montgomery Åsberg Depression Rating Scale were used to assess severity of other symptoms. The course of 3- and 5-year symptoms, psychotic relapse, substance use, remission, full recovery, suicide, and social functioning were assessed. Results: One hundred and eighty-six consecutively admitted and consenting patients were included. Five years after admission, OCS could be assessed in 172 patients. Ninety-one patients (48.9%) reported no OCS symptoms on any of the assessments. OCS restricted to the first assessments occured in 15.1%, 13.4% had persistent OCS, 7.0% had no OCS at first assessment but developed OCS subsequently, and 15.6% had intermittent OCS. The proportion of patients with comorbid OCD varied between 7.3% and 11.8% during follow-up. OCD was associated with more severe depressive symptoms and poorer premorbid functioning and social functioning at follow-up. Conclusions: The 5-year course of OCS/OCD in patients with first-episode schizophrenia or related disorders is variable. OCS/OCD comorbidity was not associated with a more severe course of psychotic symptoms and relapse. Comorbid OCD was associated with more severe depressive symptoms, social dysfunction and worse premorbid functioning. Specific treatment options for schizophrenia patients with comorbid OCD are needed.