Influenza vaccination in healthcare workers; comparison of side effects and preferred route of administration of intradermal versus intramuscular administration.

OBJECTIVE: To explore the nature and severity of side effects and future preference of intradermal versus intramuscular influenza vaccination in healthcare workers. DESIGN: Prospective cohort study. SETTING: Two University Medical Centers in The Netherlands. PARTICIPANTS: Healthcare workers receiving an influenza vaccination. METHODS: Healthcare workers that were vaccinated during the influenza vaccination season of 2012-2013 were approached for participation in a questionnaire study. The questionnaire was divided into two parts. The first part had to be answered directly after vaccination and the second part two weeks after vaccination. The motivation for vaccine uptake, whether or not the HCWs had direct contact with patients and the prevalence and severity of local and systemic side effects of influenza vaccination were explored. In addition, it was assessed how participants experienced the vaccination and which type of administration they preferred for future vaccination. RESULTS: Side effects of vaccination were more prevalent in the intradermal group versus the intramuscular group (56% versus 26%, p<0.001). Local side effects were perceived as more severe in healthcare workers receiving the intradermal vaccine. Directly after vaccination, healthcare workers preferred the intradermal vaccination. Two weeks after vaccination both types of vaccine were equally appreciated. CONCLUSIONS: This study shows that there are significant differences in the nature and severity of side effects upon intramuscular and intradermal influenza vaccination. This difference did not result in a preference among the vaccinated subjects for one type of vaccine.

Hospital-based cluster randomised controlled trial to assess effects of a multi-faceted programme on influenza vaccine coverage among hospital healthcare workers and nosocomial influenza in the Netherlands, 2009 to 2011.

Nosocomial influenza is a large burden in hospitals. Despite recommendations from the World Health Organization to vaccinate healthcare workers against influenza, vaccine uptake remains low in most European countries. We performed a pragmatic cluster randomised controlled trial in order to assess the effects of implementing a multi-faceted influenza immunisation programme on vaccine coverage in hospital healthcare workers (HCWs) and on in-patient morbidity. We included hospital HCWs of three intervention and three control University Medical Centers (UMCs), and 3,367 patients. An implementation programme was offered to the intervention UMCs to assess the effects on both vaccine uptake among hospital staff and patient morbidity. In 2009/10, the coverage of seasonal, the first and second dose of pandemic influenza vaccine as well as seasonal vaccine in 2010/11 was higher in intervention UMCs than control UMCs (all p<0.05). At the internal medicine departments of the intervention group with higher vaccine coverage compared to the control group, nosocomial influenza and/or pneumonia was recorded in 3.9% and 9.7% of patients of intervention and control UMCs, respectively (p=0.015). Though potential bias could not be completely ruled out, an increase in vaccine coverage was associated with decreased patient in-hospital morbidity from influenza and/or pneumonia.

The incidence of visual impairment due to retinopathy of prematurity (ROP) and concomitant disabilities in the Netherlands: a 30 year overview.

AIM: To determine the incidence of visual impairment (VI) caused by retinopathy of prematurity (ROP) and concomitant disabilities in preterm neonates born between 2000 and 2009 in the Netherlands. METHODS: Data were retrieved from the Dutch institutes for the visually impaired. They were compared with similar Dutch studies conducted in 1975-1987, 1986-1994 and 1994-2000. RESULTS: Records of 42 infants with VI due to ROP were included. A gradual decrease of gestational age and birthweight but an increase of duration of artificial ventilation, supplemental oxygen administration, bronchopulmonary dysplasia, developmental delay and behavioural abnormalities was found. Compared with the previous study (1994-2000), significantly fewer children were visually impaired due to ROP (1.84 per 100,000 live births/year vs 3.93 per 100,000 live births/year, p=0.000), the incidence of complete blindness decreased from 27.5% to 7.1% (p < 0.05) and more children were treated (66.7% vs 56.9%, NS). The incidence of concomitant disabilities was high and did not differ greatly from the previous study. CONCLUSION: This was a retrospective study showing a significant decrease in VI due to ROP in the Netherlands. Changes in neonatal care practices did not result in a decrease in the incidence of concomitant disabilities. More children were treated for ROP, but 33% were not treated.

Determination of factors required to increase uptake of influenza vaccination among hospital-based healthcare workers.

A questionnaire study was performed in all eight University Medical Centers in The Netherlands to determine the predictors of influenza vaccination compliance in hospital-based healthcare workers (HCWs). Demographical, behavioural and organisational determinants were assessed based on behavioural and implementation models. Multivariable regression analysis was applied to assess the independent predictors for influenza vaccine uptake. Age >40 years, the presence of a chronic illness, awareness of personal risk and awareness of risk of infecting patients, trust in the effectiveness of the vaccine to reduce the risk of infecting patients, the HCWs' duty to do no harm and their duty to ensure continuity of care, finding vaccination useful despite the constant flow of visitors and having knowledge of the Health Council's advice, social influence and convenient time for vaccination were all independently associated with vaccine uptake. The accuracy of the prediction model was very high (area under the receiver operating curve: 0.95). Intervention programmes to increase influenza vaccine uptake among HCWs should target the relevant determinants identified in this study.

Genotype distribution amongst hepatitis C patients in The Netherlands.

BACKGROUND: The prevalence of the genotypes of the hepatitis C virus (HCV) differs according to geographical location. In the United States and in European countries, the majority of patients are infected with genotype 1, 2 or 3. There is a lack of data on the distribution of HCV genotypes in The Netherlands. METHODS: The current survey determined the distribution of HCV genotypes amongst recently genotyped patients seen by physicians treating hepatitis C in The Netherlands. RESULTS: Almost half of the 351 patients (49.3%) were infected with genotype 1. Genotype 3 was the second most dominant genotype with a prevalence of 29.3%. Genotypes 2 and 4 were found in 9.7 and 10.5% of the patients, respectively. For 61.5% of the patients (n=216), the subtype was available. For genotype 1 the prevalence of subtype 1a and 1b was very similar, while for genotype 3 a large majority of patients were infected with subtype 3a. CONCLUSION: This survey gives the first estimation of the distribution of HCV genotypes amongst unselected HCV patients in The Netherlands.

Phase II trial with ISIS 5132 in patients with small-cell (SCLC) and non-small cell (NSCLC) lung cancer. A European Organization for Research and Treatment of Cancer (EORTC) Early Clinical Studies Group report.

Two multicentre phase II trials were designed to determine if tumour responses can be achieved in progressive small-cell lung cancer (SCLC) or non-small cell lung cancer (NSCLC) patients treated with ISIS 5132, an inhibitor of C-raf kinase mRNA expression (CGP 69846A; ISIS Pharmaceuticals Inc, Carlsbad, CA), and to further characterise the safety of the compound. Between August 1998 and November 1999, 26 patients (18 NSCLC, 8 SCLC) were entered. Out of these, 23 were eligible, 22 (18 NSCLC, 4 SCLC) were treated with ISIS 5132 (2 mg/kg/day, 21 days continuous intravenous (i.v.) infusion every 4 weeks) and were evaluable for toxicity and 18 (15 NSCLC, 3 SCLC) were evaluable for efficacy. For the whole group haematological toxicity did not exceed grade 2. One patient experienced a grade 4 increased prothrombin time. Non-haematological toxicity was mild to moderate, with the observation of asthenia and nausea and vomiting. Progressive disease (PD) was diagnosed in 10 patients (8 NSCLC and 2 SCLC). 8 more patients (7 NSCLC, 1 SCLC) were considered as treatment failures. In conclusion, this study using ISIS 5132 with this dose and schedule of administration excludes a 20% response rate with 95% confidence intervals for NSCLC and cannot draw any conclusions for SCLC patients as only a few were involved in the study.

Phase I clinical and pharmacokinetic study of oral S-1 in patients with advanced solid tumors.

PURPOSE: To investigate the side effects, determine the maximum-tolerated dose (MTD), and study the pharmacokinetics of S-1, an oral fluoropyrimidine-based antineoplastic agent consisting of the fluorouracil (5-FU) prodrug tegafur combined with two modulators, 5-chloro-2,4-dihydroxypyridine and potassium oxonate. PATIENTS AND METHODS: Patients with advanced solid tumors received S-1 bid for 28 days, followed by 1 week of rest. 5-FU pharmacokinetics were investigated after a single initial dose of S-1 during the first 24 hours and weekly thereafter. RESULTS: Twenty-eight patients received S-1 at the four consecutive dose levels of 25, 45, 35, and 40 mg/m(2). The MTD was initially found at 45 mg/m(2), with diarrhea as the dose-limiting toxicity (DLT). Diarrhea was also the DLT at the dose of 40 mg/m(2), which was the MTD for patients exposed to extensive prior chemotherapy. Other toxicities were generally mild. Two patients had a reduction of more than 50% in tumor dimension. Plasma pharmacokinetics of 5-FU were linear; at the highest S-1 dose level, 5-FU plasma peak concentrations reached 1 to 2 micromol/L, and the half-life of 5-FU was 3 to 4 hours. A statistically significant relationship was observed between the severity of diarrhea and pharmacokinetic parameters of 5-FU. CONCLUSION: The recommended dose of S-1 in chemotherapy-naive or minimally chemotherapy-exposed patients is 40 mg/m(2) bid on 28 consecutive days, every 5 weeks. In heavily pretreated patients, the recommended dose is 35 mg/m(2) bid. Phase II trials are warranted in tumors known to be responsive to 5-FU treatment.

Energy balance of dairy cattle in relation to milk production variables and fertility.

Variables derived from milk yield records were investigated to find an easy to measure and readily available indicator of the energy balance status of a lactating cow. Weekly energy balances during the first 180 d in milk (DIM) were calculated from weekly yield, live weight, and energy intake records for 470 first lactation heifers. The energy balance curve for each cow was estimated using a random regression model. From each curve, three measures were calculated to describe the energy balance status: 1) total energy deficit in early lactation, 2) interval for return to positive energy balance, and 3) lowest value (nadir) for energy balance. Mean energy deficit per lactation was 776.8 MJ of NE(L)/d, interval for return to positive energy balance was 41.47 d, and nadir was -33.72 MJ of NE(L)/d. Regression analysis to relate these variables to interval to start of luteal activity (measured using progesterone profiles) showed that a low nadir of energy balance was related to delayed resumption of luteal activity. In general, a 10 MJ of NE(L)/d lower nadir of energy balance corresponded to a delay of ovulation of 1.25 d. A relatively strong decrease in fat percentage during early lactation was significantly correlated with lower nadir of energy balance, larger energy deficit, and later return to positive energy balance. The maximal correlation was between nadir of energy balance and a decrease of milk fat percentage. This correlation remained above 0.60 throughout the first 26 DIM but dropped to 0.14 at 180 DIM. Large decreases in milk fat percentage were related to high initial fat percentages at the start of lactation and slightly lower fat percentages later during lactation. Hence, we concluded that a decrease in fat percentage during early lactation might serve as an indicator of energy balance.

Complete response of a gastric primary after a short but toxic course of 'S-1' EORTC Early Clinical Studies Group.

We report the case of an unresected, metastatic gastric cancer, which was treated with a very short course of the oral 5-fluorouracil (5-FU) prodrug S-1. The patient had to discontinue chemotherapy during the first treatment cycle due to severe toxicity, but achieved a pathologically confirmed, long-term complete response of her primary tumour, a diffuse-type poorly differentiated adenocarcinoma.

Prognostic factors in patients continuing in vitro fertilization or intracytoplasmic sperm injection treatment and dropouts.

OBJECTIVE: To investigate whether cumulative pregnancy rates using life table analysis but without considering dropouts are representative of the whole population of patients entering an in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) program. DESIGN: Retrospective study. SETTING: University hospital-based infertility center. PATIENT(S): One thousand one hundred sixty-nine patients entering our IVF/ICSI program from January 1993 to December 1996. INTERVENTION(S): Comparison of prognostic factors between pregnant and nonpregnant patients, and between patients continuing IVF/ICSI treatment and dropouts. MAIN OUTCOME MEASURE(S): Prognostic factors, such as patient age, cancellation of oocyte retrieval because of poor response to ovarian stimulation, number of oocytes retrieved, fertilization rate, number and quality of embryos transferred. RESULT(S): No statistical differences in prognostic factors were found between patients continuing IVF/ICSI treatment and dropouts. CONCLUSION(S): Cumulative pregnancy rates using life table analysis can be considered representative of the whole population of patients for at least the first three treatment cycles.

Modeling of energy balance in early lactation and the effect of energy deficits in early lactation on first detected estrus postpartum in dairy cows.

The general pattern of energy balance in early lactation was modeled. For this purpose, several lactation curves were investigated. The best fitting curve was fit in a random regression model that provided predicted energy balance curves for all lactations. By use of these curves, total energy deficit per lactation, postpartum interval of return to positive energy balance, and nadir of energy balance was determined. In predicted energy balances, nadir of energy balance was present, but variation in postpartum interval to nadir was small. First lactation cows had a smaller energy deficit in early lactation than did older cows. Differences among cows in nadir and total energy deficits in early lactation were large. Both were related to the postpartum interval to first detected estrus with a larger energy deficit and a smaller nadir corresponding to a larger postpartum interval to first detected estrus. From this study, it can be concluded that large energy deficits in early lactation delay first detected estrus.

The immunological and psychological effects of bereavement: does grief counseling really make a difference? A pilot study.

This study evaluates psychological and immunological functioning after bereavement and the influence of group counseling. Eighteen widows (bereaved within 3 months of enrolment) and a reference group of 10 married control subjects were asked to fill in self-report scales and to donate a blood sample (T1). After T1, half of the widows (the experimental group) were randomly assigned to grief counseling (13 sessions over 4 months), while the other subjects (the control group) received no treatment. Seven months after bereavement (T2) or, in the case of the experimental group, immediately after the intervention, a follow-up was conducted in the widowed subsample using the same measures. Blood samples were analyzed to determine the total number of white blood cells, number of lymphocyte subsets, natural killer cell activity (NKCA) and lymphocyte proliferative response to phytohemagglutinin (PHA), anti-CD3 and pokeweed mitogen (PWM). At T1, we found significant differences between widows and non-widows regarding both psychological and immunological measures. Widows felt more anxious, depressed, hostile and agoraphobic. At T1, widows had a lower number of the CD19+CD5+ B cell subpopulation. The cell function tests for T and B cells showed higher responses in widows (lymphocyte proliferation response to PHA, anti-CD3 and PWM). No significant difference in NKCA was found between widows and non-widows. At T2, there appeared to be no significant difference between widows and non-widows on the psychological measures. With respect to the immunological measures, widows and non-widows showed no significant differences for the total number of white blood cells, number of lymphocyte subsets and NKCA. Consistent with our findings at T1, the lymphocyte proliferation response to PHA, anti-CD3 and PWM at T2 appeared to be higher in widows than in non-widows. Comparing the experimental group (widows) and the control group (widows) with respect to psychological measures at T1, widows in the experimental group felt more insufficient and had more sleep disturbances. With respect to the immunological measures, no differences were found between those two groups. When the same two groups were again compared at T2, no differences were found in any of the psychological or immunological measures (lymphocyte sub-populations, proliferation tests and the NKCA).

The effects of time of disease occurrence, milk yield, and body condition on fertility of dairy cows.

The associations between occurrence of diseases, milk yield, and body condition score on conception risk after first artificial insemination (AI) were analyzed in an observational study on a convenience sample of 43 farms participating in a herd health program. Data were taken from 9369 lactations, from 4382 cows inseminated between 20 and 180 d in milk from 1990 to 1996. Two logistic regression models, one containing data from all lactations and a subset containing data from 1762 lactations with body condition scoring, were used to determine pregnancy risk at first AI. The effects of herd deviation in test-day milk yield, body condition score loss, and milk fat to protein ratio changes in early lactation were significant predictors of pregnancy risk, independent of disease; days in milk; farm; and seasonal factors. Three different methods of disease parameterization (incidence rates, binomial classes dependent on the interval in days since last occurrence with respect to AI, and a linear variable weighted for this interval) produced similar results. Metritis, cystic ovarian disease, lameness, and mastitis gave odds ratios for pregnancy risk ranging from 0.35 to 1.15, largely dependent on the interval in days from final disease occurrence to first AI. Displaced abomasum, milk fever, and retained fetal membranes resulted in odds ratios for pregnancy risk of 0.25, 0.85, and 0.55, respectively. These diseases showed little relationship between fertility and the number of days since last occurrence. Results of this study confirm the negative effects of milk yield, body score condition loss, and disease on dairy cow fertility. The effects of some diseases on first service conception were strongly dependent on the interval since last disease occurrence. This was especially valid for clinical mastitis, which has an extremely weak effect on conception if occurring prior to AI and is associated with > 50% reduction in pregnancy risk if occurring in the 3 wk directly after AI.

Use of AI technician scores for body condition, uterine tone and uterine discharge in a model with disease and milk production parameters to predict pregnancy risk at first AI in Holstein dairy cows.

Technicians recorded body condition score (BCS) and several parameters related to estrus and/or metritis for 1694 first insemination cows on 23 farms. Additional variables for modeling the adjusted odds ratios (OR) for pregnancy were data on disease prior to or within 21 days of AI and test day milk yields. Significant predictors for pregnancy were farm, year and season, BCS, uterine tone, contaminated insemination gun after AI, fat-protein corrected kilograms milk (FPCM), days in milk (DIM), and diseases. Vaginal mucus, ease of cervical passage, and lameness were not significant predictors for pregnancy. Pregnancy risk at AI increased with increasing DIM, reaching a near optimum after 82 days. Lack of uterine tone was associated with a lowered pregnancy risk (OR = 0.69) as was contaminated insemination gun (OR = 0.67), first-parity lactation, FPCM >33 kg (OR = 0.71), BCS 2.5 at AI (OR = 0.65), clinical mastitis (OR = 0.53), cystic ovarian disease (OR = 0.53), and metritis (OR = 0.74). It was concluded that data on BCS and uterine findings, as collected by AI technicians, are significant predictors of AI outcome. Dairy producers and veterinarians should jointly examine the potential costs and value of such AI technician-based data to improve herd fertility.

Higher risk of preeclampsia in the polycystic ovary syndrome. A case control study.

OBJECTIVE: To determine whether the risk of pregnancy-induced hypertensive disorders (PIHD) is higher in patients with the polycystic ovary syndrome (PCOS) than in non-PCOS controls, matched for age and parity. STUDY DESIGN: Retrospective analysis of eighty-one patients with PCOS, consecutively becoming pregnant during a seven-year period. Each PCOS-patient was matched for age and parity with one control patient. Chi-squared, Mann-Whitney or Fisher's exact-tests were used for statistical analysis. RESULTS: Overall incidence of PIHD was similar in both study groups. However, incidence of preeclampsia was significantly higher in patients with PCOS than in controls (P = 0.02). This higher incidence can not be explained by body mass index, endocrine profile before pregnancy, induction of ovulation or treatment regimens. CONCLUSIONS: PCOS-patients are at a significantly higher risk for preeclampsia than non-PCOS controls.

Phase II study of psychotherapeutic intervention in advanced cancer.

The effect of psychosocial counseling on tumor progression was studied in 96 cancer patients, who were no longer amenable to regular medical treatment. Patients were offered 12 session of individual experiential-existential counseling, each sessions lasting 1.5 to 2 hours. In addition patients participated fortnightly in group counseling meetings. In five out of 35 evaluable patients, tumor growth became stationary during or immediately following therapy. In four patients this stationary period last 3-9 months, and in one patient 2 years. Natural Killer cell activity, self-reported loneliness, depression, purpose in life and locus of control showed no change from pre- to post intervention.

Long-term trends in sperm counts of dairy bulls.

A possible decline in sperm counts in men and its potential relation to exposure to environmental contaminants are subjects of a broad discussion. Whereas data for human research in this area are limited, records over prolonged periods on sperm counts in dairy bulls are amply available and provide useful information. Therefore, 75,238 ejaculates collected between 1977 and 1996 from 2,314 bulls at Noordwest, a center for artificial insemination (AI) in the Netherlands, were used to evaluate long-term trends in sperm output. Data were adjusted for known effects, of which age was the most important, followed by interval between semen collections, breed and season of collection. Mean sperm output per year of collection from 1978 through 1996 varied between 6.2 x 10(9) and 9.5 x 10(9) without any long-term decline. Mean sperm output per year of birth from 1970 through 1995 showed less variation, between 6.7 x 10(9) and 9.0 x 10(9), also without any long-term decline. Earlier published data of 22,120 ejaculates of 3,030 bulls of the same region, tested between 1962 and 1977, showed a corresponding sperm output, confirming the absence of any decline. The unaffected sperm output in bulls in the Netherlands during the last decades in spite of exposure to pesticides and other polychlorinated organic compounds, the type of environmental contaminants under discussion, is a positive signal, although a complete extrapolation to the human situation remains difficult.

[Economic contribution of mofetil mycofenolate as preventive immunosuppressive treatment after renal transplantation from cadaver]. / Apport économique du mycophénolate mofétil comme traitement immunosuppresseur prophylactique après transplantation rénale de cadavre.

OBJECTIVES: The economic impact resulting from the clinical consequences of immunosuppressive strategy using mycophenolate mofetil in new renal transplant recipients was conducted considering the viewpoint of the health insurance system. METHODS: The analysis was based on the results of three controlled randomized double-blind clinical trials comparing mycophenolate mofetil with placebo or azathioprine in 1003 out of 1493 included patients respectively. Health care costs associated with each event were determined by 7 French experts in renal transplantation working in six different hospitals. Direct cumulative costs for each strategy were compared. RESULTS: The studies demonstrated a difference in the incidence of acute rejection and treatment failures whatever the cause. The three trials showed that, compared with current strategies, use of mycophynolate mofetil in the immunosuppression protocol generated a 19 to 38% cost reduction during the 6 months after transplantation. Cost reduction resulted from lower incidence of acute rejection and the subsequent nephrectomics and dialysis sessions. The sensitivity analysis on the most important cost factors-cost of hospitalization per day and number of hospitalization days-confirmed strength of the results. CONCLUSION: Use of mycophenolate mofetil in the immunosuppressive prophylaxis protocol after renal transplantation allows a reduction in the direct costs during the 6 months following transplantation.