Changes in physical inactivity during supervised educational and exercise therapy in patients with knee osteoarthritis: A prospective cohort study

BackgroundPhysical inactivity is a global problem and patients with knee osteoarthritis (OA) are predisposed to inactivity and its health-related consequences. Current guidelines recommend exercise as primary treatment but whether this affects time spent physically inactive is unknown. The objective was to investigate changes in physical inactivity among individuals with knee OA following an educational and exercise program.MethodsPragmatic prospective cohort study performed in six physical therapy clinics in Denmark offering a nationwide education and exercise program for knee OA. The program consists of physiotherapy guided education and group-based or home exercise sessions, performed biweekly for approximately eight weeks. The exercises target knee and hip joint stability as well as focus on increasing muscle strength. Primary outcome was time spent physically inactive (min/day), measured with a tri-axial accelerometer mounted on the lateral side of the thigh during the entire exercise program duration. OA symptoms were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS).ResultsThirty-two individuals with knee OA were analyzed. From baseline to post-intervention, no changes occurred in average time spent physically inactive (mean change: + 16.2 min [95% CI − 15.7 to 48.1]; P = 0.31), but statistically significant improvements in KOOS pain (+ 6.7 points [95% CI 2.3 to 11.0]; P = 0.0032) and KOOS function (+ 5.8 points [95% CI 1.9 to 9.7]; P = 0.0046) were found.ConclusionsParticipating and completing a widely adopted education and exercise program are not associated with spontaneous improvements in physical inactivity despite changes in self-reported pain and function. Interventions specifically targeting physical inactivity are needed.Registration number: www.clinicaltrials.gov: NCT03125954.     

Altered dynamic foot kinematics in people with medial knee osteoarthritis during walking: A cross-sectional study

BackgroundFootwear and insoles are used to reduce knee load in people with medial knee osteoarthritis (OA), despite a limited understanding of foot function in this group. The aim of this study was to investigate the differences in foot kinematics between adults with and without medial knee OA during barefoot walking.MethodsFoot kinematics were measured during walking in 30 adults; 15 with medial knee OA (mean age was 67.0 with a standard deviation (SD) of 8.9 years; height was 1.66 with SD of 0.13 m; body mass was 84.2 with SD of 15.8 kg; BMI was 30.7 with SD of 6.2 kg/m²; K–L grade 3: 5, grade 4: 10) and 15 aged and gender matched control participants with 12 motion analysis cameras using the IOR multi-segment foot model. Motion of the knee joint, hindfoot, midfoot, forefoot and hallux were compared between groups using clustered linear regression.ResultsThe knee OA group displayed reduced coronal plane range of motion of the midfoot (mean 3.8° vs. 5.4°, effect size = 1.1, p = 0.023), indicating reduced midfoot mobility. There was also a reduced sagittal plane range of motion at the hallux in the knee OA group compared to the control group (mean 29.6° vs. 36.3°, effect size = 1.2, p = 0.008). No statistically significant differences in hindfoot or forefoot motion were observed.ConclusionsPeople with medial knee OA display altered foot function compared to healthy controls. As foot and knee function are related, it is possible that altered foot function in people with knee OA may influence the effects of footwear and insoles.     

Social networks for improving healthy weight loss behaviors for overweight and obese adults: A randomized clinical trial of the social pounds off digitally (Social POD) mobile app

ObjectiveTo test the efficacy of a weight loss mobile app based on recommender systems and developed by experts in health promotion and computer science to target social support and self-monitoring of diet, physical activity (PA), and weight (Social POD app), compared to a commercially available diet and PA tracking app (standard).Materials and methodsOverweight adults [N = 51] were recruited and randomly assigned to either the experimental group [n = 26; theory-based podcasts (TBP) + Social POD app] or the comparison group (n = 25; TBP + standard app). The Social POD app issued notifications to encourage users to self-monitor and send theory-based messages to support users who had not self-monitored in the previous 48 h. Independent samples t-test were used to examine group differences in kilograms lost and change in BMI. Analysis of covariance was used to analyze secondary outcomes while controlling for baseline values.ResultsParticipant attrition was 12% (n = 3 experimental and n = 3 comparison). Experimental group participants lost significantly more weight (−5.3 kg, CI: −7.5, −3.0) than comparison group (−2.23 kg, CI: −3.6, −1.0; d = 0.8, r = 0.4, p = 0.02) and had a greater reduction in BMI (p = 0.02). While there were significant differences in positive outcome expectations between groups (p = 0.04) other secondary outcomes (e.g., caloric intake and social support) were not significant.DiscussionUse of the Social POD app resulted in significantly greater weight loss than use of a commercially available tracking app. This mobile health intervention has the potential to be widely disseminated to reduce the risk of chronic disease associated with overweight and obesity.     

Clinical outcomes after arthroscopic treatment of knee osteoarthritis

PurposeThe aim of this study was to describe the clinical outcomes of patients with knee osteoarthritis (OA) treated with arthroscopic surgery, documenting the associated injuries and defining the type of treatment selected for OA patients with different symptoms.HypothesisKnee arthroscopy is effective for treating patients with symptomatic OA and mechanical symptoms.MethodsThis was a prospective, consecutive series of 100 patients with a clinical and radiological diagnosis of OA who were treated with knee arthroscopy. The average follow-up time was 35.9 months (25–71), and the average age was 60.1 years (50–83). Inclusion criteria: > 50 years of age, a clinical imaging diagnosis of knee OA with an Ahlbäck I–III classification. Exclusion criteria: < 50 years of age, Ahlbäck IV, pathologic lower limb mechanical axis and inflammatory joint diseases. The IKDC and Lysholm scores were assessed before and after surgery.ResultsThe preoperative average scores were as follows: Lysholm, 56.9 ± 13.5 points (22–71); IKDC, 59.4 ± 21.7 points (45–80). The postoperative average scores were as follows: Lysholm, 86.9 points (22–87); IKDC, 79.5 points (45–100). Regarding the Lysholm scores, 76% were good and excellent results and 24% were moderate (p = 0.045). The associated injuries included 48% of chondral and 36% of unstable meniscal injuries. Good or excellent results were observed in 76% of the meniscal injury cases according to the Lysholm scores, while only 84.6% of the cases with unstable chondral lesions had good or excellent results (p = 0.035).ConclusionMost patients with knee OA associated with unstable cartilage or meniscal injuries reported good-to-excellent symptomatic results at the short- and mid-term follow-ups.Level of evidenceIII     

Lateral and patellofemoral compartment osteoarthritis progression after medial unicompartmental knee arthroplasty: A five- to 10-year follow-up study

BackgroundThe purpose of the study was to evaluate lateral and patellofemoral osteoarthritis (OA) progression after medial unicompartmental knee arthroplasty (UKA) and identify factors affecting the progression that were not identified previously.MethodsWe evaluated 146 patients who underwent medial UKA between 2009 and 2014. Kellgren–Lawrence grading of lateral and patellofemoral OA was performed on preoperative and final follow-up knee radiographs. Radiographic and clinical characteristics, SF-36, and Oxford knee scores were compared between the OA progressed and non-progressed groups. Risk factors for lateral and patellofemoral OA progression were evaluated.ResultsThe lateral OA progressed and non-progressed groups significantly differed in side, preoperative flexion contracture, preoperative joint line convergence angle, postoperative tibiofemoral angle, insert size, revision status (P < 0.05), and the patellofemoral OA progressed and non-progressed groups significantly differed in age, pre- and postoperative flexion contracture, postoperative tibiofemoral angle and pre- and postoperative patellofemoral OA grade (P < 0.05). At the final follow-up, Visual Analogue Scale, Oxford Knee Scores, and SF-36 sub-scores were significantly better in the lateral OA non-progressed group (P < 0.001).Dominant leg (odds ratio (OR): 2.759), insert size (> 4, OR: 2.219), revision status (+, OR: 6.692), and postoperative tibiofemoral angle (> 5.5°, OR: 1.177) were independent risk factors for lateral OA progression, whereas age (> 60 years, OR: 3.222), preoperative patellofemoral OA grade (> 1, OR: 2.085), and postoperative flexion contracture (> 10°, OR: 1.919) were those for patellofemoral OA progression.ConclusionsMild radiographic progression of 1 KL grade is frequently seen five to 10 years after medial UKA. Postoperative outcomes are significantly affected by lateral compartment OA progression but not by patellofemoral OA progression.     

Effects of escitalopram on menopause-specific quality of life and pain in healthy menopausal women with hot flashes: A randomized controlled trial

ObjectiveTo evaluate the effects of escitalopram 10–20 mg/day on menopause-related quality of life and pain in healthy menopausal women with hot flashes.Study designA double-blind, placebo-controlled randomized trial of escitalopram 10–20 mg/day vs. identical placebo was conducted among 205 women ages 40–62 years with an average of ≥4 daily hot flashes recruited at 4 clinical sites from July 2009 to June 2010.Main outcome measuresThe primary trial outcomes, reported previously, were the frequency and severity of vasomotor symptoms at 8 weeks. Here, we report on the pre-specified secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and the pain intensity and interference scale (PEG).ResultsOutcome data were collected on 97% of randomized women and 87% of women took at least 70% of their study medication. Treatment with escitalopram resulted in significantly greater improvement in total MENQOL scores (mean difference at 8 weeks of −0.41; 95% confidence interval (CI) −0.71 to −0.11; p < 0.001), as well as Vasomotor, Psychosocial, and Physical domain scores with the largest difference seen in the Vasomotor domain (mean difference −0.75; 95% CI −1.28 to −0.22; p = 0.02). There was no significant treatment group difference for the Sexual Function domain. Escitalopram treatment resulted in statistically significant improvements in PEG scores compared to placebo (mean treatment group difference at 8 weeks of −0.33; 95% CI −0.81 to 0.15; p = 0.045).ConclusionsTreatment with escitalopram 10–20 mg/day in healthy women with vasomotor symptoms significantly improved menopause-related quality of life and pain.     

Differences between opening versus closing high tibial osteotomy on clinical outcomes and gait analysis

BackgroundHigh tibial osteotomy (HTO) for medial knee osteoarthritis (OA) is mainly performed via two procedures: closing wedge HTO (CW) and opening wedge HTO (OW). In this study, differences between these procedures were assessed by serial clinical evaluation and gait analysis before and after surgery.MethodsTwenty-one patients underwent HTO for medial knee OA in 2011 and 2012, with 12 patients undergoing CW and nine undergoing OW. The severity of OA was classified according to the Kellgren–Lawrence classification. The Japanese Orthopedic Association score for assessment of knee OA (JOA score), the Numeric Rating Scale (NRS), and the femoral tibial angle (FTA) on X-ray were evaluated. For gait analysis, gait speed, varus moment, varus angle and lateral thrust were calculated.ResultsThe JOA score and NRS were improved significantly one year postoperatively in both groups. The FTA was maintained in both groups at one year. Varus angle and varus moment were significantly improved in both groups at each postoperative follow-up, when compared preoperatively. Lateral thrust was significantly improved at three months postoperatively in both groups. However, the significant improvement in lateral thrust had disappeared in the CW group six months postoperatively, whereas it was maintained for at least one year in the OW group.ConclusionsThis study found that clinical outcomes were well maintained after HTO. OW reduced knee varus moment and lateral thrust, whereas CW had little effect on reducing lateral thrust.Level of evidenceLevel IV     

Nerve-sparing radical hysterectomy versus conventional radical hysterectomy in early-stage cervical cancer. A systematic review and meta-analysis of survival and quality of life

Background and aimsSurvival after radical hysterectomy (RH) for early-stage cervical cancer is good. Hence quality of life (QOL) after treatment is an important issue. Nerve-sparing radical hysterectomy (NSRH) improves QOL by selectively sparing innervation of bladder, bowel and vagina, reducing therapy-induced morbidity. However, the oncological outcome and the functional outcome after NSRH are subjects of debate. We aim to present the best possible evidence available regarding both QOL and survival after NSRH in early-stage cervical cancer.MethodsSystematic review and meta-analysis on studies comparing NSRH and RH.ResultsForty-one studies were included, and 27 were used for the meta-analysis. There was no difference in 2-, 3- and 5-year overall survival: the risk ratios (RRs) were respectively 1.02 (95% CI 0.99–1.05, n = 879), 1.01 (95% CI 0.95–1.08, n = 1324) and 1.03 (95% CI 0.99–1.08, n = 638). No difference was found in 2-, 3- and 5-year disease-free survival: RR 1.01 (95% CI 0.95–1.05, n = 1175), 0.99 (95% CI 0.94–1.03, n = 1130) and 1.00 (95% CI 0.95–1.06, n = 933) respectively. Post-operative time to micturition was significantly shorter in the NSRH group: standardized mean difference (SMD) −0.84 (CI 95% −1.07 to −0.60).ConclusionsNSRH can be considered safe and effective for early-stage cervical cancer since short- and long-term survival do not differ from those of conventional RH, while bladder function after NSRH is significantly less impaired.     

An evidence-based recommendation for the inclusion of specific local intrinsic factors in the study of knee osteoarthritis

ObjectiveAdequate characterization of the mechanical environment of the knee with osteoarthritis (OA) is important. These local intrinsic factors are difficult to measure and there is little evidence to guide their selection. This study makes an evidence-based recommendation for the inclusion of specific factors in the future study of knee OA.MethodForty-six subjects with knee OA were examined. Observed function was measured by the Timed Chair Rise (TCR). Self-reported function was measured by the WOMAC Function Scale and pain was measured by the WOMAC Pain Scale. Local intrinsic factors measured included varus/valgus alignment, anterior/posterior (A/P) laxity, proprioception, isometric knee extension (KE) strength, isometric knee flexion (KF) strength, and knee range of motion (ROM).ResultsFactors were recommended for inclusion in future research if they were significantly correlated with at least one measure of function or pain and if the factor made a significant unique contribution to a regression model when more than one local intrinsic factor was correlated with the same measure of function or pain. Alignment was correlated with pain (r = 0.48, p = 0.001) and WOMAC function (r = 0.38, p = 0.009). A/P laxity was correlated with pain (r = 0.30, p = 0.04) and WOMAC function (r = 0.37, p = 0.01). Knee ROM was correlated to WOMAC function (r = ? 0.35, p = 0.02). KE strength was correlated with TCR (r = 0.32, p = 0.03). Alignment made a significant contribution to prediction of pain (p = 0.003). A/P laxity (p = 0.004) and ROM (p = 0.008) made a significant contribution to WOMAC function.ConclusionWe recommend future knee OA studies include the variables varus/valgus alignment, A/P laxity, ROM, and KE strength.Level of EvidenceIII (correlational study).     

PTPN22 polymorphisms,but not R620W,were associated with the genetic susceptibility of systemic lupus erythematosus and rheumatoid arthritis in a Chinese Han population

ObjectivesThe present study aimed to detect a possible association between PTPN22 gene polymorphisms and rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in a Chinese Han population.Methods7 PTPN22 SNPs were genotyped in 358 patients with RA and 713 patients with SLE, as well as 564 RA controls and 672 SLE controls by Restriction Fragment Length Polymorphism (RFLP). Association analyses were conducted on the whole data set. Significant relationships were also examined between clinical features and SNPs for both RA and SLE.ResultsRs2476601 was lack of polymorphism with a ⩽0.1% frequency in both SLE and RA patients and healthy controls in our study. The two SNPs rs1217414 and rs3811021 of PTPN22 shown strong association with both SLE (rs1217414T: p_adj = 6.07e−004, OR = 0.57; rs3811021C: p_adj = 4.68e−005, OR = 0.65) and RA (rs1217414T: p_adj = 2.01e−008, OR = 0.26; rs3811021C: p_adj = 0.028, OR = 0.70). And the rs3765598 revealed a strong risk factor for SLE (p = 9.38e−009, p_adj = 6.57e−008, OR = 1.93), but not for RA (p = 0.48, OR = 1.12). Moreover, protective haplotype ACTTC in RA (p = 7.73e−016, p_adj = 5.51−015, OR[95%CI] = 0.02[0.002–0.10]) and SLE (p = 8.29e−018, p_adj = 5.80e−017, OR[95%CI] = 0.11[0.06–0.21]) were observed. In addition, the distribution of risk haplotypes ACGTC and GCTTT in RA (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; GCTTT: p = 2.62e−005, p_adj = 1.85e−004, OR[95%CI] = 2.40[1.57–3.65]) and SLE (ACGTC: p = 0.0006, p_adj = 0.004, OR[95%CI] = 1.85[1.29–2.63]; ACGTC: p = 7.74e−011, p_adj = 6.81e−010, OR[95%CI] = 2.21[1.12–3.34]; GCTTT: p = 2.40[1.57–3.65], p_adj = 2.26e−006, OR[95%CI] = 2.64[1.79–3.87]) were significant different from that in controls. Furthermore, significant association was observed between the PTPN22 rs3765598 and antinuclear antibodies 1 (ANA1) in SLE.ConclusionsOur data provide strong evidence that the rs1217414 and rs3811021 in PTPN22 gene might be common protective factors contributed to SLE and RA susceptibility in the Chinese Han population. While, the rs3765598 might increase the genetic susceptibility of SLE, but not RA.     

Comparison of graft healing in anterior cruciate ligament reconstruction with and without a preserved remnant in rabbits

BackgroundThe remnant of the native anterior cruciate ligament (ACL) might contribute to the biological integration of the graft in ACL reconstruction. The aim of this study was to explore whether the preserved remnant enhanced graft healing in ACL reconstruction.MethodsForty New Zealand rabbits underwent bilateral anterior cruciate ligament reconstructions. One knee was treated with a 2-mm remnant preserved on the tibial side (remnant-preservation, RP group) while the contralateral knee underwent a complete removal of the remnants by cauterization (remnant-resection, RR group) in each animal. Gross observations combined with microangiography, histological evaluation, and uniaxial load testing were performed after 4, 8, and 12 weeks.ResultsThe vascular density on the graft surface was statistically higher in the RP group as compared to that of the RR group at 4 (P = 0.002) and 8 weeks (P = 0.020). Additionally, the accelerated intra-articular and intra-tunnel graft integration were histologically observed in the RP group. Histological scores in the RP group were statistically higher than the RR group at 4 weeks (P = 0.028 for the intra-articular healing and P = 0.046 for the intra-tunnel healing) and 8 weeks (P = 0.031 for the intra-articular healing and P = 0.014 for the intra-tunnel healing). The ultimate failure load (P = 0.017), yield load (P = 0.025), and stiffness (P = 0.004) were statistically higher in the RP group as compared to those of the RR group, with corresponding significant differences in the failure mode (P = 0.020) between the two groups at 8 weeks.ConclusionsThe preserved remnant enhanced ACL graft healing with improved biomechanical properties in the rabbit model.Level of evidenceLevel II.     

Mobile bearing or fixed bearing? A meta-analysis of outcomes comparing mobile bearing and fixed bearing bilateral total knee replacements

BackgroundTo compare outcomes between mobile-bearing (MB) and fixed-bearing (FB) in bilateral total knee replacements.MethodsThe MEDLINE, EMBASE and Cochrane Library databases were searched. Randomized controlled trials of bilateral total knee arthroplasty with one of each design implanted were identified. Weighted mean differences (WMDs) and pooled risk ratios (RRs) were calculated using fixed- or random-effects models.ResultsTwelve studies were identified with a total of 807 patients and 1614 knees. All RCTs were of high quality with a low risk of bias. No statistical difference was found between MB and FB at 2- to 5-year follow-up in terms of America Knee Society score (WMD: − 1.29, 95% CI: − 5.65 to 3.06), pain score (WMD: − 3.26, 95% CI: − 10.45 to 3.93), range of motion (WMD: − 4.16, 95% CI: − 9.97 to 1.66), reoperation (RR: 1.00, 95% CI: 0.28 to 3.60), and radiolucent lines (RR: 1.51, 95% CI: 0.70 to 3.24). The results were similar at 1-, 5- to 8-, or > 8-year follow-up. Patient's satisfaction (RR: 0.85, 95% CI: 0.54 to 1.34), and complication (≤ 2-year, RR: 0.55, 95% CI: 0.29 to 1.04; > 2-year, RR: 1.0, 95% CI = 0.73 to 1.38) also showed no difference between two groups.ConclusionsBased on this meta-analysis we are unable to detect the superiority of MB as compared to FB. More randomized trials with a larger sample size and longer follow-up are needed to evaluate these two kinds of prosthesis.Level of evidenceTherapeutic Level II.     

Exercise training for managing behavioral and psychological symptoms in people with dementia: A systematic review and meta-analysis

This systematic review and meta-analysis of randomized controlled trials assessed the effects of exercise on behavioral and psychological symptoms of dementia (BPSD, including depression) in people with dementia (PWD). Secondary outcomes for the effects of exercise were mortality and antipsychotic use. Twenty studies were included in this review (n = 18 in the meta-analysis). Most studies used a multicomponent exercise training (n = 13) as intervention; the control group was often a usual care (n = 10) or a socially-active (n = 8) group. Exercise did not reduce global levels of BPSD (n = 4. Weighted mean difference −3.884; 95% CI −8.969–1.201; I² = 69.4%). Exercise significantly reduced depression levels in PWD (n = 7). Standardized mean difference −0.306; 95% CI −0.571 to −0.041; I² = 46.8%); similar patterns were obtained in sensitivity analysis performed among studies with: institutionalized people (p = 0.038), multicomponent training (p = 0.056), social control group (p = 0.08), and low risk of attrition bias (p = 0.11). Exploratory analysis showed that the principal BPSD (other than depression) positively affected by exercise was aberrant motor behavior. Exercise had no effect on mortality. Data on antipsychotics were scarce. In conclusion, exercise reduces depression levels in PWD. Future studies should examine whether exercise reduces the use (and doses) of antipsychotics and other drugs often used to manage BPSD.     

Association of the calcitonin gene (CA) polymorphism with osteoarthritis of the knee in a Mexican mestizo population

Osteoarthritis (OA) is the most common form of destructive joint disease that is characterized by the degeneration of the articular cartilage, synovial membrane, joint capsule, and subchondral bone. The knee is a joint commonly affected for OA. Calcitonin (CT) has been suggested to have chondroprotective effects; therefore, could play a role in the pathogenesis of OA of the knee. Genetic variations in or adjacent to the CT gene may be associated with primary OA development. We conducted a case-control association study in which we examined the correlation between a dinucleotide (cytosine-adenine, CA) repeat polymorphism at the CT locus and OA of the knee in 88 patients with OA and in 111 control subjects from the Mexican mestizo population. Allele A and genotype AG frequencies were significantly higher in patients with OA than in control subjects (56.3 vs. 43.2%; p < 0.001 and 40.9 vs. 26.1%; p = 0.027, respectively), and were associated with the presence of OA of the knee (odds ratio [OR], 2.62; 95% confidence interval [95% CI], 1.30–5.27, and OR, 1.93; 95% CI, 1.04–3.58, respectively) using a logistic regression model adjusted for gender, age and Body mass index (BMI). The GG genotype was associated with a lower risk of OA development of the knee; thus, it may constitute a protective factor against this disease (OR, 0.40; 95% CI, 0.16–0.98).In summary, we conclude that the dinucleotide CA polymorphism in the CT gene may become a useful marker for genetic studies of OA of the knee in Mexican population.     

Association of chemokine expression in anterior cruciate ligament deficient knee with patient characteristics: Implications for post-traumatic osteoarthritis

BackgroundStromal cell-derived factor-1a (SDF-1α) and high mobility group box chromosomal protein 1 (HMGB1) are chemokines that can drive post-traumatic osteoarthritis (PTOA) induced by anterior cruciate ligament (ACL) injury. However, the influence of patient characteristics on expression of those chemokines remains unclear. Our aim was to determine the relationship between chemokine expression in synovial fluid (SF) of the ACL-deficient (ACL-D) knee and patient characteristics including time from injury, sex, and age.MethodsSF samples were collected immediately prior to the first-time ACL reconstruction (ACLR) from 82 patients. Expression of SDF-1α and HMGB1 was measured with human-specific solid phase sandwich enzyme-linked immunosorbent assays. The expression levels between groups divided by time from injury, or age, or sex was compared using Student's t-test. The association of SDF-1α or HMGB1 levels with those variables was determined using regression analysis and Pearson product–moment correlation coefficient.ResultsRegression and correlation analysis indicated significant correlation between SDF-1α expression and time from injury in the cohort (r = − 0.266, P = 0.016, n = 82) and in females (r = − 0.386, P = 0.024, n = 34). Significant correlation was also observed between SDF-1α expression and age in the cohort (r = − 0.224, P = 0.043, n = 82) and in males (r = − 0.289, P = 0.046, n = 48). No significant correlation between HMGB1 expression and patient characteristics was detected.ConclusionsSDF-1α rather than HMGB1 might serve as a protein marker for monitoring the development of PTOA in the ACL-D knee, especially in female patients.     

Improving chemotherapy processes with a protocol-based information system: A pre and post-implementation study

BackgroundThe medical application domain has been a great challenge for information technology solutions for decades, especially when the target process has been complex and multidisciplinary such as chemotherapy processes.ObjectiveTo evaluate the impact of a homegrown protocol based information system on the efficiency of chemotherapy workflow processes in an outpatient setting.MethodsA day care unit of the Hematology/Oncology outpatient clinic of Erasmus Medical Center was the setting for this study. The study consisted of comparison of pre- and post-implementation of four workflow efficiency related external indicators: turn-around times of a commonly administered chemotherapy course (Paclitaxel–Carboplatin), chemotherapy course administration postponing rate, the rate of recording course administration time, and patient admission rate of the outpatient clinic. The data was gathered retrospectively from patient charts and information systems’ log files. For the purpose of turn-around-time 109 Paclitaxel–Carboplatin chemotherapy courses of pre-implementation were compared to 118 those of post-implementation. For the other indicators: 247 chemotherapy courses pre-implementation were compared to 324 courses post-implementation. The process maps of pre- and post-implementation were also compared to each other.ResultsThe implementation of the system improved the process by removing repetition and sequencing of the tasks. Following the implementation, chemotherapy postponing decreased by 17.2% (Z = ?4.723, P = .000) and there were 5.7% less records with missing administration time (Z = ?3.047, P = .002). The admission rate increased 1.9 patient per working day (t(94) = ?5.974, P = .000). The overall turn-around-time reduced 18.9 min following the implementation (t(169) = 3.48, P = .001). In a multivariate multiple regression model the reduction in turn-around time was related to the implementation of the system (Pillai's Trace = 0.159, F(4,161) = 7.613, P = .000).ConclusionInformation systems based on treatment protocols can reduce communication and synchronization needs between the stakeholders in a complex workflow process. These systems can help reengineering the process and improve workflow efficiency by removing unnecessary sequencing and repetitions of tasks.     

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

PurposeWe assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks for BRCA1 and BRCA2 pathogenic variant carriers.MethodsRetrospective cohort data on 18,935 BRCA1 and 12,339 BRCA2 female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)–negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort.ResultsThe ER-negative PRS showed the strongest association with BC risk for BRCA1 carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25–1.33], P = 3×10⁻⁷²). For BRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27–1.36], P = 7×10⁻⁵⁰). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk for BRCA1 (HR = 1.32 [95% CI 1.25–1.40], P = 3×10⁻²²) and BRCA2 (HR = 1.44 [95% CI 1.30–1.60], P = 4×10⁻¹²) carriers. The associations in the prospective cohort were similar.ConclusionPopulation-based PRS are strongly associated with BC and EOC risks for BRCA1/2 carriers and predict substantial absolute risk differences for women at PRS distribution extremes.     

The association between radiographic severity and pre-operative function in patients undergoing primary knee replacement for osteoarthritis

ObjectiveTo determine the association between radiographic osteoarthritis (OA) and pre-operative function in patients undergoing primary knee replacement.MethodsSingle centre study examining pre-operative outcomes in a consecutive series of 525 patients who underwent primary knee replacement for OA between January 2006 and December 2007. Pre-operative data included: demographics, American Society of Anaesthesiologists (ASA) status and OA in the contralateral knee. The International Knee Society (IKS) rating and Short Form-12 (SF-12) were recorded for each patient. Pre-operative radiographs were read by a single observer for Kellgren and Lawrence (K&L) grading and Osteoarthritis Research Society International (OARSI) atlas features. Multiple linear regression was used to assess the strength of associations between radiographic OA severity and function, adjusting for clinically relevant variables.ResultsLateral tibiofemoral osteophyte grade was an independent predictor of pre-operative function as determined by the functional sub-scale of the IKS in patients undergoing primary knee replacement (coefficient = 2.58, p = 0.033). No associations were evident between pre-operative function and modified K&L, joint space narrowing, Ahlbäck attrition and coronal plane deformity. Other statistically significant predictors of poorer pre-operative function included: advancing age, female gender, knee pain and poorer SF-12 mental component summary scores which including osteophyte grade accounted for 24.6% of the variation in functional scores, (r = 0.496).ConclusionOsteophytes in the lateral compartment of the knee were associated with pre-operative function in patients with advanced knee OA. Further studies are required which examine individual radiographic features specifically in patients with advanced knee OA to determine their relationship to pre-operative pain and function.     

Association between IFNL4 rs368234815 polymorphism and sustained virological response in chronic hepatitis C patients undergoing PEGylated interferon/ribavirin therapy: A meta-analysis

Background and aimsMany studies have been published on the association between IFNL4 rs368234815 single-nucleotide polymorphism (SNP) and sustained virological response (SVR) in chronic hepatitis C (CHC) patients undergoing treatment with PEGylated interferon (PEG-IFN) plus ribavirin (RBV). Because of the variable and sometimes inconsistent results, we performed a meta-analysis to estimate the association between these factors.MethodsWe conducted a search of the literature published prior to July 1, 2014. The pooled results were analyzed as the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) using random-effect model.ResultsThe pooled results revealed that the rs368234815 TT/TT genotype was significantly correlated with SVR in HCV-1/4-infected Caucasian patients (OR = 4.65, 95% CI = 3.36–6.42, P < 0.00001) but not in HCV-2/3-infected Caucasian patients (OR = 1.44, 95% CI: 0.89–2.33, P = 0.13). Conversely, the rs368234815 ΔG/ΔG genotype was significantly linked to treatment failure in Caucasian patients (OR = 0.49, 95% CI: 0.38–0.64, P < 0.00001), regardless of the HCV genotype.ConclusionThe results of the meta-analysis suggest that IFNL4 rs368234815 polymorphism may be a predictor of SVR in Caucasian HCV-1/4-infected patients.     

Herbal medicine (Shaofu Zhuyu decoction) for treating primary dysmenorrhea: A systematic review of randomized clinical trials

Shaofu Zhuyu decoction (SFZY) or Sobokchugeo-tang, a traditional herbal formula, is used as a treatment for primary dysmenorrhea. We searched four English, seven Korean, three Chinese, and one Japanese database from inception through January 2016 without a language restriction. All randomized controlled trials (RCTs) of SFZY or modified SFZY (MSFZY) were included. Data extraction and risk of bias assessments were performed by two independent reviewers. A total of 51 potentially relevant studies were identified, and 9 RCTs met our inclusion criteria. Seven RCTs tested the effects of SFZY or modified SFZY in treating dysmenorrhea. Three RCTs showed superior effects of (M)SFZY on the response rate, while the other three RCTs failed to do so (n = 531, RR: 1.17, 95% CI: 1.09 to 1.26, P < 0.0001, I² = 0%). Three RCTs showed favorable effects of MSFZY for pain reduction compared with conventional drugs (n = 340, SMD: −1.39, 95% CI: −2.23 to −0.55, P = 0.01). Two RCTs examined the effects of modified SFZY plus conventional drugs and conventional drugs alone. The meta-analysis showed favorable effects of MSFZY (n = 206; RR, 1.12; 95% CI 1.08 to 1.36; P = 0.0009, I² = 0%). Our systemic review and meta-analysis provide suggestive evidence of the superiority of SFZY over conventional drugs for treating primary dysmenorrhea. However, the level of evidence is low because of a high risk of bias.