The Effect of a Skin Barrier Film on the Incidence of Dressing-Related Skin Blisters After Spine Surgery.

Tension blisters from adhesive dressings may lead to pain and delayed surgical wound healing for surgical patients and cause an institutional cost burden. Commercial skin barrier film products may reduce dressing-related postoperative skin blistering in surgical patients. Project investigators at an orthopedic specialty hospital randomized 185 surgical spine patients to receive either a standard wound dressing (ie, control group) or a dressing with the addition of a skin barrier film applied beneath it (eg, treatment group). During the first postoperative dressing change, the participants' skin was assessed for redness, soreness, blistering, or tearing. Approximately 15% of participants in the treatment group and 15% of participants in the control group developed a postoperative skin injury (P = .98). Multivariable analyses did not indicate the skin barrier film provided a protective effect. Additionally, there was no association between patient-specific characteristics and skin blisters among the participants. These results do not support the use of a skin barrier film in surgical spine patients.

Real-World Persistence with Tocilizumab Compared to Other Subcutaneous Biologic Disease-Modifying Antirheumatic Drugs Among Patients with Rheumatoid Arthritis Switching from Another Biologic.

INTRODUCTION: In patients with rheumatoid arthritis (RA) who have an inadequate response to or intolerance of their first biologic disease-modifying antirheumatic drug (bDMARD), guidelines recommend switching to a different biologic class. The objective of this study was to compare persistence with subcutaneous (SC) tocilizumab to persistence with other SC bDMARDs when these drugs are used as subsequent-line therapy in RA patients who previously received ≥ 1 bDMARD. METHODS: RA patients in a US administrative claims database who initiated a second- or subsequent-line SC bDMARD between January 1, 2012 and June 30, 2017 (initiation date = index date) were included. Persistence was defined as the number of days between the bDMARD initiation date and (1) the last supplied day of medication fill (primary) or (2) the day on which the patient switched or there was a gap in treatment of > 90 days (secondary). Parametric survival models utilizing an exponential distribution with a robust variance estimator were used to compare persistence with tocilizumab to persistence with other bDMARDs. RESULTS: A total of 10,301 patients with 12,704 bDMARD episodes were included. Patients receiving tocilizumab had a significantly higher adjusted median (95% CI) number of days of primary persistence [333 (311-356)] than those receiving adalimumab [280 (268-293); P < 0.001], certolizumab [262 (241-284); P < 0.001], and etanercept [289 (274-304); P = 0.001], and a similar persistence to those receiving abatacept [320 (305-335); P = 0.327] and golimumab [304 (274-333); P = 0.122]. CONCLUSION: Among patients with RA who had previously received ≥ 1 bDMARD, tocilizumab-treated patients exhibited a similar or significantly better biologic persistence than those receiving other bDMARDs.

Comparative Cost per Response for 4 Clinical Endpoints with Tocilizumab Monotherapy vs Adalimumab Monotherapy in a Head-to-Head Randomized Double-Blind Superiority Trial (ADACTA) in Patients with Rheumatoid Arthritis.

INTRODUCTION: The cost-effectiveness of different biologic therapies can be an important component in guiding treatment decisions for patients with rheumatoid arthritis (RA). The objective of this study was to compare drug and adverse event costs and cost per successful clinical response with tocilizumab (TCZ) monotherapy vs adalimumab (ADA) monotherapy in patients with RA in a phase 4 clinical trial. METHODS: Patients received either TCZ intravenously every 4 weeks or ADA subcutaneously every 2 weeks for 24 weeks. Drug and administration costs were based on wholesale acquisition costs and the Centers for Medicare and Medicaid, respectively. Outcomes included patient-level drug costs, cost of hospitalization due to adverse events, and cost per response. Cost per response was calculated by dividing the mean drug plus administration cost by the proportion of patients achieving Disease Activity Score in 28 joints (DAS28) < 2.6 (remission) or 20%, 50%, or 70% improvement in response per the American College of Rheumatology (ACR20/50/70). Hospitalization costs were calculated using the daily hospital cost and number of hospital days. RESULTS: Among the 163 patients treated with TCZ and 162 patients treated with ADA, mean total drug and administration costs per patient over 24 weeks were $18,290.60 and $25,623.10, respectively. Mean drug and administration costs per each clinical response achieved were lower with TCZ than with ADA (DAS28 < 2.6: $45,868 vs $244,174; ACR20: $28,127 vs $51,887; ACR50: $38,720 vs $92,244; ACR70: $56,253 vs $143,136). The total hospital days were 32 days with TCZ and 43 days with ADA; mean hospital costs per patient were $484.50 with TCZ and $651.10 with ADA. CONCLUSION: In this comparative assessment, the cost to achieve all 4 clinical endpoints was lower for patients receiving TCZ than for those receiving ADA.

Risk factors for Staphylococcus aureus colonization in a presurgical orthopedic population.

BACKGROUND: Preoperative colonization with Staphylococcus aureus (SA) increases risk of surgical site infection. Screening for SA followed by skin and nasal decolonization can help to reduce the risk of postoperative infections. Risk factors for colonization are, however, not completely understood. METHODS: A case-control study using questionnaires and patient demographics specifically designed to observe SA colonization risk factors in a presurgical orthopedic population. A total of 115 subjects with a positive preoperative screen for SA nasal colonization prior to orthopedic surgery completed a questionnaire to assess for SA risk factors: these subjects served as our cases. An additional 476 controls completed similar questionnaires. Data collected included demographic, health, and lifestyle information. Multivariable logistic regression was used to generate odds ratios (OR) for risk of SA colonization. RESULTS: Several risk factors were identified. Male sex (OR 2.3; 95% confidence interval [CI], [1.4-3.8]) and diabetes (OR 3.8 [1.8-7.8]) significantly increased the risk of SA colonization. Older age, visiting public places (OR 0.2 [0.1-0.3]), recent antibiotic use (OR 0.2 [0.1-0.6]), and the presence of facial hair (OR 0.3 [0.1-0.6]) significantly lowered the risk of SA colonization. CONCLUSIONS: By identifying patients who may be at greater risk of SA colonization, we can better streamline our presurgical techniques to help reduce risk of surgical site infections and improve patient outcomes.

Delayed ACL Reconstruction in Patients ≥40 Years of Age Is Associated With Increased Risk of Medial Meniscal Injury at 1 Year.

BACKGROUND: Anterior cruciate ligament (ACL) tears in the pediatric and young adult ACL-deficient knee are often associated with meniscal or chondral injury with delayed time to surgery. The incidence of ACL reconstruction performed in patients aged ≥40 years is rising, and it is unclear if delayed surgery in this cohort similarly affects the health of the meniscus and cartilage. PURPOSE: To evaluate whether delayed reconstruction in a cohort of patients aged ≥40 years is associated with an increased risk of meniscal or chondral injury. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Records of patients aged ≥40 years who underwent primary arthroscopic ACL reconstruction between 2012 and 2016 at an academic hospital were retrospectively reviewed. Patient characteristic data and time to surgery were recorded. Operative reports were analyzed for meniscal and chondral injuries as well as treatment. Patients were grouped according to time to surgery, defined as early (<90 days) or delayed (≥90 days). Logistic regression modeling was used to form associations between elapsed time to surgery and patient characteristics to meniscal and chondral damage. Additionally, risks for meniscal and chondral injury were analyzed at time points of 180 days and 1 year from injury to surgery. RESULTS: A total of 227 patients met the study criteria: 106 patients underwent early surgery, and 121 underwent delayed surgery. The authors identified 127 medial meniscal tears and 106 lateral meniscal tears. Medial, lateral, and patellofemoral compartment chondral injury was reported in 127, 82, and 130 patients, respectively. Delayed surgery (≥90 days) was not associated with increased risk of medial or lateral meniscal tears or any chondral injury at 90 days. Each year of increased age was associated with an increased odds ratio: 1.09 ( P = .001) for medial meniscal tears, 1.06 ( P = .014) for lateral meniscal tears, 1.10 ( P = .001) for medial compartment chondral injuries, and 1.07 ( P = .007) for patellofemoral compartment chondral injuries. Additionally, each unit of increased body mass index was associated with an increased odds ratio: 1.09 ( P = .039) for medial meniscal tears and 1.14 ( P = .003) for medial compartment cartilage injury. Analysis of 180-day and 1-year time points revealed an increased risk (odds ratio, 3.47; 95% CI, 1.55-7.77; P = .002) for medial meniscal injury when surgery was delayed for >1 year. CONCLUSION: Delayed ACL reconstruction (≥90 days) among patients aged ≥40 years was not associated with an increased risk of meniscal or chondral injury. Increasing age and body mass index were associated with higher risks of meniscal and chondral injuries in this cohort. Delay in surgery for >1 year was associated with increased risk of medial meniscal tear.

Prevalence of radiographic and symptomatic hip osteoarthritis in an urban United States community: the Framingham osteoarthritis study.

OBJECTIVE: The last prevalence survey encompassing urban populations was part of the First National Health and Nutrition Examination Survey, conducted in the 1970s. The aim of the present study was to perform a prevalence survey of hip osteoarthritis (OA) among individuals in the Framingham Study Community cohort. METHODS: Individuals ages 50 years and older living in Framingham, Massachusetts in 2002-2005 were recruited by random digit dialing, with selection made regardless of whether joint pain or arthritis were reported. Anteroposterior radiographs of the long limbs of the lower extremities, including the pelvis, were obtained with individuals placed in a standing position. The radiographs were read by two trained physicians for the presence of radiographic hip OA, with all possible cases of radiographic hip OA confirmed by an experienced musculoskeletal radiologist. Radiographic hip OA was defined as a Kellgren/Lawrence radiographic severity grade of ≥2. Using a homunculus in which the hip joint was depicted, participants were asked whether they had hip pain on most days. Those who responded "yes" were defined as having hip pain. Symptomatic hip OA was defined as radiographic OA with ipsilateral hip pain. We defined a person as having hip OA if at least one of the hip joints was affected. RESULTS: Of 978 subjects studied (mean age 63.5 years; 56% women), the age-standardized prevalence of radiographic hip OA was 19.6% (95% confidence interval [95% CI] 16.7-23.0%) and the age-standardized prevalence of symptomatic hip OA was 4.2% (95% CI 2.9-6.1%). Overall, men were observed to have a higher prevalence of radiographic hip OA (P < 0.0001) compared to women, but men did not have a higher prevalence of symptomatic hip OA compared to women (5.2% versus 3%; P = 0.08). CONCLUSION: Hip OA is a common condition in middle-aged and older individuals in urban and suburban areas of the US.

No association between markers of inflammation and osteoarthritis of the hands and knees.

OBJECTIVE: Local inflammation plays a prominent role in osteoarthritis (OA). This could be reflected in the presence of elevated soluble inflammatory markers. We conducted analyses to assess the association of inflammatory markers with radiographic OA of the hands and knees in a large community-based cohort. METHODS: The Framingham Offspring cohort consists of the adult children of the original cohort and their spouses. In 1998-2001 these subjects provided blood specimens that were tested for 17 markers of systemic inflammation. In 2002-2005 these subjects had radiographs of both knees and hands. Each hand and knee joint was assigned a Kellgren and Lawrence (KL) score (0-4). We used logistic regression with generalized estimating equations and adjustment for age, sex, and body mass index to examine the association between each inflammatory marker and the presence of radiographic OA (ROA = KL grade ≥ 2) in any joint. We also constructed models for hand joints and knee joints alone. RESULTS: Radiographs and measures of inflammation were done for 1235 subjects (56% women, mean age 65 yrs). Of that group, 729 subjects (59%) had ROA in ≥ 1 hand or knee joint: 179 (14.3%) had knee OA, and 694 (56.2%) had hand OA. There were no significant associations between any marker of inflammation and ROA. CONCLUSION: In this large sample, in which OA was carefully assessed and multiple markers measured, we found no evidence of an association between any inflammatory marker and the presence of radiographic OA.

Can health care databases be used to identify incident cases of osteonecrosis?

INTRODUCTION: Osteonecrosis (ON) is a rare disease associated with alcohol and glucocorticoid use. Identifying additional risk factors is difficult as the number of cases at any single center is small. We investigated whether data available in large health care databases can be used to identify incident ON cases. METHODS: Using data from the Boston Veterans Affairs Healthcare system, we identified potential cases of ON. These records, including available radiographs and reports, were reviewed. Using published criteria, we evaluated whether the subjects had confirmed ON (radiographs/reports met criteria), incident ON (onset of symptoms within 6 months of first code), or prevalent ON (onset more than 6 months prior to first code or onset could not be determined). We tested different definitions for incident ON using information derived from administrative data. These were compared to the 'gold standard' (record review) and positive predictive values (PPVs) were derived. Since PPVs for incident cases were low, we found the number of incident cases expected for every 1,000 potential cases identified, using the definitions as an initial screening tool to reduce the number of medical records that required examination. RESULTS: We identified 87 potential cases. No case of jaw ON was identified. Only 15 (17%) incident cases of ON were identified. PPVs never exceed 50% for incident ON. However, if we used the definition '(at least 1 inpatient ON code) and (no prior codes for osteoarthritis)' as an initial screen, then for every 1,000 records, we would need to review only 150 to find 69 incident cases. CONCLUSIONS: Though the precise PPVs we found may not be generalizable to other databases, we believe that administrative data alone should not be used to identify incident cases of ON without confirming the diagnosis through a review of medical records. By applying the above definition, the number of records requiring review can be markedly reduced. This method can be used to find cases for valid case-control studies of risk factors for ON.

Defining remission in rheumatoid arthritis: results of an initial American College of Rheumatology/European League Against Rheumatism consensus conference.

OBJECTIVE: Due to advances in rheumatoid arthritis (RA) therapies over the last few years, an increasing proportion of patients are able to achieve a state of remission. However, the definition of remission is unclear. Currently, randomized controlled trials around the world use different remission definitions and consequently measure different aspects of a patient's disease state. The need for a uniform definition of remission is vital for research findings to be correctly interpreted. METHODS: The American College of Rheumatology (ACR) constituted a committee that included international clinical researchers, trialists, and clinical epidemiologists in order to redefine remission in RA. This group was asked to study current definitions of remission, explore the theoretical underpinning of the concept of remission, and develop a research agenda that would inform future work in the development of an ACR definition of remission. RESULTS: In its first meeting, the committee preferred to develop a strict definition, implying no or very low disease activity. Such a definition would need to be validated against long-term outcome, e.g., physical function and damage. CONCLUSION: The committee decided to consider both a definition for trials and a modified version for clinical practice. Since the first meeting, the ACR and the European League Against Rheumatism (EULAR) have decided to sponsor this initiative as an official ACR/EULAR collaboration.

Protective effects of NSAIDs on the development of Alzheimer disease.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer disease (AD), but observational studies and trials have offered contradictory results. Prior studies have also been relatively short and small. We examined the effects on AD risk of NSAID use for >5 years and of NSAIDs that suppress formation of A beta (1-42) amyloid in a large health care database. METHODS: Cases were veterans aged 55 years and older with incident AD using the US Veterans Affairs Health Care system. Matched controls were drawn from the same population. NSAID exposure was categorized into seven time periods: no use, 1 but 5 years of use (0.68-0.85). For users of ibuprofen, it decreased from 1.03 (1.00-1.06) to 0.56 (0.42-0.75). Effects of other NSAID classes and individual NSAIDs were inconsistent. There was no difference between a group of A beta (1-42)-suppressing NSAIDs and others. DISCUSSION: Long-term nonsteroidal anti-inflammatory drug (NSAID) use was protective against Alzheimer disease. Findings were clearest for ibuprofen. A beta (1-42)-suppressing NSAIDs did not differ from others.

Classification criteria in rheumatic diseases: a review of methodologic properties.

OBJECTIVE: To identify classification criteria for the rheumatic diseases and to evaluate their measurement properties and methodologic rigor using current measurement standards. METHODS: We performed a systematic review of published literature and evaluated criteria sets for stated purpose, derivation and validation sample characteristics, methods of criteria generation and reduction, and consideration of validity, and reliability. RESULTS: We identified 47 classification criteria sets encompassing 13 conditions. Approximately 50% of the criteria sets were developed based on expert opinion rather than patient data. Of the 47 criteria sets, control samples were derived from patients with rheumatic disease in 15 (32%) sets, from patients with nonrheumatic diseases in 4 (9%) sets, and from healthy participants in 2 (4%) sets. Where patient data were used, the number of cases ranged from 20-588 and the number of controls from 50-787. In only 1 (2%) criteria set was there a distinct separation between investigators who derived the criteria set and clinicians who provided cases and controls. Authors commented on the need for individual criterion to be reliable in 5 (11%) sets, precise in 5 (11%) sets; authors noted the importance of content validity in 12 (26%) sets, and construct validity in 12 (26%) sets. CONCLUSION: The variation in methodologic rigor used in sample selection affects the validity and reliability of the criteria sets in different clinical and research settings. Despite potential deficiencies in the methods used for some criteria development, the sensitivity and specificity of many criteria sets is moderate to strong.

Glucosamine for pain in osteoarthritis: why do trial results differ?

OBJECTIVE: Investigators in trials of glucosamine report a range of estimates for efficacy, making conclusions difficult. We undertook this study to identify factors that explain heterogeneity in trials of glucosamine. METHODS: We searched for reports of trial results in Ovid Medline, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and proceedings of scientific conferences. We selected reports of randomized, double-blind, placebo-controlled trials of glucosamine for pain from osteoarthritis of the knee or hip. We extracted data regarding features of design, subjects, and markers of industry involvement, including industry funding, whether a drug was supplied by industry, industry participation, and industry-affiliated authorship. We examined which factors best accounted for differences in the effect sizes of studies grouped by these characteristics, and we examined changes in I(2), a measure of heterogeneity. RESULTS: Fifteen trials met our inclusion criteria. The summary effect size was 0.35 (95% confidence interval 0.14, 0.56). I(2) was 0.80. Except for allocation concealment, no feature of study design explained this substantial heterogeneity. Summary effect sizes ranged from 0.05 to 0.16 in trials without industry involvement, but the range was 0.47-0.55 in trials with industry involvement. The effect size was 0.06 for trials using glucosamine hydrochloride and 0.44 for trials using glucosamine sulfate. Trials using Rottapharm products had an effect size of 0.55, compared with 0.11 for the rest. CONCLUSION: Heterogeneity among trials of glucosamine is larger than would be expected by chance. Glucosamine hydrochloride is not effective. Among trials with industry involvement, effect sizes were consistently higher. Potential explanations include different glucosamine preparations, inadequate allocation concealment, and industry bias.