Colorectal cancer health and care quality indicators in a federated setting using the Personal Health Train.

OBJECTIVE: Hospitals and healthcare providers should assess and compare the quality of care given to patients and based on this improve the care. In the Netherlands, hospitals provide data to national quality registries, which in return provide annual quality indicators. However, this process is time-consuming, resource intensive and risks patient privacy and confidentiality. In this paper, we presented a multicentric 'Proof of Principle' study for federated calculation of quality indicators in patients with colorectal cancer. The findings suggest that the proposed approach is highly time-efficient and consume significantly lesser resources. MATERIALS AND METHODS: Two quality indicators are calculated in an efficient and privacy presevering federated manner, by i) applying the Findable Accessible Interoperable and Reusable (FAIR) data principles and ii) using the Personal Health Train (PHT) infrastructure. Instead of sharing data to a centralized registry, PHT enables analysis by sending algorithms and sharing only insights from the data. RESULTS: ETL process extracted data from the Electronic Health Record systems of the hospitals, converted them to FAIR data and hosted in RDF endpoints within each hospital. Finally, quality indicators from each center are calculated using PHT and the mean result along with the individual results plotted. DISCUSSION AND CONCLUSION: PHT and FAIR data principles can efficiently calculate quality indicators in a privacy-preserving federated approach and the work can be scaled up both nationally and internationally. Despite this, application of the methodology was largely hampered by ELSI issues. However, the lessons learned from this study can provide other hospitals and researchers to adapt to the process easily and take effective measures in building quality of care infrastructures.

Mid-term survival of the Optimys short stem: A prospective case series of 500 patients.

BACKGROUND: In recent years, there has been an increase in the number of total hip arthroplasty procedures in the younger patient population. This active group has higher expectations of their prosthesis in comparison to the older population, and there is a greater physical demand for the prosthesis. Short femoral stems were introduced to retain proximal bone stock and joint biomechanics and became more common to implant in this specific population. Currently, the long-term survival and functional outcomes of various short stems are still being investigated in different clinics. AIM: To determine the 5-year survival of the Optimys hip stem. METHODS: This was a prospective multicenter cohort study of 500 patients conducted in two hospitals in the Netherlands. All patients received the Optimys short stem (Mathys Ltd, Bettlach, Switzerland). The primary outcome measure was survival of the hip stem, with revision as the endpoint. The secondary outcome measurements included patient-reported outcome measures (PROMs). Kaplan-Meier analysis was used to calculate the 5-year survival rate. Log-minus-log transformation was performed to calculate the 95% confidence interval (95%CI). Mixed model analyses were performed to assess the course of the PROMs during the 1st 2 years after surgery. Analyses were modeled separately for the 1st and 2nd years to calculate the yearly change in PROMs during both follow-up periods with accompanying 95%CIs. RESULTS: The mean age of the total 500 patients was 62.3 years (standard deviation: 10.6) and 202 were male (40%). At a median follow-up of 5.5 years (interquartile range: 4.5-6.7), 7 patients were deceased and 6 revisions were registered, for infection (n = 3), subsidence (n = 2) and malposition (n = 1). This resulted in an overall 5-year survival of 98.8% (95%CI: 97.3-99.5). If infection was left out as reason for revision, a stem survival of 99.4% (95%CI: 98.1-99.8) was seen. Baseline questionnaires were completed by 471 patients (94%), 317 patients (63%) completed the 1-year follow-up questionnaires and 233 patients (47%) completed the 2-year follow-up. Both outcome measures significantly improved across all domains in the 1st year after the operation (P < 0.03 for all domains). In the 2nd year after surgery, no significant changes were observed in any domain in comparison to the 1-year follow-up. CONCLUSION: The Optimys stem has a 5-year survival of 98.8%. Patient-reported outcome measures increased significantly in the 1st postoperative year with stabilization at the 2-year follow-up.

Visit-to-visit blood pressure variability and progression of white matter hyperintensities over 14 years.

Purpose: There is evidence that blood pressure variability (BPV) is associated with cerebral small vessel disease (SVD) and may therefore increase the risk of stroke and dementia. It remains unclear if BPV is associated with SVD progression over years. We examined whether visit-to-visit BPV is associated with white matter hyperintensity (WMH) progression over 14 years and MRI markers after 14 years.Materials and methods: We included participants with SVD from the Radboud University Nijmegen Diffusion tensor Magnetic resonance-imaging Cohort (RUNDMC) who underwent baseline assessment in 2006 and follow-up in 2011, 2015 and 2020. BPV was calculated as coefficient of variation (CV) of BP at all visits. Association between WMH progression rates over 14 years and BPV was examined using linear-mixed effects (LME) model. Regression models were used to examine association between BPV and MRI markers at final visit in participants.Results: A total of 199 participants (60.5 SD 6.6 years) who underwent four MRI scans and BP measurements were included, with mean follow-up of 13.7 (SD 0.5) years. Systolic BPV was associated with higher progression of WMH (ß = 0.013, 95% CI 0.005 - 0.022) and higher risk of incident lacunes (OR: 1.10, 95% CI 1.01-1.21). There was no association between systolic BPV and grey and white matter volumes, Peak Skeleton of Mean Diffusivity (PSMD) or microbleed count after 13.7 years.Conclusions: Visit-to-visit systolic BPV is associated with increased progression of WMH volumes and higher risk of incident lacunes over 14 years in participants with SVD. Future studies are needed to examine causality of this association.

High blood pressure (BP) is very common, especially among older individuals. BP is not constant but tends to go up and down over time.Earlier studies have shown that when your BP fluctuates more, this can give a higher risk of dementia, stroke, cardiovascular events and even mortality. Large BP fluctuations are likely damaging for your brain, but it remains unknown if it leads to progression of brain damage over a longer period of time.This study examined if fluctuations in BP over 14 years are associated with progression of brain damage in older individuals with a mean age of 60.5 years.The results indicate that markers of brain damage progress more in participants with more variation in BP.This suggests that fluctuations in BP can cause damage in your brain to progress more.However, it is difficult to determine based on these results if BP fluctuations are a cause or a result of brain damage. More research is needed to determine what the temporal order of this association is.If variations in BP can indeed damage the brain, we need to focus not only on lowering BP, but also on keeping BP stable when considering treatments.

The validity of ultrasound and shear wave elastography to assess the quality of the rotator cuff.

OBJECTIVES: US with shear wave elastography (SWE) could reduce the burden and costs of the diagnostic process for patients with rotator cuff disorders. The aim of this study is to investigate the validity of US and SWE in preoperative assessment of fatty infiltration (FI) and muscle atrophy of the supraspinatus (SSP) and infraspinatus (ISP) muscles. METHODS: Patients with a rotator cuff disorder and a recent shoulder CT or MRI scan were eligible to participate. Goutallier and Warner stages of the SSP and ISP muscle were measured on the scan, for assessment of FI and muscle atrophy, respectively. These findings were compared with shear wave velocities (SWVs) assessed on US. Visual assessment of FI on US was compared with the Goutallier stage. To quantify the amount of muscle atrophy, the occupation ratio between SSP fossa and muscle was measured on MRI and US. RESULTS: Seventy-eight shoulders were included in the analysis. The correlation found between the occupation ratio on US and Warner and Goutallier stage and ratio on MRI ranged between r = - 0.550 to 0.589. The Goutallier stage of ISP and SSP muscle assessed on US showed a fair correlation with the Goutallier stage on a scan of r = 0.574 and r = 0.582, respectively. There was a poor correlation between the SWVs and scan results (r = - 0.116 to 0.07). CONCLUSION: SWE is not a valid method to measure the amount of FI or muscle atrophy in the SSP muscle. Therefore, SWE is not a suitable alternative for MRI in standard preoperative diagnostics in rotator cuff pathologies. CLINICAL RELEVANCE STATEMENT: Shear wave elastography should not be used in the diagnostics of rotator cuff pathologies. KEY POINTS: • There is a fair correlation between the Goutallier stage of the supraspinatus and infraspinatus muscle assessed on MRI and CT and visual assessment of fatty infiltration achieved on US. • Shear wave elastography is not a valid tool for the determination of the amount of fatty infiltration or muscle atrophy. • Shear wave elastography should not be used as a cheaper and less burdensome alternative for diagnostics in rotator cuff pathologies.

The prevalence and clinical course of shoulder injury related to vaccine administration (SIRVA) after COVID-19 vaccines in Dutch hospital workers.

INTRODUCTION: Shoulder Injury Related to Vaccine Administration (SIRVA) is a rare disorder characterized by persistent shoulder pain and limited range of motion presenting within 48 h after vaccine administration. With the widespread distribution of the COVID-19 vaccine, the incidence of SIRVA is expected to rise. This sudden rise in vaccine administration presents an ideal opportunity to estimate the prevalence of SIRVA and to better characterize SIRVA. OBJECTIVE: This study aims to investigate the prevalence of SIRVA following COVID-19 vaccine administration among hospital workers in the Netherlands. METHODS: A questionnaire was sent to all hospital workers from a single non-academic hospital in the Netherlands. Respondents who had active SIRVA complaints were invited for an outpatient orthopaedic clinic assessment. Data was collected on participant characteristics and physical examination including assessment of active and passive range of motion (ROM). An ultrasound was performed to identify potential abnormalities. RESULTS: 32 out of 981 (3.3%) respondents reported shoulder pain with limited ROM occurring within 48 h after vaccine administration lasting for at least 7 days. Of these 32 respondents with SIRVA, 18 (56.2%) still reported active symptoms at the time of the survey. Clinical examination of 13 (72.2%) respondents with active SIRVA complaints showed limited glenohumeral ROM, limitations in activities of daily living and injection site pain. Twelve out of thirteen (92.3%) respondents with active SIRVA complaints showed abnormalities of the soft-tissue of the shoulder on ultrasound. Physiotherapy was the most common treatment modality for persistent SIRVA complaints (38.9%). CONCLUSIONS: The prevalence of SIRVA is estimated at 3% in the adult working population. Signs and symptoms of SIRVA are variable in severity, localization and timing. Soft-tissue abnormalities is the most common clinical sign. This study contributes to clinician's knowledge on SIRVA, aiding in early recognition and treatment, which are imperative for prevention of persistent and severe shoulder pathology.

Blood-brain barrier leakage hotspots collocating with brain lesions due to sporadic and monogenic small vessel disease.

Blood-brain barrier (BBB) is known to be impaired in cerebral small vessel disease (SVD), and is measurable by dynamic-contrast enhancement (DCE)-MRI. In a cohort of 69 patients (42 sporadic, 27 monogenic SVD), who underwent 3T MRI, including DCE and cerebrovascular reactivity (CVR) sequences, we assessed the relationship of BBB-leakage hotspots to SVD lesions (lacunes, white matter hyperintensities (WMH), and microbleeds). We defined as hotspots the regions with permeability surface area product highest decile on DCE-derived maps within the white matter. We assessed factors associated with the presence and number of hotspots corresponding to SVD lesions in multivariable regression models adjusted for age, WMH volume, number of lacunes, and SVD type. We identified hotspots at lacune edges in 29/46 (63%) patients with lacunes, within WMH in 26/60 (43%) and at the WMH edges in 34/60 (57%) patients with WMH, and microbleed edges in 4/11 (36%) patients with microbleeds. In adjusted analysis, lower WMH-CVR was associated with presence and number of hotspots at lacune edges, and higher WMH volume with hotspots within WMH and at WMH edges, independently of the SVD type. In conclusion, SVD lesions frequently collocate with high BBB-leakage in patients with sporadic and monogenic forms of SVD.

Handheld Ultrasound Does not Replace Magnetic Resonance Imaging for Diagnosis of Rotator Cuff Tears.

Purpose: The purpose of this study was to examine the reliability and validity of handheld ultrasound (HHUS) alone versus conventional ultrasound (US) or magnetic resonance imaging (MRI) for diagnosis of rotator cuff tears and versus MRI plus computed tomography (CT) for diagnosis of fatty infiltration. Methods: Adult patients with shoulder complaints were included in this study. HHUS of the shoulder was performed twice by an orthopedic surgeon and once by a radiologist. RCTs, tear width, retraction and FI were measured. Inter- and intrarater reliability of the HHUS was calculated using a Cohen's kappa coefficient. Criterion and concurrent validity were calculated using a Spearman's correlation coefficient. Results: Sixty-one patients (64 shoulders) were included in this study. Intra-rater agreement of HHUS for assessment of RCTs (к = 0.914, supraspinatus) and FI (к = 0.844, supraspinatus) was moderate to strong. Interrater agreement was none to minimal for the diagnosis of RCTs (к = 0.465, supraspinatus) and FI (к = 0.346, supraspinatus). Concurrent validity of HHUS compared to MRI was fair for diagnosis of RCTs (r = 0.377, supraspinatus) and fair-to-moderate FI (r = 0.608, supraspinatus). HHUS shows a sensitivity of 81.1% and specificity of 62.5% for diagnosis of supraspinatus tears, 60% and 93.1% for subscapularis tears, 55.6% and 88.9% for infraspinatus tears. Conclusions: On the basis of findings in this study, we conclude that HHUS is an aid in diagnosis of RCTs and higher degrees of FI in patients who are not obese, but it does not replace MRI as the gold standard. Further clinical studies on the application of HHUS comparing HHUS devices in larger patient populations and healthy patients are required to identify its utility in clinical practice. Level of Evidence: Level III.

The association between reverse total shoulder arthroplasty neck-shaft angle on postoperative patient experienced shoulder disability: a retrospective cohort study.

Background: The neck-shaft angle (NSA) of the glenoid component used in reverse total shoulder arthroplasty (RTSA) was reduced to improve functional outcomes. This led to a decreased abduction but increased external rotation ability of patients who underwent RTSA. The impact of the decreased NSA on patient-reported shoulder disability is unknown but may have important implications for functional ability. Therefore, the aim of this study was to assess the difference in patient experienced shoulder disability between an NSA of 135° and 155° 12 months after RTSA. Methods: In this retrospective cohort study, 109 patients undergoing RTSA were included. In 68 patients, a glenoid component with an NSA of 135° was used and 41 patients received a glenoid component with an NSA of 155°. The primary outcome was Disabilities of the Arm, Shoulder, and Hand (DASH) scores at 12 months and change scores between baseline and 12-month follow-up. Secondary outcomes were complications, Constant Murley Score, Numeric Rating Scale, active forward elevation and external rotation ability. Differences between groups were tested with t-tests or Mann-Whitney U-tests. Results: A mean difference of 10.0 in 12 months postoperative DASH scores between NSA groups was observed in favor of the 135° NSA (P = .004), which did not exceed the Minimal Clinically Important Difference. DASH changes scores did not differ between NSA groups (P = .652). Mean postoperative Constant Murley Score at 12 months was 11.1 higher in the 135° NSA group (P = .013). No differences were observed in complications (P = .721) and postoperative pain (P = .710) between groups. Difference in postoperative external rotation and forward elevation at 12 months was 10° (P = .022) and 20° (P = .046), respectively, in favor of the 135° NSA group, exceeding Minimal Clinically Important Differences. Conclusions: No clinically important difference in patient-reported shoulder disability (DASH) was found between both groups, despite a larger range of motion in the 135° NSA group. This study is the first to show the impact of NSA on patient-reported shoulder disability using the DASH.

Preoperative community based functional high intensity interval training (f-HIIT) with high-risk patients opting for lumbar spinal fusion: a pilot study.

PURPOSE: To determine the feasibility, safety and preliminary effectiveness of preoperative functional high-intensity interval training (f-HIIT) for high-risk patients undergoing LSF. MATERIALS AND METHODS: High-risk patients eligible for elective 1-3 level LSF were included. Feasibility and safety of the preoperative f-HIIT program was determined by measuring participation and attrition rates, training adherence, adverse events, reached training intensity and preoperative progression in physical fitness. Preliminary effect of the preoperative f-HIIT program was estimated on time to postoperative functional recovery and length of hospital stay (LoS) between high-risk patients who did and did not participate in the prehabilitation program. RESULTS: Eleven out of 23 high-risk patients opted to participate in the f-HIIT program, which was safe and feasible, as no adverse events occurred and only one out of 74 sessions was missed (1.4%). Trained high-risk patients improved their physical fitness with 21.2% on average and obtained faster time to functional recovery compared to matched untrained patients (median 4.5 vs 7.5 days; p = 0.013). No effect was seen on LoS (median 7 vs 8 days (p = 0.58)). CONCLUSIONS: The preoperative f-HIIT program is feasible, safe and shortened time to postoperative functional recovery in patients who underwent LSF.Implications for rehabilitationPreoperative high-intensity interval training is safe and feasible for high-risk patients opting for lumbar spinal fusion.In a relatively small sample the study shows preoperative high-intensity interval training could reduce time to functional recovery in high-risk patients opting for lumbar spinal fusion.

Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study.

BACKGROUND: Small hyperintense lesions are found on diffusion-weighted imaging (DWI) in patients with sporadic small vessel disease (SVD). Their exact role in SVD progression remains unclear due to their asymptomatic and transient nature. The main objective is to investigate the role of DWI+lesions in the radiological progression of SVD and their relationship with clinical outcomes. METHODS: Participants with SVD were included from the Radboud University Nijmegen Diffusion tensor MRI Cohort. DWI+lesions were assessed on four time points over 14 years. Outcome measures included neuroimaging markers of SVD, cognitive performance and clinical outcomes, including stroke, all-cause dementia and all-cause mortality. Linear mixed-effect models and Cox regression models were used to examine the outcome measures in participants with a DWI+lesion (DWI+) and those without a DWI+lesion (DWI-). RESULTS: DWI+lesions were present in 45 out of 503 (8.9%) participants (mean age: 66.7 years (SD=8.3)). Participants with DWI+lesions and at least one follow-up (n=33) had higher white matter hyperintensity progression rates (ß=0.36, 95% CI=0.05 to 0.68, p=0.023), more incident lacunes (incidence rate ratio=2.88, 95% CI=1.80 to 4.67, p<0.001) and greater cognitive decline (ß=-0.03, 95% CI=-0.05 to -0.01, p=0.006) during a median follow-up of 13.2 (IQR: 8.8-13.8) years compared with DWI- participants. No differences were found in risk of all-cause mortality, stroke or dementia. CONCLUSION: Presence of a DWI+lesion in patients with SVD is associated with greater radiological progression of SVD and cognitive decline compared with patients without DWI+lesions.

The Hyperintense study: Assessing the effects of induced blood pressure increase and decrease on MRI markers of cerebral small vessel disease: Study rationale and protocol.

Background: Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to examine cerebrovascular and structural abnormalities, possibly preceding SVD, in young adults with hypertension. These patients undergo a diagnostic work-up that requires patients to temporarily discontinue their antihypertensive agents, often leading to an increase in blood pressure followed by a decrease once effective medication is restarted. This allows examination of the effects of blood pressure increase and decrease on the cerebral small vessels. Methods: Hyperintense is a prospective observational cohort study in 50 hypertensive adults (18-55 years) who will temporarily discontinue antihypertensive medication for diagnostic purposes. MRI and clinical data is collected at four timepoints: before medication withdrawal (baseline), once antihypertensives are largely or completely withdrawn (T = 1), when patients have restarted medication (T = 2) and reached target blood pressure and 1 year later (T = 3). The 3T MRI protocol includes conventional structural sequences and advanced techniques to assess various aspects of microvascular integrity, including blood-brain barrier function using Dynamic Contrast Enhanced MRI, white matter integrity, and microperfusion. Clinical assessments include motor and cognitive examinations and blood sampling. Discussion: The Hyperintense study will improve the understanding of the pathophysiological mechanisms following hypertension that may cause SVD. This knowledge can ultimately help to identify new targets for treatment of SVD, aimed at prevention or limiting disease progression.

Exploring clinically relevant risk profiles in patients undergoing lumbar spinal fusion: a cohort study.

PURPOSE: To explore risk profiles of patients scheduled for lumbar spinal fusion (LSF) and their association with short-term recovery of patient after surgery. METHODS: Forty-nine patients scheduled for elective 1-3 level LSF between March 2019 and June 2020 were included. Patients underwent a preoperative risk screening, consisting of an anamnesis, questionnaires and physical performance tests. A latent profile analysis (LPA) was used to identify possible risk profiles within this population. RESULTS: Two risk profiles could be established: a fit and deconditioned risk profile. A significant between-profile difference was found in smoking status (p = 0.007), RAND36-PCS (p < 0.001), Timed Up and Go (TUG) (p < 0.001), de Morton Morbidity Index (DEMMI) (p < 0.001), finger floor distance (p = 0.050), motor control (p = 0.020) and steep ramp test (p = 0.005). Moreover, the fit risk profile had a significant shorter time to functional recovery (3.65 days versus 4.89 days, p = 0.013) and length of hospital stay (5.06 days versus 6.00 days, p = 0.008) compared to the deconditioned risk profile. No differences in complication rates between both risk profiles could be established. Allocation to a risk profile was associated with the functional recovery rate (p = 0.042), but not with LOS or complications. CONCLUSION: This study found a fit and deconditioned risk profile. The patients with a fit risk profile perceived a better quality of life, performed better in mobility, motor control, cardiopulmonary tests and showed also a significant shorter stay in the hospital and a shorter time to functional recovery. Preoperatively establishing a patient's risk profile could aid in perioperative care planning and preoperative decision-making.

Effectiveness and cost-effectiveness of dynamic bracing versus standard care alone in patients suffering from osteoporotic vertebral compression fractures: protocol for a multicentre, two-armed, parallel-group randomised controlled trial with 12 months of follow-up.

INTRODUCTION: Patients with osteoporosis may suffer from a fracture after minimal trauma. Osteoporotic vertebral compression fractures (OVCFs) are among the most common fractures, often leading to substantial pain. There is a need for evidence-based conservative treatment to aid in the management of OVCFs. The objective of this randomised controlled trial (RCT) is to evaluate the effectiveness and cost-effectiveness of dynamic bracing in addition to standard care for improving quality of life (QoL) in patients suffering from an OVCF. METHODS AND ANALYSIS: Ninety-eight postmenopausal women from two academic and four community hospitals with a recent symptomatic thoracolumbar OVCF will be randomised into either the standard care or dynamic bracing group. In the dynamic bracing group, the Spinova Osteo orthosis will be used in addition to standard care. Standard care comprises pain control with analgesics, physical therapy and osteoporosis medication. The primary outcome parameter is QoL 1 year after inclusion, as measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO-41). Secondary outcome parameters are pain, pain medication used, functional disability, sagittal spinal alignment, recurrence rate of OVCFs and physical activity in daily life. A trial-based economic evaluation consisting of both cost-effectiveness analysis and cost-utility analysis will be performed based on empirical data obtained in the RCT. A process evaluation will assess the feasibility of dynamic bracing. All outcomes will be assessed at baseline, 6 weeks, 3 months, 6 months, 9 months and 12 months. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee, University Hospital Maastricht and Maastricht University (METC azM/UM) (NL74552.068.20/METC 20-055). Patients will be included only after verification of eligibility and obtaining written informed consent. Results will be disseminated via the Dutch National Osteoporosis Patient Society and via publications and conferences. TRIAL REGISTRATION NUMBER: NL8746.

Effects of Cilostazol and Isosorbide Mononitrate on Cerebral Hemodynamics in the LACI-1 Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Cerebral small vessel disease-a major cause of stroke and dementia-is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging-measured cerebrovascular function in patients with lacunar ischemic stroke. METHODS: Participants were randomized to ISMN alone, cilostazol alone, both ISMN and cilostazol, or no medication. Participants underwent structural, cerebrovascular reactivity (to 6% carbon dioxide) and phase-contrast pulsatility magnetic resonance imaging at baseline and after 8 weeks of medication. RESULTS: Of 27 participants (mean age, 68±7.7; 44% female), 22 completed cerebrovascular reactivity and pulsatility imaging with complete datasets. White matter cerebrovascular reactivity increased in the ISMN (ß=0.021%/mm Hg [95% CI, 0.003-0.040]) and cilostazol (ß=0.035%/mm Hg [95% CI, 0.014-0.056]) monotherapy groups and in those taking any versus no medication (ß=0.021%/mm Hg [95% CI, 0.005-0.037]). CONCLUSIONS: While limited by small sample size, we demonstrate that measuring cerebrovascular function with magnetic resonance imaging is feasible in clinical trials and that ISMN and cilostazol may improve cerebrovascular function. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481323. URL: www.isrctn.com; Unique identifier: ISRCTN12580546. URL: www.clinicaltrialsregister.eu; Unique identifier: EudraCT 2015-001953-33.

Exploring Associations of Preoperative Physical Performance With Postoperative Outcomes After Lumbar Spinal Fusion: A Machine Learning Approach.

OBJECTIVE: To explore the association between preoperative physical performance with short- and long-term postoperative outcomes in patients undergoing lumbar spinal fusion (LSF). DESIGN: Retrospective cohort. SETTING: University hospital. PARTICIPANTS: Seventy-seven patients (N=77) undergoing elective LSF were preoperatively screened on patient demographics, patient-reported outcome measures, and physical performance measures (movement control, back muscle endurance strength and extensor strength, aerobic capacity, flexibility). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Associations between preoperative variables and inpatient functional recovery, hospital length of stay (LOS), and 1- to 2-year postoperative pain reduction were explored using random forest analyses assessing the relative influence of the variable on the outcome. RESULTS: Aerobic capacity was associated with fast functional recovery <4 days and prolonged functional recovery >5 days (median z scores=7.1 and 12.0). Flexibility (median z score=4.3) and back muscle endurance strength (median z score=7.8) were associated with fast functional recovery <4 days. Maximum back extensor strength was associated with prolonged functional recovery >5 days (median z score=8.6). Flexibility (median z score=5.1) and back muscle endurance strength (median z score=13.5) were associated with short LOS <5 days. Aerobic capacity (median z score=8.7) was associated with prolonged LOS >7 days. Maximum back extensor strength (median z score=3.8) was associated with 1- to 2-year postoperative pain reduction and aerobic capacity (median z score=2.8) was tentative. CONCLUSIONS: Physical performance measures were associated with both short- and long-term outcomes after LSF. Adding these measures to prediction models predicting outcomes after LSF may increase their accuracy.

Current Prehabilitation Programs Do Not Improve the Postoperative Outcomes of Patients Scheduled for Lumbar Spine Surgery: A Systematic Review With Meta-analysis.

OBJECTIVE: To assess the effectiveness of prehabilitation in patients with degenerative disorders of the lumbar spine who are scheduled for spine surgery. DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: Seven electronic databases were systematically searched for randomized controlled trials or propensity-matched cohorts. STUDY SELECTION CRITERIA: Studies that measured the effect of prehabilitation interventions (ie, exercise therapy and cognitive behavioral therapy [CBT]) on physical functioning, pain, complications, adverse events related to prehabilitation, health-related quality of life, psychological outcomes, length of hospital stay, use of analgesics, and return to work were included. DATA SYNTHESIS: Data were extracted at baseline (preoperatively) and at short-term (6 weeks or less), medium-term (greater than 6 weeks and up to 6 months), and long-term (greater than 6 months) follow-ups. Pooled effects were analyzed as mean differences and 95% confidence intervals (CIs). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: Cognitive behavioral therapy interventions were no more effective than usual care for all outcomes. Pooled effect sizes were -2.0 (95% CI: -4.4, 0.4) for physical functioning, -1.9 (95% CI: -5.2, 1.4) for back pain, and -0.4 (95% CI: -4.1, 0.4) for leg pain. Certainty of evidence for CBT ranged from very low to low. Only 1 study focused on exercise therapy and found a positive effect on short-term outcomes. CONCLUSION: There was very low-certainty to low-certainty evidence of no additional effect of CBT interventions on outcomes in patients scheduled for lumbar surgery. Existing evidence was too limited to draw conclusions about the effects of exercise therapy. J Orthop Sports Phys Ther 2021;51(3):103-114. Epub 25 Dec 2020. doi:10.2519/jospt.2021.9748.

Cognitive impairment in sporadic cerebral small vessel disease: A systematic review and meta-analysis.

This paper is a proposal for an update on the characterization of cognitive impairments associated with sporadic cerebral small vessel disease (SVD). We pose a series of questions about the nature of SVD-related cognitive impairments and provide answers based on a comprehensive review and meta-analysis of published data from 69 studies. Although SVD is thought primarily to affect executive function and processing speed, we hypothesize that SVD affects all major domains of cognitive ability. We also identify low levels of education as a potentially modifiable risk factor for SVD-related cognitive impairment. Therefore, we propose the use of comprehensive cognitive assessments and the measurement of educational level both in clinics and research settings, and suggest several recommendations for future research.

Development and validation of a prediction tool for pain reduction in adult patients undergoing elective lumbar spinal fusion: a multicentre cohort study.

PURPOSE: On average, 56% of patients report a clinically relevant reduction in pain after lumbar spinal fusion (LSF). Preoperatively identifying which patient will benefit from LSF is paramount to improve clinical decision making, expectation management and treatment selection. Therefore, this multicentre study aimed to develop and validate a clinical prediction tool for a clinically relevant reduction in pain 1 to 2 years after elective LSF. METHODS: The outcomes were defined as a clinically relevant reduction in predominant (worst reported pain in back or legs) pain 1 to 2 years after LSF. Patient-reported outcome measures and patient characteristics from 202 patients were used to develop a prediction model by logistic regression. Data from 251 patients were used to validate the model. RESULTS: Nonsmokers (odds ratio = 0.41 [95% confidence interval = 0.19-0.87]), with lower Body Mass Index (0.93 [0.85-1.01]), shorter pain duration (0.49 [0.20-1.19]), lower American Society of Anaesthesiologists score (4.82 [1.35-17.25]), higher Visual Analogue Scale score for predominant pain (1.05 [1.02-1.08]), lower Oswestry Disability Index (0.96 [0.93-1.00]) and higher RAND-36 mental component score (1.03 [0.10-1.06]) preoperatively had a higher chance of a clinically relevant reduction in predominant pain. The area under the curve of the externally validated model yielded 0.68. A nomogram was developed to aid clinical decision making. CONCLUSIONS: Using the developed nomogram surgeons can estimate the probability of achieving a clinically relevant pain reduction 1 to 2 years after LSF and consequently inform patients on expected outcomes when considering treatment.

Dose evaluation of lamivudine in human immunodeficiency virus-infected children aged 5 months to 18 years based on a population pharmacokinetic analysis.

AIM: The objectives of this study were to characterize age-related changes in lamivudine pharmacokinetics in children and evaluate lamivudine exposure, followed by dose recommendations for subgroups in which target steady state area under the daily plasma concentration-time curve (AUC0-24h ) is not reached. METHODS: Population pharmacokinetic modelling was performed in NONMEM using data from two model-building datasets and two external datasets [n = 180 (age 0.4-18 years, body weight 3.4-60.5 kg); 2061 samples (median 12 per child); daily oral dose 60-300 mg (3.9-17.6 mg kg-1 )]. Steady state AUC0-24h was calculated per individual (adult target 8.9 mg·h l-1 ). RESULTS: A two-compartment model with sequential zero order and first order absorption best described the data. Apparent clearance and central volume of distribution (% RSE) were 13.2 l h-1 (4.2%) and 38.9 l (7.0%) for a median individual of 16.6 kg, respectively. Bodyweight was identified as covariate on apparent clearance and volume of distribution using power functions (exponents 0.506 (20.2%) and 0.489 (32.3%), respectively). The external evaluation supported the predictive ability of the final model. In 94.5% and 35.8% of the children with a body weight >14 kg and <14 kg, respectively, the target AUC0-24h was reached. CONCLUSION: Bodyweight best predicted the developmental changes in apparent lamivudine clearance and volume of distribution. For children aged 5 months-18 years with a body weight <14 kg, the dose should be increased from 8 to 10 mg kg-1  day-1 if the adult target for AUC0-24h is aimed for. In order to identify whether bodyweight influences bioavailability, clearance and/or volume of distribution, future analysis including data on intravenously administered lamivudine is needed.