[The relationship of mental health providers with health insurers; an exploration]. / De ggz in relatie tot zorgverzekeraars; een verkenning.

BACKGROUND: In 2020, Zorgverzekeraars Nederland (ZN), the umbrella organization of nine health insurers in The Netherlands. presented a vision of the future of mental health care in the Netherlands in ‘De GGZ in 2025. Vergezicht op de geestelijke gezondheidszorg’ (‘Outlook on mental health care’). This document can be seen as marking the fact that key stakeholders share a common vision on the future of the GGZ in the Netherlands. Contracting care is often difficult. The tension between providing quality and sufficient care and available funding leads to friction. Congruence in vision, goals and practices are important conditions for adequate relationship building. Does the vision document contribute to this? AIM: To discuss the experiences of mental health care administrators and health insurers in contracting and collaboration. METHOD: Conducting interviews with both directors of mental health institutions and the strategic (policy) advisors of health insurers. In the approach we used the salience model. RESULTS: The relationship between mental health care administrators and health insurers is perceived to be distrustful and complex, and has deteriorated slightly in 2021 compared to 2019. Perceived power, legitimacy and urgency affect the relationship. Almost all health insurers are characterized as dominant stakeholders based on the salience model. Both parties are open to improving the relationship, which requires more transparency and mutual understanding. CONCLUSION: With the supported content of the vision document, there is to some extent shared governance. The change steps (shared innovation) considered desirable will be promoted by partly granting the intended benefits to each other (shared savings).

Clinical outcomes of uninterrupted embryo culture with or without time-lapse-based embryo selection versus interrupted standard culture (SelecTIMO): a three-armed, multicentre, double-blind, randomised controlled trial.

BACKGROUND: Time-lapse monitoring is increasingly used in fertility laboratories to culture and select embryos for transfer. This method is offered to couples with the promise of improving pregnancy chances, even though there is currently insufficient evidence for superior clinical results. We aimed to evaluate whether a potential improvement by time-lapse monitoring is caused by the time-lapse-based embryo selection method itself or the uninterrupted culture environment that is part of the system. METHODS: In this three-armed, multicentre, double-blind, randomised controlled trial, couples undergoing in-vitro fertilisation or intracytoplasmic sperm injection were recruited from 15 fertility clinics in the Netherlands and randomly assigned using a web-based, computerised randomisation service to one of three groups. Couples and physicians were masked to treatment group, but embryologists and laboratory technicians could not be. The time-lapse early embryo viability assessment (EEVA; TLE) group received embryo selection based on the EEVA time-lapse selection method and uninterrupted culture. The time-lapse routine (TLR) group received routine embryo selection and uninterrupted culture. The control group received routine embryo selection and interrupted culture. The co-primary endpoints were the cumulative ongoing pregnancy rate within 12 months in all women and the ongoing pregnancy rate after fresh single embryo transfer in a good prognosis population. Analysis was by intention to treat. This trial is registered on the ICTRP Search Portal, NTR5423, and is closed to new participants. FINDINGS: 1731 couples were randomly assigned between June 15, 2017, and March 31, 2020 (577 to the TLE group, 579 to the TLR group, and 575 to the control group). The 12-month cumulative ongoing pregnancy rate did not differ significantly between the three groups: 50·8% (293 of 577) in the TLE group, 50·9% (295 of 579) in the TLR group, and 49·4% (284 of 575) in the control group (p=0·85). The ongoing pregnancy rates after fresh single embryo transfer in a good prognosis population were 38·2% (125 of 327) in the TLE group, 36·8% (119 of 323) in the TLR group, and 37·8% (123 of 325) in the control group (p=0·90). Ten serious adverse events were reported (five TLE, four TLR, and one in the control group), which were not related to study procedures. INTERPRETATION: Neither time-lapse-based embryo selection using the EEVA test nor uninterrupted culture conditions in a time-lapse incubator improved clinical outcomes compared with routine methods. Widespread application of time-lapse monitoring for fertility treatments with the promise of improved results should be questioned. FUNDING: Health Care Efficiency Research programme from Netherlands Organisation for Health Research and Development and Merck.

Economic evaluation of endometrial scratching before the second IVF/ICSI treatment: a cost-effectiveness analysis of a randomized controlled trial (SCRaTCH trial).

STUDY QUESTION: Is a single endometrial scratch prior to the second fresh IVF/ICSI treatment cost-effective compared to no scratch, when evaluated over a 12-month follow-up period? SUMMARY ANSWER: The incremental cost-effectiveness ratio (ICER) for an endometrial scratch was €6524 per additional live birth, but due to uncertainty regarding the increase in live birth rate this has to be interpreted with caution. WHAT IS KNOWN ALREADY: Endometrial scratching is thought to improve the chances of success in couples with previously failed embryo implantation in IVF/ICSI treatment. It has been widely implemented in daily practice, despite the lack of conclusive evidence of its effectiveness and without investigating whether scratching allows for a cost-effective method to reduce the number of IVF/ICSI cycles needed to achieve a live birth. STUDY DESIGN, SIZE, DURATION: This economic evaluation is based on a multicentre randomized controlled trial carried out in the Netherlands (SCRaTCH trial) that compared a single scratch prior to the second IVF/ICSI treatment with no scratch in couples with a failed full first IVF/ICSI cycle. Follow-up was 12 months after randomization.Economic evaluation was performed from a healthcare and societal perspective by taking both direct medical costs and lost productivity costs into account. It was performed for the primary outcome of biochemical pregnancy leading to live birth after 12 months of follow-up as well as the secondary outcome of live birth after the second fresh IVF/ICSI treatment (i.e. the first after randomization). To allow for worldwide interpretation of the data, cost level scenario analysis and sensitivity analysis was performed. PARTICIPANTS/MATERIALS, SETTING, METHODS: From January 2016 until July 2018, 933 women with a failed first IVF/ICSI cycle were included in the trial. Data on treatment and pregnancy were recorded up until 12 months after randomization, and the resulting live birth outcomes (even if after 12 months) were also recorded.Total costs were calculated for the second fresh IVF/ICSI treatment and for the full 12 month period for each participant. We included costs of all treatments, medication, complications and lost productivity costs. Cost-effectiveness analysis was carried out by calculating ICERs for scratch compared to control. Bootstrap resampling was used to estimate the uncertainty around cost and effect differences and ICERs. In the sensitivity and scenario analyses, various unit costs for a single scratch were introduced, amongst them, unit costs as they apply for the United Kingdom (UK). MAIN RESULTS AND THE ROLE OF CHANCE: More live births occurred in the scratch group, but this also came with increased costs over a 12-month period. The estimated chance of a live birth after 12 months of follow-up was 44.1% in the scratch group compared to 39.3% in the control group (risk difference 4.8%, 95% CI -1.6% to +11.2%). The mean costs were on average €283 (95% CI: -€299 to €810) higher in the scratch group so that the point average ICER was €5846 per additional live birth. The ICER estimate was surrounded with a high level of uncertainty, as indicated by the fact that the cost-effectiveness acceptability curve (CEAC) showed that there is an 80% chance that endometrial scratching is cost-effective if society is willing to pay ∼€17 500 for each additional live birth. LIMITATIONS, REASONS FOR CAUTION: There was a high uncertainty surrounding the effects, mainly in the clinical effect, i.e. the difference in the chance of live birth, which meant that a single straightforward conclusion could not be ascertained as for now. WIDER IMPLICATIONS OF THE FINDINGS: This is the first formal cost-effectiveness analysis of endometrial scratching in women undergoing IVF/ICSI treatment. The results presented in this manuscript cannot provide a clear-cut expenditure for one additional birth, but they do allow for estimating costs per additional live birth in different scenarios once the clinical effectiveness of scratching is known. As the SCRaTCH trial was the only trial with a follow-up of 12 months, it allows for the most complete estimation of costs to date. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMW, the Dutch organization for funding healthcare research. A.E.P.C., F.J.M.B., E.R.G. and C.B. L. reported having received fees or grants during, but outside of, this trial. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NL5193/NTR 5342).

Is home-based monitoring of ovulation to time frozen embryo transfer a cost-effective alternative for hospital-based monitoring of ovulation? Study protocol of the multicentre, non-inferiority Antarctica-2 randomised controlled trial.

STUDY QUESTION: The objective of this trial is to compare the effectiveness and costs of true natural cycle (true NC-) frozen embryo transfer (FET) using urinary LH tests to modified NC-FET using repeated ultrasound monitoring and ovulation trigger to time FET in the NC. Secondary outcomes are the cancellation rates of FET (ovulation before hCG or no dominant follicle, no ovulation by LH urine test, poor embryo survival), pregnancy outcomes (miscarriage rate, clinical pregnancy rates, multiple ongoing pregnancy rates, live birth rates, costs) and neonatal outcomes (including gestational age, birthweight and sex, congenital abnormalities or diseases of babies born). WHAT IS KNOWN ALREADY: FET is at the heart of modern IVF. To allow implantation of the thawed embryo, the endometrium must be prepared either by exogenous oestrogen and progesterone supplementation (artificial cycle (AC)-FET) or by using the NC to produce endogenous oestradiol before and progesterone after ovulation to time the transfer of the thawed embryo (NC-FET). During an NC-FET, women visit the hospital repeatedly and receive an ovulation trigger to time FET (i.e. modified (m)NC-FET or hospital-based monitoring). From the woman's point of view, a more natural approach using home-based monitoring of the ovulation with LH urine tests to allow a natural ovulation to time FET may be desired (true NC-FET or home-based monitoring). STUDY DESIGN SIZE DURATION: This is a multicentre, non-inferiority prospective randomised controlled trial design. Consenting women will undergo one FET cycle using either true NC-FET or mNC-FET based on randomisation. PARTICIPANTS/MATERIALS SETTING METHODS: Based on our sample size calculation, the study group will consist of 1464 women between 18 and 45 years old who are scheduled for FET. Women with anovulatory cycles, women who need ovulation induction and women with a contra indication for pregnancy will be excluded. The primary outcome is ongoing pregnancy. Secondary outcomes are cancellation rates of FET, pregnancy outcomes (including miscarriage rate, clinical pregnancy, multiple pregnancy rate and live birth rate). Costs will be estimated by counting resource use and calculating unit prices. STUDY FUNDING/COMPETING INTERESTS: The study received a grant from the Dutch Organisation for Health Research and Development (ZonMw 843002807; www.zonmw.nl). ZonMw has no role in the design of the study, collection, analysis, and interpretation of data or writing of the manuscript. F.B. reports personal fees from member of the external advisory board for Merck Serono, grants from Research support grant Merck Serono, outside the submitted work. A.E.P.C. reports and Unrestricted grant of Ferring B.V. to the Center for Reproductive medicine, no personal fee. Author up-to-date on Hyperthecosis. Congress meetings 2019 with Ferring B.V. and Theramex B.V. M.G. reports Department research and educational grants from Guerbet, Merck and Ferring (location VUMC) outside the submitted work. E.R.G. reports personal fees from Titus Health Care, outside the submitted work. C.B.L. reports grants from Ferring, grants from Merck, from Guerbet, outside the submitted work. The other authors have none to declare. TRIAL REGISTRATION NUMBER: Dutch Trial Register (Trial NL6414 (NTR6590), https://www.trialregister.nl/). TRIAL REGISTRATION DATE: 23 July 2017. DATE OF FIRST PATIENT'S ENROLMENT: 10 April 2018.

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH).

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratching could have no or even a small negative effect. Biochemical pregnancy loss and miscarriage rate did not differ between the two groups: in the scratch group 27/153 biochemical pregnancy losses and 14/126 miscarriages occurred, while this was 19/130 and 17/111 for the control group (RR 1.21 (95% CI 0.71-2.07) and RR 0.73 (95% CI 0.38-1.40), respectively). After 12 months of follow-up, 5.1% more live births were observed in the scratch group (202/467 versus 178/466), of which the true difference most likely lies between -1.2% and +11.4% (95% CI). LIMITATIONS, REASONS FOR CAUTION: This study was not blinded. Knowledge of allocation may have been an incentive for participants allocated to the scratch group to continue treatment in situations where they may otherwise have cancelled or stopped. In addition, this study was powered to detect a difference in live birth rate of 9%. WIDER IMPLICATIONS OF THE FINDINGS: The results of this study are an incentive for further assessment of the efficacy and clinical implications of endometrial scratching. If a true effect exists, it may be smaller than previously anticipated or may be limited to specific groups of women undergoing IVF/ICSI. Studying this will require larger sample sizes, which will be provided by the ongoing international individual participant data-analysis (PROSPERO CRD42017079120). At present, endometrial scratching should not be performed outside of clinical trials. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMW, the Dutch organisation for funding healthcare research. J.S.E. Laven reports grants and personal fees from AnshLabs (Webster, Tx, USA), Ferring (Hoofddorp, The Netherlands) and Ministry of Health (CIBG, The Hague, The Netherlands) outside the submitted work. A.E.P. Cantineau reports 'other' from Ferring BV, personal fees from Up to date Hyperthecosis, 'other' from Theramex BV, outside the submitted work. E.R. Groenewoud reports grants from Titus Health Care during the conduct of the study. A.M. van Heusden reports personal fees from Merck Serono, personal fees from Ferring, personal fees from Goodlife, outside the submitted work. F.J.M. Broekmans reports personal fees as Member of the external advisory board for Ferring BV, The Netherlands, personal fees as Member of the external advisory board for Merck Serono, The Netherlands, personal fees as Member of the external advisory for Gedeon Richter, Belgium, personal fees from Educational activities for Ferring BV, The Netherlands, grants from Research support grant Merck Serono, grants from Research support grant Ferring, personal fees from Advisory and consultancy work Roche, outside the submitted work. C.B. Lambalk reports grants from Ferring, grants from Merck, grants from Guerbet, outside the submitted work. TRIAL REGISTRATION NUMBER: Registered in the Netherlands Trial Register (NL5193/NTR 5342). TRIAL REGISTRATION DATE: 31 July 2015. DATE OF FIRST PATIENT'S ENROLMENT: 26 January 2016.

Study protocol of a double-blind randomised placebo-controlled trial on the effect of a multispecies probiotic on the incidence of antibiotic-associated diarrhoea in persons with spinal cord injury.

STUDY DESIGN: Multi-centre, double-blind randomised placebo-controlled study. OBJECTIVE: To investigate whether the use of a multispecies probiotic can prevent antibiotic-associated diarrhoea in people with spinal cord injury (SCI). SETTING: Three Dutch SCI rehabilitation centres. METHODS: Fifty-six people aged 18-75 years with SCI during inpatient rehabilitation, who require antibiotics, will be given probiotics or placebo randomly assigned (T0). After cessation of the antibiotics (T1), the participants will use probiotics/placebo for 3 more weeks (T2). Defaecation, assessed by the Bristol Stool Scale, and bowel management will be monitored daily until 2 weeks after cessation of probiotics/placebo intake (T3). Also, the degree of nausea and information on quality of life will be collected at T0, T1, T2 and T3. MAIN OUTCOME MEASURES: The difference between the incidence of antibiotic-associated diarrhoea between people with SCI using probiotics compared to those using a placebo at the moment the antibiotics stops, the probiotics stops and two weeks thereafter. SECONDARY OUTCOME MEASURES: The time to reach effective bowel management, degree of nausea and quality of life. REGISTRATION: The Dutch Trial Register- NTR 5831.

Endometrial scratching in women with implantation failure after a first IVF/ICSI cycle; does it lead to a higher live birth rate? The SCRaTCH study: a randomized controlled trial (NTR 5342).

BACKGROUND: Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called 'scratching', has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle. METHOD: Multicenter randomized controlled trial in Dutch academic and non-academic hospitals. A total of 900 women will be included of whom half will undergo an endometrial scratch in the luteal phase of the cycle prior to controlled ovarian hyperstimulation using an endometrial biopsy catheter. The primary endpoint is the live birth rate after the 2nd fresh IVF/ICSI cycle. Secondary endpoints are costs, cumulative live birth rate (after the full 2nd IVF/ICSI cycle and over 12 months of follow-up); clinical and ongoing pregnancy rate; multiple pregnancy rate; miscarriage rate and endometrial tissue parameters associated with implantation failure. DISCUSSION: Multiple studies have been performed to investigate the effect of endometrial scratching on live birth rates in women undergoing IVF/ICSI cycles. Due to heterogeneity in both the method and population being scratched, it remains unclear which group of women will benefit from the procedure. The SCRaTCH trial proposed here aims to investigate the effect of endometrial scratching prior to controlled ovarian hyperstimulation in a large group of women undergoing a second IVF/ICSI cycle. TRIAL REGISTRATION: NTR 5342 , registered July 31st, 2015. PROTOCOL VERSION: Version 4.10, January 4th, 2017.

Interactions of full-fat canola seed, oat hulls as an insoluble fiber source and pellet temperature for nutrient utilization and growth performance of broiler chickens.

The effectiveness of the addition of oat hulls (OH) as an insoluble fiber for improving nutrient digestibility and performance of birds fed diets containing full-fat canola seed (CS) was studied. A 2 × 2 × 2 factorial arrangement of treatments was used to assess the main effects of canola source (CS vs canola meal plus oil as control), OH (0 or 3%), pellet temperature (75 and 90°C) and their interactions. A total of 576 male day-old Ross 308 chickens were assigned to 8 experimental treatments, each replicated 6 times (12 birds per replicate). All birds were fed a same commercial starter diet for the first 10 d of age. Canola meal and canola oil in the control diets were replaced with CS at 11.6% and 13.5% in the grower (d 10 to 24) and finisher (d 24 to 35) diets, respectively. An interaction was observed between canola source and OH led to improved body weight gain (P < 0.01) and FCR (P < 0.05) in birds fed the combination of CS and OH in grower phase. Pelleting temperature at 75 vs 90°C did not affect performance of broilers. Birds fed diets containing OH had heavier gizzards at 24 and 35 d of age. Inclusion of CS in the diets depressed fat digestibility at d 24 (P < 0.001) and AME of the grower diets. At d 35, there was a significant interaction (P < 0.05) between CS and pellet temperature where birds fed CS diets pelleted at 75°C had higher fat digestibility than birds fed CS pelleted at 90°C. Regardless of canola source or pellet temperature, OH increased fat utilization at d 35 (P < 0.001) but had no effect on AME of the grower diets. In conclusion, CS can replace supplemental oil in broiler diets when an adequate source of insoluble fiber is included in the diet, which may help to maintain feed intake of broilers fed CS in steam-pelleted diets.

Trace metal distributions in the sediments of the Little Akaki River, Addis Ababa, Ethiopia.

The levels and distribution of trace metals (Cr, Mn, Co, Ni, Cu, Zn, Cd and Pb) at eleven water and sediment stations on the Little Akaki River (LAR) in Addis Ababa, Ethiopia, were determined. The binding forms of the metals in various geochemical fractions of the sediments were also quantified. The molar ratio of the sum of the simultaneously extractable metals (∑SEM) and acid-volatile sulphide (AVS)-as a measure for predicting metal-induced toxicity-was estimated. LAR trace levels in water for Cu, Zn, and, particularly Mn were, in most instances, higher than the recommended guidelines for healthy aquatic ecosystems. Total trace metal (TTM) contents in the LAR sediments at certain stations exceeded "threshold effect concentrations" and even "probable effect concentrations", especially in the cases of Zn, Cu, Ni, Pb, and at all stations for Mn. This became more apparent after applying "normalizations" to the relatively lower TTM adsorption capacities of coarse-grained, organic-poor sediments. Sequential extraction of the sediments showed that trace metals generally have a higher affinity for Fe-Mn oxide and organic matter/sulphidic fractions, followed by the residual fraction. Mn was relatively strongly bound to the exchangeable, carbonate bound fractions, whereas a large proportion of Cr was found in the residual fraction. The Σ[SEM]/[AVS] ratio pointed to potential metal-induced toxicity of sediments collected from seven out of the eleven stations. The results indicate that trace metal pollution pose risks to the health of ecosystems, and to human communities that use the river for a range of different purposes.

Randomized clinical trial on the effect of a multispecies probiotic on visceroperception in hypersensitive IBS patients.

BACKGROUND: Irritable bowel syndrome (IBS) is characterized by heterogeneous pathophysiology and low response to treatment. Up to 60% of IBS patients suffers from visceral hypersensitivity, which is associated with symptom severity and underlying pathophysiological mechanisms. Recently, positive effects of probiotics in IBS have been reported, but overall the response was modest. We performed a study in IBS patients, characterized by visceral hypersensitivity measured with the rectal barostat, aiming to assess the effect of 6 weeks of multispecies probiotic mix on visceral pain perception. METHODS: We conducted a randomized, placebo-controlled, double-blind trial in forty Rome III IBS patients with visceral hypersensitivity. Prior to intake, patients kept a 2-week symptom diary and underwent a rectal barostat measurement. When hypersensitivity was confirmed, participation was allowed and patients received a multispecies probiotic with in vitro proven potential beneficial effects on mechanisms contributing to visceral hypersensitivity (six different probiotic strains; 10(9)  cfu/g), or a placebo product of one sachet (5 g) per day for 6 weeks. At the end of the intervention period, visceroperception and symptoms were reassessed. KEY RESULTS: Thirty-five patients completed the trial. The percentage of patients with visceral hypersensitivity decreased significantly in the probiotic and placebo group (76.5% and 71.4%, respectively; N.S. between groups). Improvement in pain scores and mean symptom score did not differ between the probiotic and placebo group. CONCLUSIONS & INFERENCES: In this placebo-controlled trial in IBS patients with visceral hypersensitivity, no significant effect of a multispecies probiotic on viscerperception was observed. The study has been registered in the US National Library of Medicine (http://www.clinicaltrials.gov, NCT00702026).

A new cinnamoylglycoflavonoid, antimycobacterial and antioxidant constituents from Heritiera littoralis leaf extracts.

A new cinnamolyglycoflavonoid 3-cinnamoyltribuloside (1), its precursor tribuloside and two known flavonoid glycosides afzelin and astilbin were isolated from Heritiera littoralis Dryand (Sterculiaceae) ethanolic leaf extract. The dichloromethane leaf extract afforded two known pentacyclic triterpenoids, 3ß-taraxerol and friedelin. Extracts and compounds isolated therefrom, with the exception of 3ß-taraxerol, exhibited antimycobacterial activity against the non-pathogenic Mycobacterium species Mycobacterium madagascariense and Mycobacterium indicus pranii, with a minimum inhibitory concentration (MIC) 5.0 mg/mL for the crude extracts and MICs in the range of 1.6-0.8 mg/mL for the pure compounds. The extracts together with 3-cinnamoyltribuloside (1), tribuloside and astilbin exhibited 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity. The compounds that showed dual activities could be further evaluated under clinical settings for co-administration with standard anti-tuberculosis drugs.

Benefits and drawbacks of short-course preoperative radiotherapy in rectal cancer patients aged 75 years and older.

PURPOSE: To study incidence of local recurrences, postoperative complications and survival, in patients with rectal carcinoma aged 75 years and older, treated with either surgery and pre-operative 5 × 5 Gy radiotherapy or surgery alone. PATIENTS AND METHODS: A random sample of patients aged over 75 years with pT2-T3, N0-2, M0 rectal carcinoma diagnosed between 2002 and 2004 in the Netherlands was included, treated with surgery alone (N = 296) or surgery in combination with pre-operative radiotherapy (N = 346). Information on local recurrent disease, postoperative complications, ECOG-performance score and comorbidity was gathered from the medical files. RESULTS: Local recurrences developed less frequently in patients treated with pre-operative radiotherapy compared to surgery alone (2% vs 6%, p = 0.002). Postoperative complications developed more frequently in irradiated patients (58% vs 42%, p < 0.0001). Especially deep infections (anastomotic leakage, pelvic abscess) were significantly increased in this group (16% vs 10%, p = 0.02). 30-day mortality was equal in both groups (8%). A significant increase in postoperative complication rate and 30-day mortality was only seen in those with "severe comorbidity" compared to patients without comorbidity (respectively 58% and 10% vs 43% and 3%), COPD (59% and 12%), diabetes (60% and 11%) and cerebrovascular disease (62% and 14%). In multivariable analysis, postoperative complications predicted 5-year survival. CONCLUSION: Elderly patients receiving pre-operative radiotherapy show a lower local recurrence rate. However, as incidence rates of local recurrent disease are low and incidence of postoperative complications is increased in irradiated patients, omitting preoperative RT may be suitable in elderly patients with additional risks for complications or early death.

[Immunoadsorption in thrombangiitis obliterans: a promising therapeutic option: results of a consecutive patient cohort treated in clinical routine care]. / Immunadsorption bei Thrombangiitis obliterans - eine vielversprechende therapeutische Option. Behandlungsergebnisse einer konsekutiven Patientenkohorte der klinischen Routineversorgung.

BACKGROUND: Thrombangiitis obliterans or Buerger's disease is a segmental inflammatory disease affecting small and medium-sized veins and arteries, which most often affects young smokers leading to thrombophlebitis and acral ischaemic syndromes, inducing high amputation rates. Based on positive results of a former pilot study we report on our results of immunoadsorption (IA) in clinical routine care, where IA was offered as a treatment option. PATIENTS AND METHODS: The uncontrolled course of 12 consecutive TAO-patients treated by IA on a series of 5 consecutive days was observed. Follow-up period was 14.1 (ranging from 1-26) months. RESULTS: Eight patients were treated with one, four patients completed 2 IA-series. In 9 patients an early onset and lasting clinical improvement and an improvement of ischaemia was noted. The intake of pain-relievers (especially opioids) sank drastically. Eight patients returned to work. Retrospectively, in two out of three treatment failures the correct diagnosis of TAO was questionable. CONCLUSION: IA seems to be a promising treatment option for patients suffering from TAO which should be further evaluated in controlled clinical trials.

Brachytherapy after external beam radiotherapy and limited surgery preserves bladders for patients with solitary pT1-pT3 bladder tumors.

BACKGROUND: Several French, Belgian and Dutch radiation oncologists have reported good results with the combination of limited surgery after external beam radiotherapy (EBRT) followed by brachytherapy in early-stage muscle-invasive bladder cancer. PATIENTS AND METHODS: Data from 12 of 13 departments which are using this approach have been collected retrospectively, in a multicenter database, resulting in 1040 patients: 811 males and 229 females with a median age of 66 years, range 28-92 years. Results were analyzed according to tumor stage and diameter, histology grade, age and brachytherapy technique, continuous low-dose rate (CLDR) and pulsed dose rate (PDR). RESULTS: At 1, 3 and 5 years, the local recurrence-free probability was 91%, 80% and 75%, metastasis-free probability was 91%, 80% and 74%, disease-free probability was 85%, 68% and 61% and overall survival probability was 91%, 74% and 62%, respectively. The differences in the outcome between the contributing departments were small. After multivariate analysis, the only factor influencing the local control rate was the brachytherapy technique. Toxicity consisted mainly of 24 fistula, 144 ulcers/necroses and 93 other types. CONCLUSIONS: EBRT followed by brachytherapy, combined with limited surgery, offers excellent results in terms of bladder sparing for selected groups of patients suffering from bladder cancer.

Short communication: Effect of automatic postmilking teat disinfection and cluster flushing on the milking work routine.

The importance of a consistent and comprehensive milking routine as a critical component of any mastitis control program is well documented. However, as pressure on time increases, farmers are faced with 3 options: (1) adjust the milking routine to suit the time available, (2) undertake the task less thoroughly, or (3) examine which elements of the milking routine can be automated and substitute capital expenditure for labor. A study was undertaken on 5 farms in the United Kingdom in October and November 2007 to assess the effect on milking time of installing a commercial automatic postmilking teat disinfection and cluster back flushing system (ADF). Two of the farms recruited for the study were intending to purchase the ADF system in the near future and 3 farms had already invested in the technology. The farms ranged in size from 120 to 550 cows and included three 90° rapid exit parlors, a herringbone parlor, and an abreast parlor. All 5 farms were visited for 2 successive milkings before the ADF was installed or disabled, and a detailed time and motion analysis was undertaken. After ADF was installed or the system reactivated, a further 2 milkings were monitored. All monitored farms showed a measurable reduction in milking time after the ADF system was installed. However, the magnitude of the reduction was greater than would be expected by simply removing the elements of postmilking teat disinfection and cluster sanitization. The benefits of ADF are greater than simply disinfecting teats and back flushing clusters and the time saving obtained may allow a more structured milking routine that may have additional benefits in terms of mastitis prevention and control.

Mapping use of radiotherapy for patients with non-small cell lung cancer in the Netherlands between 1997 and 2008.

AIM: After the publication of several reports that the utilisation rate of radiotherapy for patients with non-small cell lung cancer (NSCLC) varies for both medical and non-medical reasons, the utilisation of radiotherapy was studied in four regions in the Netherlands. MATERIALS AND METHODS: Data from 1997-2008 were collected from the population-based cancer registries of four comprehensive cancer centres ('regions'), which represent about half of the Dutch population, resulting in 24 185 non-metastatic patients with NSCLC. Treatment had to be started or planned within 6 months of diagnosis. We evaluated the utilisation of radiotherapy according to age, gender and period for each region. RESULTS: The utilisation of radiotherapy alone decreased over time (from 35 to 19%), whereas the utilisation of radiotherapy in combination with chemotherapy increased (from 5 to 19%). The total utilisation rate remained rather stable at about 40%. The differences between the four regions remained in general no more than 15%. Elderly patients with stage I and II disease had increased odds of receiving radiotherapy (≥75 versus <50 years: odds ratio 2.6, 95% confidence interval 2.0-3.3, whereas this was the opposite for patients with stage III disease: odds ratio 0.5, 95% confidence interval 0.4-0.6). For 17-24% of all patients, especially the elderly, best supportive care was applied. CONCLUSIONS: In the Netherlands, with good accessibility to medical care and well-implemented national guidelines, variation between the four regions is limited for the treatment of non-metastatic NSCLC with radiotherapy.

Use of primary radiotherapy for rectal cancer in the Netherlands between 1997 and 2008: a population-based study.

AIMS: To describe variation in the utilisation rates of primary radiotherapy for patients with rectal cancer in the Netherlands, focusing on time trends and age effects. MATERIALS AND METHODS: Data on primary non-metastatic rectal cancer were derived from the population-based cancer registries of four comprehensive cancer centres (regions) in the Netherlands (1997-2008, n=13,055). RESULTS: An increase in the utilisation rate was noted for the four regions, from 37-46% in 1997 to 66-76% in 2008, for both genders. This increase was found predominately for preoperative radiotherapy (from 13-31% to 58-67%) and (unsurprisingly) was most pronounced for stage T2-3 patients (from 9-27% to 68-80%). The probability of receiving radiotherapy decreased with age: the odds of receiving preoperative radiotherapy was reduced in patients aged 65 years and older, as well as the odds of receiving postoperative radiotherapy in those aged 75 years and older, which remained significant after adjustment for stage, gender and region. Regional differences persisted in multivariable analyses, i.e. the odds of receiving preoperative radiotherapy was reduced in two regions: odds ratio: 0.4 (95% confidence interval: 0.4-0.5) and 0.7 (0.6-0.8). The odds of receiving postoperative radiotherapy was significantly increased in these regions [odds ratio: 2.6 (2.2-3.2) and 1.6 (1.3-1.9), respectively] and reduced in another [odds ratio 0.8 (0.6-0.96)]. CONCLUSIONS: The utilisation rate of radiotherapy for rectal cancer increased significantly over time, particularly for preoperative radiotherapy and was most pronounced for T2-3 patients. Due to national multidisciplinary treatment guidelines, regional differences became limited in recent years after adjustment for age and stage of the disease. A low utilisation rate of radiotherapy was seen in women and elderly patients.

Assessing cancer patients' trust in their oncologist: development and validation of the Trust in Oncologist Scale (TiOS).

PURPOSE: The aim of this study was to develop and validate the Trust in Oncologist Scale (TiOS), which aims to measure cancer patients' trust in their oncologist. Structure, reliability and validity were examined. METHODS: Construction of the TiOS was based on a multidimensional theoretical framework. Cancer patients were surveyed within a week after their consultation. Trust, satisfaction, trust in health care, self-reported health and background variables were assessed. Dimensionality, internal consistency, test-retest reliability and construct validity were investigated. RESULTS: Data of 423 patients were included (response rate = 65%). After item reduction, the TiOS included 18 items. Trust scores were high. Exploratory factor analysis suggested one-dimensionality. Confirmatory factor analysis nevertheless indicated a reasonable fit of our four-dimensional theoretical model, distinguishing competence, fidelity, honesty and caring. Internal consistency and test-retest reliabilities were high. Good construct validity was indicated by moderate correlations of trust (TiOS) with satisfaction, trust in health care, willingness to recommend and number of consultations with the oncologist. Exploratory analyses suggested significant correlations of trust with ethnicity and age. CONCLUSIONS: The TiOS reliably and validly assesses cancer patients' trust in their oncologist. The questionnaire can be employed in both clinical practice and future research of cancer patients' trust.