Female sex is a risk factor for painful diabetic peripheral neuropathy: the EURODIAB prospective diabetes complications study.

AIMS/HYPOTHESIS: While the risk factors for diabetic peripheral neuropathy (DPN) are now well recognised, the risk factors for painful DPN remain unknown. We performed analysis of the EURODIAB Prospective Complications Study data to elucidate the incidence and risk factors of painful DPN. METHODS: The EURODIAB Prospective Complications Study recruited 3250 participants with type 1 diabetes who were followed up for 7.3±0.6 (mean ± SD) years. To evaluate DPN, a standardised protocol was used, including clinical assessment, quantitative sensory testing and autonomic function tests. Painful DPN (defined as painful neuropathic symptoms in the legs in participants with confirmed DPN) was assessed at baseline and follow-up. RESULTS: At baseline, 234 (25.2%) out of 927 participants with DPN had painful DPN. At follow-up, incident DPN developed in 276 (23.5%) of 1172 participants. Of these, 41 (14.9%) had incident painful DPN. Most of the participants who developed incident painful DPN were female (73% vs 48% painless DPN p=0.003) and this remained significant after adjustment for duration of diabetes and HbA1c (OR 2.69 [95% CI 1.41, 6.23], p=0.004). The proportion of participants with macro- or microalbuminuria was lower in those with painful DPN compared with painless DPN (15% vs 34%, p=0.02), and this association remained after adjusting for HbA1c, diabetes duration and sex (p=0.03). CONCLUSIONS/INTERPRETATION: In this first prospective study to investigate the risk factors for painful DPN, we definitively demonstrate that female sex is a risk factor for painful DPN. Additionally, there is less evidence of diabetic nephropathy in incident painful, compared with painless, DPN. Thus, painful DPN is not driven by cardiometabolic factors traditionally associated with microvascular disease. Sex differences may therefore play an important role in the pathophysiology of neuropathic pain in diabetes. Future studies need to look at psychosocial, genetic and other factors in the development of painful DPN.

Association of synovial fluid and urinary C2C-HUSA levels with surgical outcomes post-total knee arthroplasty.

OBJECTIVES: After total knee arthroplasty (TKA), ∼30% of knee osteoarthritis (KOA) patients show little symptomatic improvement. Earlier studies have correlated urinary (u) type 2 collagen C terminal cleavage peptide assay (C2C-HUSA), which detects a fragment of cartilage collagen breakdown, with KOA progression. This study determines whether C2C levels in urine, synovial fluid, or their ratio, are associated with post-surgical outcomes. METHODS: From a large sample of 489 subjects, diagnosed with primary KOA undergoing TKA, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function scores were collected at baseline (time of surgery) and one-year post-TKA. Baseline urine (u) and synovial fluid (sf) were analysed using the IBEX-C2C-HUSA assay, with higher values indicating higher amounts of cartilage degradation. For urine, results were normalised to creatinine. Furthermore, subjects' changes in WOMAC scores were categorised based on percent reduction in pain or improvement in function, compared to baseline, such that >66.7%, >33.3 to ≤66.7%, and ≤33.3% denoted "strong", "moderate" and "mild/worse" responses, respectively. Associations of individual biofluid C2C-HUSA levels, or their ratio, with change in WOMAC pain and function scores up to one-year post-TKA, or category of change, were analysed by linear, logistic, or cumulative odds models. RESULTS: Higher baseline uC2C-HUSA levels or a lower ratio of baseline sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC pain by linear multivariable modelling [odds ratio -0.40 (95% confidence interval -0.76, -0.05) p = 0.03; 0.36 (0.01, 0.71), p = 0.04, respectively], while sfC2C-HUSA alone was not. However, lower ratios of sfC2C-HUSA to uC2C-HUSA were associated with improvements in WOMAC function [1.37 (0.18, 2.55), p = 0.02], while sfC2C-HUSA and uC2C-HUSA alone were not. Lower ratios of sfC2C-HUSA to uC2C-HUSA were also associated with an increased likelihood of a subject being categorised in a group where TKA was beneficial in both univariable [pain, 0.81 (0.68, 0.96), p = 0.02; function, 0.92 (0.85, 0.99), p = 0.035] and multivariable [pain, 0.81 (0.68, 0.97) p = 0.02; function, 0.92 (0.85, 1.00), p = 0.043] ordinal modelling, while sfC2C-HUSA and uC2C-HUSA alone were not. CONCLUSIONS: Overall, ratios of baseline sfC2C-HUSA to uC2C-HUSA, and baseline uC2C-HUSA, may play an important role in studying post-TKA surgical outcomes.

Total Hip Arthroplasty Versus Education and Exercise: A Propensity-Matched Analysis of 266 Patients Who Have Hip Osteoarthritis.

BACKGROUND: Total hip arthroplasty (THA) for osteoarthritis (OA) is a major health system cost. Education and exercise (Edu + Ex) programs may reduce the number of THAs needed, but supporting data are limited. This study aimed to estimate the treatment effect of THA versus Edu + Ex on pain, function, and quality of life outcomes 3 and 12 months after treatment initiation for hip OA. METHODS: Patients who had hip OA who underwent THA or an Edu + Ex program were included in this propensity-matched study. In 778 patients (Edu + Ex, n = 303; THA, n = 475), propensity scores were based on pretreatment characteristics, and patients were matched on a 1:1 ratio. Between-group treatment effects (pain, function, and quality of life) were estimated as the mean difference (MD) in change from pretreatment to 3-month and 12-month follow-up using linear mixed models. RESULTS: The matched sample consisted of 266 patients (Edu + Ex, n = 133; THA, n = 133) who were balanced on all pretreatment characteristics except opioid use. At 12-month follow-up, THA resulted in significantly greater improvements in pain (MD 35.4; 95% confidence interval [CI] 31.4 to 39.4), function (MD 30.5; 95% CI 26.3 to 34.7), and quality of life (MD 33.6; 95% CI 28.8 to 38.4). Between 17% and 30% of patients receiving Edu + Ex experienced a surgical threshold for clinically meaningful improvement in outcomes, compared to 84% and 90% of THA patients. CONCLUSIONS: A THA provides greater improvements in pain, function, and quality of life. A notable proportion of Edu + Ex patients had clinically meaningful improvements, suggesting Edu + Ex may result in THA deferral in some patients, but confirmatory trials are needed.

Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial.

BACKGROUND: Diabetic peripheral neuropathic pain (DPNP) is common and often distressing. Most guidelines recommend amitriptyline, duloxetine, pregabalin, or gabapentin as initial analgesic treatment for DPNP, but there is little comparative evidence on which one is best or whether they should be combined. We aimed to assess the efficacy and tolerability of different combinations of first-line drugs for treatment of DPNP. METHODS: OPTION-DM was a multicentre, randomised, double-blind, crossover trial in patients with DPNP with mean daily pain numerical rating scale (NRS) of 4 or higher (scale is 0-10) from 13 UK centres. Participants were randomly assigned (1:1:1:1:1:1), with a predetermined randomisation schedule stratified by site using permuted blocks of size six or 12, to receive one of six ordered sequences of the three treatment pathways: amitriptyline supplemented with pregabalin (A-P), pregabalin supplemented with amitriptyline (P-A), and duloxetine supplemented with pregabalin (D-P), each pathway lasting 16 weeks. Monotherapy was given for 6 weeks and was supplemented with the combination medication if there was suboptimal pain relief (NRS >3), reflecting current clinical practice. Both treatments were titrated towards maximum tolerated dose (75 mg per day for amitriptyline, 120 mg per day for duloxetine, and 600 mg per day for pregabalin). The primary outcome was the difference in 7-day average daily pain during the final week of each pathway. This trial is registered with ISRCTN, ISRCTN17545443. FINDINGS: Between Nov 14, 2017, and July 29, 2019, 252 patients were screened, 140 patients were randomly assigned, and 130 started a treatment pathway (with 84 completing at least two pathways) and were analysed for the primary outcome. The 7-day average NRS scores at week 16 decreased from a mean 6·6 (SD 1·5) at baseline to 3·3 (1·8) at week 16 in all three pathways. The mean difference was -0·1 (98·3% CI -0·5 to 0·3) for D-P versus A-P, -0·1 (-0·5 to 0·3) for P-A versus A-P, and 0·0 (-0·4 to 0·4) for P-A versus D-P, and thus not significant. Mean NRS reduction in patients on combination therapy was greater than in those who remained on monotherapy (1·0 [SD 1·3] vs 0·2 [1·5]). Adverse events were predictable for the monotherapies: we observed a significant increase in dizziness in the P-A pathway, nausea in the D-P pathway, and dry mouth in the A-P pathway. INTERPRETATION: To our knowledge, this was the largest and longest ever, head-to-head, crossover neuropathic pain trial. We showed that all three treatment pathways and monotherapies had similar analgesic efficacy. Combination treatment was well tolerated and led to improved pain relief in patients with suboptimal pain control with a monotherapy. FUNDING: National Institute for Health Research (NIHR) Health Technology Assessment programme.

Individual participant data meta-analysis of metabolomics on sustained knee pain in primary osteoarthritis patients.

OBJECTIVES: Knee pain is the major driver for OA patients to seek healthcare, but after pursuing both conservative and surgical pain interventions, ∼20% of patients continue to report long-term pain following total knee arthroplasty (TKA). This study aimed to identify a metabolomic signature for sustained knee pain after TKA to elucidate possible underlying mechanisms. METHODS: Two independent cohorts from St John's, NL, Canada (n = 430), and Toronto, ON, Canada (n = 495) were included in the study. Sustained knee pain was assessed using the WOMAC pain subscale (five questions) at least 1 year after TKA for primary OA. Those reporting any pain on all five questions were considered to have sustained knee pain. Metabolomic profiling was performed on fasted pre-operative plasma samples using the Biocrates Absolute IDQ p180 kit. Associations between metabolites and pair-wise metabolite ratios with sustained knee pain in each individual cohort were assessed using logistic regression with adjustment for age, sex and BMI. Random-effects meta-analysis using inverse variance as weights was performed on summary statistics from both cohorts. RESULTS: One metabolite, phosphatidylcholine (PC) diacyl (aa) C28:1 (odds ratio = 0.66, P = 0.00026), and three metabolite ratios, PC aa C32:0 to PC aa C28:1, PC aa C28:1 to PC aa C32:0, and tetradecadienylcarnitine (C14:2) to sphingomyelin C20:2 (odds ratios = 1.59, 0.60 and 1.59, respectively; all P < 2 × 10-5), were significantly associated with sustained knee pain. CONCLUSIONS: Though further investigations are needed, our results provide potential predictive biomarkers and drug targets that could serve as a marker for poor response and be modified pre-operatively to improve knee pain and surgical response to TKA.

A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID-19.

AIMS: To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. MATERIALS AND METHODS: Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression. RESULTS: In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment. CONCLUSIONS: Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.

Surgical management of high-grade paediatric spondylolisthesis: meta-analysis and systematic review.

PURPOSE: There is currently no consensus on the management of high-grade spondylolisthesis (HGS) in paediatric populations. The objective of this analysis is to compare the outcomes of reduction followed by fusion (RFF) or in situ fusion (ISF) in paediatric patients. METHODS: Using major databases, a systematic literature search was performed. Primary studies comparing ISF with RFF in paediatric and adolescent patients were identified. Study data including patient-reported outcomes, complications, and spinopelvic parameters were collected and analysed. RESULTS: Seven studies were included, comprising 97 ISF and 131 RFF. Average patient age was 14.4 ± 2.1 years and follow up was 8.2 ± 5.1 years. Patients undergoing RFF compared to patients undergoing ISF alone were less likely to develop pseudarthrosis (RR 0.51, 95% CI, [0.26, 0.99], p = 0.05). On average, RFF led to 11.97º more reduction in slip angle and 34.8% more reduction in sagittal translation (p < 0.00001) compared to ISF. There was no significant difference between patient satisfaction and pain at follow up. Neurologic complications and reoperation rates were not significantly different. CONCLUSIONS: Both RFF and ISF are effective techniques for managing HGS. Performing a reduction followed by fusion reduces the likelihood of pseudarthrosis in paediatric patients. The difference between risk of neurologic complications, need for reoperation, patient satisfaction, and pain outcomes did not reach statistical significance. Correlation with patient-reported outcomes still needs to be further explored. LEVEL 3 EVIDENCE: Meta-analysis of Level 3 studies.

Hospital spending and length of stay attributable to perioperative adverse events for inpatient hip, knee, and spine surgery: a retrospective cohort study.

BACKGROUND: The incremental hospital cost and length of stay (LOS) associated with adverse events (AEs) has not been well characterized for planned and unplanned inpatient spine, hip, and knee surgeries. METHODS: Retrospective cohort study of hip, knee, and spine surgeries at an academic hospital in 2011-2012. Adverse events were prospectively collected for 3,063 inpatient cases using the Orthopaedic Surgical AdVerse Event Severity (OrthoSAVES) reporting tool. Case costs were retrospectively obtained and inflated to equivalent 2021 CAD values. Propensity score methodology was used to assess the cost and LOS attributable to AEs, controlling for a variety of patient and procedure factors. RESULTS: The sample was 55% female and average age was 64; 79% of admissions were planned. 30% of cases had one or more AEs (82% had low-severity AEs at worst). The incremental cost and LOS attributable to AEs were $8,500 (95% confidence interval [CI]: 5100-11,800) and 4.7 days (95% CI: 3.4-5.9) per admission. This corresponded to a cumulative $7.8 M (14% of total cohort cost) and 4,290 bed-days (19% of cohort bed-days) attributable to AEs. Incremental estimates varied substantially by (1) admission type (planned: $4,700/2.4 days; unplanned: $20,700/11.5 days), (2) AE severity (low: $4,000/3.1 days; high: $29,500/11.9 days), and (3) anatomical region (spine: $19,800/9 days; hip: $4,900/3.8 days; knee: $1,900/1.5 days). Despite only 21% of admissions being unplanned, adverse events in these admissions cumulatively accounted for 59% of costs and 62% of bed-days attributable to AEs. CONCLUSIONS: This study comprehensively demonstrates the considerable cost and LOS attributable to AEs in orthopaedic and spine admissions. In particular, the incremental cost and LOS attributable to AEs per admission were almost five times as high among unplanned admissions compared to planned admissions. Mitigation strategies focused on unplanned surgeries may result in significant quality improvement and cost savings in the healthcare system.

No Benefits of Adding Dexmedetomidine, Ketamine, Dexamethasone, and Nerve Blocks to an Established Multimodal Analgesic Regimen after Total Knee Arthroplasty.

BACKGROUND: An optimal opioid-sparing multimodal analgesic regimen to treat severe pain can enhance recovery after total knee arthroplasty. The hypothesis was that adding five recently described intravenous and regional interventions to multimodal analgesic regimen can further reduce opioid consumption. METHODS: In a double-blinded fashion, 78 patients undergoing elective total knee arthroplasty were randomized to either (1) a control group (n = 39) that received spinal anesthesia with intrathecal morphine, periarticular local anesthesia infiltration, intravenous dexamethasone, and a single injection adductor canal block or (2) a study group (n = 39) that received the same set of analgesic treatments plus five additional interventions: local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intraoperative intravenous dexmedetomidine and ketamine, and postoperatively, one additional intravenous dexamethasone bolus and two additional adductor canal block injections. The primary outcome measure was 24-h cumulative opioid consumption after surgery and secondary outcomes were other analgesics, patient recovery, functional outcomes, and adverse events. RESULTS: Opioid consumption was not different between groups at 24 h (oral morphine equivalents, mean ± SD; study: 23.7 ± 18.0 mg vs. control: 29.3 ± 18.7 mg; mean difference [95% CI], -5.6 mg [-2.7 to 13.9]; P = 0.189) and all other time points after surgery. There were no major differences in pain scores, quality of recovery, or time to reach rehabilitation milestones. Hypotensive episodes occurred more frequently in the study group (25 of 39 [64.1%] vs. 13 of 39 [33.3%]; P = 0.010). CONCLUSIONS: In the presence of periarticular local anesthesia infiltration, intrathecal morphine, single-shot adductor canal block and dexamethasone, the addition of five analgesic interventions-local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intravenous dexmedetomidine, intravenous ketamine, an additional intravenous dexamethasone dose, and repeated adductor canal block injections-failed to further reduce opioid consumption or pain scores or to improve functional outcomes after total knee arthroplasty.

A UK nationwide study of people with type 1 diabetes admitted to hospital with COVID-19 infection.

AIMS/HYPOTHESIS: The aim of this work was to describe the clinical characteristics of adults with type 1 diabetes admitted to hospital and the risk factors associated with severe coronavirus disease-2019 (COVID-19) in the UK. METHODS: A retrospective cohort study was performed using data collected through a nationwide audit of people admitted to hospital with diabetes and COVID-19, conducted by the Association of British Clinical Diabetologists from March to October 2020. Prespecified demographic, clinical, medication and laboratory data were collected from the electronic and paper medical record systems of the participating hospitals by local clinicians. The primary outcome of the study, severe COVID-19, was defined as death in hospital and/or admission to the adult intensive care unit (AICU). Logistic regression models were used to generate age-adjusted ORs. RESULTS: Forty UK centres submitted data. The final dataset included 196 adults who were admitted to hospital and had both type 1 diabetes and COVID-19 on admission (male sex 55%, white 70%, with mean [SD] age 62 [19] years, BMI 28.3 [7.3] kg/m2 and last recorded HbA1c 76 [31] mmol/mol [9.1 (5.0)%]). The prevalence of pre-existing microvascular disease and macrovascular disease was 56% and 39%, respectively. The prevalence of diabetic ketoacidosis on admission was 29%. A total of 68 patients (35%) died or were admitted to AICU. The proportions of people that died were 7%, 38% and 38% of those aged <55, 55-74 and ≥75 years, respectively. BMI, serum creatinine levels and having one or more microvascular complications were positively associated with the primary outcome after adjusting for age. CONCLUSIONS/INTERPRETATION: In people with type 1 diabetes and COVID-19 who were admitted to hospital in the UK, higher BMI, poorer renal function and presence of microvascular complications were associated with greater risk of death and/or admission to AICU. Risk of severe COVID-19 is reassuringly very low in people with type 1 diabetes who are under 55 years of age without microvascular or macrovascular disease. IN PEOPLE WITH TYPE 1 DIABETES AND COVID-19 ADMITTED TO HOSPITAL IN THE UK, BMI AND ONE OR MORE MICROVASCULAR COMPLICATIONS HAD A POSITIVE ASSOCIATION AND LOW SERUM CREATINE LEVELS HAD A NEGATIVE ASSOCIATION WITH DEATH/ADMISSION TO INTENSIVE CARE UNIT AFTER ADJUSTING FOR AGE.

What Goes Bump in the Night: An Evaluation of Emergency Department Visits Following Total Joint Arthroplasty.

BACKGROUND: Interest in postoperative healthcare utilization has increased following the implementation of episode-of-care funding for elective orthopedic surgery. Most efforts have focused on readmission; however, little has been reported on emergency department (ED) presentation. We analyzed elective, primary total hip or knee arthroplasty (THA and TKA) cases to determine the rate, reasons, risk factors, timing, and hospital cost associated with 30-day ED presentations. METHODS: An observational study of patients who underwent primary, elective TKA and THA between January 1, 2016, and December 31, 2017, was performed. The primary outcome was an ED visit within 30-days of the index operation. Secondary outcomes included reasons, risk factors, timing, and hospital cost of ED visits. A multivariable logistic regression was undertaken to determine patient factors associated with ED presentation. RESULTS: Overall, 1690 patients were included, of which 9.2% presented to the ED within 30-days of surgery. Approximately two-thirds of the visits were after-hours, and most were discharged home without readmission (81.4%). The most commonly reported reasons were wound concerns (30.1%) and pain (20.5%). Older age (OR 1.1, P = .03) and preoperative dyspnea (OR 2.1, P < .001) increased the odds of ED visits. The mean cost of an ED visit was significantly greater after-hours (P = .015). CONCLUSION: Overall, 1 in 10 patients undergoing TKA/THA presented to the ED within 30-days of surgery, of which over 80% were not readmitted, and most occurred after-hours where cost is greatest. Our observations suggest ED visits following TKA/THA are common, and most are likely preventable. Future efforts should focus on developing interventions to reduce these visits.

Radiofrequency Procedures for the Treatment of Symptomatic Knee Osteoarthritis: A Systematic Review.

OBJECTIVE: To evaluate the effectiveness and safety of radiofrequency (RF) ablation and neuromodulation modalities for knee osteoarthritis (OA). METHODS: The Pubmed, Medline, Embase, and Cochrane Library databases were searched from inception to August 2018. All comparative and noncomparative studies that reported clinical outcome measures and adverse events related to RF modalities for knee OA were included. Pain scores, physical function measures, quality of life (QOL), patient satisfaction, and adverse events for three months and beyond of postprocedure follow-up were analyzed qualitatively. RESULTS: Thirty-three studies, including 13 randomized controlled trials (RCTs), two nonrandomized comparative studies, and 18 noncomparative cohort studies, were identified, with 1,512 patients (mean age = 64.3 years, 32.5% males). All 33 studies were considered to be of moderate or high methodological quality. All 33/33 (100%) studies reported alleviation of OA-related knee pain from baseline until three to 12 months with RF modalities, with six comparative studies reporting 194/296 (65.5%) and 29/150 (19.3%) RF and control patients achieving >50% pain relief, respectively. Three of the 33 studies reported QOL, with three of three studies (100%) achieving improvements in disease-specific QOL from baseline until three to 12 months. Twenty-eight of the 33 studies reported functional outcomes, with 27/28 (96%) studies obtaining enhanced functionality from baseline up until three to 12 months. Ten of the 33 studies reported patient satisfaction, with eight of 10 studies (80%) indicating that patients were significantly satisfied after RF procedures, and from these eight studies, four were comparative studies that indicated that 86/154 (56%) and 33/104 (32%) RF and control patients were extremely satisfied or satisfied, respectively. Regarding adverse events (AEs), 29 of the 33 studies reported AEs, with 20/29 (69%) studies indicating no AEs related to the RF modalities and the remaining nine studies only indicating minor localized AEs. Twenty-nine of the 33 studies indicated no serious knee-related AEs pertaining to RF modalities. CONCLUSIONS: Current evidence substantiates that RF modalities for knee OA potentially improve pain, functionality, and disease-specific QOL for up to three to 12 months with minimal localized complications. This suggests that RF modalities are perhaps an effective adjunct therapy for patients with knee OA who are unresponsive to conservative therapies. Further RCTs with larger sample sizes and long-term follow-up that directly compare the three primary RF modalities are warranted to confirm the clinical efficaciousness and superiority of these RF modalities for knee OA.

Emergency Department Presentation After Total Hip and Knee Arthroplasty: A Systematic Review.

BACKGROUND: Recent changes to payment models for elective total joint arthroplasty (TJA) have led to increased interest in postdischarge health care utilization. Although readmission has historically been of primary interest, emergency department (ED) presentation is increasingly a point of focus. The purpose of this review was to summarize the available literature pertaining to ED visits after total hip arthroplasty and total knee arthroplasty. METHODS: PubMed, MEDLINE, and Embase were searched. Clinical studies reporting rate, reasons, and/or risk factors associated with ED presentation after TJA were included. Pooled return to ED rates were calculated using weighted means. RESULTS: Twenty-seven studies (n = 1,484,043) were included. After TJA, the mean 30-day and 90-day rates of ED presentation were 8.1% and 10.3%, respectively. Rates were slightly higher in total knee arthroplasty vs total hip arthroplasty patients at 30 days (11.5% vs 6.5%) and 90 days (10.8% vs 9.7%). The most common reasons for ED presentation after TJA were pain (4.6%-35%), medical concerns (5.6%-24.5%), and swelling (1.4%-17.5%). Studies analyzing the timing of ED visits found that most occurred within the first 2 weeks postdischarge. Black race and Medicaid/Medicare insurance coverage were identified as risk factors associated with ED visits. CONCLUSION: ED visits present a high burden for the health care system, as upward of 1 in 10 patients will return to the ED within 90 days of TJA. Future efforts should be made to develop cost-effective and patient-centered interventions that reduce preventable ED visits after TJA. As well, these rates should be taken into consideration when allocating resources for the care of TJA patients.

Serum-based soluble markers differentiate psoriatic arthritis from osteoarthritis.

OBJECTIVES: We aimed to identify soluble biomarkers that differentiate psoriatic arthritis (PsA) from osteoarthritis (OA). METHODS: Markers of cartilage metabolism (cartilage oligomeric matrix protein [COMP], hyaluronan), metabolic syndrome (adiponectin, adipsin, resistin, hepatocyte growth factor [HGF], insulin, leptin) and inflammation (C-reactive protein [CRP], interleukin-1ß [IL-1ß], IL-6, IL-8, tumour necrosis factor alpha [TNFα], monocyte chemoattractant protein-1 [MCP-1], nerve growth factor [NGF]) were compared in serum samples from 201 patients with OA, 77 patients with PsA and 76 controls. Levels across the groups were compared using the Kruskal-Wallis test. Pairwise comparisons were made with Wilcoxon rank-sum test. Multivariate logistic regression analyses were performed to identify markers that differentiate PsA from OA. Receiver operating characteristic (ROC) curves were constructed based on multivariate models. The final model was further validated in an independent set of 73 PsA and 75 OA samples using predicted probabilities calculated with coefficients of age, sex and biomarkers. RESULTS: Levels of the following markers were significantly different across the three groups (p<0.001)-COMP, hyaluronan, resistin, HGF, insulin, leptin, CRP, IL-6, IL-8, TNFα, MCP-1, NGF. In multivariate analysis, COMP (OR 1.24, 95% CI 1.06 to 1.46), resistin (OR 1.26, 95% CI 1.07 to 1.48), MCP-1 (OR 1.10, 95% CI 0.07 to 1.48) and NGF (OR<0.001, 95% CI <0.001 to 0.25) were found to be independently associated with PsA versus OA. The area under the ROC curve (AUROC) for this model was 0.99 compared with model with only age and sex (AUROC 0.87, p<0.001). Similar results were obtained using the validation sample. CONCLUSION: A panel of four biomarkers may distinguish PsA from OA. These results need further validation in prospective studies.

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints.

OBJECTIVES: We recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration. METHODS: We used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression. RESULTS: miR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects. CONCLUSIONS: Our data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA.

Painful and Painless Diabetic Neuropathies: What Is the Difference?

PURPOSE OF REVIEW: The prevalence of diabetes mellitus and its chronic complications are increasing to epidemic proportions. This will unfortunately result in massive increases in diabetic distal symmetrical polyneuropathy (DPN) and its troublesome sequelae, including disabling neuropathic pain (painful-DPN), which affects around 25% of patients with diabetes. Why these patients develop neuropathic pain, while others with a similar degree of neuropathy do not, is not clearly understood. This review will look at recent advances that may shed some light on the differences between painful and painless-DPN. RECENT FINDINGS: Gender, clinical pain phenotyping, serum biomarkers, brain imaging, genetics, and skin biopsy findings have been reported to differentiate painful- from painless-DPN. Painful-DPN seems to be associated with female gender and small fiber dysfunction. Moreover, recent brain imaging studies have found neuropathic pain signatures within the central nervous system; however, whether this is the cause or effect of the pain is yet to be determined. Further research is urgently required to develop our understanding of the pathogenesis of pain in DPN in order to develop new and effective mechanistic treatments for painful-DPN.

Can Patient Selection Explain the Obesity Paradox in Orthopaedic Hip Surgery? An Analysis of the ACS-NSQIP Registry.

BACKGROUND: The "obesity paradox" is a phenomenon described in prior research in which patients who are obese have been shown to have lower postoperative mortality and morbidity compared with normal-weight individuals. The paradox is that clinical experience suggests that obesity is a risk factor for difficult wound healing and adverse cardiovascular outcomes. We suspect that the obesity paradox may reflect selection bias in which only the healthiest patients who are obese are offered surgery, whereas nonobese surgical patients are comprised of both healthy and unhealthy individuals. We questioned whether the obesity paradox (decreased mortality for patients who are obese) would be present in nonurgent hip surgery in which patients can be carefully selected for surgery but absent in urgent hip surgery where patient selection is minimized. QUESTIONS/PURPOSES: (1) What is the association between obesity and postoperative mortality in urgent and nonurgent hip surgery? (2) How is obesity associated with individual postoperative complications in urgent and nonurgent hip surgery? (3) How is underweight status associated with postoperative mortality and complications in urgent and nonurgent hip surgery? METHODS: We used 2011 to 2014 data from the American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) to identify all adults who underwent nonurgent hip surgery (n = 63,148) and urgent hip surgery (n = 29,047). We used logistic regression models, controlling for covariants including age, sex, anesthesia risk, and comorbidities, to examine the relationship between body mass _index (BMI) category (classified as underweight < 18.5 kg/m, normal 18.5-24.9 kg/m, overweight 25-29.9 kg/m, obese 30-39.9 kg/m, and morbidly obese > 40 kg/m) and adverse outcomes including 30-day mortality and surgical complications including wound complications and cardiovascular events. RESULTS: For patients undergoing nonurgent hip surgery, regression models demonstrate that patients who are morbidly obese were less likely to die within 30 days after surgery (odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.57; p = 0.038) compared with patients with normal BMI, consistent with the obesity paradox. For patients undergoing urgent hip surgery, patients who are morbidly obese had similar odds of death within 30 days compared with patients with normal BMI (OR, 1.18; 95% CI, 0.76-1.76; p = 0.54). Patients who are morbidly obese had higher odds of wound complications in both nonurgent (OR, 4.93; 95% CI, 3.68-6.65; p < 0.001) and urgent cohorts (OR, 4.85; 95% CI, 3.27-7.01; p < 0.001) compared with normal-weight patients. Underweight patients were more likely to die within 30 days in both nonurgent (OR, 3.79; 95% CI, 1.10-9.97; p = 0.015) and urgent cohorts (OR, 1.47; 95% CI, 1.23-1.75; p < 0.001) compared with normal-weight patients. CONCLUSIONS: Patients who are morbidly obese appear to have a reduced risk of death in 30 days after nonurgent hip surgery, but not for urgent hip surgery. Our results suggest that the obesity paradox may be an artifact of selection bias introduced by careful selection of the healthiest patients who are obese for elective hip surgery. Surgeons should continue to consider obesity a risk factor for postoperative mortality and complications such as wound infections for both urgent and nonurgent surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.

Understanding the Relationship Between 3-Month and 2-Year Pain and Function Scores After Total Knee Arthroplasty for Osteoarthritis.

BACKGROUND: Research to understand predictors of poor outcomes after total knee arthroplasty (TKA) has largely focused on presurgery factors. We examined whether pain and function 3-month postsurgery were predictive of longer-term outcomes ascertained 2 years after TKA. METHODS: Western Ontario McMaster University Osteoarthritis Index pain and physical function scores (scaled 0-20 and 0-68; higher = worse) were recorded pre-TKA and 3, 12, and 24 months post-TKA. A sequential series of regression models was used to examine the relative contribution of baseline score and baseline to 3-month and 3 to 12-month change score to explaining variability (R2) in 2-year pain and function scores, with consideration for presurgery covariates. RESULTS: Data from 560 patients were analyzed. Mean pain and function scores improved significantly presurgery to 2 years postsurgery; 10-4 and 33-16 (P < .001), respectively. Considerable variability in 2-year scores was observed. Overall, 80.3% and 79.9% of changes in pain and function scores over the 2 years occurred within the first 3 months. Change over these 3 months explained the greatest proportion of variability in 2-year scores, 16% and 23% for pain and function, respectively. The influences of these early changes were similar to those of baseline status. CONCLUSION: Changes in patient-reported pain and function occurring within the first 3 months post-TKA strongly determine pain and function status at 2 years. Research to identify pre-/intra-/early postoperative factors associated with change in this early postoperative period that may be amenable to modification or used to better inform education and decision-making is warranted.

The effect of patient, provider and surgical factors on survivorship of high tibial osteotomy to total knee arthroplasty: a population-based study.

PURPOSE: The aim of this study was to identify the survivorship of high tibial osteotomy (HTO) to total knee arthroplasty (TKA) on a population level, and identify the patient, provider and surgical factors that influenced eventual TKA. METHODS: Administrative records from physician billings and hospital admissions were used to identify all adults in Ontario, Canada, who underwent an HTO from 1994 to 2010. The primary outcome was time to TKA, which was estimated using Kaplan-Meier (KM) survival analysis. A Cox proportional hazards model examined the risk associated with patient factors (age, sex, income and co-morbidity score), provider factors (hospital status, surgeon volume and surgeon year in practice) and surgical factors (concurrent ligament reconstruction or bone grafting; and previous chondral or meniscal surgery). RESULTS: A total of 2671 patients who underwent HTO met inclusion. The median age was 46 years (interquartile range 39-53 years), and 62 % were male. The KM survivorship of HTO to TKA at 10 years was 0.67 ± 0.01. Older age [HR 1.05 (95 % CI 1.04, 1.06), p < 0.001; 5 % increased risk for each year over age 46], female sex [HR 1.35 (95 % CI 1.17, 1.55), p < 0.001], higher comorbidity score [HR 1.58 (95 % CI 1.12, 2.22), p = 0.009] and a prior history of arthroscopy/meniscectomy [HR 1.24 (95 % CI 1.08, 1.43), p = 0.002] increased the risk of eventual TKA. However, HTO with concurrent ligament reconstruction was associated with lower [HR 0.62 (95 % CI 0.43, 0.88), p = 0.008] risk of eventual TKA. CONCLUSION: In this population, two-thirds of patients were able to avoid a TKA for 10 years after HTO. Specific factors such as older age, female sex, higher comorbidity and prior meniscectomy lowered survival rates. An understanding of patient risk factors for conversion to TKA may help guide surgeons in their selection of patients who will benefit most from HTO. LEVEL OF EVIDENCE: Retrospective cohort study, III.

Selective nonoperative management in 1106 patients with abdominal gunshot wounds: conclusions on safety, efficacy, and the role of selective CT imaging in a prospective single-center study.

OBJECTIVE: The primary aim of this study was to delineate the role of computed tomography (CT) in patients undergoing NOM for AGSW. BACKGROUND: Nonoperative management (NOM) of abdominal gunshot wounds (AGSWs) remains controversial. METHODS: This prospective study included all patients with abdominal gunshot injuries admitted to our trauma center from April 1, 2004 to September 30, 2009. Exclusion criteria included patients with peritonitis, hemodynamic instability, unreliable physical examination, head and spinal cord injury with an AGSW underwent immediate laparotomy. The remaining patients were selected for NOM. Nonperitonitic stable patients with right-sided thoracoabdominal/right upper quadrant gunshots and/or hematuria underwent mandatory CT with intravenous contrast. CT to detect missile trajectory was optional. The primary outcome measure was failure of NOM. Secondary outcomes were unnecessary laparotomy rates and mortality. RESULTS: A total of 1106 patients with abdominal gunshot injuries were admitted. Of these, 834 (75.4%) underwent immediate laparotomy, whereas 272 (24.6%) were selected for NOM. In the former group, there were 56 (6.7%) deaths and 29 (3.5%) unnecessary laparotomies, whereas in the latter NOM group, 82 (30.1%) patients were managed by serial clinical examination alone, whereas 190 (69.9%) patients underwent abdominal CT scanning, in addition to serial clinical examination. The overall NOM success rate was 95.2%. Of the 13 patients undergoing delayed laparotomy, there were 10 therapeutic, 2 nontherapeutic, and 1 negative laparotomy. CONCLUSIONS: The NOM of appropriately selected patients with AGSW with selective use of CT scanning is feasible, safe, and effective, but largely based on findings from serial clinical examinations.