6-Month Change in Pain and Function by Pre-Operative Pain and Function among Patients Selected for Total Knee Replacement in the United States

Background/Purpose: The increase in total knee replacements (TKRs) between 1979 and 2006 is staggering. Debate is growing regarding the appropriate utilization of TKRs. We examined pain, function, quality of life (QOL), and satisfaction at 6-month post-surgery by pain and function at time of surgery. Methods: Data came from the nationally representative FORCE-TJR cohort of patients from 150 surgeons. Participants had primary, unilateral TKRs due to osteoarthritis between 2011 and 2014. Their knee pain (KOOS), physical functions (SF36), and QOL were measured at pre- and 6 months post-surgery. We classified patients as having high or low pre-operative pain (KOOS Pain \u3c 70 vs. ≥70), low or high pre-operative physical function (SF-36 PCS \u3c 40 vs. ≥40), and grouped as: 1) Low pain-High function (LP-HF), 2) Low pain-Low function (LP-LF), 3) High pain-High function (HP-HF), and 4) High pain-Low function (HP-LF). We compared pre- and post-operative changes in pain and function scores among the four groups. Results: Of 4,563 participants, 5% had pre-operative LP-HF and 75% HP-LF. By 6-month post-surgery, 85% of LP-HF patients reported no change and 4% reported worse symptoms; the HP-LF group had 18% no change and 52% with large improvement. For function in the LP-HF group, mean 6-month change (SD) was 2.6 (7.8), with post-operative mean of 50.0 (7.4). Mean change for the HP-LF group was 11.9 (9.0), with post-operative mean of 42.0 (9.5). For pain score in the LP-HF group, mean 6-month change was 8.3 (14.6), with post-operative mean (SD) of 88.9 (13.0). The HP-LF group had average improvement of 37.2 (19.7), and post-operative mean of 79.9 (17.3). QOL was better among the LP-HF than HP-LF groups; satisfaction was similar. Conclusion: The majority of patients had appropriate TKR utilization and achieved large improvement in pain and function. Patients with pre-operative LP-HF achieved the smaller mean change, but better absolute outcomes

Improvement in mental health following total hip arthroplasty: the role of pain and function

BACKGROUND: Mental health has been shown to improve after total hip arthroplasty (THA). Little is known about the role of pain and function in this context. We assessed whether change in mental health was associated with improvement in pain and function 1 year post-surgery. METHODS: This prospective study included patients enrolled in a THA registry from 2010 to 2014. We examined the mental component score (MCS) before and 1 year post-surgery, and 1-year change, in association with Western Ontario McMaster Universities (WOMAC) pain and function scores. All scores were normalized, ranging from 0 to 100 (larger score indicating better outcome). Analyses were adjusted for potential confounders. RESULTS: Our study included 610 participants, of which 53% were women. Descriptive statistics are as follows: the average (SD) for age (years) was 68.5 (11.8), and for BMI was 26.9 (4.9). In addition, the MCS average (SD) at baseline was 44.7 (11.2), and at 1-year after THA was 47.5 (10.5). The average change from baseline to 1-year post-THA in MCS was 2.8 (95% CI: 1.9, 3.6), for an effect size of 0.26. As for the WOMAC pain score, the average change from baseline to 1-year post-THA was 44.2 (95%CI: 42.4, 46.0), for an effect size of 2.5. The equivalent change in WOMAC function was 38.1 (95% CI: 36.2, 40.0), for an effect size of 2.0. Results from multivariable analysis controlling for covariates showed that an improvement of 10 points in the 1-year change in pain score resulted in a 0.78 point (95%: CI 0.40, 1.26) increase in the 1-year change in MCS, whereas a 10-point improvement in the 1-year change in function was associated with a 0.94 point (95% CI: 0.56, 1.32) increase. CONCLUSIONS: Mental health significantly improved from baseline to 1-year post-THA. Greater improvement in pain and function was associated with greater improvement in mental health 1 year post-THA

Racial Differences in the Effectiveness of Total Knee Arthroplasty (TKA) on Postoperative Pain and Function

Objective: African Americans are less likely than Caucasians to perceive TKA as an effective treatment option. We examined post-TKA pain and function by race, with and without adjusting for demographic and clinical factors on determining racial differences. Methods: We analyzed data from FORCE-TJR, a national cohort of TJR patients. Patients had primary and unilateral TKA surgeries 07/01/2011-12/31/2014, and completed surveys on demographic and clinical information, including a pre- and 6-month postoperative Knee Injury and Osteoarthritis Outcome Score (KOOS). The KOOS pain and function scores ranged from 0-100 (higher=better). We examined baseline, 6-month, and 6-month change in pain and function by race, and estimated the association between race and outcomes, adjusting for demographic and clinical factors. Results: Analyses included 5028 white (63% female, 65% income\u3e45k; mean age of 67. BMI of 31) and 270 black patients (80% female, 39% income\u3e45k; mean age of 63, BMI of 34). At baseline, black compared with white patients reported worse knee pain (mean: 39vs.48), and poorer function (mean: 46vs.54). While all patients reported significant gains at 6-month post-surgery, black patients had lower postoperative pain (mean: 71vs.82) and function scores (mean: 73vs.84) than white patients. Although not statistically significant, black patients on average had lower 6-month change than white patients in pain -1.9 (95%CI: -4.4, 0.6) and function -1.6 (95%CI: -3.9, 0.7). Adjusting for covariates, racial differences were significantly more pronounced in change in pain -5.5 (95%CI: -8.3, -2.7) and function -5.6 (95%CI: -8.2, -3.0). Conclusions: TKAs were as effective in reducing pain and improving functions in blacks as in whites. Adjusting for certain demographic and clinical factors can impact assessment of racial differences and the effectiveness of TKA on postoperative outcomes, as black patients were very different from white patients on these important factors

Total hip arthroplasty and mental health status

Purpose. Total hip arthroplasty (THA) effectively restores function and alleviates pain in patients with end-stage hip osteoarthritis. Pain affects mood through its effect on disability and fatigue. Few studies have examined mental health as a consequence of pain or function after THA. We assessed change in mental health 1-year post-surgery, and examined whether change in pain and function predict change in mental health. Methods. We used data from a prospective THA registry that began in 1996 at a large public Geneva University hospital. We included surgeries performed 2010 and 2012-2014, with demographic information, body mass index (BMI), co-morbidities, baseline and 1-year post-surgery WOMAC pain and function scores, and the SF-12 mental health component score (MCS). The pain, function, and MCS scores were normalized and ranged from 0-100; increasing score indicating better outcome. We calculated descriptive statistics, and used multivariable linear regression to predict 1-year change in MCS. Results. Of 610 participants, mean (SD) age was 68.5 (11.8) years and BMI of 26.9 (4.9), 53% were women. Mean MCS was 44.7 (11.2) at baseline and 47.5 (10.5) at 1-year post surgery; average 1-year change was 2.8 (95% CI 1.9-3.6). WOMAC pain score was 39.6 (18.3) at baseline and 83.8 (20.4) at 1-year post surgery; 1-year change was 44.2 (95% CI 42.4-46.0). Corresponding WOMAC function was 40.2 (18.8) and 78.3 (22.1); 1-year change was 38.1 (95% CIs 36.2-40.0). On average, a 10-point increase in 1-year change in pain score was associated with a 0.7 point increase in the adjusted 1-year change in MCS (95% CI 0.2-1.1). The change in function was associated with a 0.9 point increase in 1-year change in MCS (95% CI 0.5-1.4). Conclusion. Mental health significantly improved from baseline to 1-year post-surgery. Patients whose pain and function scores improved the most had also the greatest improvement in mental health

Reference Ranges for Bone Mineral Density and Prevalence of Osteoporosis in Vietnamese Men and Women

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to examine the effect of different reference ranges in bone mineral density on the diagnosis of osteoporosis.</p> <p>Methods</p> <p>This cross-sectional study involved 357 men and 870 women aged between 18 and 89 years, who were randomly sampled from various districts within Ho Chi Minh City, Vietnam. BMD at the femoral neck, lumbar spine and whole body was measured by DXA (Hologic QDR4500). Polynomial regression models and bootstraps method were used to determine peak BMD and standard deviation (<it>SD</it>). Based on the two parameters, we computed T-scores (denoted by <it>T</it>_VN) for each individual in the study. A similar diagnosis was also done based on T-scores provided by the densitometer (<it>T</it>_DXA), which is based on the US White population (NHANES III). We then compared the concordance between <it>T</it>_VNand <it>T</it>_DXAin the classification of osteoporosis. Osteoporosis was defined according to the World Health Organization criteria.</p> <p>Results</p> <p>In post-menopausal women, the prevalence of osteoporosis based on femoral neck <it>T</it>_VNwas 29%, but when the diagnosis was based on <it>T</it>_DXA, the prevalence was 44%. In men aged 50+ years, the <it>T</it>_VN-based prevalence of osteoporosis was 10%, which was lower than <it>T</it>_DXA-based prevalence (30%). Among 177 women who were diagnosed with osteoporosis by <it>T</it>_DXA, 35% were actually osteopenia by <it>T</it>_VN. The kappa-statistic was 0.54 for women and 0.41 for men.</p> <p>Conclusion</p> <p>These data suggest that the <it>T-</it>scores provided by the Hologic QDR4500 over-diagnosed osteoporosis in Vietnamese men and women. This over-diagnosis could lead to over-treatment and influence the decision of recruitment of participants in clinical trials.</p

Pharmacological and Toxicological Properties of the Potent Oral γ-Secretase Modulator BPN-15606.

Alzheimer's disease (AD) is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid amyloid-β peptide (Aβ), as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance, are postulated to initiate and drive the AD pathologic process. We initially introduced a novel class of bridged aromatics referred tγ-secretase modulatoro as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides. These modulators potently lower Aβ42 levels without inhibiting the γ-secretase-mediated proteolysis of Notch or causing accumulation of carboxyl-terminal fragments of APP. In this study, we report a large number of pharmacological studies and early assessment of toxicology characterizing a highly potent γ-secretase modulator (GSM), (S)-N-(1-(4-fluorophenyl)ethyl)-6-(6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-4-methylpyridazin-3-amine (BPN-15606). BPN-15606 displayed the ability to significantly lower Aβ42 levels in the central nervous system of rats and mice at doses as low as 5-10 mg/kg, significantly reduce Aβ neuritic plaque load in an AD transgenic mouse model, and significantly reduce levels of insoluble Aβ42 and pThr181 tau in a three-dimensional human neural cell culture model. Results from repeat-dose toxicity studies in rats and dose escalation/repeat-dose toxicity studies in nonhuman primates have designated this GSM for 28-day Investigational New Drug-enabling good laboratory practice studies and positioned it as a candidate for human clinical trials

Analytical study of the sth-order perturbative corrections to the solution to a one-dimensional harmonic oscillator perturbed by a spatially power-law potential Vper(x) = λxα

In this work, we present a rigorous mathematical scheme for the derivation of the sth-order perturbative corrections to the solution to a one-dimensional harmonic oscillator perturbed by the potential V-per(x) = lambda x(alpha), where alpha is a positive integer, using the non-degenerate time-independent perturbation theory. To do so, we derive a generalized formula for the integral I = integral(+infinity)(-infinity)x(alpha)exp(-x(2))H-n(x)H-m(x)d(x), where H-n(x) denotes the Hermite polynomial of degree n, using the generating function of orthogonal polynomials. Finally, the analytical results with alpha = 3 and alpha = 4 are discussed in detail and compared with the numerical calculations obtained by the Lagrange-mesh method

The Smoking Paradox in the Development of Psoriatic Arthritis among Psoriasis Patients – A Population-Based Study

Objectives: Smoking is strongly associated with an increased risk of psoriatic arthritis (PsA) in the general population, but not among psoriasis patients. We sought to clarify the possible methodologic mechanisms behind this paradox. Methods: Using 1995-2015 data from The Health Improvement Network, we performed survival analysis to examine the association between smoking and incident PsA in the general population and among psoriasis patients. We clarified the paradox using mediation analysis and conducted bias sensitivity analyses to evaluate the potential impact of index event bias and quantify its magnitude from uncontrolled/unmeasured confounders. Results: Of 6.65 million subjects without PsA at baseline, 225,213 participants had psoriasis and 7,057 developed incident PsA. Smoking was associated with an increased risk of PsA in the general population (RR, 1.27; 95% CI, 1.19-1.36), but with a decreased risk among psoriasis patients (RR 0.91; 95% CI, 0.85-0.99). Mediation analysis showed that the effect of smoking on the risk of PsA was mediated almost entirely through its effect on psoriasis. Bias sensitivity analyses indicated that even when the relation of uncontrolled confounders to either smoking or PsA was modest (both RRs = ~1.50), it could reverse the biased estimate of effect of smoking among psoriasis patients (RR=0.9). Conclusions: In this large cohort representative of the UK general population, smoking was positively associated with PsA risk in the general population, but negatively associated among psoriasis patients. Conditioning on a causal intermediate variable (psoriasis) can reverse the association between smoking and PsA, explaining the smoking paradox for the risk of PsA among psoriasis patients

Antibiotic use and prescription and its effects on Enterobacteriaceae in the gut in children with mild respiratory infections in Ho Chi Minh City, Vietnam. A prospective observational outpatient study.

BACKGROUND AND OBJECTIVES: Treatment guidelines do not recommend antibiotic use for acute respiratory infections (ARI), except for streptococcal pharyngitis/tonsillitis and pneumonia. However, antibiotics are prescribed frequently for children with ARI, often in absence of evidence for bacterial infection. The objectives of this study were 1) to assess the appropriateness of antibiotic prescriptions for mild ARI in paediatric outpatients in relation to available guidelines and detected pathogens, 2) to assess antibiotic use on presentation using questionnaires and detection in urine 3) to assess the carriage rates and proportions of resistant intestinal Enterobacteriaceae before, during and after consultation. MATERIALS AND METHODS: Patients were prospectively enrolled in Children's Hospital 1, Ho Chi Minh City, Vietnam and diagnoses, prescribed therapy and outcome were recorded on first visit and on follow-up after 7 days. Respiratory bacterial and viral pathogens were detected using molecular assays. Antibiotic use before presentation was assessed using questionnaires and urine HPLC. The impact of antibiotic usage on intestinal Enterobacteriaceae was assessed with semi-quantitative culture on agar with and without antibiotics on presentation and after 7 and 28 days. RESULTS: A total of 563 patients were enrolled between February 2009 and February 2010. Antibiotics were prescribed for all except 2 of 563 patients. The majority were 2nd and 3rd generation oral cephalosporins and amoxicillin with or without clavulanic acid. Respiratory viruses were detected in respiratory specimens of 72.5% of patients. Antibiotic use was considered inappropriate in 90.1% and 67.5%, based on guidelines and detected pathogens, respectively. On presentation parents reported antibiotic use for 22% of patients, 41% of parents did not know and 37% denied antibiotic use. Among these three groups, six commonly used antibiotics were detected with HPLC in patients' urine in 49%, 40% and 14%, respectively. Temporary selection of 3rd generation cephalosporin resistant intestinal Enterobacteriaceae during antibiotic use was observed, with co-selection of resistance to aminoglycosides and fluoroquinolones. CONCLUSIONS: We report overuse and overprescription of antibiotics for uncomplicated ARI with selection of resistant intestinal Enterobacteriaceae, posing a risk for community transmission and persistence in a setting of a highly granular healthcare system and unrestricted access to antibiotics through private pharmacies. REGISTRATION: This study was registered at the International Standard Randomised Controlled Trials Number registry under number ISRCTN32862422: http://www.isrctn.com/ISRCTN32862422

Early Pandemic Influenza (2009 H1N1) in Ho Chi Minh City, Vietnam: A Clinical Virological and Epidemiological Analysis

Rogier van Doorn and colleagues analyze the initial outbreak, attempts at containment, and establishment of community transmission of pandemic H1N1 influenza in Ho Chi Minh City, Vietnam