Oxygen debt repayment in the early phase of veno-arterial extracorporeal membrane oxygenation: a cluster analysis.

INTRODUCTION: Early oxygen debt repayment is predictive of successful weaning from veno-arterial extracorporeal membrane oxygenation (V-A ECMO). However, studies are limited by the patient cohort's heterogeneity. This study aimed to understand the early state of oxygen debt repayment and its association with end-organ failure and 30-day survival using cluster analysis. METHODS: A retrospective, single-center study was conducted on 153V-A ECMO patients. Patients were clustered using a two-step cluster analysis based on oxygen debt and its repayment during the first 24 h of ECMO. Primary outcomes were end-organ failure and 30-day survival. RESULTS: The overall mortality was 69.3%. For cluster analysis, 137 patients were included, due to an incomplete data set. The mortality rate in this subset was 67.9%. Three clusters were generated, representing increasing levels of total oxygen debt from cluster 1 to cluster 3. Thirty-day survival between clusters was significantly different (cluster 1: 46.9%, cluster 2: 23.4%, and cluster 3: 4.8%, p = 0.001). Patients in cluster 3 showed less decrement in liver enzymes, creatinine, and urea blood levels. There were significant differences in the baseline oxygen debt and the need for continuous veno-venous hemofiltration (CVVH) between survivors and non-survivors (p < 0.05). Forty-seven patients (34.3%) migrated between clusters within the first 24 h of support. Among these patients, 43.4% required CVVH. Notably, patients requiring CVVH and who migrated to a cluster with a higher oxygen debt repayment showed better survival rates compared to those who migrated to a cluster with a lower oxygen debt repayment. CONCLUSIONS: Oxygen debt repayment during the first 24 h of V-A ECMO shows to correspond with survival, where the baseline oxygen debt value and the necessity for continuous kidney replacement therapy appear to be influential.

Revision for coronal malalignment will improve functional outcome up to 5 years postoperatively.

PURPOSE: Revision of a total knee arthroplasty (TKA) for the diagnosis of malalignment is widely performed. However, very little is known about the functional outcome in revision TKA surgery for malalignment. The aim of this study was to assess the functional outcome and to identify factors influencing the functional outcome of patients who have had a revision of a TKA for the diagnosis of malalignment at 5 years follow-up. METHODS: All patients with a revision of a TKA for malalignment as the primary reason were selected from a prospective database. The diagnosis of symptomatic malalignment was made by the surgeon and quantified by radiologic examination. Functional outcome was scored by the functional score of the Knee Society Clinical Rating System (fKSS) at 0, 12, 24 and 60 months. Multiple imputation for missing data and multivariable analysis were performed to identify factors influencing functional outcome. RESULTS: After selection, 105 patients (age: 65.1 ± 9.1 years, gender M:F 30:75) were eligible for outcome analysis. Functional outcome significantly improved from the preoperative (fKSS: 44.1 ± 22.0) to 5 years postoperative (64.7 ± 24.0, p < 0.001) time frames. Higher degree of coronal deviation, younger age and lower preoperative KSS were found to be strongest positive influencing factors for the change in fKSS. CONCLUSION: Revision of TKA for malalignment appears to be an effective treatment to improve functional outcome up to 5 years postoperatively. Higher degree of coronal deviation, younger age and lower preoperative KSS are the strongest contributing factors for functional improvement. LEVEL OF EVIDENCE: Level III; Therapeutic prospective cohort study.

A multicentre cluster-randomized clinical trial to improve antibiotic use and reduce length of stay in hospitals: comparison of three measurement and feedback methods.

BACKGROUND: Various metrics of hospital antibiotic use might assist in guiding antimicrobial stewardship (AMS). OBJECTIVES: To compare patient outcomes in association with three methods to measure and feedback information on hospital antibiotic use when used in developing an AMS intervention. METHODS: Three methods were randomly allocated to 42 clusters from 21 Dutch hospitals: (1) feedback on quantity of antibiotic use [DDD, days-of-therapy (DOT) from hospital pharmacy data], versus feedback on (2) validated, or (3) non-validated quality indicators from point prevalence studies. Using this feedback together with an implementation tool, stewardship teams systematically developed and performed improvement strategies. The hospital length of stay (LOS) was the primary outcome and secondary outcomes included DOT, ICU stay and hospital mortality. Data were collected before (February-May 2015) and after (February-May 2017) the intervention period. RESULTS: The geometric mean hospital LOS decreased from 9.5 days (95% CI 8.9-10.1, 4245 patients) at baseline to 9.0 days (95% CI 8.5-9.6, 4195 patients) after intervention (P < 0.001). No differences in effect on LOS or secondary outcomes were found between methods. Feedback on quality of antibiotic use was used more often to identify improvement targets and was preferred over feedback on quantity of use. Consistent use of the implementation tool seemed to increase effectiveness of the AMS intervention. CONCLUSIONS: The decrease in LOS versus baseline likely reflects improvement in the quality of antibiotic use with the stewardship intervention. While the outcomes with the three methods were otherwise similar, stewardship teams preferred data on the quality over the quantity of antibiotic use.

Can the PROPER intervention reduce psychotropic drug prescription in nursing home residents with dementia? Results of a cluster-randomized controlled trial.

OBJECTIVES: To evaluate the effect of the PROPER intervention in nursing home residents with dementia on the prevalence of psychotropic drug use and neuropsychiatric symptoms. DESIGN: A cluster-randomized controlled design with two parallel groups (intervention versus usual care) and assessments at 0, 6, 12, and 18 months. SETTING: Thirty-one dementia special care units within 13 long-term care organizations in the Netherlands. PARTICIPANTS: Three hundred eighty nursing home residents with dementia. INTERVENTION: The PROPER intervention consisted of a structured and repeated multidisciplinary medication review, supported by education and continuous evaluation. MEASUREMENTS: Prescriptions of antipsychotics, antidepressants, anxiolytics, and hypnotics, and occurrence of neuropsychiatric symptoms. RESULTS: The prescription of any type of psychotropic drugs increased in the intervention group, and decreased in the control group, with an estimated difference of 3.9 percentage points per 6 months (p = 0.01). Effects for the individual drug groups were minor (differences of 1.6 percentage points and below per 6 months) and not statistically significant. The occurrence of neuropsychiatric symptoms remained stable in both the intervention and control groups during the follow-up of 18 months. CONCLUSIONS: The PROPER intervention failed to demonstrate effectiveness in reducing the prevalence of psychotropic drugs. It may be interesting to enrich the intervention with components that address personal attitudes and communication between nursing home professionals, not only with respect to the prescription of psychotropic drugs, but also to neuropsychiatric symptoms.The study has been registered in The Netherlands Trial Register (NTR3569).

Evaluating the social fitness Programme for older people with cognitive problems and their caregivers: lessons learned from a failed trial.

BACKGROUND: This process evaluation article describes the lessons learned from a failed trial which aimed to assess effectiveness of the tailor-made, multidisciplinary Social Fitness Programme to improve social participation of community-dwelling older people with cognitive problems (clients) and their caregivers (couples). METHODS: A process evaluation was performed to get insight in 1) the implementation of the intervention, 2) the context of intervention delivery from professionals' point of view, and 3) the potential impact of intervention delivery from participants' perspectives. Data was gathered using mixed-methods: questionnaires, focus group discussions, interviews, medical records. RESULTS: 1) Implementation. High study decline (65,3%) was mainly caused by a lack of internal motivation to increase social participation expressed by clients. 17 couples participated, however, intervention delivery was insufficient. 2) Context. Barriers during intervention delivery were most often related to client (changing needs), caregiver (increased burden) and health professional factors (delivery of integrated care lacked routine). 3) Impact Qualitative analyses revealed participants to be satisfied with intervention delivery, we were unable to capture these results through our primary outcome measure. CONCLUSIONS: This process evaluation revealed the Social Fitness study did not fit in three ways. First, framing the intervention on social participation promotion was as threatening to clients. The feeling of being unable to adequately contribute to social interactions seemed to be causing embarrassment. Second, the intervention seemed to be too complex to implement in the way it was designed. Third, there is a tension between the offering of a personalised tailor-made intervention and evaluation through a fixed study design. TRIAL REGISTRATION: The trial which is evaluated in this article (the Social Fitness study) is registered with the Dutch Trial Register (NTR), clinical trial number NTR4347 .

Meta-analysis of ultrasound-guided biopsy of suspicious axillary lymph nodes in the selection of patients with extensive axillary tumour burden in breast cancer.

BACKGROUND: Recent studies show that not all patients with breast cancer and positive axillary lymph nodes need additional axillary surgery. A systematic review and meta-analysis of the literature was performed to test the hypothesis that ultrasound-guided biopsy of suspicious nodes can be a useful tool to identify patients with extensive axillary tumour burden. METHODS: PubMed and Embase were searched to identify articles reporting on ultrasound-guided techniques to stage the axilla of patients with breast cancer. The emphasis was to study the number of positive nodes found after axillary lymph node dissection (ALND) following a positive ultrasound-guided biopsy or a positive sentinel lymph node biopsy (SLNB). Information regarding the number of positive nodes thus had to be available. Results were tested for heterogeneity and a meta-analysis was performed. RESULTS: A total of 894 articles were identified, and 115 were selected based on title and abstract information by two independent reviewers. After extensive review, 18 articles were eligible for analysis. Eight studies reported sufficient data to perform a meta-analysis comparing 532 patients with a positive ultrasound-guided biopsy with 248 patients with a negative ultrasound-guided biopsy but a positive SLNB. The number of involved nodes was significantly higher in patients in whom axillary metastasis was detected by ultrasound-guided biopsy (P < 0·001). No heterogeneity in the observed effect was found (I(2) = 22 per cent, P = 0·26). CONCLUSION: Patients with breast cancer in whom axillary metastases are detected by ultrasound-guided biopsy have significantly more involved nodes than SLNB-positive patients. This finding enables further preoperative tailoring of axillary treatment in breast cancer.

Single-arm trials supporting the approval of anticancer medicinal products in the European Union: contextualization of trial results and observed clinical benefit.

BACKGROUND: Single-arm trials (SATs) can sometimes be used to support marketing authorization of anticancer medicinal products in the European Union. The level and durability of antitumor activity of the product as well as context are important aspects to determine the relevance of trial results. The aim of this study is to provide details on the contextualization of trial results and to evaluate the magnitude of benefit of medicinal products approved based on SATs. MATERIALS AND METHODS: We focused on anticancer medicinal products for solid tumors approved on the basis of SAT results (2012-2021). Data were retrieved from European public assessment reports and/or published literature. The benefit of these medicinal products was evaluated via the European Society for Medical Oncology (ESMO)-Magnitude of Clinical Benefit Scale (MCBS). RESULTS: Eighteen medicinal products were approved based on 21 SATs-few medicinal products were supported by >1 SAT. For the majority of clinical trials, a clinically relevant treatment effect was (pre)specified (71.4%) and most often an accompanying sample size calculation was provided. For 10 studies, each testing a different medicinal product, a justification for the threshold for a clinically relevant treatment effect could be identified. At least 12 out of 18 applications included information to facilitate the contextualization of trial results, including six supportive studies. Of the pivotal SATs analyzed (n = 21), three were assigned an ESMO-MCBS score of 4, which corresponds to 'substantial' benefit. CONCLUSIONS: The clinical relevance of the treatment effects shown by medicinal products for solid tumors tested in SATs is dependent on the effect size and context. To better facilitate regulatory decision making, prespecifying and motivating a clinically relevant effect and aligning the sample size to that effect is important. External controls may facilitate in the contextualization process, but the associated limitations must be addressed.

MicroRNA expression in formalin-fixed paraffin embedded tissue using real time quantitative PCR: the strengths and pitfalls.

MicroRNAs (miRNAs) are a group of small non-coding RNAs with a huge impact in a wide range of biological processes, including cancer. The evidence collected to date demonstrates that miRNAs represent valid diagnostic, prognostic and predictive markers in cancer. The identification of these miRNA biomarkers in archived tissues has been facilitated by novel development and refinement of detection methodologies. Quantitative real-time reverse-transcription PCR (qRT-PCR) is one of the most common methods used to detect low levels of miRNAs with high sensitivity and specificity. However, several technical parameters should be identified and optimized in order to obtain meaningful and reproducible results. The purpose of this review is to describe some of these technical parameters and improve the validity and reliability of miRNA expression studies.

KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients.

BACKGROUND: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor antibody in metastatic colorectal cancer (CRC). KRAS mutation analysis is usually performed on primary tumour tissue because metastatic tissue is often not available. However, controversial data are available on the concordance of test results between primary tumours and corresponding metastases. We assessed the concordance of KRAS mutation status in a study of 305 primary colorectal tumours and their corresponding liver metastases. METHODS: Patients with histologically confirmed CRC who underwent surgical resection of the primary tumour and biopsy or surgical resection of the corresponding liver metastasis were included. KRAS mutation analysis was performed for codons 12 and 13. RESULTS: KRAS mutation was detected in 108 out of 305 primary tumours (35.4%). In 11 cases (3.6%), we found a discordance between primary tumour and metastasis: 5 primary tumours had a KRAS mutation with a wild-type metastasis, 1 primary tumour was wild type with a KRAS mutation in the metastasis, and in 5 cases the primary tumour and the metastasis had a different KRAS mutation. CONCLUSION: We observed a high concordance of KRAS mutation status of 96.4% (95% CI 93.6-98.2%) between primary colorectal tumours and their corresponding liver metastases. In only six patients (2.0%; 95% CI 0.7-4.2%), the discordance was clinically relevant. In this largest and most homogenous study to date, we conclude that both primary tumours and liver metastases can be used for KRAS mutation analysis.

Systematic review of the effect of external beam radiation therapy to the breast on axillary recurrence after negative sentinel lymph node biopsy.

BACKGROUND: Axillary recurrence after negative sentinel lymph node biopsy (SLNB) in patients with invasive breast carcinoma remains a concern. Previous investigations to identify prognostic factors for axillary recurrence identified that a disproportionate number of patients with an axillary recurrence after negative SLNB were not treated with external beam radiation therapy (EBRT) of the breast as part of initial treatment. This finding prompted a systematic review to test the hypothesis that EBRT to the breast reduces the risk of axillary recurrence after negative SLNB. METHODS: A literature search was performed in PubMed, the Cochrane Library and the Spanish-language database LILACS to identify articles publishing data regarding follow-up of sentinel lymph node (SLN)-negative patients. Reports and articles lacking information on the initial treatment were excluded. RESULTS: Forty-five articles were accepted for review. A total of 23,357 SLN-negative patients were identified with median follow-up ranging from 15 to 102 months. Some 18,878 patients were treated with EBRT to the breast as part of their initial treatment. One hundred and twenty-seven patients with an axillary recurrence were identified, of whom 73 had EBRT as part of their initial treatment. Meta-analysis showed that EBRT was associated with a lower rate of axillary recurrence (P < 0·001), but this finding was subject to heterogeneity. CONCLUSION: This review and meta-analysis showed that EBRT is associated with a significantly lower axillary recurrence rate after negative SLNB.

High body mass index and pre-existing autoimmune disease are associated with an increased risk of immune-related adverse events in cancer patients treated with PD-(L)1 inhibitors across different solid tumors.

BACKGROUND: Treatment with anti-PD-(L)1 antibodies, approved for several oncology indications, can lead to immune-related adverse events (irAEs). We aimed to investigate risk factors associated with an increased reporting of irAEs in patients treated with PD-(L)1 inhibitors approved for solid tumor indications. PATIENTS AND METHODS: A retrospective review was performed of individual data from patients in phase II/III registrational studies for PD-(L)1 inhibitors in solid tumors. Data on baseline characteristics and adverse events were extracted. Univariate and multivariable logistic regression models were used to identify risk factors. RESULTS: In total, 5123 patients were included from 15 studies reporting on the use of four PD-(L)1 inhibitors for five solid tumor indications. Univariate analysis suggested that type of study drug (P < 0.001), indication (P = 0.003), body mass index (BMI) (P = 0.001), and baseline autoimmune disease (P < 0.001) were associated with an increased occurrence of any irAE. Using logistic regression analyses, three factors were identified as increasing the risk of irAE: BMI ≥ 30 kg/m2 [odds ratio (OR) 1.5, 95% confidence interval (CI) 1.2-1.8] in comparison to normal BMI, having an autoimmune disease at baseline (OR 1.8, 95% CI 1.1-2.7), and use of a PD-L1 inhibitor (OR 1.6, 95% CI 1.2-2.0). The latter finding is probably biased due to the selection of the studies in the dataset with complete information on baseline characteristics. CONCLUSION: This study was conducted using a large dataset of individual patient data from clinical trials comprising multiple solid tumor indications. We demonstrated that patients with obesity and concurrent autoimmune disease were at increased risk of developing irAEs.

Clinicopathological features and outcome in advanced colorectal cancer patients with synchronous vs metachronous metastases.

BACKGROUND: Synchronous metastases of colorectal cancer (CRC) are considered to be of worse prognostic value compared with metachronous metastases, but only few and conflicting data have been reported on this issue. METHODS: We retrospectively investigated patient demographics, primary tumour characteristics and overall survival (OS) in 550 advanced CRC patients with metachronous vs synchronous metastases, who participated in the phase III CAIRO study. For this purpose only patients with a prior resection of the primary tumour were considered. RESULTS: The clinical and pathological characteristics associated with poor prognosis that we observed more often in patients with synchronous metastases (n=280) concerned an abnormal serum lactate dehydrogenase (LDH) concentration (P=0.01), a worse WHO performance status (P=0.02), primary tumour localisation in the colon (P=0.002) and a higher T stage (P=0.0006). No significant difference in median OS was observed between patients with synchronous metastases and metachronous metastases (17.6 vs 18.5 months, respectively, P=0.24). CONCLUSION: Despite unfavourable clinicopathological features in patients with synchronous metastases with a resected primary tumour compared to patients with metachronous metastases, no difference in the median OS was observed. Possible explanations include a (partial) chemoresistance in patients with metachronous disease because of previous adjuvant treatment, whereas differences between the two groups in screening procedures resulting in a lead time bias to diagnosis or in prognostic molecular markers remain speculative.

A narrative review of estimands in drug development and regulatory evaluation: old wine in new barrels?

BACKGROUND: An estimand defines the target of estimation for a clinical trial through specification of the treatment, target population, variable, population-level summary and of the strategies for intercurrent events. A carefully defined estimand aligns the clinical trial design and analysis with the scientific question of interest and adequately accounts for so-called intercurrent events. The ICH E9(R1) addendum suggests five estimand strategies. We evaluated to what extent current practice in drug development and regulatory assessment fits in the estimand framework. METHODS: We systematically evaluated what estimands, especially what strategies for intercurrent events are advised in European Medicines Agency disease guidelines, used in sponsors' trials and additionally requested by the European Medicines Agency in assessment dossiers. We selected four therapeutic areas: nervous system, oncology, cardiovascular diseases and respiratory diseases. For each, we evaluated all disease guidelines with approved drugs, the dossiers of the most recently approved drugs matching the guidelines and corresponding regulatory questions. RESULTS: Strategies for intercurrent events were present in 18 (53%) of 34 guidelines, in all 34 sponsor documentations and in 15 (44%) of 34 sets of regulatory questions. Treatment policy was advised in 13 (38%) guidelines and was applied in 9 corresponding sponsor documentations. Of these 9, it was the sole strategy in 4 cases and accompanied by another strategy in 5 cases. Hypothetical strategy was not advised in guidelines. However, it was the leading strategy applied in 25 (74%) sponsor documentations. Composite strategy was advised in 3 (9%) guidelines and applied accompanied by another strategy in 2 corresponding sponsor documentations. While on treatment strategy was not advised in guidelines, but was applied in 2 sponsor documentations. Principal stratum strategy was advised in 2 guidelines but not applied in corresponding sponsor documentations. Of the regulatory questions, treatment policy was present in 2 cases (6%), hypothetical in 6 cases (18%), composite in 6 cases (18%) and while on treatment in 1 case (3%). CONCLUSIONS: Estimand attributes are present in guidelines, sponsor documentations and regulatory questions, but not described as estimands. Treatment policy was most often advised in guidelines, but hypothetical was the leading strategy applied in sponsor documentations. Thus, results indicate not a full concordance between the regulatory target of estimation and what is actually estimated. The lack of concordance was mostly due to limitations in collection of intercurrent events data to enable a treatment policy strategy. There is, therefore, a need to better define estimands at the design stage and throughout the applications dossiers and assessment reports.

Toxicity testing of human assisted reproduction devices using the mouse embryo assay.

Systems to assess the toxicity of materials used in human assisted reproduction currently lack efficiency and/or sufficient discriminatory power. The development of 1-cell CBA/B6 F1 hybrid mouse embryos to blastocysts, expressed as blastocyst rate (BR), is used to measure toxicity. The embryos were divided into control and test groups, and were exposed to either control medium or to a potentially toxic test medium. Inferences on toxicity were based on differences in BR between the two groups. The mouse embryo assay followed a stratified (mouse), randomized (embryo), and balanced (equal number of embryos per group and per mouse) design. The number of embryos needed was calculated using power analysis. The basal BR of the hybrid strain was determined in a historical population. Sixty-nine mouse embryos per group were required to detect toxic materials with sufficient sensitivity and to account for the considerable inter-mouse variation in blastocyst development. Fifty-two samples, divided over batches of seven different products were tested before use in the study IVF centre and five of these were found to be toxic. This test system, presented as the Nijmegen mouse embryo assay (NMEA), can be used to detect embryo-toxic materials in daily IVF practice, and this report may provide a starting point for standardization.

An in-home geriatric programme for vulnerable community-dwelling older people improves the detection of dementia in primary care.

BACKGROUND/OBJECTIVE: Dementia is under-diagnosed in primary care. This study investigated whether an in-home geriatric assessment and management programme could improve the identification of patients with dementia in primary care. METHODS: A secondary analysis was performed, using data of a randomised controlled trial that studied the effects of an in-home geriatric evaluation and management programme compared with usual care. In this trial, 151 vulnerable community-dwelling patients, aged 70 years and older, participated: 86 in the intervention group and 66 in de control group. The effect of the programme on the dementia detection rate was determined by comparing the number of new dementia diagnoses in both study arms at 6 months follow-up. RESULTS: Of all 151 participants, 38 (25%) had a registered dementia diagnosis at baseline. During follow-up, 23 of 113 patients without a registered dementia diagnosis at baseline were identified as suffering from dementia. The difference between the numbers of new dementia diagnoses in the intervention group (19 of 66 patients) and the control group (4 of 47 patients) was significant. (p = 0.02) CONCLUSION: An in-home geriatric assessment and management programme for vulnerable older patients improves the detection of dementia and can therefore contribute to overcoming of under-diagnosis of dementia.

Pseudo cluster randomization dealt with selection bias and contamination in clinical trials.

BACKGROUND AND OBJECTIVES: When contamination is present, randomization on a patient level leads to dilution of the treatment effect. The usual solution is to randomize on a cluster level, but at the cost of efficiency and more importantly, this may introduce selection bias. Furthermore, it may slow down recruitment in the clusters that are randomized to the "less interesting" treatment. We discuss an alternative randomization procedure to approach these problems. METHODS: Pseudo cluster randomization is a two-stage randomization procedure that balances between individual randomization and cluster randomization. For common scenarios, the design factors needed to calculate the appropriate sample size are tabulated. RESULTS: A pseudo cluster randomized design can reduce selection bias and contamination, while maintaining good efficiency and possibly improving enrollment. To make a well-informed choice of randomization procedure, we discuss the advantages of each method and provide a decision flow chart. CONCLUSION: When contamination is thought to be substantial in an individually randomized setting and a cluster randomized design would suffer from selection bias and/or slow recruitment, pseudo cluster randomization can be considered.

Physical therapy aimed at self-management versus usual care physical therapy after hip arthroscopy for femoroacetabular impingement: study protocol for a randomized controlled trial.

BACKGROUND: Femoroacetabular impingement has been recognized as a common cause of hip pain and dysfunction, especially in athletes. Femoroacetabular impingement can now be better treated by hip arthroscopy but it is unclear what postoperative rehabilitation of hip arthroscopy should look like. Several rehabilitation protocols have been described, but none presented clinical outcome data. These protocols also differ in frequency, duration and level of supervision. We developed a rehabilitation protocol with supervised physical therapy which showed good clinical results and is considered usual care in our treatment center. However, it is unknown whether, due to the relatively young age and low complication rate of hip arthroscopy patients, rehabilitation based on self-management might lead to similar results. The aims of this pilot study are (1) to determine feasibility and acceptability of the self-management intervention, (2) to obtain a preliminary estimate of the difference in effect between physical therapy aimed at self-management versus usual care physical therapy in patients who undergo hip arthroscopy for femoroacetabular impingement. METHODS/DESIGN: Thirty participants (aged 18-50 years) scheduled for hip arthroscopy will be included and randomized (after surgery) to either self-management or usual care physical therapy in this assessor-blinded randomized controlled trial. After surgery, the self-management group will perform a home-based exercise program three times a week and will receive physical therapy treatment once every 2 weeks for 14 weeks. The usual care group will receive physical therapy treatment twice a week for 14 weeks and will perform an additional home-based exercise program once a week. Assessment will occur preoperatively and at 6, 14, 26 and 52 weeks after surgery. Primary outcomes are feasibility, acceptability and preliminary effectiveness. Feasibility and acceptability will be determined by the willingness to enroll, recruitment rate, adherence to treatment, patient satisfaction, drop-out rate and adverse events. Preliminary effectiveness will be determined using the following outcomes: the International Hip Outcome Tool 33 and hip functional performance as measured with the Single Leg Squat Test 14 weeks after surgery. DISCUSSION: The results of this study will be used to help decide on the need, feasibility and acceptability of a large-scale randomized controlled trial. TRIAL REGISTRATION: This protocol was registered with the Dutch Trial Registry (NTR5168) on 8 May 2015.

Mechanical vs. manual cleaning of hospital beds: a prospective intervention study.

BACKGROUND: Cleaning regimens for hospital beds were evaluated in the context of a rising prevalence of highly resistant micro-organisms and increasing financial pressure on healthcare systems. Dutch hospitals have to choose between standardized, mechanical bed-washers advised in national guidance and manual cleaning. AIM: To evaluate the quality of mechanical and manual bed-cleaning regimens. METHODS: The multi-faceted analysis of bed-cleaning regimens consisted of three steps. In Step 1, the training of the domestic service team was evaluated. In Step 2, the cleaning quality of manual and mechanical regimens was assessed. Soiled beds, obtained at random, from different departments were evaluated using microbiological analysis (N = 40) and ATP (N = 20). ATP and microbiological contamination were measured in five predetermined locations on all beds. In Step 3, manual cleaning was introduced over a two-month pilot study at the surgical short-stay unit, and beds from other departments were processed according to the 'gold standard' mechanical cleaning. ATP levels were evaluated in three locations on 300 beds after cleaning. FINDINGS: Training was found to improve the quality of cleaning significantly. Mechanical cleaning resulted in significantly lower ATP levels than manual cleaning. CONCLUSIONS: Mechanical cleaning shows less variation and results in consistently lower ATP levels than manual cleaning.

Interchangeability of gabapentin generic formulations in the Netherlands: a comparative bioavailability study.

To investigate the so-called "drift" with generic-generic drug substitution, a single-dose, four-way crossover comparative bioavailability study was performed involving 24 healthy subjects and three generic and one branded formulation of a tablet containing 800 mg gabapentin as test medication. The results showed that the 90% confidence intervals (CIs) for the area under the drug concentration-time curve (AUC(0-t)) and for the peak drug concentration (C(max)) were within the acceptance range of 80-125% for all comparisons. The safety profiles of the different gabapentin formulations were comparable. To conclude, all three generic formulations of gabapentin were found to be bioequivalent with the branded formulation and with each other, indicating that the formulations are interchangeable. These results strongly indicate the absence of "drift" with gabapentin generic-generic substitution.