The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).

Background: Many patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP).

Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non-Small Cell Lung Cancer-Results from the Drug Rediscovery Protocol.

Purpose: To provide patients with MET-mutated advanced non-small cell lung cancer (METmut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse.

Patients And Methods: In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping or other MET mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity.

The evolution of precision oncology: The ongoing impact of the Drug Rediscovery Protocol (DRUP).

Background And Purpose: The Drug Rediscovery Protocol (DRUP) is a Dutch, pan-cancer, nonrandomized clinical trial that aims to investigate the efficacy and safety of targeted and immunotherapies outside their registered indication in patients with advanced or metastatic cancer.

Patients: Patients with advanced or metastatic cancer are eligible when there are no standard of care treatment options left and the tumor possesses a molecular genomic variant for which commercially available anticancer treatment is accessible off-label in DRUP. Clinical benefit is the study's primary endpoint, characterized by a confirmed objective response or stable disease after at least 16 weeks of treatment.

Generating and using real-world data: A worthwhile uphill battle.

The precision oncology paradigm challenges the feasibility and data generalizability of traditional clinical trials. Consequently, an unmet need exists for practical approaches to test many subgroups, evaluate real-world drug value, and gather comprehensive, accessible datasets to validate novel biomarkers. Real-world data (RWD) are increasingly recognized to have the potential to fill this gap in research methodology.

Cemiplimab in locally advanced or metastatic cutaneous squamous cell carcinoma: prospective real-world data from the DRUG Access Protocol.

Background: The DRUG Access Protocol provides patients with cancer access to registered anti-cancer drugs that are awaiting reimbursement in the Netherlands and simultaneously collects prospective real-world data (RWD). Here, we present RWD from PD-1 blocker cemiplimab in patients with locally advanced or metastatic cutaneous squamous cell carcinoma (laCSCC; mCSCC).

Methods: Patients with laCSCC or mCSCC received cemiplimab 350 mg fixed dose every three weeks.

Interrater agreement in classifying infections during extracorporeal membrane oxygenation.

Infectious complications are common during extracorporeal membrane oxygenation (ECMO) and may negatively impact outcomes. However, there is considerable variation in the reported rates of incidence, which hampers the use of infections as a quality benchmark for ECMO centers. To assess the contributing role of poor interrater agreement, three independent raters reviewed medical records from all intensive care unit (ICU) patients who received ECMO for >24 h in our tertiary center between October 2019 and October 2021 for suspected episodes of infection, which were rated based on their date of onset and presumed site/diagnosis.

Idiopathic hyperammonemic encephalopathy secondary to gemcitabine-cisplatin treatment.

Idiopathic hyperammonemic encephalopathy is a rare complication of chemotherapy, which has previously mainly been associated with L-asparaginase, cytarabine and 5-FU. We present a case following treatment with gemcitabine-cisplatin in a patient with cholangiocarcinoma. The etiology of chemotherapy-induced idiopathic hyperammonemic encephalopathy remains unclear and existing theories differ per chemotherapeutic agent.

Prognosis and course of work-participation in patients with chronic non-specific low back pain: a 12-month follow-up cohort study.

Objective: To investigate the clinical course of, and prognostic factors for, work-participation in patients with chronic non-specific low back pain.

Methods: A total of 1,608 patients with chronic non-specific low back pain received a multidisciplinary therapy and were evaluated at baseline and 2-, 5- and 12-month follow-ups. Recovery was defined as absolute recovery if the patient worked 90% of his contract hours at follow-up.

Effect of routine diagnostic imaging for patients with musculoskeletal disorders: A meta-analysis.

Purpose: The increasing use of diagnostic imaging has led to high expenditures, unnecessary invasive procedures and/or false-positive diagnoses, without certainty that the patients actually benefit from these imaging procedures. This review explores whether diagnostic imaging leads to better patient-reported outcomes in individuals with musculoskeletal disorders.

Method: Databases were searched from inception to September 2013, together with scrutiny of selected bibliographies.

Prognosis and course of pain in patients with chronic non-specific low back pain: A 1-year follow-up cohort study.

Background: It remains unclear to what extent patients recover from chronic non-specific low back pain (NSLBP). The objective of this study was to determine (1) the course of chronic NSLBP in tertiary care and (2) which factors predicted 5- and 12-month outcomes.

Methods: This prospective study includes 1760 chronic NSLBP patients from a rehabilitation clinic (mean age 40.

Prognostic factors and course for successful clinical outcome quality of life and patients' perceived effect after a cognitive behavior therapy for chronic non-specific low back pain: A 12-months prospective study.

This study investigates the clinical course of and prognostic factors for quality of life (Short Form 36 items Health survey (SF-36)) and global perceived effect (GPE) in patients treated for chronic non-specific low back pain at 5 and 12-months follow-up. Data from a prospective cohort (n = 1760) of a rehabilitation center were used, where patients followed a 2-months cognitive behavior treatment. The outcome 'improvement in quality of life (SF-36)' was defined as a 10% increase in score on the SF-36 at follow-up compared with baseline.

Is manipulative therapy more effective than sham manipulation in adults : a systematic review and meta-analysis.

Background: Manipulative therapy is widely used in the treatment of spinal disorders. Manipulative techniques are under debate because of the possibility of adverse events. To date, the efficacy of manipulations compared to sham manipulations is unclear.

Prognosis and course of disability in patients with chronic nonspecific low back pain: a 5- and 12-month follow-up cohort study.

Background: Few data are available on the course of and predictors for disability in patients with chronic nonspecific low back pain (CNSLBP).

Objective: The purpose of this study was to describe the course of disability and identify clinically important prognostic factors of low-back-pain-specific disability in patients with CNSLBP receiving multidisciplinary therapy.

Design: A prospective cohort study was conducted.

Prognostic factors for recovery in chronic nonspecific low back pain: a systematic review.

Background: Few data are available on predictors for a favorable outcome in patients with chronic nonspecific low back pain (CNLBP).

Purpose: The aim of this study was to assess prognostic factors for pain intensity, disability, return to work, quality of life, and global perceived effect in patients with CNLBP at short-term (≤ 6 months) and long-term (>6 months) follow-up.

Data Sources: Relevant studies evaluating the prognosis of CNLBP were searched in PubMed, CINAHL, and EMBASE (through March 2010).

Lack of uniform diagnostic criteria for cervical radiculopathy in conservative intervention studies: a systematic review.

Purpose: Cervical radiculopathy (CR) is a common diagnosis. It is unclear if intervention studies use uniform definitions and criteria for patient selection. Our objective was to assess the uniformity of diagnostic criteria and definitions used in intervention studies to select patients with CR.

Course and prognosis of recovery for chronic non-specific low back pain: design, therapy program and baseline data of a prospective cohort study.

Background: There has been increasing focus on factors predicting the development of chronic musculoskeletal disorders. For patients already experiencing chronic non-specific low back pain it is also relevant to investigate which prognostic factors predict recovery. We present the design of a cohort study that aims to determine the course and prognostic factors for recovery in patients with chronic non-specific low back pain.

Considered judgement in evidence-based guideline development.

Background: Clinical practice guidelines should be based on the best available evidence. However, this evidence is often incomplete, controversial, or lacking. Other considerations beyond the evidence are therefore needed to be able to formulate specific and applicable recommendations for clinical practice.

Reproducibility of the measurement of active and passive cervical range of motion.

Objective: The primary aim of this study was to assess the reproducibility of tests for the active and passive range of motion used in the physical examination for patients with neck pain. The secondary aim was to determine whether the history of the patients influences the reproducibility and the prevalence of positive findings.

Methods: Sixty-nine participants were recruited in 3 physical therapy practices.

Effect of bracing and other conservative interventions in the treatment of idiopathic scoliosis in adolescents: a systematic review of clinical trials.

Background And Purpose: Many conservative treatments are available for adolescents with idiopathic scoliosis, but the evidence for their accepted use is still unclear. The purpose of this study was to evaluate the effectiveness of braces and other conservative treatments of idiopathic scoliosis in adolescents by systematically reviewing the literature.

Methods: The literature was searched in the PubMed, CINAHL, Cochrane, and PEDro databases.