Outcomes of complex colorectal polyps managed by multi-disciplinary team strategies-a multi-centre observational study.

PURPOSE: Team management strategies for complex colorectal polyps are recommended by professional guidelines. Multi-disciplinary meetings are used across the UK with limited information regarding their impact. The aim of this multi-centre observational study was to assess procedures and outcomes of patients managed using these approaches. METHOD: This was a retrospective, observational study of patients managed by six UK sites. Information was collected regarding procedures and outcomes including length of stay, adverse events, readmissions and cancers. RESULTS: Two thousand one hundred ninety-two complex polyps in 2109 patients were analysed with increasing referrals annually. Most presented symptomatically and the mean polyp size was 32.1 mm. Primary interventions included endoscopic therapy (75.6%), conservative management (8.3%), colonic resection (8.1%), trans-anal surgery (6.8%) or combined procedures (1.1%). The number of primary colonic resections decreased over the study period without a reciprocal increase in secondary procedures or recurrence. Secondary procedures were required in 7.8%. The median length of stay for endoscopic procedures was 0 days with 77.5% completed as day cases. Median length of stay was 5 days for colonic resections. Overall adverse event and 30-day readmission rates were 9.0% and 3.3% respectively. Malignancy was identified in 8.8%. Benign polyp recurrence occurred in 13.1% with a median follow up of 30.4 months. Screening detected lesions were more likely to undergo bowel resection. Colonic resection was associated with longer stays, higher adverse events and more cancers on final histology. CONCLUSION: Multi-disciplinary team management of complex polyps is safe and effective. Standardisation of organisation and quality monitoring is needed to continue positive effects on outcomes and services.

Enthesis: not the same in each localisation - a molecular, histological and biomechanical study.

The interphase between tendon and bone consists of a highly specialised tissue called enthesis. Typically, the enthesis is described as a succession of four different zones: tendon, non-mineralised fibrocartilage, mineralised fibrocartilage and bone. However, the microstructure of the entheses, cellular composition and mechanical properties vary depending on their anatomical location. The present study aimed to characterise three of the most relevant sites of enthesis injury in a rat model: the patellar tendon, the Achilles tendon and the supraspinatus enthesis, in terms of biomechanics, histology and genetic expression. The patellar enthesis presented the highest ultimate load and lowest stiffness of the three, while the supraspinatus was the weakest and stiffest. The histological characterisation revealed key differences at the insertion site for each enthesis. The patellar enthesis showed a large cartilaginous area at the tendon-to-bone interphase whilst this interphase was smaller in the supraspinatus entheses samples. Furthermore, the Achilles tendon enthesis displayed a more abrupt transition from tendon to bone. Additionally, each enthesis exhibited a particular and distinct pattern of expression of tenogenic, chondrogenic and osteogenic markers. This study provided valuable insights for a better understanding of the three entheses at relevant anatomical sites. Moreover, the larger cross-sectional area of the patellar enthesis, the strong mechanical properties and the easier surgical access to this location led to the conclusion that the patellar tendon enthesis site could be most suitable for the development of a preclinical model for general enthesis regeneration studies in rats.

Manufacture of magnesium-fortified Chihuahua cheese.

The aim of this study was to manufacture magnesium-fortified Chihuahua cheese and to evaluate the effect of magnesium fortification on quality parameters. Addition of magnesium chloride to milk during pasteurization (5.44, 10.80, 16.40, 22.00, and 25.20 g of MgCl2·6H2O/L of milk) resulted in cheese with increased magnesium content, proportional to the amount of magnesium added (up to 2,957.13 mg of Mg/kg of cheese). As magnesium content increased, coagulation time and moisture content also increased, whereas calcium content decreased. Higher levels of magnesium fortification (16.40 g of MgCl2·6H2O/L of milk or more) induced the development of bitter-acid flavors and softer texture. Addition of 10.80 g of MgCl2·6H2O/L to milk resulted in Chihuahua cheese that meets regulatory standards and possesses physicochemical and sensory characteristics similar to those of nonfortified Chihuahua cheese. Under this milk fortification level, the manufactured cheese is able to provide 148.4 mg of magnesium per day (35% of the recommended daily intake of magnesium for adult males and 46% for adult females) assuming 3 portions (28 g each) are consumed.

A dynamic and integrated in vitro/ex vivo gastrointestinal model for the evaluation of the probability and severity of infection in humans by Salmonella spp. vehiculated in different matrices.

The lack of proper gastrointestinal models assessing the inter-strain virulence variability of foodborne pathogens and the effect of the vehicle (food matrix) affects the risk estimation. This research aimed to propose a dynamic and integrated in vitro/ex vivo gastrointestinal model to evaluate the probability and severity of infection of foodborne pathogens at different matrices. An everted gut sac was used to determine the adhesion and invasion of Salmonella enterica and tissue damage. S. Typhimurium ATCC 14028 was used as a representative bacterium, and two matrices (water and cheese) were used as vehicles. No differences (p > 0.05) in the probability of infection (Pinf) were found for intra-experimental repeatability. However, the Pinf of cheese-vehiculated S. Typhimurium was different compared to water- vehiculated S. Typhimurium, 7.2-fold higher. The histological analysis revealed Salmonella-induced tissue damage, compared with the control (p < 0.05). In silico proposed interactions between two major Salmonella outer membrane proteins (OmpA and Rck) and digested peptides from cheese casein showed high binding affinity and stability, suggesting a potential protective function from the food matrix. The results showed that the everted gut sac model is suitable to evaluate the inter-strain virulence variability, considering both physiological conditions and the effect of the food matrix.

Population and breast cancer patients' analysis reveals the diversity of genomic variation of the BRCA genes in the Mexican population.

Interpretation of variants of unknown significance (VUS) in genetic tests is complicated in ethnically diverse populations, given the lack of information regarding the common spectrum of genetic variation in clinically relevant genes. Public availability of data obtained from high-throughput genotyping and/or exome massive parallel sequencing (MPS)-based projects from several thousands of outbred samples might become useful tools to evaluate the pathogenicity of a VUS, based on its frequency in different populations. In the case of the Mexican and other Latino populations, several thousands of samples have been genotyped or sequenced during the last few years as part of different efforts to identify common variants associated to common diseases. In this report, we analyzed Mexican population data from a sample of 3985 outbred individuals, and additional 66 hereditary breast cancer patients were analyzed in order to better define the spectrum of common genomic variation of the BRCA1 and BRCA2 genes. Our analyses identified the most common genetic variants in these clinically relevant genes as well as the presence and frequency of specific pathogenic mutations present in the Mexican population. Analysis of the 3985 population samples by MPS identified three pathogenic mutations in BRCA1, only one population sample showed a BRCA1 exon 16-17 deletion by MLPA. This resulted in a basal prevalence of deleterious mutations of 0.10% (1:996) for BRCA1 and 11 pathogenic mutations in BRCA2, resulting in a basal prevalence of deleterious mutations of 0.276% (1:362) for BRCA2, combined of 0.376% (1:265). Separate analysis of the breast cancer patients identified the presence of pathogenic mutations in 18% (12 pathogenic mutations in 66 patients) of the samples by MPS and 13 additional alterations by MLPA. These results will support a better interpretation of clinical studies focused on the detection of BRCA mutations in Mexican and Latino populations and will help to define the general prevalence of deleterious mutations within these populations.

Effects of FK506 on the healing of diaphyseal, critical size defects in the rat femur.

There is much interest in understanding the influence of the immune system on bone healing, including a number of reports suggesting a beneficial effect of FK506 (tacrolimus) in this regard. The influence of FK506 in a rat, femoral, critical size defect was examined using locally implanted, recombinant, human (rh) BMP-2 and adenovirally-transduced, autologous, adipose-derived mesenchymal stromal cells (AD-MSCs) expressing BMP-2. FK506 was delivered systemically using an implanted osmotic pump. Empty defects and those implanted with unmodified AD-MSCs did not heal in the presence or absence of FK506. Defects treated with rhBMP-2 healed with a large callus containing thin cortices and wispy trabeculae; this, too, was unaffected by FK506. A third of defects implanted with adenovirally-transduced AD-MSCs healed, but this improved to 100 % in the presence of FK506. New bone formed in response to BMP-2 synthesised endogenously by the genetically modified cells had a slimmer callus than those healed by rhBMP-2, with improved cortication and advanced reconstitution of marrow. These results suggest that FK506 may have had little effect on the intrinsic biology of bone healing, but improved healing in response to adenovirally-transduced cells by inhibiting immune responses to the first-generation adenovirus used here. Because the genetically modified cells produced bone of higher quality at far lower doses of BMP-2, this approach should be explored in subsequent research.

Protonation of Planar and Nonplanar Porphyrins: A Calorimetric and Computational Study.

Herein, we report the first calorimetric study of the protonation of planar and nonplanar free-base porphyrins: H2OETPP (strongly saddled by its substituents), H2T(tBu)P (strongly ruffled by its substituents), and the nominally planar porphyrins (npPs) H2OEP, H2TPP, H2T(nPe)P, and H2T(iPr)P. The observed enthalpies of protonation in solution (ΔHprotsoln) for formation of the dications in 1,1,2,2-tetrachloroethane with 2% trifluoroacetic acid are -45 ± 1 kcal mol-1 for the npPs, -52.0 kcal mol-1 for H2T(tBu)P, and -70.9 kcal mol-1 for H2OETPP. The corresponding enthalpies of protonation (ΔHDFT) obtained from DFT calculations (-27 ± 5, -42, and -63 kcal mol-1, respectively) reproduce this trend. The much more negative enthalpy of protonation seen for H2OETPP is consistent with this molecule being pre-deformed into the saddle structure favored by porphyrin dications. Except for OETPP, the calculated enthalpies of the first protonations (ΔH1) are significantly more positive than the enthalpies of the second protonations (ΔH2). In addition, the structural strain energies for the first protonations (ΔEst(1)) are also significantly more positive than ΔEst(2). According to the calculations, the monocations thus have higher proton affinities than the corresponding free-base porphyrins due to a structural strain effect, which is consistent with the generally elusive nature of the porphyrin monocation. The recent observations of monocations for free-base porphyrins with a high degree of saddling can be rationalized in terms of ΔH1 and ΔH2 being similar; so, the monocation is no longer an unstable intermediate.

Medial opening wedge high tibial osteotomy: more than ten years of experience with Puddu plate technique supports its indication.

PURPOSE: To describe the short-term and long-term results of patients who underwent a medial opening wedge high tibial osteotomy (MOW-HTO) for unicompartmental medial knee joint osteoarthritis. METHODS: A retrospective review was conducted of patients with MOW-HTO using a Puddu plate®, with more than ten year follow-up. The degree of correction, initial chondral damage, number of meniscal lesions, preoperative and 1-year postoperative functional scale scores (IKDC and Lysholm), and arthroplasty conversion rates at the ten year follow-up were registered. We assumed early indication when patients underwent the operation before they were 40 years old and delayed ≥ 40. Functional outcomes were analyzed by adjusting for pre-operative values. Fisher's exact test was used to study the association between the arthroplasty conversion rates and the timing of indication. RESULTS: Fifty-five patients were included, 37 of whom were male (67%). Twenty-nine patients had early indications for surgery (53%). All patients completed ten year follow-up. All patients improved IKDC (p < 0.01) and Lysholm (p < 0.01) scores compared to their presurgical scores at the one year post-operative evaluation. We had six minor complications, none requiring revision surgery. We had three conversions to arthroplasty, all in the late indication group, not statistically significant different. Linear regression showed that early indication was associated with a higher IKDC score when adjusting for the Outerbridge chondral damage score, the number of meniscal lesions, and sex (p < 0.01). CONCLUSION: All patients improved functional scores one year after surgery. Early indication (i.e., younger than 40 years of age) was independently associated with better functional outcomes than late indication at one year follow-up.

The associations between menopausal symptoms and sleep quality in Spanish postmenopausal women.

Objectives: Around the menopause, sleep disturbances frequently occur or worsen and are associated with decreased health quality and physical and psychological problems. The aim of this study was to analyze sleep quality and its association with the impact of menopausal symptoms in Spanish postmenopausal women. Methods: A total of 278 postmenopausal women (age 60.95 ± 8.01 years) participated in this cross-sectional study. The Medical Outcomes Study Sleep Scale (MOS-SS) and the Menopause Rating Scale (MRS) were used to analyze sleep quality and severity of menopausal symptoms, respectively. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Results: The linear regression showed that a greater impact of menopausal symptoms (MRS total score) was associated with worse scores regarding sleep adequacy (p < 0.001, R2 = 0.056), snoring (p = 0.020, R2 = 0.036), awaken short of breath (p < 0.001, R2 = 0.089), and quantity of sleep (p < 0.001, R2 = 0.075) domains. Anxiety (p < 0.001) and worse somatic symptoms (p = 0.001) were related to greater sleep disturbances (R2 = 0.164). We also found relationships of heightened psychological symptoms (p < 0.001) and low physical activity level (p = 0.003) with increased daytime somnolence (R2 = 0.064). Finally, higher MRS total score and anxiety levels were associated with worse sleep quality assessed by MOS-SS Sleep Problems Index I (R2 = 0.179, p < 0.001 and p = 0.001, respectively) and Sleep Problems Index II (R2 = 0.146, p < 0.001 and p = 0.011, respectively). Conclusions: Anxiety and severity of menopausal symptoms were associated with poorer sleep quality. Furthermore, low physical activity level and worse psychological symptoms in menopause were predictors for increased somnolence. Therefore, screening for these factors in postmenopausal women is important, since they may be susceptible for intervention.

Rare coding variant analysis in a large cohort of Ashkenazi Jewish families with inflammatory bowel disease.

Rare variants are thought to contribute to the genetics of inflammatory bowel disease (IBD), which is more common amongst the Ashkenazi Jewish (AJ) population. A family-based approach using exome sequencing of AJ individuals with IBD was employed with a view to identify novel rare genetic variants for this disease. Exome sequencing was performed on 960 Jewish individuals including 513 from 199 multiplex families with up to eight cases. Rare, damaging variants in loci prioritized by linkage analysis and those shared by multiple affected individuals within the same family were identified. Independent evidence of association of each variant with disease was assessed. A number of candidate variants were identified, including in genes involved in the immune system. The ability to achieve statistical significance in independent case/control replication data was limited by power and was only achieved for variants in the well-established Crohn's disease gene, NOD2. This work demonstrates the challenges of identifying disease-associated rare damaging variants from exome data, even amongst a favorable cohort of familial cases from a genetic isolate. Further research of the prioritized rare candidate variants is required to confirm their association with the disease.

Needs of adolescents and young adults after cancer treatment: a systematic review.

The aim of this study was to conduct a systematic review of the literature on the needs of adolescents and young adults (AYAs) who have survived cancer. PRISMA recommendations for systematic reviews were followed, and the quality of the studies reviewed was also assessed with a specific checklist. The following databases were searched from their inception to May 2016: ERIC, EMBASE, MEDLINE, PILOTS, ProQuest, PsycARTICLES, PsycBOOKS, psycCRITIQUES, PsycINFO, Social Services Abstracts and Sociological Abstracts. Fourteen studies were identified and analysed. The results show that the most common needs for AYA cancer survivors are as follows: "individualised information and advice," "counselling and psychological support" and "social support, and social relationships." These results are different from those reported in studies on adults, which shows the importance of specifically addressing the needs of this population. In order to advance in this emerging area of study and facilitate the work of health professionals, it is crucial to reach a consensus on two central issues: how the needs of AYA survivors should be conceptualised and what the most valid and reliable procedure for assessing patient's needs is.

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis.

Disease-modifying osteoarthritis drugs (DMOADs) should reach their intra-tissue target sites at optimal doses for clinical efficacy. The dense, negatively charged matrix of cartilage poses a major hindrance to the transport of potential therapeutics. In this work, electrostatic interactions were utilised to overcome this challenge and enable higher uptake, full-thickness penetration and enhanced retention of dexamethasone (Dex) inside rabbit cartilage. This was accomplished by using the positively charged glycoprotein avidin as nanocarrier, conjugated to Dex by releasable linkers. Therapeutic effects of a single intra-articular injection of low dose avidin-Dex (0.5 mg Dex) were evaluated in rabbits 3 weeks after anterior cruciate ligament transection (ACLT). Immunostaining confirmed that avidin penetrated the full cartilage thickness and was retained for at least 3 weeks. Avidin-Dex suppressed injury-induced joint swelling and catabolic gene expression to a greater extent than free Dex. It also significantly improved the histological score of cell infiltration and morphogenesis within the periarticular synovium. Micro-computed tomography confirmed the reduced incidence and volume of osteophytes following avidin-Dex treatment. However, neither treatment restored the loss of cartilage stiffness following ACLT, suggesting the need for a combinational therapy with a pro-anabolic factor for enhancing matrix biosynthesis. The avidin dose used caused significant glycosaminoglycan (GAG) loss, suggesting the use of higher Dex : avidin ratios in future formulations, such that the delivered avidin dose could be much less than that shown to affect GAGs. This charge-based delivery system converted cartilage into a drug depot that could also be employed for delivery to nearby synovium, menisci and ligaments, enabling clinical translation of a variety of DMOADs.

Interventional therapies and in-hospital outcomes in acute coronary syndromes complicated by von Willebrand disease.

INTRODUCTION: von Willebrand disease (VWD) is one of the most common inherited bleeding disorders. AIM: Investigate the impact of the VWD bleeding tendency on in-hospital management of acute coronary syndromes (ACS). METHODS: Using discharge data from the National Inpatient Sample (NIS), the features of presentation and in-hospital treatment among ACS hospital discharges with and without a VWD diagnosis were investigated. A total of 264 case discharges and 705 860 control discharges were identified. RESULTS AND CONCLUSIONS: There was a significantly higher percentage of women among the case discharges compared to the control discharges (59.5% and 39.4%, respectively; P < 0.001). The rate of medical therapy alone [i.e. avoidance of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)] was significantly higher among unstable angina cases than controls (55.0% vs. 46.4%; P = 0.01), and among cases undergoing PCI, bare-metal stents (BMS) were utilized in preference to drug-eluting stents (DES) (adjusted OR = 3.5); P < 0.001). No difference in in-hospital death was identified, but reported bleeding among discharges that underwent CABG was higher in cases compared to controls (12.9% vs. 5.2%; P = 0.047). Although medical and interventional management of ACS appears to be well tolerated in the majority of hospitalized patients with VWD, the gender ratio is reversed, interventions and DES are utilized less frequently and procedure-related bleeding may be increased, calling for further study.

What are the needs of adolescents and young adults after a cancer treatment? A Delphi study.

Advances in the early detection of cancer and the development of more effective treatments have resulted in a larger number of adolescents and young adults (AYAs), becoming cancer survivors. However, knowledge regarding their needs and if those needs are adequately addressed remains limited. The aims of this study were to: (1) better understand the needs of AYAs after cancer treatment; (2) analyse the importance of those needs; (3) determine which needs are not adequately addressed; and (4) test the hypothesis that AYA cancer survivors have different needs than adult survivors. Twenty-nine health oncology professionals, 17 AYA survivors and 12 relatives of AYA survivors participated in the Delphi study. The needs identified could be classified into six categories, and all were rated as highly important by all participants. The category perceived as least adequately addressed across the three groups was 'Counselling and psychological support.' The findings provide important new information regarding the needs of AYA cancer survivors that can inform the development of interventions to improve the quality of life of these individuals.

Production of reuterin in a fermented milk product by Lactobacillus reuteri: Inhibition of pathogens, spoilage microorganisms, and lactic acid bacteria.

We assessed the antimicrobial activity of reuterin produced in vitro in glycerol aqueous solutions in situ by Lactobacillus reuteri ATCC 53608 as part of a fermented milk product against starter (Lactobacillus delbrueckii ssp. bulgaricus and Streptococcus thermophilus), spoilage (Penicillium expansum), pathogenic (Staphylococcus aureus Salmonella enterica ssp. enterica, and Listeria monocytogenes), and pathogen surrogate (Escherichia coli DH5α) microorganisms. We also assayed the influence of cold storage (28 d at 4°C) and reuterin on the color and rheology of the fermented milk product. We obtained maximum reuterin concentrations of 107.5 and 33.97 mM in glycerol aqueous solution and fermented milk product, respectively. Reuterin was stable throughout its refrigerated shelf life. Gram-positive microorganisms were more resistant to reuterin than gram-negative microorganisms. Penicillium expansum and Lactobacillus reuteri ATCC 53608 survived at concentrations up to 10 and 8.5 mM, respectively. Escherichia coli DH5α was the most sensitive to reuterin (0.9 mM). The presence of reuterin did not cause relevant changes in the quality parameters of the fermented milk product, including pH, acidity, soluble solids, color, and rheological aspects (storage and loss moduli and viscosity). This study demonstrated the viability of using Lactobacillus reuteri ATCC 53608 as a biopreservative in a fermented milk product through reuterin synthesis, without drastically modifying its quality parameters.

Effects of 6 Weeks of Balance Training on Chronic Ankle Instability in Athletes: A Randomized Controlled Trial.

The objective of the present study was to determine the effectiveness of a 6-week balance training program on patients with Chronic Ankle Instability (CAI) in relation to the results obtained in Dynamic Balance, subjective feeling of instability and pain using a single-blind randomized controlled trial. 70 athletes were randomly assigned to control or intervention group. The control group performed their usual training, and the intervention group was administered the same usual activity in addition to a balance program. The paired t-test was performed to evaluate the change scores in each group. The t-test for independent samples was performed to evaluate between-group differences in change scores. Significance level was assigned for p-values less than 0.05 for all analyses. There were significant differences between groups in change scores in CAIT and all of the SEBTs reach distances (p<0.001) but not in Pain (p=0.586). The effect sizes were larger for the outcomes measures that showed significant differences. In the within-group change, the experimental groups showed larger effect sizes in CAIT, SEBT posteromedial and SEBT posterolateral, and moderate effect sizes in SEBT anterior. Exercise therapy training based on multi-station balance tasks led to significant improvements in dynamic balance and self-reported sensation of instability in patients with CAI.

Active angiogenesis in metastatic renal cell carcinoma predicts clinical benefit to sunitinib-based therapy.

BACKGROUND: Sunitinib represents a widely used therapy for metastatic renal cell carcinoma patients. Even so, there is a group of patients who show toxicity without clinical benefit. In this work, we have analysed pivotal molecular targets involved in angiogenesis (vascular endothelial growth factor (VEGF)-A, VEGF receptor 2 (KDR), phosphorylated (p)KDR and microvascular density (MVD)) to test their potential value as predictive biomarkers of clinical benefit in sunitinib-treated renal cell carcinoma patients. METHODS: Vascular endothelial growth factor-A, KDR and pKDR-Y1775 expression as well as CD31, for MVD visualisation, were determined by immunohistochemistry in 48 renal cell carcinoma patients, including 23 metastatic cases treated with sunitinib. Threshold was defined for each biomarker, and univariate and multivariate analyses for progression-free survival (PFS) and overall survival (OS) were carried out. RESULTS: The HistoScore mean value obtained for VEGF-A was 121.6 (range, 10-300); for KDR 258.5 (range, 150-300); for pKDR-Y1775 10.8 (range, 0-65) and the mean value of CD31-positive structures for MVD visualisation was 49 (range, 10-126). Statistical differences for PFS (P=0.01) and OS (P=0.007) were observed for pKDR-Y1775 in sunitinib-treated patients. Importantly, pKDR-Y1775 expression remained significant after multivariate Cox analysis for PFS (P=0.01; HR: 5.35, 95% CI, 1.49-19.13) and for OS (P=0.02; HR: 5.13, 95% CI, 1.25-21.05). CONCLUSIONS: Our results suggest that the expression of phosphorylated (i.e., activated) KDR in tumour stroma might be used as predictive biomarker for the clinical outcome in renal cell carcinoma first-line sunitinib-treated patients.

Implementation frameworks guiding digital self-management intervention in chronic pain: A scoping review.

BACKGROUND AND OBJECTIVE: The development, evaluation and implementation of digital self-management interventions for chronic pain have increased exponentially. While intervention outcomes appear promising to improve well-being and functioning in target populations, it is unclear how the development and evaluation processes were structured and how implementation was planned and executed. The aim of this systematic review is to provide a comprehensive overview of implementation frameworks used to guide and evaluate scientific innovation in chronic pain. DATABASES AND DATA TREATMENT: Four bibliography databases (Medline, Web of Science, PsycInfo, CINAHL) and two registries (PubMed Central, MedaRxiv) were systematically searched. Hits (n = 6830) and full texts (n = 351) were screened and read by two independent reviewers. Peer-reviewed articles that met the inclusion criteria were included in the narrative synthesis. RESULTS: In total, 10 studies were identified that report on seven distinct interventions. Five implementation frameworks were utilized across these studies: Behavioural Interventions using Technology (BIT); Consolidated Framework for Implementation Research (CFIR); mHealth Agile and User-Centered Research and Development Lifecycle; Medical Research Council (MRC); Reach, Effectiveness, Adoption Implementation, and Maintenance (RE-AIM). Frameworks were operationalized using qualitative and quantitative methods, evaluating the innovation on various levels (e.g., individual vs. organizational) and applying a variety of study designs (e.g., single-arm or large trials). CONCLUSIONS: By utilizing implementation frameworks, access to evidence-based chronic pain care may be increased. Although the evidence on the utility of implementation frameworks to guide and evaluate digital self-management interventions is still limited, the body of literature is increasing. Future studies are urged to operationalize, communicate and discuss the innovation process, to promote transparency and replicability. SIGNIFICANCE: The use of implementation frameworks to guide and evaluate digital self-management interventions for chronic pain is a recent development in the field. Several promising examples exist and are presented in this review. Currently, the evidence is still limited, and prospective studies need to transparently operationalize, communicate and discuss their efforts. By utilizing an implementation framework, promising interventions can be made available to end-users, closing the research-to-clinical practice gap and increasing access to evidence-based care to people with chronic pain.

Psychological profiles and prescription opioid misuse, craving, and withdrawal in people with chronic pain.

BACKGROUND: The negative consequences of prescription opioid misuse and opioid use disorder make it relevant to identify factors associated with this problem in individuals with chronic pain. This cross-sectional study aimed at identifying subgroups of people with chronic pain based on their psychological profiles, prescription opioid misuse, craving, and withdrawal. METHODS: The sample comprised 185 individuals with chronic pain. We performed hierarchical cluster analysis on impulsivity, anxiety sensitivity, pain acceptance, pain intensity, opioid misuse, craving, and withdrawal. RESULTS: The four-cluster solution was the optimal one. Misuse, craving, and anxiety sensitivity were higher among people in the Severe-problems cluster than among people in the other three clusters. Withdrawal was the highest in the High-withdrawal cluster. Impulsivity was higher among people in the Severe-problems and High-withdrawal clusters than those in the Moderate-problems and Mild-problems clusters. Pain acceptance was higher among people in the Mild-problems cluster than among people in the other three clusters. Anxiety sensitivity and misuse were higher among people in the Moderate-problems cluster than among people in the Mild-problems cluster. CONCLUSIONS: These results support that impulsivity, anxiety sensitivity, and pain acceptance are useful constructs to identify subgroups of people with chronic pain according to their level of prescription opioid misuse, craving, and withdrawal. The results of this study may help in selecting the early intervention most suitable for each of the identified profiles. SIGNIFICANCE: The psychological profile of individuals with chronic pain, prescription opioid misuse, craving, and withdrawal is characterized by fearing anxiety-related symptoms due to the catastrophic interpretation of such symptoms and reacting impulsively to negative moods. In contrast, participants with high pain acceptance had less prescription opioid misuse, craving, and withdrawal. The profiles identified in this study could help clinicians select targets for intervention among profiles with similar needs and facilitate early interventions to prevent opioid misuse onset or aggravation.

Cross-cultural adaptation and psychometric evaluation of the Spanish version of the Knowledge and Attitudes of Pain questionnaire (KNAP) in physiotherapists.

BACKGROUND: Healthcare providers' attitudes and beliefs can influence how patients with persistent musculoskeletal pain are treated. A biopsychosocial approach is more effective than a purely biomedical approach. Ensuring healthcare professionals have appropriate pain science education (PSE) is essential for successful treatment outcomes. OBJECTIVE: To validate the Spanish version of the Knowledge and Attitudes of Pain (KNAP-SP) questionnaire among Spanish physiotherapists and students and analyze its psychometric properties. METHODS: From May to October 2022, two independent teams adapted the KNAP questionnaire from English to both European and Hispanic-Spanish. A cross-sectional validation study was conducted with 517 physiotherapists examining internal consistency (Cronbach's alpha), structural validity (exploratory factor analysis), and construct validity (hypothesis testing). Longitudinal analyses assessed test-retest reliability (intraclass correlation coefficient [ICC2,1; n = 63]) and responsiveness following a PSE intervention using Receiver Operating Characteristic (ROC) curve analysis and hypothesis testing (n = 70). RESULTS: The KNAP-SP showed strong internal consistency [overall α coefficient = 0.86; domain 1 (α = 0.82); domain 2 (α = 0.70)], explaining 32.3% of the variance. Construct validity was supported by 75% of the hypotheses. Test-retest reliability was high (ICC2,1 = 0.84). KNAP-SP's responsiveness was confirmed by ROC analysis (area under the curve [AUC] = 0.87 [95% CI: 0.79-0.96, p-value <.01]) and accepting 75% of prior hypotheses. The minimal clinically important change was 6.96 points. No floor or ceiling effects were detected. CONCLUSIONS: The KNAP-SP, with robust psychometric properties and successful adaptation and validation, is a valuable tool for assessing pain knowledge and attitudes among Spanish-speaking physiotherapists.