Pain catastrophizing contributes to acute and long-term pain after knee arthroplasty (KA), but the association between pain catastrophizing and physical function is not clear. We examined the ...association between preoperative pain catastrophizing and physical function one year after surgery, as well as differences in physical function, pain and general health in two groups of patients with high and low preoperative pain catastrophizing score.
We included 615 patients scheduled for KA between March 2011 and December 2013. Patients completed The Pain Catastrophizing Scale (PCS) prior to surgery. The Oxford Knee Score (OKS), Short Form-36 (SF-36) and the EuroQol-5D (EQ-5D) were completed prior to surgery, and 4 and 12 months after the surgery.
Of the 615 patients, 442 underwent total knee arthroplasty (TKA) and 173 unicompartmental knee arthroplasty (UKA). Mean age was 67.3 (SD: 9.7) and 53.2% were females. Patients with PCS > 21 had statistically significantly larger improvement in mean OKS for both TKA and UKA than patients with PCS < 11; 3.2 (95% CI: 1.0, 5.4) and 5.4 (95% CI: 2.2, 8.6), respectively. Furthermore, patients with preoperative PCS > 21 had statistically significantly lower OKS, SF-36 and EQ-5D and higher pain score than patients with PCS < 11 both preoperatively and 4 and 12 months postoperatively.
Patients with high levels of preoperative pain catastrophizing have lower physical function, more pain and poorer general health both before and after KA than patients without elevated pain catastrophizing.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with colorectal metastatic disease have a poor prognosis, limited therapeutic options, and frequent development of resistance. Strategies based on tumor-derived organoids are a powerful tool ...to assess drug sensitivity at an individual level and to suggest new treatment options or re-challenge. Here, we evaluated the method's feasibility and clinical outcome as applied to patients with no satisfactory treatment options.
In this phase 2, single-center, open-label, non-comparative study (ClinicalTrials.gov, register NCT03251612), we enrolled 90 patients with metastatic colorectal cancer following progression on or after standard therapy. Participants were 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and metastasis available for biopsy. Biopsies from the metastatic site were cultured using organoids model. Sensitivity testing was performed with a panel of drugs with proven activity in phase II or III trials. At the discretion of the investigator considering toxicity, the drug with the highest relative activity was offered. The primary endpoint was the proportion of patients alive without disease progression at two months per local assessment.
Biopsies available from 82 to 90 patients were processed for cell culture, of which 44 successfully generated organoids with at least one treatment suggested. The precision cohort of 34 patients started treatment and the primary endpoint, progression-free survival (PFS) at two months was met in 17 patients (50%, 95% CI 32-68), exceeding the pre-defined level (14 of 45; 31%). The median PFS was 67 days (95% CI 51-108), and the median overall survival was 189 days (95% CI 103-277).
Patient-derived organoids and in-vitro sensitivity testing were feasible in a cohort of metastatic colorectal cancer. The primary endpoint was met, as half of the patients were without progression at two months. Cancer patients may benefit from functional testing using tumor-derived organoids.
ClinicalTrials.gov, register NCT03251612.
'Fast-track' surgery was introduced more than 20 years ago and may be defined as a co-ordinated peri-operative approach aimed at reducing surgical stress and facilitating post-operative recovery.The ...fast-track programmes have now been introduced into total hip arthroplasty (THA) surgery with reduction in post-operative length of stay, shorter convalescence and rapid functional recovery without increased morbidity and mortality. This has been achieved by focusing on a multidisciplinary collaboration and establishing 'fast-track' units, with a well-defined organisational set-up tailored to deliver an accelerated peri-operative course of fast-track surgical THA procedures.Fast-track THA surgery now works extremely well in the standard THA patient. However, all patients are different and fine-tuning of the multiple areas in fast-track pathways to get patients with special needs or high co-morbidity burden through a safe and effective fast-track THA pathway is important.In this narrative review, the principles of fast-track THA surgery are presented together with the present status of implementation and perspectives for further improvements. Cite this article:
2017;2. DOI: 10.1302/2058-5241.2.160060. Originally published online at www.efortopenreviews.org.
We aimed to determine the prognosis after early MRI on clinical suspicion of scaphoid fracture, hypothesising that MRI pathology is associated with more disability and that MRI pathology and high ...occupational mechanical hand-arm exposures are associated with slower return to work (RTW).
We conducted a follow-up study of a cohort of 469 patients, who were scanned in the period 2006 to 2010. The respondents constituted our cohort for disability analysis and the subset that was in the labour market at the time of the trauma constituted our sub-cohort for RTW analysis. Questionnaires included disability scores, job title, and lifestyle factors. Job titles were linked with a job exposure matrix to estimate occupational exposures. Register information was obtained on time until RTW. We used logistic regression analysis of disability and Cox regression analysis of time until RTW.
The proportion that responded was 53% (249/469) for the disability analysis and 59% (125/212) for the RTW analysis. The mean age at follow up was 43.5 years, the mean time since trauma was 4.8 years, 53% had injury of the dominant hand, and 54% had MRI pathology. Men constituted 43% of the cohort and 56% of the sub-cohort. MRI pathology was not associated with more disability e.g., for a 'Disabilities of the Arm Shoulder and Hand'-score ≥20 the odds ratio was 0.58 (95% confidence interval 0.26-1.17). Patients without MRI pathology and with low occupational exposures were off work for an average of four weeks. Patients with MRI pathology or high occupational exposures were off work for twice as long time.
MRI pathology was not associated with more disability. For patients, who were in the labour market at the time of the trauma, MRI pathology and high occupational mechanical hand-arm exposures were associated with slower RTW.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature ...cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN.
The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy.
If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival.
ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25
. 2023.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims/hypothesis
Individuals with type 2 diabetes have an altered bacterial composition of their gut microbiota compared with non-diabetic individuals. However, these alterations may be confounded by ...medication, notably the blood-glucose-lowering biguanide, metformin. We undertook a clinical trial in healthy and previously drug-free men with the primary aim of investigating metformin-induced compositional changes in the non-diabetic state. A secondary aim was to examine whether the pre-treatment gut microbiota was related to gastrointestinal adverse effects during metformin treatment.
Methods
Twenty-seven healthy young Danish men were included in an 18-week one-armed crossover trial consisting of a pre-intervention period, an intervention period and a post-intervention period, each period lasting 6 weeks. Inclusion criteria were men of age 18–35 years, BMI between 18.5 kg/m
2
and 27.5 kg/m
2
, HbA
1c
< 39 mmol/mol (5.7%) and plasma creatinine within the normal range. No prescribed medication, including antibiotics, for 2 months prior to recruitment were allowed and no previous gastrointestinal surgery, discounting appendectomy or chronic illness requiring medical treatment. During the intervention the participants were given metformin up to 1 g twice daily. Participants were examined five times in the fasting state with blood sampling and recording of gastrointestinal symptoms. Examinations took place at Frederiksberg Hospital, Denmark before and after the pre-intervention period, halfway through and immediately after the end of intervention and after the wash-out period. Faecal samples were collected at nine evenly distributed time points, and bacterial DNA was extracted and subjected to 16S rRNA gene amplicon sequencing in order to evaluate gut microbiota composition. Subjective gastrointestinal symptoms were reported at each visit.
Results
Data from participants who completed visit 1 (
n
=23) are included in analyses. For the primary outcome the relative abundance of 11 bacterial genera significantly changed during the intervention but returned to baseline levels after treatment cessation. In line with previous reports, we observed a reduced abundance of
Intestinibacter
spp. and
Clostridium
spp., as well as an increased abundance of
Escherichia/Shigella
spp. and
Bilophila wadsworthia
. The relative abundance at baseline of 12 bacterial genera predicted self-reported gastrointestinal adverse effects.
Conclusions/interpretation
Intake of metformin changes the gut microbiota composition in normoglycaemic young men. The microbiota changes induced by metformin extend and validate previous reports in individuals with type 2 diabetes. Secondary analyses suggest that pre-treatment gut microbiota composition may be a determinant for development of gastrointestinal adverse effects following metformin intake. These results require further investigation and replication in larger prospective studies.
Trial registration
Clinicaltrialsregister.eu 2015-000199-86 and ClinicalTrials.gov NCT02546050
Funding
This project was funded by Danish Diabetes Association and The Novo Nordisk Foundation
Smoking is a critical risk factor responsible for over eight million annual deaths worldwide. It is essential to obtain information on smoking habits to advance research and implement preventive ...measures such as screening of high-risk individuals. In most countries, including Denmark, smoking habits are not systematically recorded and at best documented within unstructured free-text segments of electronic health records (EHRs). This would require researchers and clinicians to manually navigate through extensive amounts of unstructured data, which is one of the main reasons that smoking habits are rarely integrated into larger studies. Our aim is to develop machine learning models to classify patients' smoking status from their EHRs.
This study proposes an efficient natural language processing (NLP) pipeline capable of classifying patients' smoking status and providing explanations for the decisions. The proposed NLP pipeline comprises four distinct components, which are; (1) considering preprocessing techniques to address abbreviations, punctuation, and other textual irregularities, (2) four cutting-edge feature extraction techniques, i.e. Embedding, BERT, Word2Vec, and Count Vectorizer, employed to extract the optimal features, (3) utilization of a Stacking-based Ensemble (SE) model and a Convolutional Long Short-Term Memory Neural Network (CNN-LSTM) for the identification of smoking status, and (4) application of a local interpretable model-agnostic explanation to explain the decisions rendered by the detection models. The EHRs of 23,132 patients with suspected lung cancer were collected from the Region of Southern Denmark during the period 1/1/2009-31/12/2018. A medical professional annotated the data into 'Smoker' and 'Non-Smoker' with further classifications as 'Active-Smoker', 'Former-Smoker', and 'Never-Smoker'. Subsequently, the annotated dataset was used for the development of binary and multiclass classification models. An extensive comparison was conducted of the detection performance across various model architectures.
The results of experimental validation confirm the consistency among the models. However, for binary classification, BERT method with CNN-LSTM architecture outperformed other models by achieving precision, recall, and F1-scores between 97% and 99% for both Never-Smokers and Active-Smokers. In multiclass classification, the Embedding technique with CNN-LSTM architecture yielded the most favorable results in class-specific evaluations, with equal performance measures of 97% for Never-Smoker and measures in the range of 86 to 89% for Active-Smoker and 91-92% for Never-Smoker.
Our proposed NLP pipeline achieved a high level of classification performance. In addition, we presented the explanation of the decision made by the best performing detection model. Future work will expand the model's capabilities to analyze longer notes and a broader range of categories to maximize its utility in further research and screening applications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patient-Reported Outcome Measures (PROM) provide important information, however, missing PROM data threaten the interpretability and generalizability of findings by introducing potential bias. This ...study aims to provide insight into missingness mechanisms and inform future researchers on generalizability and possible methodological solutions to overcome missing PROM data problems during data collection and statistical analyses.
We identified 10,236 colorectal cancer survivors (CRCs) above 18y, diagnosed between 2014 and 2018 through the Danish Clinical Registries. We invited a random 20% (2,097) to participate in a national survey in May 2023. We distributed reminder e-mails at day 10 and day 20, and compared Initial Responders (response day 0-9), Subsequent Responders (response day 10-28) and Non-responders (no response after 28 days) in demographic and cancer-related characteristics and PROM-scores using linear regression.
Of the 2,097 CRCs, 1,188 responded (57%). Of these, 142 (7%) were excluded leaving 1,955 eligible CRCs. 628 (32%) were categorized as initial responders, 418 (21%) as subsequent responders, and 909 (47%) as non-responders. Differences in demographic and cancer-related characteristics between the three groups were minor and PROM-scores only marginally differed between initial and subsequent responders.
In this study of long-term colorectal cancer survivors, we showed that initial responders, subsequent responders, and non-responders exhibit comparable demographic and cancer-related characteristics. Among respondents, Patient-Reported Outcome Measures were also similar, indicating generalizability. Assuming Patient-Reported Outcome Measures of subsequent responders represent answers by the non-responders (would they be available), it may be reasonable to judge the missingness mechanism as Missing Completely At Random.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since the late 1990s, therapy for metastatic colorectal cancer (mCRC) has changed considerably, and the combination of doublet or triplet chemotherapy and a targeted agent are now routinely used. The ...targeting of angiogenesis, the development of new blood vessels, represents a key element in the overall treatment strategy. Since the approval in 2004 of the first anti-angiogenetic drug, multiple agents have been approved and others are currently under investigation. We present an overview of the recent literature on approved systemic treatment of mCRC, with a focus on anti-angiogenic drugs, and current treatment approaches, and elaborate on the future role of angiogenesis in colorectal cancer as seen from a clinical perspective. The treatment of mCRC, in general, has changed from "one strategy fits all" to a more personalized approach. This is, however, not entirely the case for anti-angiogenetic treatments, partly due to a lack of validated biomarkers. The anti-angiogenetic standard treatment at the present primarily includes monoclonal antibodies. The therapeutic field of angiogenesis, however, has received increased interest after the introduction of newer combinations. These approaches will likely change the current treatment strategy, once again, to the overall benefit of patients.
During the past 7 years, genome-wide association studies have shed light on the contribution of common genomic variants to the genetic architecture of type 2 diabetes, obesity and related ...intermediate phenotypes. The discoveries have firmly established more than 175 genomic loci associated with these phenotypes. Despite the tight correlation between type 2 diabetes and obesity, these conditions do not appear to share a common genetic background, since they have few genetic risk loci in common. The recent genetic discoveries do however highlight specific details of the interplay between the pathogenesis of type 2 diabetes, insulin resistance and obesity. The focus is currently shifting towards investigations of data from targeted array-based genotyping and exome and genome sequencing to study the individual and combined effect of low-frequency and rare variants in metabolic disease. Here we review recent progress as regards the concepts, methodologies and derived outcomes of studies of the genetics of type 2 diabetes and obesity, and discuss avenues to be investigated in the future within this research field.
PDF
