Safety and Outcome of High-Flow Nasal Oxygen Therapy Outside ICU Setting in Hypoxemic Patients With COVID-19.

OBJECTIVE: High-flow nasal oxygen (HFNO) therapy is frequently applied outside ICU setting in hypoxemic patients with COVID-19. However, safety concerns limit more widespread use. We aimed to assess the safety and clinical outcomes of initiation of HFNO therapy in COVID-19 on non-ICU wards. DESIGN: Prospective observational multicenter pragmatic study. SETTING: Respiratory wards and ICUs of 10 hospitals in The Netherlands. PATIENTS: Adult patients treated with HFNO for COVID-19-associated hypoxemia between December 2020 and July 2021 were included. Patients with treatment limitations were excluded from this analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included intubation and mortality rate, duration of hospital and ICU stay, severity of respiratory failure, and complications. Using propensity-matched analysis, we compared patients who initiated HFNO on the wards versus those in ICU. Six hundred eight patients were included, of whom 379 started HFNO on the ward and 229 in the ICU. The intubation rate in the matched cohort ( n = 214 patients) was 53% and 60% in ward and ICU starters, respectively ( p = 0.41). Mortality rates were comparable between groups (28-d [8% vs 13%], p = 0.28). ICU-free days were significantly higher in ward starters (21 vs 17 d, p < 0.001). No patient died before endotracheal intubation, and the severity of respiratory failure surrounding invasive ventilation and clinical outcomes did not differ between intubated ward and ICU starters (respiratory rate-oxygenation index 3.20 vs 3.38; Pa o2 :F io2 ratio 65 vs 64 mm Hg; prone positioning after intubation 81 vs 78%; mortality rate 17 vs 25% and ventilator-free days at 28 d 15 vs 13 d, all p values > 0.05). CONCLUSIONS: In this large cohort of hypoxemic patients with COVID-19, initiation of HFNO outside the ICU was safe, and clinical outcomes were similar to initiation in the ICU. Furthermore, the initiation of HFNO on wards saved time in ICU without excess mortality or complicated course. Our results indicate that HFNO initiation outside ICU should be further explored in other hypoxemic diseases and clinical settings aiming to preserve ICU capacity and healthcare costs.

Externally validated treatment algorithm acceptably predicts nonoperative treatment success in patients with anterior cruciate ligament rupture.

PURPOSE: This study aims to develop and externally validate a treatment algorithm to predict nonoperative treatment success or failure in patients with anterior cruciate ligament (ACL) rupture. METHODS: Data were used from two completed studies of adult patients with ACL ruptures: the Conservative versus Operative Methods for Patients with ACL Rupture Evaluation study (development cohort) and the KNee osteoArthritis anterior cruciate Ligament Lesion study (validation cohort). The primary outcome variable is nonoperative treatment success or failure. Potential predictor variables were collected, entered into the univariable logistic regression model and then incorporated into the multivariable logistic regression model for constructing the treatment algorithm. Finally, predictive performance and goodness-of-fit were assessed and externally validated by discrimination and calibration measures. RESULTS: In the univariable logistic regression model, a stable knee measured with the pivot shift test and a posttrauma International Knee Documentation Committee (IKDC) score <50 were predictive of needing an ACL reconstruction. Age >30 years and a body mass index > 30 kg/m2 were predictive for not needing an ACL reconstruction. Age, pretrauma Tegner score, the outcome of the pivot shift test and the posttrauma IKDC score are entered into the treatment algorithm. The predictability of needing an ACL reconstruction after nonoperative treatment (discrimination) is acceptable in both the development and the validation cohort: area under the curve = resp. 0.69 (95% confidence interval [CI]: 0.58-0.81) and 0.68 (95% CI: 0.58-0.78). CONCLUSION: This study shows that the treatment algorithm can acceptably predict whether an ACL injury patient will have a(n) (un)successful nonoperative treatment (discrimination). Calibration of the treatment algorithm suggests a systematical underestimation of the need for ACL reconstruction. Given the limitations regarding the sample size of this study, larger data sets must be constructed to improve the treatment algorithm further. LEVEL OF EVIDENCE: Level II.

Ipsilateral Aorto-Iliac Calcification is Not Directly Associated With eGFR After Kidney Transplantation: A Prospective Cohort Study Analyzed Using a Linear Mixed Model.

Aorto-iliac calcification (AIC) is a well-studied risk factor for post-transplant cardiovascular events and mortality. Its effect on graft function remains unknown. The primary aim of this prospective cohort study was to assess the association between AIC and estimated glomerular filtration rate (eGFR) in the first year post-transplant. Eligibility criteria were: ≥50 years of age or ≥30 years with at least one risk factor for vascular disease. A non-contrast-enhanced CT-scan was performed with quantification of AIC using the modified Agatston score. The association between AIC and eGFR was investigated with a linear mixed model adjusted for predefined variables. One-hundred-and-forty patients were included with a median of 31 (interquartile range 26-39) eGFR measurements per patient. No direct association between AIC and eGFR was found. We observed a significant interaction between follow-up time and ipsilateral AIC, indicating that patients with higher AIC scores had lower eGFR trajectory over time starting 100 days after transplant (p = 0.014). To conclude, severe AIC is not directly associated with lower post-transplant eGFR. The significant interaction indicates that patients with more severe AIC have a lower eGFR trajectory after 100 days in the first year post-transplant.

Is there an association between serum soluble interleukin-2 receptor levels and syndrome severity in persistent Complex Regional Pain Syndrome?

OBJECTIVE: A potentially useful biomarker for Complex Regional Pain Syndrome (CRPS) is the serum soluble interleukin-2 receptor (sIL-2R) level, which is a marker for T-cell activation. Elevated serum sIL-2R levels have been described in CRPS patients compared to healthy controls. In T-cell mediated inflammatory diseases such as sarcoidosis and rheumatoid arthritis, the serum sIL-2R levels correlate with disease severity. In this study, we investigate whether an association exists between serum sIL-2R levels in CRPS patients and CRPS severity. METHODS: A cross-sectional cohort study was conducted in a tertiary pain referral center in the Netherlands. Adult CRPS patients diagnosed by the IASP criteria were included between October 2018 until October 2022. The main study parameters were serum sIL-2R levels and the CRPS severity score. RESULTS: Fifty-three CRPS patients were included with a mean syndrome duration of 84 months (Q3 - Q1:180 - 48). The majority had persistent CRPS with a syndrome duration >1 year (n = 52, 98%). The median pain Numerical Rating Score (NRS) was 7 (Q3 - Q1: 8 - 5) and the mean CRPS severity score was 11 (SD ± 2.3). The median serum sIL-2R level was 330 U/mL (Q3 - Q1:451 - 256). No statistically significant correlation was observed between serum sIL-2R levels and the CRPS severity score (rs = 0.15, P = .28). CONCLUSIONS: Our findings suggest that serum sIL-2R levels cannot be used as a biomarker for syndrome severity in persistent CRPS (syndrome duration >1 year). Serial measurements of serum sIL-2R from early CRPS to persistent CRPS are needed to investigate whether serum sIL-2R levels can be used to monitor T-cell mediated inflammatory syndrome activity.

Intermittent versus continuous esketamine infusions for long-term pain modulation in complex regional pain syndrome: protocol of a randomized controlled non-inferiority study (KetCRPS-2).

BACKGROUND: Complex regional pain syndrome (CRPS) is a chronic pain condition of an extremity. While achieving pain relief in CRPS is challenging, esketamine infusions can accomplish pain relief for several weeks post-infusion in a subgroup of CRPS patients. Unfortunately, CRPS esketamine protocols are very heterogeneous in advice on dosage, administration and treatment setting. Currently, no trials are available that study differences between intermittent and continuous esketamine infusions for CRPS. With the current situation of bed shortages, it is difficult to admit patients for several consecutive days for inpatient esketamine treatments. In this study, we investigate whether 6 intermittent outpatient esketamine treatments are not inferior to a continuous 6-day inpatient esketamine treatment in establishing pain relief. In addition, several secondary study parameters will be assessed in order to investigate mechanisms responsible for pain relief by esketamine infusions. Furthermore, the cost-effectiveness will be analyzed. METHODS: In this RCT, the primary objective is to demonstrate that an intermittent esketamine dosing regimen is non-inferior to a continuous esketamine dosing regimen at 3 months follow-up. We will include 60 adult CRPS patients. The inpatient treatment group receives a continuous intravenous esketamine infusion for 6 consecutive days. The outpatient treatment group receives a 6-hour intravenous esketamine infusion every 2 weeks for 3 months. Esketamine dose will be individually tailored and is started at 0.05 mg/kg/h and can be increased to a maximum of 0.2 mg/kg/h. Each patient will be followed for 6 months. The primary study parameter is perceived pain intensity, measured by an 11-point Numerical Rating Scale. Secondary study parameters are conditioned pain modulation, quantitative sensory testing, adverse events, thermography, blood inflammatory parameter, questionnaires about functionality, quality of life and mood and costs per patient. DISCUSSION: If our study reveals non-inferiority between intermittent and continuous esketamine infusions, these findings can be beneficial to increase the availability and flexibility of esketamine infusions through outpatient treatments. Furthermore, the costs of outpatient esketamine infusions could be lower than inpatient esketamine infusions. In addition, secondary parameters may predict response to esketamine treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT05212571 , date of registration 01-28-2022. PROTOCOL VERSION: Version 3, February 2022.

Allodynia, Hyperalgesia, (Quantitative) Sensory Testing and Conditioned Pain Modulation in Patients With Complex Regional Pain Syndrome Before and After Spinal Cord Stimulation Therapy.

OBJECTIVES: Complex regional pain syndrome (CRPS) is a chronic debilitating disease characterized by sensory abnormalities. Spinal cord stimulation (SCS) is an effective therapy for CRPS, but few studies have investigated the effects of SCS therapy on sensory characteristics. Therefore, this study investigated the effect of SCS on allodynia, hyperalgesia, electrical quantitative sensory testing (QST) parameters, and conditioned pain modulation (CPM) effect. MATERIALS AND METHODS: This study is part of a multicenter randomized controlled trial (ISRCTN 36655259). Patients with CRPS in one extremity and eligible for SCS were included. The outcome parameters allodynia (symptom and sign), hyperalgesia (symptom), sensory thresholds with QST, CPM effect, and pain scores were tested before and after three months of SCS (40-Hz tonic SCS). Both the CRPS-affected extremity and the contralateral, clinically unaffected extremity were used to test three sensory thresholds with electrical QST: current perception threshold (CPT), pain perception threshold (PPT), and pain tolerance threshold (PTT). The PTT also was used as a test stimulus for the CPM paradigm both before and after the conditioning ice-water test. Nonparametric testing was used for all statistical analyses. RESULTS: In total, 31 patients were included for analysis. Pain, allodynia (sign and symptom), and hyperalgesia (symptom) were all significantly reduced after SCS therapy. On the unaffected side, none of the QST thresholds (CPT, PPT, and PTT) was significantly altered after SCS therapy. However, the CPT on the CRPS-affected side was significantly increased after SCS therapy. A CPM effect was present both before and after SCS. CONCLUSIONS: Standard 40-Hz tonic SCS significantly reduces pain, hyperalgesia, and allodynia in patients with CRPS. These findings suggest that SCS therapy should not be withheld from patients who suffer from allodynia and hyperalgesia, which contradicts previous findings derived from retrospective analysis and animal research. ISRCTN Registry: The ISRCTN registration number for the study is ISRCTN 36655259.

Safety and tolerability of pirfenidone in asbestosis: a prospective multicenter study.

BACKGROUND: Pirfenidone slows down disease progression in idiopathic pulmonary fibrosis (IPF). Recent studies suggest a treatment effect in progressive pulmonary fibrosis other than IPF. However, the safety and effectiveness of pirfenidone in asbestosis patients remain unclear. In this study, we aimed to investigate the safety, tolerability and efficacy of pirfenidone in asbestosis patients with a progressive phenotype. METHODS: This was a multicenter prospective study in asbestosis patients with progressive lung function decline. After a 12-week observational period, patients were treated with pirfenidone 801 mg three times a day. Symptoms and adverse events were evaluated weekly and patients completed online patient-reported outcomes measures. At baseline, start of therapy, 12 and 24 weeks, in hospital measurement of lung function and a 6 min walking test were performed. Additionally, patients performed daily home spirometry measurements. RESULTS: In total, 10 patients were included of whom 6 patients (66.7%) experienced any adverse events during the study period. Most frequently reported adverse events were fatigue, rash, anorexia and cough, which mostly occurred intermittently and were reported as not very bothersome. No significant changes in hospital pulmonary function (forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), 6 min walking test or patient-reported outcomes measures before and after start of pirfenidone were found. Home spirometry demonstrated a FVC decline in 12 weeks before start of pirfenidone, while FVC did not decline during the 24 week treatment phase, but this difference was not statistically significant. CONCLUSIONS: Treatment with pirfenidone in asbestosis has an acceptable safety and tolerability profile and home spirometry data suggest this antifibrotic treatment might attenuate FVC decline in progressive asbestosis. Trial registration MEC-2018-1392; EudraCT number: 2018-001781-41.

Electrical neurostimulation for the treatment of chronic pruritus: A systematic review.

Approximately one fifth of the world population experiences continuous itch for 6 weeks or more during their life, that is chronic itch. It is diverse in its aetiologies, and it is notoriously hard to treat. Because itch and pain have largely overlapping pathophysiology and the demonstrated efficacy of neurostimulation in treatment of selected chronic pain conditions, we conducted a systematic review to investigate whether neurostimulation could be an effective treatment for chronic itch. We identified two randomized controlled trials and 17 open label studies or case reports investigating various neurostimulation modalities for the treatment of refractory itch of various aetiologies. Transcutaneous electrical nerve stimulation (TENS) was the most investigated modality (n = 17), and in the largest number of conditions. Other modalities were cutaneous field stimulation (n = 2), painscrambler (n = 1), transcranial direct current stimulation (n = 1) and peripheral nerve field stimulation (n = 1). Atopic dermatitis was the most studied condition (n = 5). Despite the large heterogeneity in used stimulation paradigms and outcome parameters, all studies reported a positive effect of at least one neurostimulation modality. Our review indicates that electrical neurostimulation could be considered for the treatment of refractory chronic itch of selected aetiologies, such as atopic dermatitis or burn pruritus. However, better understanding of the mechanisms of action of the neurostimulation modalities and regimens in various pruritic conditions is necessary.

Development and validation of a multivariable prediction model for early prediction of chronic postsurgical pain in adults: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of developing chronic postsurgical pain (CPSP) is an essential step in reducing pain chronification in postsurgical patients. We aimed to develop and validate a prognostic model for the early prediction of CPSP including pain characteristics indicating altered pain processing within 2 weeks after surgery. METHODS: A prospective cohort study was conducted in adult patients undergoing orthopaedic, vascular, trauma, or general surgery between 2018 and 2019. Multivariable logistic regression models for CPSP were developed using data from the University Medical Centre (UMC) Utrecht and validated in data from the Erasmus UMC Rotterdam, The Netherlands. RESULTS: In the development (n=344) and the validation (n=150) cohorts, 28.8% and 21.3% of patients reported CPSP. The best performing model (area under the curve=0.82; 95% confidence interval [CI], 0.76-0.87) included preoperative treatment with opioids (odds ratio [OR]=4.04; 95% CI, 2.13-7.70), bone surgery (OR=2.01; 95% CI, 1.10-3.67), numerical rating scale pain score on postoperative day 14 (OR=1.57; 95% CI, 1.34-1.83), and the presence of painful cold within the painful area 2 weeks after surgery (OR=4.85; 95% CI, 1.85-12.68). Predictive performance was confirmed by external validation. CONCLUSIONS: As only four easily obtainable predictors are necessary for reliable CPSP prediction, the models are useful for the clinician to be alerted to further assess and treat individual patients at risk. Identification of the presence of painful cold within 2 weeks after surgery as a strong predictor supports altered pain processing as an important contributor to CPSP development.

Home monitoring of lung function, symptoms and quality of life after admission with COVID-19 infection: The HOMECOMIN' study.

BACKGROUND AND OBJECTIVE: To develop targeted and efficient follow-up programmes for patients hospitalized with coronavirus disease 2019 (COVID-19), structured and detailed insights in recovery trajectory are required. We aimed to gain detailed insights in long-term recovery after COVID-19 infection, using an online home monitoring programme including home spirometry. Moreover, we evaluated patient experiences with the home monitoring programme. METHODS: In this prospective multicentre study, we included adults hospitalized due to COVID-19 with radiological abnormalities. For 6 months after discharge, patients collected weekly home spirometry and pulse oximetry measurements, and reported visual analogue scales on cough, dyspnoea and fatigue. Patients completed the fatigue assessment scale (FAS), global rating of change (GRC), EuroQol-5D-5L (EQ-5D-5L) and online tool for the assessment of burden of COVID-19 (ABCoV tool). Mixed models were used to analyse the results. RESULTS: A total of 133 patients were included in this study (70.1% male, mean age 60 years [SD 10.54]). Patients had a mean baseline forced vital capacity of 3.25 L (95% CI: 2.99-3.44 L), which increased linearly in 6 months with 19.1% (Δ0.62 L, p < 0.005). Patients reported substantial fatigue with no improvement over time. Nevertheless, health status improved significantly. After 6 months, patients scored their general well-being almost similar as before COVID-19. Overall, patients considered home spirometry useful and not burdensome. CONCLUSION: Six months after hospital admission for COVID-19, patients' lung function and quality of life were still improving, although fatigue persisted. Home monitoring enables detailed follow-up for patients with COVID-19 at low burden for patients and for the healthcare system.

Postoperative Pain and Age: A Retrospective Cohort Association Study.

BACKGROUND: As the population ages, the number of elderly people undergoing surgery increases. Literature on the incidence and intensity of postoperative pain in the elderly is conflicting. This study examines associations between age and pain-related patient reported outcomes and perioperative pain management in a dataset of surgical patients undergoing four common surgeries: spinal surgery, hip or knee replacement, or laparoscopic cholecystectomy. Based on the authors' clinical experience, they hypothesize that pain scores are lower in older patients. METHODS: In this retrospective cohort, study data were collected between 2010 and 2018 as part of the international PAIN OUT program. Patients filled out the International Pain Outcomes Questionnaire on postoperative day 1. RESULTS: A total of 11,510 patients from 26 countries, 59% female, with a mean age of 62 yr, underwent one of the aforementioned types of surgery. Large variation was detected within each age group for worst pain, yet for each surgical procedure, mean scores decreased significantly with age (mean Numeric Rating Scale range, 6.3 to 7.3; ß = -0.2 per decade; P ≤ 0.001), representing a decrease of 1.3 Numeric Rating Scale points across a lifespan. The interference of pain with activities in bed, sleep, breathing deeply or coughing, nausea, drowsiness, anxiety, helplessness, opioid administration on the ward, and wish for more pain treatment also decreases with age for two or more of the procedures. Across the procedures, patients reported being in severe pain on postoperative day one 26 to 38% of the time, and pain interfered moderately to severely with movement. CONCLUSIONS: The authors' findings indicate that postoperative pain decreases with increasing age. The change is, however, small and of questionable clinical significance. Additionally, there are still too many patients, at any age, undergoing common surgeries who suffer from moderate to severe pain, which interferes with function, supporting the need for tailoring care to the individual patient.

Risk Factors, Dynamics, and Clinical Consequences of Aortic Neck Dilatation after Standard Endovascular Aneurysm Repair.

OBJECTIVE: Aortic neck dilatation (AND) occurs after endovascular aneurysm repair (EVAR) with self expanding stent grafts (SESs). Whether it continues, ultimately exceeding the endograft diameter leading to abdominal aortic aneurysm (AAA) rupture, remains uncertain. Dynamics, risk factors, and clinical relevance of AND were investigated after EVAR with standard SESs. METHODS: All intact EVAR patients treated from 2000 to 2015 at a tertiary institution were included. Demographic, anatomical, and device related characteristics were investigated as risk factors for AND. Outer to outer diameters were measured at a single standardised aortic level on reconstructed computed tomography (CT) images. RESULTS: A total of 460 patients were included (median follow up 5.2 years, interquartile range [IQR] 3.0, 7.7 years; CT imaging follow up 3.3 years, IQR 1.3, 5.4). Baseline neck diameter was 24 mm (IQR 22, 26) and increased 11.1% (IQR 1.5%, 21.9%) at last CT imaging. Endograft oversizing was 20.0% (IQR 13.6, 28.0). AND was greater during the first year (5.2% [IQR 0, 11.7]) decreasing subsequently (two to four years to 1.4%/year [IQR 0.0, 4.5%], p ≤ .001) and was associated with suprarenal fixation endografts (t value = 7.9, p < .001) and oversizing (t value = 4.4, p < .001). AND exceeding the endograft was 3.5% (95% CI 2.2% - 4.8%) and 14.4% (95% CI 11.0% - 17.8%) at five and eight years, respectively. Excessive AND was associated with baseline neck diameter (OR 1.2/mm, 95% CI 1.05 - 1.41) while the Excluder endograft had a protective effect (OR 0.15, 95% CI 0.04 - 0.58). Excessive AND was associated with type 1A endoleak (HR 3.3, 95% CI 1.1 - 9.7) and endograft migration > 5 mm (HR 3.1, 95% CI 1.4 - 6.9). CONCLUSION: AND after EVAR with SES is associated with endograft oversizing and radial force but decelerates after the first post-operative year. Baseline aortic neck diameter and suprarenal stent bearing endografts were associated with an increased risk of AND beyond nominal stent graft diameter. However, it remains unclear whether patient selection, differences in endograft radial force or the suprarenal stent are accountable for this difference.

The Value of the Surprise Question to Predict One-Year Mortality in Idiopathic Pulmonary Fibrosis: A Prospective Cohort Study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease with a heterogeneous disease course. Timely initiation of palliative care is often lacking. The surprise question "Would you be surprised if this patient died within the next year?" is increasingly used as a clinical prognostic tool in chronic diseases but has never been evaluated in IPF. OBJECTIVE: We aimed to evaluate the predictive value of the surprise question for 1-year mortality in IPF. METHODS: In this prospective cohort study, clinicians answered the surprise question for each included patient. Clinical parameters and mortality data were collected. The sensitivity, specificity, accuracy, negative, and positive predictive value of the surprise question with regard to 1-year mortality were calculated. Multivariable logistic regression analysis was performed to evaluate which factors were associated with mortality. In addition, discriminative performance of the surprise question was assessed using the C-statistic. RESULTS: In total, 140 patients were included. One-year all-cause mortality was 20% (n = 28). Clinicians identified patients with a survival of <1 year with a sensitivity of 68%, a specificity of 82%, an accuracy of 79%, a positive predictive value of 49%, and a negative predictive value of 91%. The surprise question significantly predicted 1-year mortality in a multivariable model (OR 3.69; 95% CI 1.24-11.02; p = 0.019). The C-statistic of the surprise question to predict mortality was 0.75 (95% CI 0.66-0.85). CONCLUSIONS: The answer on the surprise question can accurately predict 1-year mortality in IPF. Hence, this simple tool may enable timely focus on palliative care for patients with IPF.

Percutaneous Cervical Cordotomy for the Treatment of Cancer Pain: A Prospective Case Series of 52 Patients with a Long-Term Follow-Up.

AIM: The aim of this study is to describe the effects of percutaneous cervical cordotomy (PCC) on pain, opioid consumption, adverse events, and satisfaction in palliative care patients with cancer pain after PCC until end of life. METHODS: This is a prospective observational case series of 58 PCCs in 52 consecutive patients. Indication for PCC was unilateral cancer pain with a maximum numeric rating scale (NRS) of pain above 5 despite maximal conservative treatment. The PCC was fluoroscopy guided. A radiofrequency lesion was made at 95°C for 20 seconds. The pain location and pain scores, analgesic medication, the cranial and caudal borders of dermatomes hypoesthetic for pin pricks, dysesthesia, urinary retention, Horner's syndrome, muscle strength, Karnofsky performance scale (KPS) score, patient satisfaction, hospital anxiety and distress score (HADS), and RAND 36 score were evaluated at 1 day; 1 and 6 weeks; and 3, 6, 9, 12 18, and 24 months after PCC, or until death if death occurred during the follow-up period. RESULTS: Pain relief after PCC was intense (change in median maximum NRS from 9 to 0) and persistent. Median opioid use per day was 240 mg (145 to 565 mg) before PCC and 55 mg (0 to 120 mg) after PCC. The upper and lower borders of dermatomes hypoesthetic for pin pricks were stable over time. The most common side effects were short-term (< 1 week) neck pain (28%), dysesthesia (40%), and mild loss of muscle strength (11%). Approximately 83% of the patients were satisfied or very satisfied with the results of PCC 1 week after the procedure, and this percentage remained high in the long term. There was no significant change in the KPS score, HADS, and RAND 36 score. CONCLUSION: Percutaneous cervical cordotomy is an effective treatment for unilateral cancer pain. The reduction in pain, reduction in opioid consumption, and hypoesthetic area remain stable until death.

Joint models for longitudinal and time-to-event data in a case-cohort design.

Studies with longitudinal measurements are common in clinical research. Particular interest lies in studies where the repeated measurements are used to predict a time-to-event outcome, such as mortality, in a dynamic manner. If event rates in a study are low, however, and most information is to be expected from the patients experiencing the study endpoint, it may be more cost efficient to only use a subset of the data. One way of achieving this is by applying a case-cohort design, which selects all cases and only a random samples of the noncases. In the standard way of analyzing data in a case-cohort design, the noncases who were not selected are completely excluded from analysis; however, the overrepresentation of the cases will lead to bias. We propose to include survival information of all patients from the cohort in the analysis. We approach the fact that we do not have longitudinal information for a subset of the patients as a missing data problem and argue that the missingness mechanism is missing at random. Hence, results obtained from an appropriate model, such as a joint model, should remain valid. Simulations indicate that our method performs similar to fitting the model on a full cohort, both in terms of parameters estimates and predictions of survival probabilities. Estimating the model on the classical version of the case-cohort design shows clear bias and worse performance of the predictions. The procedure is further illustrated in data from a biomarker study on acute coronary syndrome patients, BIOMArCS.

Personalized dynamic risk assessment in nephrology is a next step in prognostic research.

In nephrology, repeated measures are frequently available (glomerular filtration rate or proteinuria) and linked to adverse outcomes. However, several features of these longitudinal data should be considered before making such inferences. These considerations are discussed, and we describe how joint modeling of repeatedly measured and time-to-event data may help to assess disease dynamics and to derive personalized prognosis. Joint modeling combines linear mixed-effects models and Cox regression model to relate patient-specific trajectory to their prognosis. We describe several aspects of the relationship between time-varying markers and the endpoint of interest that are assessed with real examples to illustrate the aforementioned aspects of the longitudinal data provided. Thus, joint models are valuable statistical tools for study purposes but also may help health care providers in making well-informed dynamic medical decisions.

Patient-specific evolution of renal function in chronic heart failure patients dynamically predicts clinical outcome in the Bio-SHiFT study.

Renal dysfunction is an important component of chronic heart failure (CHF), but its single assessment does not sufficiently reflect clinically silent progression of CHF prior to adverse clinical outcome. Therefore, we aimed to investigate temporal evolutions of glomerular and tubular markers in 263 stable patients with CHF, and to determine if their patient-specific evolutions during this clinically silent period can dynamically predict clinical outcome. We determined the risk of clinical outcome (composite endpoint of Heart Failure hospitalization, cardiac death, Left Ventricular Assist Device placement, and heart transplantation) in relation to marker levels, slopes and areas under their trajectories. In each patient, the trajectories were estimated using repeatedly measured glomerular markers: creatinine/estimated glomerular filtration rate (eGFR), cystatin C (CysC), and tubular markers: urinary N-acetyl-beta-D-glucosaminidase (NAG) and kidney injury molecule (KIM)-1, plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL). During 2.2 years of follow-up, we collected on average 8 urine and 9 plasma samples per patient. All glomerular markers predicted the endpoint (univariable hazard ratio [95% confidence interval] per 20% increase: creatinine: 1.18[1.07-1.31], CysC: 2.41[1.81-3.41], and per 20% eGFR decrease: 1.13[1.05-1.23]). Tubular markers, NAG, and KIM-1 also predicted the endpoint (NAG: 1.06[1.01-1.11] and KIM-1: 1.08[1.04-1.11]). Larger slopes were the strongest predictors (creatinine: 1.57[1.39-1.84], CysC: 1.76[1.52-2.09], eGFR: 1.59[1.37-1.90], NAG: 1.26[1.11-1.44], and KIM-1: 1.64[1.38-2.05]). Associations persisted after multivariable adjustment for clinical characteristics. Thus, during clinically silent progression of CHF, glomerular and tubular functions deteriorate, but not simultaneously. Hence, patient-specific evolutions of these renal markers dynamically predict clinical outcome in patients with CHF.

Conduction dynamics after transcatheter aortic valve implantation and implications for permanent pacemaker implantation and early discharge: the CONDUCT-study.

Aims: To correlate dynamics in electrical conduction after transcatheter aortic valve implantation (TAVI) with need for permanent pacemaker implantation (PPM) and assess implications for early discharge. Methods and results: Daily electrocardiograms after TAVI were analysed for rhythm and conduction times and were correlated with PPM. Transcatheter aortic valve implantation was performed in 291 consecutive patients with three contemporary transcatheter heart valve designs: Medtronic CoreValve (n = 111), Edwards Sapien XT (n = 29) and Sapien 3 (n = 72), and Boston Lotus (n = 79). We considered two cohorts: (A) Patients with normal baseline conduction; and (B) patients with pre-existent conduction disturbances. Based on QRS dynamics, three patterns were discerned: stable normal QRS duration, transient QRS prolongation, and persistent QRS prolongation. In Cohort B, QRS dynamics did not correlate with PPM. In contrast, in Cohort A, QRS dynamics and PPM appeared highly correlated. Neither patients with stable normal QRS duration (0/47), nor patients with transient QRS prolongation required PPM (0/26). All PPMs occurred in patients with persistent QRS prolongation until discharge (27/85). Persistent QRS prolongation was typically seen with Lotus and CoreValve, whereas stable normal QRS duration was typically seen with Sapien XT and Sapien 3. Conclusion: Three distinct patterns of QRS dynamics can be discerned after TAVI and their predictive probabilities for PPM strongly relate to the baseline conduction status. Patients with normal conduction at baseline and stable QRS duration after TAVI are potentially eligible for early discharge.

Parent reports of health-related quality of life and heart failure severity score independently predict outcome in children with dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy in children causes heart failure and has a poor prognosis. Health-related quality of life in this patient group is unknown. Moreover, results may provide detailed information of parents' sense of their child's functioning. We hypothesised that health-related quality of life, as rated by parents, and the paediatric heart failure score, as assessed by physicians, have both predictive value on outcome. Methods and results In this prospective study, health-related quality of life was assessed by parent reports: the Infant Toddler Quality of Life questionnaire (0-4 years) or Child Health Questionnaire-Parent Form 50 (4-18 years) at 3-6-month intervals. We included 90 children (median age 3.8 years, interquartile range (IQR) 0.9-12.3) whose parents completed 515 questionnaires. At the same visit, physicians completed the New York University Pediatric Heart Failure Index. Compared with Dutch normative data, quality of life was severely impaired at diagnosis (0-4 years: 7/10 subscales and 4-18 years: 8/11 subscales) and ⩾1 year after diagnosis (3/10 and 6/11 subscales). Older children were more impaired (p<0.05). After a median follow-up of 3 years (IQR 2-4), 15 patients underwent transplantation. Using multivariable time-dependent Cox regression, "physical functioning" subscale and the Heart Failure Index were independently predictive of the risk of death and heart transplantation (hazard ratio 1.24 per 10% decrease of predicted, 95% confidence interval (CI) 1.06-1.47 and hazard ratio 1.38 per unit, 95% CI 1.19-1.61, respectively). CONCLUSION: Physical impairment rated by parents and heart failure severity assessed by physicians independently predicted the risk of death or heart transplantation in children with dilated cardiomyopathy.

Evaluating Community-Based Intrathecal Baclofen Therapy: Effectiveness, Safety, and Feasibility.

Background: Intrathecal baclofen (ITB) is used for the treatment of intractable spasticity. The burden of traveling for ITB screening and aftercare is problematic for nursing home residents with severe spasticity and seems to result in undertreatment of spasticity. The aim of this study is to evaluate the effectiveness, safety, and feasibility of ITB for nursing home residents treated in their home, describing the selection phase, the initial trial of ITB, and aftercare up to 3 months after implantation of an ITB pump. Methods: This retrospective database study included immobile, adult nursing home residents with severe spasticity, referred to an Ambulatory Care Clinic between 2016 and 2021. When eligible, an ITB trial was performed by ITB experts in the nursing home. If a permanent pump was implanted, dose titration and aftercare were performed on location. Results: A total of 102 patients were referred; 80 underwent an ITB trial on location, and 94% improved significantly on the Modified Ashworth Scale and clonus scale pre-ITB trial versus post-ITB trial, as well as at 3 months post-implantation. There was a low incidence of adverse events, mostly procedure- and drug-related. Conclusions: This study indicates that selection, testing, and aftercare for ITB on location is effective and safe.