ABSTRACT
The interplay between humans and their microbiome is crucial for various physiological processes, including nutrient absorption, immune defense, and maintaining homeostasis. Microbiome alterations can directly contribute to diseases or heighten their likelihood. This relationship extends beyond humans; microbiota play vital roles in other organisms, including eukaryotic pathogens causing severe diseases. Notably, Wolbachia, a bacterial microbiota, is essential for parasitic worms responsible for lymphatic filariasis and onchocerciasis, devastating human illnesses. Given the lack of rapid cures for these infections and the limitations of current treatments, new drugs are imperative. Here, we disrupt Wolbachia's symbiosis with pathogens using boron-based compounds targeting an unprecedented Wolbachia enzyme, leucyl-tRNA synthetase (LeuRS), effectively inhibiting its growth. Through a compound demonstrating anti-Wolbachia efficacy in infected cells, we use biophysical experiments and x-ray crystallography to elucidate the mechanism behind Wolbachia LeuRS inhibition. We reveal that these compounds form adenosine-based adducts inhibiting protein synthesis. Overall, our study underscores the potential of disrupting key microbiota to control infections.
Subject(s)
Microbiota , Wolbachia , Wolbachia/drug effects , Humans , Animals , Leucine-tRNA Ligase/metabolism , Leucine-tRNA Ligase/antagonists & inhibitors , Amino Acyl-tRNA Synthetases/metabolism , Amino Acyl-tRNA Synthetases/antagonists & inhibitors , Crystallography, X-Ray , Boron Compounds/pharmacology , Boron Compounds/chemistry , Symbiosis , Models, MolecularABSTRACT
BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare, severe, fatal neuromuscular disease characterized by progressive atrophy and muscle weakness, resulting in loss of ambulation, decreased upper body function, and impaired cardiorespiratory function. This study aimed to generate qualitative evidence to describe the primary symptoms and impacts of DMD in ambulatory and non-ambulatory patients as reported by patient/caregiver dyads. Information was also gathered on expectations for future DMD treatments. METHODS: Forty-six dyads (caregiver and patients with DMD aged 4 to 22 years) participated in 60-min semi-structured video interviews. Interview transcripts were analyzed using thematic analysis. Differences in experiences with DMD by ambulation status were examined. RESULTS: Mean ages of ambulatory (n = 28) and non-ambulatory participants (n = 18) were 8.7 and 11.3 years, respectively, with an average age of diagnosis of 3.7 years (SD = 2.3). The primary symptoms reported by both groups were lack of strength (ambulatory: n = 28, 100.0%; non-ambulatory: n = 17, 94.4%) and fatigue (ambulatory: n = 24, 85.7%; non-ambulatory: n = 14, 77.8%). Physical function was the domain that was most impacted by DMD, with participants describing progressive decline of physical function due to loss of physical strength as the primary defining feature of the disease across all stages of ambulatory ability. For those who maintained ambulatory ability at the time of the interview, physical function impacts described impaired mobility (e.g., climbing stairs: n = 16, 57.1%; running: n = 13, 46.4%), impaired upper body function, in particular fine motor skills like holding a pen/pencil or buttoning clothes (n = 17, 60.7%), problem with transfers (e.g., getting off the floor: n = 10, 35.7%), and activities of daily living (ADLs; n = 15, 53.6%). For non-ambulatory participants, the functional impacts most frequently described were problems with transfers (e.g., getting in/out of bed: n = 13, 72.2%; getting in/out of chair or position in bed: both n = 10, 55.6%), impaired upper body function (reaching: n = 14, 77.8%), and ADLs (n = 15, 83.3%). Meaningful treatment goals differed by ambulatory status; for ambulatory participants, goals included maintaining current functioning (n = 20, 71.4%), improving muscle strength (n = 7, 25.9%), and reducing fatigue (n = 6, 22.2%). For non-ambulatory participants, these included increased upper body strength (n = 8, 42.1%) and greater independence in ADLs (n = 6, 31.6%). A preliminary conceptual model was developed to illustrate the primary symptoms and physical function impacts of DMD and capture their relationship to disease progression. CONCLUSION: This study contributes to the limited qualitative literature by characterizing impacts of physical limitations and symptoms of DMD on disease progression and thus providing insights into the lived experience with DMD. Differences in treatment goals were also identified based on ambulatory status. Taken together, these findings can help inform patient-centered measurement strategies for evaluating outcomes in DMD clinical research.
Subject(s)
Muscular Dystrophy, Duchenne , Humans , Child, Preschool , Child , Muscular Dystrophy, Duchenne/diagnosis , Activities of Daily Living , Walking , Parents , Disease ProgressionABSTRACT
INTRODUCTION: Limb girdle muscular dystrophies (LGMDs) are a group of rare and heterogeneous disorders involving progressive wasting of shoulder and pelvic girdle musculature. This study aimed to generate qualitative evidence on patient and caregiver experiences with symptoms and impacts of LGMD on overall function and daily life for sarcoglycanopathy subtypes 2C/R5, 2D/R3, and 2E/R4. METHODS: Twenty-three individuals with LGMD with (n = 5) or without (n = 18) a caregiver participated in 60-minute semi-structured video interviews. Interview transcripts were analyzed using thematic analysis. Differences in patient experience by ambulation status and LGMD subtype were examined. RESULTS: Participants were ambulatory (n = 14) and non-ambulatory (n = 9), representing three subtypes: 2C/R5 (n = 4), 2D/R3 (n = 12), and 2E/R4 (n = 7), with mean age of 34.8 years (SD = 16.08). 56.5% identified as female. Conceptual saturation was achieved within 18/23 interviews. Ambulatory participants identified difficulty with complex physical activities, e.g., running (n = 11, 78.6%), physical strength (n = 14, 100%), and difficulty with transfers, e.g., difficulty getting off the floor (n = 10, 71.4%). All non-ambulatory participants discussed problems with activities of daily living (ADLs) and transfers, e.g., getting in/out of bed and upper extremity function, particularly reaching (n = 8, 88.9%) and fine motor skills (n = 6, 66.7%). Fatigue and pain were reported by the majority of participants (n = 16, 69.6% and n = 19, 82.6%, respectively). A conceptual disease model was developed illustrating symptoms and impacts and their relationships to disease stage, capturing the patient experience across LGMD disease trajectory. CONCLUSIONS: This study contributes to the limited evidence describing the patient experience of living with LGMD. The conceptual model can inform patient-centered assessment in future LGMD clinical trials.
Subject(s)
Activities of Daily Living , Muscular Dystrophies, Limb-Girdle , Humans , Female , Adult , Muscular Dystrophies, Limb-Girdle/diagnosis , Upper Extremity , Patient Outcome AssessmentABSTRACT
Femoral de-rotation osteotomy (FDO) and hip arthroscopy are both recognized surgical options for the management of femoroacetabular impingement (FAI) in the setting of decreased femoral anteversion (<5°). Minimal comparative data exist regarding the difference in outcomes between these two techniques, and we believe this is the first study to provide that comparison. This retrospective cohort study included a total of 20 patients with such pathology, matched for age, gender and body mass index. A total of 10 patients were included in the FDO group [median anteversion -0.5° (true retroversion); average follow-up 17.9 months]. In total, 10 patients were included in the hip arthroscopy group [median anteversion -0.5° (true retroversion); average follow-up 28.5 months]. Both groups demonstrated statistically and clinically significant improvement in the post-operative International Hip Outcome Tool (iHOT-33) scores [median improvement: FDO group, 37.7 points (r 14-58.8; P < 0.041); hip arthroscopy group, 35.9 points (r 11.1-81; P < 0.05)], noting that the minimal clinically important difference for the iHOT-33 is 6.1 points. However, the study was not adequately powered to delineate a difference in improvement between the two groups. The findings suggest significant improvement in patient-reported outcomes, and clinical findings can be achieved with either FDO or hip arthroscopy for FAI in the setting of decreased femoral anteversion. However, selection of the most suitable surgical procedure using a patient-specific approach may optimize outcomes in this challenging population.
ABSTRACT
BACKGROUND: Patients with metal-on-metal hip arthroplasty may develop adverse reactions to metal debris that can lead to clinically concerning symptoms, often needing revision surgery. As such, many regulatory authorities advocate for routine blood metal ion measurement. This study compares whole blood metal ion levels obtained 1 year following Birmingham Hip Resurfacing (BHR) to levels obtained at a minimum 10-year follow-up. METHODS: A retrospective chart review was conducted to identify all patients who underwent a BHR for osteoarthritis with a minimum 10-year follow-up. Whole blood metal ion levels were obtained at final follow-up in June 2019. These results were compared with patients' metal ion levels at 1 year. RESULTS: Of the 211 patients who received a BHR, 71 patients (54 males and 17 females) had long-term metal ion levels assessed (mean follow-up 12.7 ± 1.4 yr). The mean cobalt and chromium levels for patients with unilateral BHRs (43 males and 13 females) were 3.12 ± 6.31 µg/L and 2.62 ± 2.69 µg/L, respectively; for patients with bilateral BHRs (11 males and 4 females) cobalt and chromium levels were 2.78 ± 1.02 µg/L and 1.83 ± 0.65 µg/L, respectively. Thirty-five patients (27 male and 8 female) had metal ion levels tested at 1 year postoperatively. The mean changes in cobalt and chromium levels were 2.29 µg/L (p = 0.0919) and 0.57 µg/L (p = 0.1612), respectively. CONCLUSION: Our results suggest that regular metal ion testing as per current regulatory agency guidelines may be impractical for asymptomatic patients. Metal ion levels may in fact have little utility in determining the risk of failure and should be paired with radiographic and clinical findings to determine the need for revision.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Metal-on-Metal Joint Prostheses , Osteoarthritis, Hip , Osteoarthritis , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Chromium , Cobalt , Female , Hip Prosthesis/adverse effects , Humans , Male , Metal-on-Metal Joint Prostheses/adverse effects , Metals , Osteoarthritis/surgery , Osteoarthritis, Hip/etiology , Osteoarthritis, Hip/surgery , Prosthesis Design , Prosthesis Failure , Retrospective StudiesABSTRACT
BACKGROUND: A high prevalence of femoral version abnormalities has been observed in hip pain patients, with impact on hip range of motion and muscle strength that should be elucidated. METHODS: Cross-sectional study. Thirty-one patients with hip pain (16 men and 15 female) were subjected to Biplanar X-Rays to quantify femoral version using three-dimensional measurements. The 62 hips were divided into normal version (10-20°, n = 18), anteverted (>20°, n = 19), and retroverted (<10°, n = 25). Joint range of motion for flexion, internal rotation, and external rotation was assessed through digital goniometry. Maximal isometric hip strength (flexion, extension, internal rotation, external rotation at 0° and 30°, abduction, adduction) was evaluated through hand-held dynamometry. Hip rotation index was calculated as external rotation minus internal rotation. FINDINGS: Anteverted hips had greater internal rotation, while retroverted hips had greater external rotation (p = 0.001). Anteverted hips were weaker than retroverted hips for external rotation at 30° (p < 0.001), abduction (p = 0.006) and adduction (p < 0.001), and weaker than normal version hips for extension (p = 0.018). All three groups had different rotation index: retroverted>normal>anteverted (p < 0.001). The ordinal logistic regression found higher values of rotation index with higher probability of being retroverted (common odds ratio = 1.20). There was a strong correlation between femoral version group and rotation index (rS = 0.76, p < 0.001). There was probability >70% of a hip being anteverted if the rotation index was <11°, and being retroverted if the index was >40°. INTERPRETATION: Range of motion and muscle strength differed in hips with different femoral versions. The hip rotation index was a strong femoral version predictor.
Subject(s)
Hip Joint , Hip , Arthralgia , Cross-Sectional Studies , Female , Humans , Male , Pain , Range of Motion, Articular/physiologyABSTRACT
BACKGROUND: Young men with osteoarthritis of the hip are a growing segment of the population requiring arthroplasty, and there is compelling evidence that the Birmingham Hip Resurfacing (BHR) system provides good functional outcomes and durability in young, active men. We reviewed the survivorship and clinical outcomes of patients who underwent BHR with a minimum follow-up of 10 years. METHODS: We analyzed survivorship using the Kaplan-Meier method. Functional scoring was performed using the Harris Hip Score (HHS), the University of California, Los Angeles (UCLA) Activity Score, and a visual analogue scale (VAS). RESULTS: In total, 211 patients (243 hips) were included in the study. Of these, 107 patients (127 hips) were available for long-term clinical follow-up, with a mean duration of 12.4 ± 1.4 years. The proportion of male participants with BHRs surviving past 13 years was 93.8% (95% confidence interval [CI] 87.9%-100%) compared with 87% (95% CI 77.8%-97.3%) of female patients. Eleven patients (11 hips) underwent BHR revision. Upon final follow-up, the median HHS was 93.9 in males and 93.6 in females (p = 0.27); median UCLA Activity Score was 8.2 in males and 7.2 in females (p < 0.001), and the median VAS score was 81.9 in males and 81.3 in females (p = 0.35). The median acetabular component inclination was 45.5° ± 6.0° (range 34.6°-57.2°) in males and 44.6° ± 5.9° (range 29°-58.9°) in females. The most common femoral head size was 50 mm with a 56 mm or 58 mm cup (36.3%). CONCLUSION: This study confirms that BHR provides good to excellent functional outcomes, lasting functional improvements, and acceptable durability beyond 10 years in men. Survivorship following BHR is inferior in women; however, HHS and VAS scores were similar in women and men.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Osteoarthritis, Hip , Arthroplasty, Replacement, Hip/adverse effects , Canada , Female , Follow-Up Studies , Humans , Male , Osteoarthritis, Hip/etiology , Osteoarthritis, Hip/surgery , Reoperation , Retrospective Studies , Treatment OutcomeABSTRACT
Background: A subset of patients with femoroacetabular impingement (FAI) fail arthroscopic management. It is not clear which patients will fail surgical management; however, several surgical and patient factors, such as type of procedure and age, are thought to be important predictors. Purpose: This time-to-event analysis with a 27-month follow-up analysis compared the effect of (1) arthroscopic osteochondroplasty with or without labral repair versus (2) arthroscopic lavage with or without labral repair on the time to reoperation in adults aged 18 to 50 years with FAI. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Eligible participants had been randomized in a previous study trial to a treatment of arthroscopic osteochondroplasty or arthroscopic lavage with or without labral repair. Using the comprehensive data set from the Multinational Femoroacetabular Impingement Randomized controlled Trial, all reoperations until 27 months after surgery were identified. The analysis was conducted using a Cox proportional hazards model, with percentage of patients with a reoperation evaluated in a time-to-event analysis as the outcome. The independent variable was the procedure, with age and impingement subtype explored as potential covariates. The effects from the Cox model were expressed as the hazard ratio (HR). All tests were 2-sided, with an alpha level of .05. Results: A total of 108 patients in the osteochondroplasty group and 106 patients in the lavage group were included. The mean age of the patients included in the study was 36 ± 8.5 years. Overall, 27 incident reoperations were identified within the 27-month follow-up, with an incidence rate of 6 per 100 person-years. Within the osteochondroplasty group, 8 incident reoperations were identified (incidence rate, 3.4 per 100 person-years), while within the lavage group, 19 incident reoperations were identified (incidence rate, 8.7 per 100 person-years). The hazard of reoperation for patients undergoing osteochondroplasty was 40% of that of patients undergoing lavage (HR, 0.40 [95% CI, 0.17-0.91] P = .029). Conclusion: This study demonstrated that for adults between the ages of 18 and 50 years with FAI, arthroscopic osteochondroplasty was associated with a 2.5-fold decrease in the hazard of reoperation at any point in time compared with arthroscopic lavage. Registration: NCT01623843 (ClinicalTrials.gov identifier).
ABSTRACT
Lymphatic filariasis is a vector-borne neglected tropical disease prioritized for global elimination. The filarial nematodes that cause the disease host a symbiotic bacterium, Wolbachia, which has been targeted using antibiotics, leading to cessation of parasite embryogenesis, waning of circulating larvae (microfilariae [mf]), and gradual cure of adult infection. One of the benefits of the anti-Wolbachia mode of action is that it avoids the rapid killing of mf, which can drive inflammatory adverse events. However, mf depleted of Wolbachia persist for several months in circulation, and thus patients treated with antibiotics are assumed to remain at risk for transmitting infections. Here, we show that Wolbachia-depleted mf rapidly lose the capacity to develop in the mosquito vector through a defect in exsheathment and inability to migrate through the gut wall. Transcriptomic and Western blotting analyses demonstrate that chitinase, an enzyme essential for mf exsheathment, is down-regulated in Wolbachia-depleted mf and correlates with their inability to exsheath and escape the mosquito midgut. Supplementation of in vitro cultures of Wolbachia-depleted mf with chitinase enzymes restores their ability to exsheath to a similar level to that observed in untreated mf. Our findings elucidate a mechanism of rapid transmission-blocking activity of filariasis after depletion of Wolbachia and adds to the broad range of biological processes of filarial nematodes that are dependent on Wolbachia symbiosis.
Subject(s)
Anti-Bacterial Agents , Chitinases , Elephantiasis, Filarial , Microfilariae , Wolbachia , Animals , Anti-Bacterial Agents/pharmacology , Chitinases/genetics , Elephantiasis, Filarial/transmission , Humans , Microfilariae/enzymology , Microfilariae/growth & development , Microfilariae/microbiology , Mosquito Vectors/parasitology , Wolbachia/drug effects , Wolbachia/geneticsABSTRACT
The aim of this study was to determine the incidence, annual trend, and perioperative outcomes and identify risk factors of early-onset ( ≤ 90 â¯d) deep surgical site infection (SSI) following primary total hip arthroplasty (THA) for osteoarthritis. We performed a retrospective study using prospectively collected patient-level data from January 2013 to March 2020. The diagnosis of deep SSI was based on the published Centre for Disease Control/National Healthcare Safety Network (CDC/NHSN) definition. The Mann-Kendall trend test was used to detect monotonic trends. Secondary outcomes were 90â¯d mortality and 90â¯d readmission. A total of 22â¯685 patients underwent primary THA for osteoarthritis. A total of 46 patients had a confirmed deep SSI within 90â¯d of surgery representing a cumulative incidence of 0.2â¯%. The annual infection rate decreased over the 7-year study period ( p = 0.026 ). Risk analysis was performed on 15â¯466 patients. Risk factors associated with early-onset deep SSI included a BMI⯠> â¯30â¯kgâ¯m - 2 (odds ratio (OR) 3.42 [95â¯% CI 1.75-7.20]; p < 0.001 ), chronic renal disease (OR, 3.52 [95â¯% CI 1.17-8.59]; p = 0.011 ), and cardiac illness (OR, 2.47 [1.30-4.69]; p = 0.005 ), as classified by the Canadian Institute for Health Information. Early-onset deep SSI was not associated with 90â¯d mortality ( p = 0.167 ) but was associated with an increased chance of 90â¯d readmission ( p < 0.001 ). This study establishes a reliable baseline infection rate for early-onset deep SSI after THA for osteoarthritis through the use of a robust methodological process. Several risk factors for early-onset deep SSI are potentially modifiable, and therefore targeted preoperative interventions of patients with these risk factors is encouraged.
ABSTRACT
For many families, young children's engagement with screen-based technology is an ongoing concern in terms of physical, social and cognitive development. They are uneasy with the difficulty children have disengaging from screens and concerned that this behavior is obsessive or a sign of addiction. However, technology is recognized as having a "rightful role" in early childhood contexts. This scoping paper reports on a review of literature relating to digital play for children aged birth to five years, with the aim of further understanding digital wellbeing. Csikszentmihalyi's flow theory serves as a theoretical framework for understanding why many young children enjoy digital play and become deeply engaged, with a disconnect between how young children and adults perceive digital play. Concerns about children's deep immersion with digital play are interrogated to understand the connections with perceived addictive traits. The review highlights the critical importance of supporting children's agency and digital citizenship skills from a young age, including the ability to critique content, balance screen-time with non-screen time and to develop self-control and self-regulation as a means to promote long-term positive outcomes for children in their digital lifeworlds and beyond.
Subject(s)
Immersion , Adult , Child , Child, Preschool , HumansABSTRACT
Anti-Wolbachia therapy has been identified as a viable treatment for combating filarial diseases. Phenotypic screening revealed a series of pyrazolopyrimidine hits with potent anti-Wolbachia activity. This paper focuses on the exploration of the SAR for this chemotype, with improvement of metabolic stability and solubility profiles using medicinal chemistry approaches. Organic synthesis has enabled functionalization of the pyrazolopyrimidine core at multiple positions, generating a library of compounds of which many analogues possess nanomolar activity against Wolbachia in vitro with improved DMPK parameters. A lead compound, 15f, was selected for in vivo pharmacokinetics (PK) profiling in mice. The combination of potent anti-Wolbachia activity in two in vitro assessments plus the exceptional oral PK profiles in mice puts this lead compound in a strong position for in vivo proof-of-concept pharmacodynamics studies and demonstrates the strong potential for further optimization and development of this series for treatment of filariasis in the future.
ABSTRACT
The mutualistic association between Wolbachia endosymbionts and their filarial nematode hosts has been exploited as a validated drug target delivering macrofilaricidal outcomes. Limitations of existing antibiotics to scale-up have driven the search for new drugs, which are effective in shorter regimens of 7 days or less. Here, we review the last 14 years of anti-Wolbachia drug discovery by the anti-Wolbachia (A·WOL) consortium, which has screened more than two million compounds, delivering thousands of hit compounds. Refined screening models integrated with robust pharmacokinetic/pharmacodynamic (PK/PD) driven optimisation and selection strategies have delivered the first two drug candidates specifically designed to target Wolbachia. AWZ1066S and ABBV-4083 are currently progressing through clinical trials with the aim of delivering safe and effective macrofilaricides to support the elimination of onchocerciasis and lymphatic filariasis.
Subject(s)
Elephantiasis, Filarial , Nematode Infections , Onchocerciasis , Wolbachia , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Discovery , Elephantiasis, Filarial/drug therapy , Humans , Nematode Infections/drug therapy , Onchocerciasis/drug therapyABSTRACT
AIM: How reduced femoral neck anteversion alters the distribution of pressure and contact area in Hip Resurfacing Arthroplasty (HRA) remains unclear. The purpose of this study was to quantitatively describe the biomechanical implication of different femoral neck version angles on HRA using a finite element analysis. MATERIALS AND METHODS: A total of sixty models were constructed to assess the effect of different femoral neck version angles on three different functional loads: 0°of hip flexion, 45°of hip flexion, and 90° of hip flexion. Femoral version was varied between 30° of anteversion to 30° of retroversion. All models were tested with the acetabular cup in four different positions: (1) 40°/15° (inclination/version), (2) 40°/25°, (3) 50°/15°, and (4) 50°/25°. Differences in range of motion due to presence of impingement, joint contact pressure, and joint contact area with different femoral versions and acetabular cup positions were calculated. RESULTS: Impingement was found to be most significant with the femur in 30° of retroversion, regardless of acetabular cup position. Anterior hip impingement occurred earlier during hip flexion as the femur was progressively retroverted. Impingement was reduced in all models by increasing acetabular cup inclination and anteversion, yet this consequentially led to higher contact pressures. At 90° of hip flexion, contact pressures and contact areas were inversely related and showed most notable change with 30° of femoral retroversion. In this model, the contact area migrated towards the anterior implant-bone interface along the femoral neck. CONCLUSION: Femoral retroversion in HRA influences impingement and increases joint contact pressure most when the hip is loaded in flexion. Increasing acetabular inclination decreases the area of impingement but doing so causes a reciprocal increase in joint contact pressure. It may be advisable to study femoral neck version pre-operatively to better choose hip resurfacing arthroplasty candidates.
Subject(s)
Computer Simulation , Femur Neck/physiopathology , Arthroplasty, Replacement, Hip , Biomechanical Phenomena , Elastic Modulus , Femur Neck/diagnostic imaging , Finite Element Analysis , Hip Joint/physiopathology , Humans , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: Osteoarthritis (OA) is a chronic and painful condition where the articular cartilage surfaces progressively degenerate, resulting in loss of function and progressive disability. Obesity is a primary risk factor for the development and progression of knee OA, defined as the "metabolic OA" phenotype. Metabolic OA is associated with increased fat deposits that release inflammatory cytokines/adipokines, thereby resulting in systemic inflammation which can contribute to cartilage degeneration. There is currently no cure for OA. Prebiotics are a type of dietary fiber that can positively influence gut microbiota thereby reducing systemic inflammation and offering protection of joint integrity in rodents. However, no human clinical trials have tested the effects of prebiotics in adults with obesity suffering from knee OA. Therefore, the purpose of this double-blind, placebo-controlled, randomized trial is to determine if prebiotic supplementation can, through positive changes in the gut microbiota, improve knee function and physical performance in adults with obesity and knee OA. METHODS: Adults (n = 60) with co-morbid obesity (BMI > 30 kg/m2) and knee OA (Kellgren-Lawrence grade II-III) will be recruited from the Alberta Hip and Knee Clinic and the Rocky Mountain Health Clinic and surrounding community of Calgary, Canada, and randomized (stratified by sex, BMI, and age) to prebiotic (oligofructose-enriched inulin; 16 g/day) or a calorie-matched placebo (maltodextrin) for 6 months. Anthropometrics, performance-based tests, knee pain, serum inflammatory markers and metabolomics, quality of life, and gut microbiota will be assessed at baseline, 3 months, 6 months (end of prebiotic supplementation), and 3 months following the end of the prebiotic supplementation. CLINICAL SIGNIFICANCE: There is growing pressure on health care systems for aggressive OA treatment such as total joint replacement. Less aggressive, yet effective, conservative treatment options have the potential to address the growing prevalence of co-morbid obesity and knee OA by delaying the need for joint replacement or ideally preventing its need altogether. The results of this clinical trial will provide the first evidence regarding the efficacy of prebiotic supplementation on knee joint function and pain in adults with obesity and knee OA. If successful, the results may provide a simple, safe, and easy to adhere to intervention to reduce knee joint pain and improve the quality of life of adults with co-morbid knee OA and obesity. TRIAL REGISTRATION: Clinical Trials.gov NCT04172688 . Registered on 21 November 2019.
Subject(s)
Gastrointestinal Microbiome , Obesity, Morbid , Osteoarthritis, Knee , Adult , Alberta , Dietary Supplements , Double-Blind Method , Humans , Inflammation/diagnosis , Knee Joint , Osteoarthritis, Knee/diagnosis , Osteoarthritis, Knee/therapy , Prebiotics , Quality of Life , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
We previously developed a three-item screener for identifying respondents with any personality disorder (PD) using the Inventory of Interpersonal Problems (IIP). The current goal was to examine the convergent validity of the IIP-3 with other PD screeners and diagnostic tools and to investigate its relationship to measures of adult attachment and emotion regulation. The sample consisted of participants from five studies (total N = 852), with data from collateral informants available for a subsample (N = 353). Despite its brevity, the IIP-3 showed moderate to strong relationships with other longer PD screeners, with PD symptom scores from the Structured Interview for DSM-IV Personality (SIDP-IV), and with a global rating of PD severity. It was most sensitive to the stylistic aspects of PD typical of the traditional DSM cluster B (dramatic, expressive) PDs. These results emerged with data from both participants and informants, although correlations using informant data were generally smaller.
Subject(s)
Personality Disorders , Adult , Diagnostic and Statistical Manual of Mental Disorders , Humans , Personality Disorders/diagnosis , Personality Inventory , Psychometrics , Reproducibility of ResultsABSTRACT
BACKGROUND: Femoroacetabular impingement (FAI) is a condition known to cause hip pain in young adults. PURPOSE: To evaluate the efficacy of the surgical correction of FAI via arthroscopic osteochondroplasty with or without labral repair compared with arthroscopic lavage of the hip joint with or without labral repair. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 220 male and female participants aged 18 to 50 years with nonarthritic FAI suitable for surgical treatment were recruited for the trial at 10 clinical centers in Canada, Finland, and Denmark between October 2012 and November 2017, of whom 214 were included in the final analysis. In the osteochondroplasty group, cam- and/or pincer-type lesions were resected using fluoroscopic guidance. In the lavage group, the joint was washed out with 3 L of normal saline. Surgeons were instructed to repair the labrum in both groups if it was mechanically unstable once probed, showing visible displacement or chondrolabral separation. The primary outcome was patient-reported pain (using the 100-point visual analog scale [VAS]) at 12 months. Secondary outcomes included hip function (Hip Outcome Score [HOS] and International Hip Outcome Tool), physical and mental health (12-Item Short Form Health Survey), and health utility (EuroQol-5 Dimensions) at 12 months as well as any reoperations and other hip-related adverse events at 24 months. RESULTS: At 12 months, there was no difference in pain (VAS) between the groups (mean difference [MD], 0.11 [95% CI, -7.22 to 7.45]; P = .98). Also, 88.3% (189/214) of participants had a labral tear, of which 60.3% were repaired. For the secondary outcomes, there were no significant differences between treatment groups, with the exception of the HOS activities of daily living domain in which lavage showed significant improvement compared with osteochondroplasty (MD, -5.03 [95% CI, -10.40 to -0.03]; P = .049). By 24 months, there were significantly fewer reoperations reported in the osteochondroplasty group (8/105) than the lavage group (19/104) (odds ratio, 0.37 [95% CI, 0.15-0.89]; P = .026). The primary reasons for a reoperation included hip pain (15/27; 55.6%) and a reinjury of the labrum (11/27; 40.7%). CONCLUSION: Both the osteochondroplasty and the lavage groups with or without labral repair for FAI had significantly improved pain or function significantly at 1 year. By 2 years, the reoperation rate was significantly lower in the osteochondroplasty group. REGISTRATION: NCT01623843 (ClinicalTrials.gov identifier).
Subject(s)
Femoracetabular Impingement , Activities of Daily Living , Adolescent , Adult , Arthroscopy , Canada , Female , Femoracetabular Impingement/surgery , Finland , Follow-Up Studies , Hip Joint , Humans , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
CASE: A healthy 36-year-old man developed compartment syndrome of the posterior thigh with an associated sciatic nerve palsy secondary to an acute proximal hamstring tendon avulsion injury. CONCLUSION: Compartment syndrome of the thigh is rare and is usually associated with high-energy trauma. Atraumatic causes have been described, typically involving the anterior compartment. Posterior thigh compartment syndrome is especially uncommon. This case highlights the potential occurrence of posterior thigh compartment syndrome after proximal hamstring tendon rupture. Given the morbidity associated with compartment syndrome, it is important to recognize the risk factors and injury patterns that can cause thigh compartment syndrome.
Subject(s)
Compartment Syndromes/etiology , Fasciotomy , Hamstring Tendons/injuries , Tendon Injuries/complications , Adult , Compartment Syndromes/surgery , Humans , Male , Negative-Pressure Wound Therapy , Tendon Injuries/surgeryABSTRACT
BACKGROUND: Surgical fixation of tibial plateau fracture in elderly patients with open reduction and internal fixation (ORIF) provides inferior outcomes compared with younger patients. Primary total knee arthroplasty (TKA) may be of benefit in elderly patients with a combination of osteoporotic bone and metaphyseal comminution. However, there continues to be conflicting evidence on the use of TKA for primary treatment of tibial plateau fracture. This systematic review was performed to quantify the outcomes and perioperative complication rates of TKA for primary treatment of tibial plateau fracture. MATERIALS AND METHODS: A comprehensive search of MEDLINE, Embase, and PubMed databases from inception through March 2018 was performed in accordance with PRISMA guidelines. Two reviewers independently screened papers for inclusion and identified studies featuring perioperative complications and outcomes of primary TKA for tibial plateau fracture. Weighted means and standard deviations are presented for each outcome. RESULTS: Seven articles (105 patients) were eligible for inclusion. All-cause mortality was 4.75 ± 4.85%. The total complication rate was 15.2 ± 17.3%. Regarding outcomes, Knee Society scores were most commonly reported. The average Knee Society Knee Score was 85.6 ± 5.5, while the average Knee Society Function Score was 64.6 ± 13.7. Average range of motion at final follow-up was 107.5 ± 10.0°. CONCLUSIONS: Primary TKA for select tibial plateau fractures has acceptable clinical outcomes but does not appear to be superior to ORIF. It may be appropriate to treat certain geriatric patients with TKA to allow for early mobilization and reduce the need for reoperation. Other factors may need to be considered in deciding the optimal treatment. LEVEL OF EVIDENCE: Level III.