Appropriate medication use in Dutch terminal care: study protocol of a multicentre stepped-wedge cluster randomized controlled trial (the AMUSE study).

BACKGROUND: Polypharmacy is common among patients with a limited life expectancy, even shortly before death. This is partly inevitable, because these patients often have multiple symptoms which need to be alleviated. However, the use of potentially inappropriate medications (PIMs) in these patients is also common. Although patients and relatives are often willing to deprescribe medication, physicians are sometimes reluctant due to the lack of evidence on appropriate medication management for patients in the last phase of life. The aim of the AMUSE study is to investigate whether the use of CDSS-OPTIMED, a software program that gives weekly personalized medication recommendations to attending physicians of patients with a limited life expectancy, improves patients' quality of life. METHODS: A multicentre stepped-wedge cluster randomized controlled trial will be conducted among patients with a life expectancy of three months or less. The stepped-wedge cluster design, where the clusters are the different study sites, involves sequential crossover of clusters from control to intervention until all clusters are exposed. In total, seven sites (4 hospitals, 2 general practices and 1 hospice from the Netherlands) will participate in this study. During the control period, patients will receive 'care as usual'. During the intervention period, CDSS-OPTIMED will be activated. CDSS-OPTIMED is a validated software program that analyses the use of medication based on a specific set of clinical rules for patients with a limited life expectancy. The software program will provide the attending physicians with weekly personalized medication recommendations. The primary outcome of this study is patients' quality of life two weeks after baseline assessment as measured by the EORTC QLQ-C15-PAL questionnaire, quality of life question. DISCUSSION: This will be the first study investigating the effect of weekly personalized medication recommendations to attending physicians on the quality of life of patients with a limited life expectancy. We hypothesize that the CDSS-OPTIMED intervention could lead to improved quality of life in patients with a life expectancy of three months or less. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05351281, Registration Date: April 11, 2022).

[The revised version of the Y-BOCS: responsivity and other psychometric properties]. / De herziene versie van de Y-BOCS: responsiviteit en andere psychometrische eigenschappen.

BACKGROUND: The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) is a widely used semi structured clinician-rated interview to assess the presence and severity of obsessive-compulsive disorder (OCD). The scale is revised (Y-BOCS-II) to overcome several psychometric limitations, for example by extending the scoring for better discrimination within higher severity levels. AIM: To examine the responsiveness and other psychometric properties of the Y-BOCS-II in a Dutch clinical sample. METHOD: The Y-BOCS-II was translated into Dutch (Y-BOCS-II) and administered to 110 patients seeking therapy for OCD. This was done twice, before and after treatment. The original Y-BOCS was simultaneously rated. Self-report measures regarding depression, symptom severity and OCD symptoms were assessed. RESULTS: The Y-BOCS-II had a good internal consistency (Cronbach’s α = 0.84), test-retest (ICC = 0.81) and inter-rater reliability (ICC = 0.94). The construct validity proved to be modest to good. The responsiveness over time was in favour of the Y-BOCS-II, compared with the YBOCS-I, particularly in the severely affected OCD patients. CONCLUSION: The Y-BOCS-II severity scale is a reliable and valid instrument for accurately assessing the severity of OCD symptoms and for measuring treatment-induced change. This second version also has clinical and psychometric advantages over the YBOCS-I. When these findings are sufficiently replicated, use of the YBOCS-II as the new common standard seems recommendable.

Transdiagnostic factors predicting the 2-year disability outcome in patients with anxiety and depressive disorders.

BACKGROUND: Both anxiety and depressive disorders are associated with significant long-term disability. Since experienced impairments vary between patients independent of diagnosis and disease severity, identifying transdiagnostic factors that predict the course of disability may provide new targets to reduce disability. This study examines transdiagnostic factors predicting the 2-year disability outcome in patients with anxiety and/or depressive disorders (ADD), focusing on potentially malleable factors. METHODS: Six hundred fifteen participants with a current diagnosis of ADD from the Netherlands Study of Depression and Anxiety (NESDA) were included. Disability was assessed at baseline and after 2 years of follow-up, using the 32-item WHODAS II questionnaire. Transdiagnostic predictors of 2-year disability outcome were identified using linear regression analysis. RESULTS: In univariable analyses, transdiagnostic factors associated with the 2-year disability outcome were locus of control (standardized ß = -0.116, p = 0.011), extraversion (standardized ß = -0.123 p = 0.004) and experiential avoidance (standardized ß = 0.139, p = 0.001). In multivariable analysis, extraversion had a unique predictive value (standardized ß = -0.143 p = 0.003). A combination of sociodemographic, clinical and transdiagnostic variables resulted in an explained variance (R2) of 0.090). The explained variance of a combination of transdiagnostic factors was 0.050. CONCLUSION: The studied transdiagnostic variables explain a small but unique part of variability in the 2-year disability outcome. Extraversion is the only malleable transdiagnostic factor predictive of the course of disability independent of other variables. Due to the small contribution to the variance in the disability outcome, the clinical relevance of targeting extraversion seems limited. However, its predictive value is comparable to that of accepted disease severity measures, supporting the importance of looking beyond using disease severity measures as predictors. Furthermore, studies including extraversion in combination with other transdiagnostic and environmental factors may elucidate the unexplained part of variability of the course of disability in patients with ADD.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Does endometrial scratching increase the rate of spontaneous conception in couples with unexplained infertility and a good prognosis (Hunault > 30%)? Study protocol of the SCRaTCH-OFO trial: a randomized controlled trial.

BACKGROUND: In the Netherlands, couples with unexplained infertility and a good prognosis to conceive spontaneously (i.e. Hunault > 30%) are advised to perform timed intercourse for at least another 6 months. If couples fail to conceive within this period, they will usually start assisted reproductive technology (ART). However, treatment of unexplained infertility by ART is empirical and can involve significant burdens. Intentional endometrial injury, also called 'endometrial scratching', has been proposed to positively affect the chance of embryo implantation in patients undergoing in vitro fertilization (IVF). It might also be beneficial for couples with unexplained infertility as defective endometrial receptivity may play a role in these women. The primary aim of this study is to determine whether endometrial scratching increases live birth rates in women with unexplained infertility. METHOD: A multicentre randomized controlled trial will be conducted in Dutch academic and non-academic hospitals starting from November 2017. A total of 792 women with unexplained infertility and a good prognosis for spontaneous conception < 12 months (Hunault > 30%) will be included, of whom half will undergo endometrial scratching in the luteal phase of the natural cycle. The women in the control group will not undergo endometrial scratching. According to Dutch guidelines, both groups will subsequently perform timed intercourse for at least 6 months. The primary endpoint is cumulative live birth rate. Secondary endpoints are clinical and ongoing pregnancy rate; miscarriage rate; biochemical pregnancy loss; multiple pregnancy rate; time to pregnancy; progression to intrauterine insemination (IUI) or IVF; pregnancy complications; complications of endometrial scratching; costs and endometrial tissue parameters associated with reproductive success or failure. The follow-up duration is 12 months. DISCUSSION: Several small studies show a possible beneficial effect of endometrial scratching in women with unexplained infertility trying to conceive naturally or through IUI. However, the quality of this evidence is very low, making it unclear whether these women will truly benefit from this procedure. The SCRaTCH-OFO trial aims to investigate the effect of endometrial scratching on live birth rate in women with unexplained infertility and a good prognosis for spontaneous conception < 12 months. TRIAL REGISTRATION: NTR6687 , registered August 31st, 2017. PROTOCOL VERSION: Version 2.6, November 14th, 2018.

[The general practitioner in charge of treatment of patients with bipolar disorder: an exploratory study]. / De huisarts als primaire behandelaar van patiënten met een bipolaire stoornis: een exploratief onderzoek.

BACKGROUND: The role of the general practitioner (gp) in the treatment of severe psychiatric disorders, including bipolar disorder (bd), is under discussion. AIM: To investigate how many patients with a recognised bd are being treated for their illness exclusively in the setting of primary care and to find out how many patients are registrated as having bd on their gp's file. METHOD: We made an exploratory study in a gp's database containing data for 14,254 Dutch adult patients in the Amsterdam over a period of 3.5 years (2010-2013). RESULTS: We found that the gp was in charge of the treatment of bd in less than one patient per practice. The percentage of patients officially recognised as having bd in the database we studied was 0.15%, a percentage that is much lower than the percentage of bd in the Dutch population as a whole. There are several possible explanations for this discrepancy. CONCLUSION: Given these low numbers, it is unlikely that the gps can have adequate experience of giving their bd patients the latest type of treatment. In view of the increasing role played by gps in the treatment of bd, it is important that there is strong collaboration with specialised mental health care, and that a low threshold prevails for consultation and referral.

Quality of life of patients with chronic lymphocytic leukaemia in the Netherlands: results of a longitudinal multicentre study.

PURPOSE: To describe the health-related quality of life (HRQoL) of an unselected population of patients with chronic lymphocytic leukaemia (CLL) including untreated patients. METHODS: HRQoL was measured by the EORTC QLQ-C30 including the CLL16 module, EQ-5D, and VAS in an observational study over multiple years. All HRQoL measurements per patient were connected and analysed using area under the curve analysis over the entire study duration. The total patient group was compared with the general population, and three groups of CLL patients were described separately, i.e. patients without any active treatment ("watch and wait"), chlorambucil treatment only, and patients with other treatment(s). RESULTS: HRQoL in the total group of CLL patients was compromised when compared with age- and gender-matched norm scores of the general population. CLL patients scored statistically worse on the VAS and utility score of the EQ-5D, all functioning scales of the EORTC QLQ-C30, and the symptoms of fatigue, dyspnoea, sleeping disturbance, appetite loss, and financial difficulties. In untreated patients, the HRQoL was slightly reduced. In all treatment stages, HRQoL was compromised considerably. Patients treated with chlorambucil only scored worse on the EORTC QLQ-C30 than patients who were treated with other treatments with regard to emotional functioning, cognitive functioning, bruises, uncomfortable stomach, and apathy. CONCLUSIONS: CLL patients differ most from the general population on role functioning, fatigue, concerns about future health, and having not enough energy. Once treatment is indicated, HRQoL becomes considerably compromised. This applies to all treatments, including chlorambucil, which is considered to be a mild treatment.

Vaginal birth after a caesarean section: the development of a Western European population-based prediction model for deliveries at term.

OBJECTIVE: To develop and internally validate a model that predicts the outcome of an intended vaginal birth after caesarean (VBAC) for a Western European population that can be used to personalise counselling for deliveries at term. DESIGN: Registration-based retrospective cohort study. SETTING: Five university teaching hospitals, seven non-university teaching hospitals, and five non-university non-teaching hospitals in the Netherlands. POPULATION: A cohort of 515 women with a history of one caesarean section and a viable singleton pregnancy, without a contraindication for intended VBAC, who delivered at term. METHODS: Potential predictors for a vaginal delivery after caesarean section were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN OUTCOME MEASURES: Predictors for VBAC. For model validation, the area under the receiver operating characteristic curve (AUC) for discriminative capacity and calibration-per-risk-quantile for accuracy were calculated. RESULTS: A total of 371 out of 515 women had a VBAC (72%). Variables included in the model were: estimated fetal weight greater than the 90(th) percentile in the third trimester; previous non-progressive labour; previous vaginal delivery; induction of labour; pre-pregnancy body mass index; and ethnicity. The AUC was 71% (95% confidence interval, 95% CI = 69-73%), indicating a good discriminative ability. The calibration plot shows that the predicted probabilities are well calibrated, especially from 65% up, which accounts for 77% of the total study population. CONCLUSION: We developed an appropriate Western European population-based prediction model that is aimed to personalise counselling for term deliveries.

Predicting successful intended vaginal delivery after previous caesarean section: external validation of two predictive models in a Dutch nationwide registration-based cohort with a high intended vaginal delivery rate.

OBJECTIVE: To externally validate two models from the USA (entry-to-care [ETC] and close-to-delivery [CTD]) that predict successful intended vaginal birth after caesarean (VBAC) for the Dutch population. DESIGN: A nationwide registration-based cohort study. SETTING: Seventeen hospitals in the Netherlands. POPULATION: Seven hundred and sixty-three pregnant women, each with one previous caesarean section and a viable singleton cephalic pregnancy without a contraindication for an intended VBAC. METHODS: The ETC model comprises the variables maternal age, prepregnancy body mass index (BMI), ethnicity, previous vaginal delivery, previous VBAC and previous nonprogressive labour. The CTD model replaces prepregnancy BMI with third-trimester BMI and adds estimated gestational age at delivery, hypertensive disease of pregnancy, cervical examination and induction of labour. We included consecutive medical records of eligible women who delivered in 2010. For validation, individual probabilities of women who had an intended VBAC were calculated. MAIN OUTCOME MEASURES: Discriminative performance was assessed with the area under the curve (AUC) of the receiver operating characteristic and predictive performance was assessed with calibration plots and the Hosmer-Lemeshow (H-L) statistic. RESULTS: Five hundred and fifteen (67%) of the 763 women had an intended VBAC; 72% of these (371) had an actual VBAC. The AUCs of the ETC and CTD models were 68% (95% CI 63-72%) and 72% (95% CI 67-76%), respectively. The H-L statistic showed a P-value of 0.167 for the ETC model and P = 0.356 for the CTD model, indicating no lack of fit. CONCLUSION: External validation of two predictive models developed in the USA revealed an adequate performance within the Dutch population.

Bacterial killing and the dimensions of bacterial death.

Bacteria can be dead, alive, or exhibit slowed or suspended life forms, making bacterial death difficult to establish. Here, agar-plating, microscopic-counting, SYTO9/propidium-iodide staining, MTT-conversion, and bioluminescence-imaging were used to determine bacterial death upon exposure to different conditions. Rank correlations between pairs of assay outcomes were low, indicating different assays measure different aspects of bacterial death. Principal-component analysis yielded two principal components, named "reproductive-ability" (PC1) and "metabolic-activity" (PC2). Plotting of these principal components in two-dimensional space revealed a dead region, with borders defined by the PC1 and PC2 values. Sensu stricto implies an unpractical reality that all assays determining PC1 and PC2 must be carried out in order to establish bacterial death. Considering this unpracticality, it is suggested that at least one assay determining reproductive activity (PC1) and one assay determining metabolic activity (PC2) should be used to establish bacterial death. Minimally, researchers should specifically describe which dimension of bacterial death is assessed, when addressing bacterial death.

Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Difference in the risk of serious infections in patients with rheumatoid arthritis treated with adalimumab, infliximab and etanercept: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry.

BACKGROUND: Tumour necrosis factor (TNF)-inhibiting therapy increases the risk of serious infections in rheumatoid arthritis (RA). However, it is not clear whether this risk differs between TNF inhibitors. OBJECTIVE: To analyse whether the risk of serious infections in patients with RA treated with an anti-TNF inhibitor is different for adalimumab, infliximab and etanercept. METHODS: Data from the Dutch RA monitoring registry were used. Incidence rates were calculated from the observed number of first serious infections and follow-up time up to 5 years. A Cox proportional hazards model with time-to-first-serious infection was used to estimate risk differences among the anti-TNF treatment groups, with correction for confounders. RESULTS: The unadjusted incidence rate of a first serious infection in patients with RA per 100 patient-years was 2.61 (95% CI 2.21 to 3.00) for adalimumab, 3.86 (95% CI 3.33 to 4.40) for infliximab and 1.66 (95% CI 1.09 to 2.23) for etanercept. Age, year of starting anti-TNF therapy, comorbidities at baseline and disease activity score 28 over time were included as confounders. No difference in risk for serious infections was found between adalimumab and infliximab with an adjusted HR (adjHR) of 0.90 (95% CI 0.55 to 1.48). The risk of serious infections was significantly lower in etanercept than in both infliximab (adjHR=0.49 (95% CI 0.29 to 0.83)) and adalimumab (adjHR=0.55 (95% CI 0.44 to 0.67)). CONCLUSIONS: The risk of serious infections in patients with RA treated with adalimumab or infliximab was similar, while the risk of serious infections in patients with RA treated with etanercept was lower than with both adalimumab and infliximab.

[Forcing patients with bipolar disorder to make a financial contribution to secondary psychiatric care may make them forsake care completely]. / Vraaguitval bij poliklinische patiënten met een bipolaire stoornis als gevolg van de eigen bijdrage in de tweedelijns-ggz.

BACKGROUND: In 2012 patients were required to make a personal financial contribution for secondary mental health care over and above their standard insurance fee. According to current guidelines, the majority of patients with bipolar disorder must be treated as outpatients at psychiatric clinics. It was to be expected that some patients would decide to discontinue their outpatient treatment on account of the newly imposed personal financial contribution. AIM: To obtain insight into the size and characteristics of the group of patients with bipolar disorder who were thinking about giving up treatment or had already decided to give it up because of the imposition of the personal financial contribution; also to find out which factors influenced patients' decisions and to discover how patients perceived the role of the GP as the provider of subsequent psychiatric care. METHOD: We conducted an exploratory study by sending a survey to all outpatients receiving treatment at three clinics specialising in the treatment of bipolar disorder. RESULTS: 640 patients responded to the survey (55% response); 15% of these patients were thinking about giving up treatment or had already decided to stop their treatment. They were influenced primarily by financial considerations. Two-thirds of the respondents did not consider that the GP was as a suitable alternative to outpatient care at a clinic. Even patients with moderate to serious symptoms were considering leaving secondary care. CONCLUSION: The obligatory financial contribution for secondary mental health care could have considerable consequences for a small number of patients with severe mood disorder who are currently treated as outpatients in secondary facilities. The increase in the compulsory & squo;own risk' insurance fee as from 2013 could have similar consequences.

Using visible light to activate antiviral and antimicrobial properties of TiO2 nanoparticles in paints and coatings: focus on new developments for frequent-touch surfaces in hospitals.

The COVID-19 pandemic refocused scientists the world over to produce technologies that will be able to prevent the spread of such diseases in the future. One area that deservedly receives much attention is the disinfection of health facilities like hospitals, public areas like bathrooms and train stations, and cleaning areas in the food industry. Microorganisms and viruses can attach to and survive on surfaces for a long time in most cases, increasing the risk for infection. One of the most attractive disinfection methods is paints and coatings containing nanoparticles that act as photocatalysts. Of these, titanium dioxide is appealing due to its low cost and photoreactivity. However, on its own, it can only be activated under high-energy UV light due to the high band gap and fast recombination of photogenerated species. The ideal material or coating should be activated under artificial light conditions to impact indoor areas, especially considering wall paints or frequent-touch areas like door handles and elevator buttons. By introducing dopants to TiO2 NPs, the bandgap can be lowered to a state of visible-light photocatalysis occurring. Naturally, many researchers are exploring this property now. This review article highlights the most recent advancements and research on visible-light activation of TiO2-doped NPs in coatings and paints. The progress in fighting air pollution and personal protective equipment is also briefly discussed. Graphical Abstract: Indoor visible-light photocatalytic activation of reactive oxygen species (ROS) over TiO2 nanoparticles in paint to kill bacteria and coat frequently touched surfaces in the medical and food industries.

Risk factors of recurrent hamstring injuries: a systematic review.

BACKGROUND: Although recurrent hamstring injury is a frequent problem with a significant impact on athletes, data on factors determining the risk for a recurrent hamstring injury are scarce. OBJECTIVE: To systematically review the literature and provide an overview of risk factors for re-injury of acute hamstring muscle injuries. STUDY DESIGN: Prospective studies on risk factors for re-injury following acute hamstring injuries were systematically reviewed. Medical databases and reference lists of the included articles were searched. Two reviewers independently selected potential studies and assessed methodological quality; one reviewer extracted the data. A best-evidence synthesis of all studied risk factors was performed. RESULTS: Of the 131 articles identified, five prospective follow-up studies fulfilled our inclusion criteria. These studies reported a recurrence incidence of 13.9-63.3% in the same playing season up to 2 years after initial injury. Limited evidence for three risk factors and one protective factor for recurrent hamstring injury was found; patients with a recurrent hamstring injury had an initial injury with a larger volume size as measured on MRI (47.03 vs 12.42 cm(3)), more often had a Grade 1 initial trauma (Grade 0: 0-30.4%; Grade 1: 60.9-100%; Grade 2: 8.7%) and more often had a previous ipsilateral anterior cruciate ligament (ACL) reconstruction (66.6% vs 17.1%) independent of graft selection. Athletes in a rehabilitation programme with agility/stabilisation exercises rather than strength/stretching exercises had a lower risk for re-injury (7.7% vs 70%). No significant relationship with re-injury was found for 11 related determinants. There was conflicting evidence that a larger cross-sectional area is a risk factor for recurrent hamstring injury. CONCLUSIONS: There is limited evidence that athletes with a larger volume size of initial trauma, a Grade 1 hamstring injury and a previous ipsilateral ACL reconstruction are at increased risk for recurrent hamstring injury. Athletes seem to be at lower risk for re-injury when following agility/stabilisation exercises.

5-(Trifluoro-meth-oxy)isatin.

THE TITLE COMPOUND [SYSTEMATIC NAME: 5-(trifluoro-meth-oxy)-1H-indole-2,3-dione], C9H4F3NO3, crystallized with two mol-ecules in the asymmetric unit. Inter-molecular N-H⋯O hydrogen bonds link the mol-ecules to form layers parallel to the ab plane. In addition, π-π stacking inter-actions are observed with a centroid-centroid distance of 3.721 (1) Å. The near planarity of the two isatin ring systems is illustrated by by the maximum deviations of 0.023 (1) and 0.025 (1) Šfor the N atom in each case.

(µ(1)-Methano-lato-κ(1)O)-µ(1)-methoxo-κ(1)O-(µ(2)-2-amino-1-methyl-5H-imidazol-4-one-κ(2)N:N')-hexa-carbonyl-dirhenium(I).

In the title compound, [Re(2)(CH(3)O)(2)(CO)(6)(C(4)H(6)N(3)O)], the two Re(I) atoms are linked by a methoxo and methanolato bridge, as well as by a creatinine ligand that coordinates in a bidentate fashion. Three fac-carbonyl ligands occupy the rest of the slightly distorted octa-hedral geometry around each Re(I) atom. The bridging methanolato and methoxo ligands are bent out of the Re(2)O(2) plane by 49.2 (4) and 47.8 (3)° respectively. This is normally associated with a methanolato-bridging-type coordination rather that the more planar methoxo-type bridging. Furthermore, the creatinine bridging molecule is very slightly distorted from the Re(2)N(2)C plane, indicating that the pyrazolo N atom bonded to the Rh(I) atom is not protonated. Charge balance can thus only be attained if one assumes a positional disorder for the methanolato/methoxo H atom. All attempts to locate disordered protons around these O atoms were unsuccessful. Four hydrogen bonds, one N-H⋯O and three C-H⋯O, are observed in the structure. The mol-ecules pack in a head-to-head and tail-to-tail fashion when viewed along the c axis, in alternating columns.

N-Benzyl-isatin.

In the title compound, C(15)H(11)NO(2), two C-H⋯O hydrogen bonds are observed in the crystal structure, as well as π-π stacking with a centroid-centroid distance of 3.623 (2) Å. The planarity of the two ring systems is illustrated by very small deviations of all the atoms from these planes [largest deviations = 0.003 (3) and 0.010 (3) Šfor the phenyl and fused-benzene rings, respectively]. The dihedral angle between these two planes is 77.65 (9)°.