What Are the Mortality, Infection, and Nonunion Rates After Periprosthetic Femoral Fractures in the United States?

BACKGROUND: Periprosthetic femoral fractures are a serious complication that put a high burden on patients. However, comprehensive analyses of their incidence, mortality, and complication rates based on large-registry data are scarce. QUESTIONS/PURPOSES: In this large-database study, we asked: (1) What is the incidence of periprosthetic femoral fractures in patients 65 years and older in the United States? (2) What are the rates of mortality, infection, and nonunion, and what factors are associated with these outcomes? METHODS: In this retrospective, comparative, large-database study, periprosthetic femoral fractures occurring between January 1, 2010, and December 31, 2019, were identified from Medicare physician service records encompassing services rendered in medical offices, clinics, hospitals, emergency departments, skilled nursing facilities, and other healthcare institutions from approximately 2.5 million enrollees. These were grouped into proximal, distal, and shaft fractures after TKA and THA. We calculated the incidence of periprosthetic femur fractures by year. Incidence rate ratios (IRR) were calculated by dividing the incidence in 2019 by the incidence in 2010. The Kaplan-Meier method with Fine and Gray subdistribution adaptation was used to calculate the cumulative incidence rates of mortality, infection, and nonunion. Semiparametric Cox regression was applied with 23 measures as covariates to determine factors associated with these outcomes. RESULTS: From 2010 to 2019, the incidence of periprosthetic femoral fractures increased steeply (TKA for distal fractures: IRR 3.3 [95% CI 1 to 9]; p = 0.02; THA for proximal fractures: IRR 2.3 [95% CI 1 to 4]; p = 0.01). One-year mortality rates were 23% (95% CI 18% to 28%) for distal fractures treated with THA, 21% (95% CI 19% to 24%) for proximal fractures treated with THA, 22% (95% CI 19% to 26%) for shaft fractures treated with THA, 21% (95% CI 18% to 25%) for distal fractures treated with TKA , 22% (95% CI 17% to 28%) for proximal fractures treated with TKA, and 24% (95% CI 19% to 29%) for shaft fractures treated with TKA. The 5-year mortality rate was 63% (95% CI 54% to 70%) for distal fractures treated with THA, 57% (95% CI 54% to 62%) for proximal fractures treated with THA, 58% (95% CI 52% to 63%) for shaft fractures treated with THA, 57% (95% CI 52% to 62%) for distal fractures treated with TKA , 57% (95% CI 49% to 65%) for proximal fractures treated with TKA, and 57% (95% CI 49% to 64%) for shaft fractures treated with TKA. Age older than 75 years, male sex, chronic obstructive pulmonary disease (HR 1.48 [95% CI 1.32 to 1.67] after THA and HR 1.45 [95% CI 1.20 to 1.74] after TKA), cerebrovascular disease after THA, chronic kidney disease (HR 1.28 [95% CI 1.12 to 1.46] after THA and HR 1.50 [95% CI 1.24 to 1.82] after TKA), diabetes mellitus, morbid obesity, osteoporosis, and rheumatoid arthritis were clinical risk factors for an increased risk of mortality. Within the first 2 years, fracture-related infections occurred in 5% (95% CI 4% to 7%) of patients who had distal fractures treated with THA, 5% [95% CI 5% to 6%]) of patients who had proximal fractures treated with THA, 6% (95% CI 5% to 7%) of patients who had shaft fractures treated with THA, 6% (95% CI 5% to 7%) of patients who had distal fractures treated with TKA , 7% (95% CI 5% to 9%) of patients who had proximal fractures treated with TKA, and 6% (95% CI 4% to 8%) of patients who had shaft fractures treated with TKA. Nonunion or malunion occurred in 3% (95% CI 2% to 4%) of patients with distal fractures treated with THA, 1% (95% CI 1% to 2%) of patients who had proximal fractures treated with THA, 2% (95% CI 1% to 3%) of patients who had shaft fractures treated with THA, 4% (95% CI 3% to 5%) of those who had distal fractures treated with TKA, , 2% (95% CI 1% to 4%) of those who had proximal fractures treated with TKA, and 3% (95% CI 2% to 4%) of those who had shaft fractures treated with TKA. CONCLUSION: An increasing number of periprosthetic fractures were observed during the investigated period. At 1 and 5 years after periprosthetic femur fracture, there was a substantial death rate in patients with Medicare. Conditions including cerebrovascular illness, chronic kidney disease, diabetes mellitus, morbid obesity, osteoporosis, and rheumatoid arthritis are among the risk factors for increased mortality. After the surgical care of periprosthetic femur fractures, the rates of fracture-related infection and nonunion were high, resulting in a serious risk to affected patients. Patient well-being can be enhanced by an interdisciplinary team in geriatric traumatology and should be improved to lower the risk of postoperative death. Additionally, it is important to ensure that surgical measures to prevent fracture-related infections are followed diligently. Furthermore, there is a need to continue improving implants and surgical techniques to avoid often-fatal complications such as fracture-associated infections and nonunion, which should be addressed in further studies. LEVEL OF EVIDENCE: Level III, therapeutic study.

Strikingly High Rates of Periprosthetic Joint Infection Following Revision Surgery for Periprosthetic Fractures Regardless of Surgery Timing.

BACKGROUND: Periprosthetic fractures following total hip arthroplasty (THA) often occur in the early postoperative period. Recent data has indicated that early revisions are associated with higher complication rates, particularly periprosthetic joint infection (PJI). The purpose of this study was to assess the effect of timing of periprosthetic fracture surgery on complication rates. We hypothesized that complication rates would be significantly higher in revision surgeries performed within 3 months of the index THA. METHODS: The Medicare Part A claims database was queried from 2010 to 2017 to identify patients who underwent surgery for a periprosthetic fracture following primary THA. Patients were divided based on time between index and revision surgeries: <1, 1 to 2, 2 to 3, 3 to 6, 6 to 9, 9 to 12, and >12 months. Complication rates were compared between groups using multivariate analyses to adjust for demographics, comorbidities, and types of revision surgery. RESULTS: Of 492,340 THAs identified, 4,368 (0.9%) had a subsequent periprosthetic fracture requiring surgery: 1,725 (39.4%) at <1 month, 693 (15.9%) at 1 to 2 months, 202 (4.6%) at 2 to 3 months, 250 (5.7%) at 3 to 6 months, 134 (3.1%) at 6 to 9 months, 85 (19.4%) at 9 to12 months, and 1,279 (29.3%) at >12 months. The risk of PJI was 11.0% in the <1 month group, 11.1% at 1 to 2 months, 7.9% at 2 to 3 months, 6.8% at 3 to 6 months, 8.2% at 6 to 9 months, 9.4% at 9 to 12 months, and 8.5% at >12 months (P = .12). Adjusting for confounding factors, risk of PJI following periprosthetic fracture surgery was similar regardless of timing (P > .05). Rates of subsequent dislocation and aseptic loosening were also similar regardless of timing. CONCLUSIONS: The risk of PJI following repeat surgery for a periprosthetic fracture was strikingly high regardless of timing (6.8 to 11.1%), underscoring the high-risk of complications.

Impact of cystic fibrosis multidisciplinary virtual clinics on patient experience, time commitments and costs.

BACKGROUND AND AIMS: The experience of outpatient care may differ for select patient groups. This prospective study evaluates the adult patient experience of multidisciplinary outpatient cystic fibrosis (CF) care with videoconferencing through telehealth compared with face-to-face care the year prior. METHODS: People with CF without a lung transplant were recruited. Patient-reported outcomes were obtained at commencement and 12 months into the study, reflecting both their face-to-face and telehealth through videoconferencing experience, respectively. Three patient cohorts were analysed: (i) participants with a regional residence, (ii) participants with a nonregional including metropolitan residence and (iii) participants with colonised multiresistant microbiota. RESULTS: Seventy-four patients were enrolled in the study (mean age, 37 ± 11 years; 50% male; mean forced expiratory volume in the first second of expiration, 60% [standard deviation, 23]) between February 2020 and May 2021. No differences between models were observed in the participants' rating of the health care team, general and mental health rating, and their confidence in handling treatment plans at home. No between-group differences in the Cystic Fibrosis Questionnaire - Revised (CFQ-R) were observed. Travel duration and the cost of attending a clinic was significantly reduced, particularly for the regional group (4 h, AU$108 per clinic; P < 0.05). A total of 93% respondents preferred to continue with a hybrid approach. CONCLUSION: In this pilot study, participants' experience of care and quality of life were no different with face-to-face and virtual care between the groups. Time and cost-savings, particularly for patients living in regional areas, were observed. Most participants preferred to continue with a hybrid model for outpatient care.

Acute Vasoreactivity Testing and Outcomes in Pulmonary Arterial Hypertension: A Call for Increased Testing.

BACKGROUND: Pulmonary arterial hypertension (PAH) has a progressive, unremitting clinical course. Vasoreactivity testing (VdT) during right heart catheterisation (RHC) identifies a subgroup with excellent long-term response to calcium channel blockade (CCB). Reporting on these patients is limited. Established in 2011, the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry offers the opportunity to assess the frequency of VdT during RHC, treatment and follow up of PAH patients. METHODS: Registry data from 3,972 PAH patients with index RHC revealed 1,194 VdT appropriate patients. Data was analysed in three groups: 1) VdT+CCB+: VdT positive, CCB treated; 2) VdT+CCB-: VdT positive, no CCB prescribed, 3) VdT-/noVdT: VdT negative, or VdT not tested. Data was reviewed for adherence to guidelines, clinical response (World Health Organization functional class [WHO FC], 6-minute-walk-distance [6MWD], RHC), and outcomes (survival or lung transplantation). RESULTS: Patients included had idiopathic (IPAH=1,087), heritable (HPAH=67) and drug or toxin-induced PAH (DPAH=40). A VdT was performed in 22% (268/1,194), with incomplete data in 26% (70/268); 28% (55/198) were VdT+. Analysis group allocation was: VdT+CCB+ (33/55), VdT+CCB- (22/55), VdT- (143)/noVdT (996). From patients with 1-year data VdT+CCB+ and VdT-/noVdT patients improved WHO FC, 6MWD and cardiac index (CI); VdT+CCB- data remained similar. Within the VdT+CCB+ group, 30% (10/33) were long-term CCB responders with a 100% 5-year survival; non-responders had a 61% survival at 5.4 years. Long-term responders were younger at diagnosis (40 yrs vs 54 yrs). CONCLUSION: Use of VdT testing and documentation is poor in this contemporary patient cohort. Nonetheless, survival in VdT+CCB+ patients from the PHSANZ registry is excellent, supporting guidelines promoting VdT testing. Strategies to promote the use of VdT are warranted.

Factors associated with mortality after proximal femoral fracture.

Proximal femoral fractures are a serious complication, especially for elderly patients. Therefore, we have aimed to answer the following research question: What is the postfracture mortality rate in the elderly population and what are associated risk factors? For this, proximal femoral fractures that occurred between 1 January 2009 and 31 December 2019 were identified from the Medicare Physician Service Records database. The Kaplan-Meier (KM) method with the Fine and Gray subdistribution adaptation was used to determine rates of mortality. A semiparametric Cox regression model was applied, incorporating 23 measures as covariates to identify risk factors. The estimated 1 year mortality rate was 26.8% after head/neck fracture, 28.2% after intertrochanteric fracture, and 24.2% after subtrochanteric fracture. Male sex, age over 70 years, chronic obstructive pulmonary disease (COPD), cerebrovascular disease, chronic kidney disease, a concomitant fracture, congestive heart failure, diabetes mellitus, hypertension, insulin use, ischemic heart disease, morbid obesity, osteoporosis, tobacco dependence, and median household income were determined as risk factors for increased mortality. An early assessment of individual risk factors accessible for therapeutic treatment is crucial in the management of proximal femur fractures to aid in attempts at reducing the high mortality apparent in the elderly US population.

Cryobiopsy for Identification of Usual Interstitial Pneumonia and Other Interstitial Lung Disease Features. Further Lessons from COLDICE, a Prospective Multicenter Clinical Trial.

Rationale: Transbronchial lung cryobiopsy (TBLC) is an emerging technique for interstitial lung disease diagnosis. Good histopathologic agreement between TBLC and surgical lung biopsy (SLB) was demonstrated in the COLDICE (Cryobiopsy versus Open Lung Biopsy in the Diagnosis of Interstitial Lung Disease Alliance) study; however, diagnostic confidence was frequently lower for TBLC than SLB. Objectives: To characterize specific features of TBLC predictive of usual interstitial pneumonia (UIP) in corresponding SLB and to identify clinical indices predictive of biopsy concordance. Methods: The COLDICE study was a prospective, multicenter study investigating diagnostic agreement between TBLC and SLB. The participants underwent both procedures with blinded pathologist analysis of specimens, applying international guideline criteria. The TBLC features predictive of UIP in the paired SLB and predictive features of overall concordance were analyzed. Measurements and Main Results: A total of 65 patients (66.1 ± 9.3 yr; FVC, 84.7 ± 14.2%; DlCO, 63.4 ± 13.8%) participated in the COLDICE study. UIP was identified in 33/65 (50.8%) SLB, and 81.5% were concordant with corresponding TBLC (κ, 0.61; 95% confidence interval [CI], 0.38-0.77). The UIP guideline criteria of "predominantly subpleural or paraseptal fibrosis" was infrequently reported in TBLC (8/33, 24.2%), whereas "patchy fibrosis," "fibroblast foci," and the "absence of alternative diagnostic features" were frequently observed in TBLC. The combination of these three features strongly predicted UIP in paired SLB (odds ratio [OR], 23.4; 95% CI, 6.36-86.1; P < 0.0001). Increased numbers of TBLC samples predicted histopathologic concordance with SLB (OR, 1.8; 95% CI, 1.08-3.01; P = 0.03). The predictors of discordance included older age, family history, and radiologic asymmetry. Conclusions: Subpleural and/or paraseptal fibrosis were not essential for diagnosing UIP in TBLC, provided that other guideline criteria features were present. The diagnostic accuracy of TBLC was strengthened when increased numbers of samples were taken. Clinical trial registered with www.anzctr.org.au (ACTRN12615000718549).

Receipt of Electroconvulsive Therapy and Subsequent Development of Amyotrophic Lateral Sclerosis: A Cohort Study.

We investigated the potential relationship between receipt of electroconvulsive therapy (ECT) and development of amyotrophic lateral sclerosis (ALS). We conducted a cohort study using a sample of more than one million beneficiaries enrolled in the U.S. Medicare health insurance program from 1997 to 2017. Using time-varying proportional hazard modeling, we compared ALS occurrence among patients diagnosed with psychiatric conditions who received ECT to ALS occurrence among patients diagnosed with psychiatric conditions but who did not receive ECT. We observed moderately increased, but imprecise, hazard ratios (HR) for ALS following ECT (HR = 1.39, 95% confidence interval [CI]: 0.69-2.80). A statistically significant increase in the HR of ALS was observed among those who received more than 10 ECT treatments (>10 treatments, HR = 2.24, 95% CI: 1.00-5.01), compared to those receiving no ECT, with an even stronger association observed among subjects older than 65 years (HR = 3.03, 95% CI: 1.13-8.10). No monotonic exposure-response relationship was detected in categorical analyses. Our results provide weak support for the hypothesis that receipt of ECT increases the risk of developing ALS. Additional studies in larger populations, or in populations where ECT is more common, will be needed to refute or confirm an association between receipt of ECT and subsequent development of ALS. Bioelectromagnetics. 43:81-89, 2022. © 2021 Bioelectromagnetics Society.

Hospital Costs for Unsuccessful Two-Stage Revisions for Periprosthetic Joint Infection.

BACKGROUND: Although 2-stage exchange arthroplasty is the preferred surgical treatment for periprosthetic joint infection (PJI) in the United States, little is known about the risk of complications between stages, mortality, and the economic burden of unsuccessful 2-stage procedures. METHODS: The 2015-2019 Medicare 100% inpatient sample was used to identify 2-stage PJI revisions in total hip and knee arthroplasty patients using procedural codes. We used the Fine and Gray sub-distribution adaptation of the conventional Kaplan-Meier method to estimate the probability of completing the second stage of the 2-stage PJI infection treatment, accounting for death as a competing risk. Hospital costs were estimated from the hospital charges using "cost-to-charge" ratios from Centers for Medicare and Medicaid Services. RESULTS: A total of 5094 total hip arthroplasty and 13,062 total knee arthroplasty patients had an index revision for PJI during the study period. In the first 12 months following the first-stage explantation, the likelihood of completing a second-stage PJI revision was 43.1% (95% confidence interval [CI] 41.7-44.5) for hips and 47.9% (95% CI 47.0-48.8) for knees. Following explantation, 1-year patient survival rates for hip and knee patients were 87.4% (95% CI 85.8-88.9) and 91.4% (95% CI 90.6-92.2), respectively. The median additional cost for hospitalizations between stages was $23,582 and $20,965 per patient for hips and knees, respectively. Hospital volume, Northeast or Midwest region, and younger age were associated with reduced PJI costs (P < .05). CONCLUSION: Although viewed as the most preferred, the 2-stage revision strategy for PJI had less than a 50% chance of successful completion within the first year, and was associated with high mortality rates and substantial costs for treatment failure.

Screening for pulmonary arterial hypertension in adults carrying a BMPR2 mutation.

BACKGROUND: Heritable pulmonary arterial hypertension (PAH) is most commonly due to heterozygous mutations of the BMPR2 gene. Based on expert consensus, guidelines recommend annual screening echocardiography in asymptomatic BMPR2 mutation carriers. The main objectives of this study were to evaluate the characteristics of asymptomatic BMPR2 mutation carriers, assess their risk of occurrence of PAH and detect PAH at an early stage in this high-risk population. METHODS: Asymptomatic BMPR2 mutation carriers underwent screening at baseline and annually for a minimum of 2 years (DELPHI-2 study; ClinicalTrials.gov: NCT01600898). Annual screening included clinical assessment, ECG, pulmonary function tests, 6-min walk distance, cardiopulmonary exercise testing, chest radiography, echocardiography and brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP level. Right heart catheterisation (RHC) was performed based on predefined criteria. An optional RHC at rest and exercise was proposed at baseline. RESULTS: 55 subjects (26 males; median age 37 years) were included. At baseline, no PAH was suspected based on echocardiography and NT-proBNP levels. All subjects accepted RHC at inclusion, which identified two mild PAH cases (3.6%) and 12 subjects with exercise pulmonary hypertension (21.8%). At long-term follow-up (118.8 patient-years of follow-up), three additional cases were diagnosed, yielding a PAH incidence of 2.3% per year (0.99% per year in males and 3.5% per year in females). All PAH cases remained at low-risk status on oral therapy at last follow-up. CONCLUSIONS: Asymptomatic BMPR2 mutation carriers have a significant risk of developing incident PAH. International multicentre studies are needed to confirm that refined multimodal screening programmes with regular follow-up allow early detection of PAH.

Chronic thromboembolic pulmonary hypertension in Australia and New Zealand: An analysis of the PHSANZ registry.

BACKGROUND AND OBJECTIVE: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition occurring in 2%-4% of patients after acute pulmonary embolism. Pulmonary endarterectomy (PEA) is a potential cure for technically operable disease. The epidemiology and long-term outcomes of CTEPH have not been previously described in Australia and New Zealand. METHODS: Data were extracted from the Pulmonary Hypertension Society of Australia and New Zealand (PHSANZ) registry for patients diagnosed with CTEPH between January 2004 and March 2020. Baseline characteristics, treatment strategies, outcome data and long-term survival are reported. RESULTS: A total of 386 patients were included with 146 (37.8%) undergoing PEA and 240 (62.2%) in the non-PEA group. PEA patients were younger (55 ± 16 vs. 62 ± 16 years, p < 0.001) with higher baseline 6-min walk distance (6MWD; 405 ± 122 vs. 323 ± 146 m, p = 0.021), whilst both groups had similar baseline pulmonary haemodynamics. Pulmonary hypertension-specific therapy was used in 54% of patients post-PEA and 88% in the non-PEA group. The 1-, 3- and 5-year survival rates were 93%, 87% and 84% for the PEA group compared to 86%, 73% and 62%, respectively, for the non-PEA group (p < 0.001). Multivariate survival analysis showed baseline 6MWD was an independent predictor of survival in both operated and medically managed patients. CONCLUSION: In this first multicentre report of CTEPH in Australia and New Zealand, long-term survival is comparable to that in other contemporary CTEPH registries. However, PEA was only performed in a minority of CTEPH patients (37.8%) and significantly less than overseas reports. Greater awareness of PEA and improved patient access to experienced CTEPH centres are important priorities.

Priorities and expectations of patients attending a multidisciplinary interstitial lung disease clinic.

BACKGROUND AND OBJECTIVE: The significant and progressive morbidity associated with ILD mean that patients often struggle with the impact of this disease on their QOL and independence. To date, no studies have investigated the importance of multidisciplinary care on patient experience in ILD. We aimed to determine the expectations and priorities of patients attending a tertiary referral centre multidisciplinary ILD clinic. In particular, we sought to learn how important the multidisciplinary element of the clinic was to patients and which aspects of the clinic were most valued. METHODS: An 18-item patient questionnaire was developed in conjunction with expert physicians and specialist nurses involved in the ILD clinic and sent to all patients on the centre's ILD registry at the time of the study (n = 240). Patients rated the importance of different aspects of their experience of attending the clinic. Data collected were analysed using descriptive statistics. Comparisons across disease severity were made using two-sided Z-tests for independent proportions. RESULTS: A total of 100 respondents comprised the study group. Almost all respondents valued the multidisciplinary aspect of the clinic. Obtaining an accurate diagnosis and improving their disease understanding was most important to respondents. The importance of the ILD specialist nurse for both education and support increased with worsening disease severity. CONCLUSION: Our results suggest that a multidisciplinary approach to the management of ILD with additional focus on patient education, as well as tailoring care to disease severity, is a plausible pathway to improving the patient experience with ILD.

Baseline Characteristics and Survival of an Australian Interstitial Pneumonia with Autoimmune Features Cohort.

BACKGROUND AND OBJECTIVE: The research term "interstitial pneumonia with autoimmune features" (IPAF) encompasses interstitial lung disease (ILD) patients with autoimmune features not meeting diagnostic criteria for a defined connective tissue disease (CTD). It remains unclear if IPAF is a distinct disease entity with implications for management and prognosis. We describe an Australian IPAF population and compare their baseline characteristics and outcomes with distinct cohorts of idiopathic interstitial pneumonia (IIP), CTD-ILD, and unclassifiable ILD. METHODS: Review of 291 consecutive patients attending a specialist ILD clinic was performed. Patients with a diagnosis of IIP, CTD-ILD, and unclassifiable ILD by ILD-multidisciplinary meeting (ILD-MDM) were included. Patients meeting the IPAF criteria were identified. Baseline clinical data, survival, and progression were compared between ILD groups. RESULTS: 226 patients were included, 36 meeting the IPAF criteria. IPAF patients demonstrated a high prevalence of autoantibodies to tRNA synthetase (35.3%), Ro52 (27.8%), and neutrophilic cytoplasmic antigens (ANCA; 20.0%). IPAF and CTD-ILD patients demonstrated similar clinical characteristics (mean age 66.6 and 63.7 years, respectively, female predominant, frequent CTD-manifestations). Lung function did not differ between ILD groups. Disease severity, pulmonary hypertension (PH), and ILD-MDM diagnosis were strong predictors of worse transplant-free survival (TFS). Meeting the IPAF criteria was not associated with TFS. CONCLUSIONS: We identified IPAF as a heterogeneous phenotype that overlaps considerably with CTD-ILD. Disease severity, PH, and ILD-MDM diagnosis were more powerful predictors of survival outcomes than meeting the IPAF criteria.

Revision Surgery for Instability After Total Hip Arthroplasty: Does Timing Matter?

BACKGROUND: Instability is a common reason for revision surgery after total hip arthroplasty (THA). Recent studies suggest that revisions performed in the early postoperative period are associated with higher complication rates. The purpose of this study is to assess the effect of timing of revision for instability on subsequent complication rates. METHODS: The Medicare Part A claims database was queried from 2010 to 2017 to identify revision THAs for instability. Patients were divided based on time between index and revision surgeries: <1, 1-2, 2-3, 3-6, 6-9, 9-12, and >12 months. Complication rates were compared between groups using multivariate analyses to adjust for demographics and comorbidities. RESULTS: Of 445,499 THAs identified, 9298 (2.1%) underwent revision for instability. Revision THA within 3 months had the highest rate of periprosthetic joint infection (PJI): 14.7% at <1 month, 12.7% at 1-2 months, and 10.6% at 2-3 months vs 6.9% at >12 months (P < .001). Adjusting for confounding factors, PJI risk remained elevated at earlier periods: <1 month (adjusted odds ratio [aOR]: 1.84, 95% confidence interval [CI]: 1.51-2.23, P < .001), 1-2 months (aOR: 1.45, 95% CI: 1.16-1.82, P = .001), 2-3 months (aOR: 1.35, 95% CI: 1.02-1.78, P = .036). However, revisions performed within 9 months of index surgery had lower rates of subsequent instability than revisions performed >12 months (aOR: 0.67-0.85, P < .050), which may be due to lower rates of acetabular revision and higher rates of head-liner exchange in this later group. CONCLUSION: When dislocation occurs in the early postoperative period, delaying revision surgery beyond 3 months from the index procedure may be warranted to reduce risk of PJI.

Inspiratory Muscle Training Improves Inspiratory Muscle Strength and Functional Exercise Capacity in Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Randomised Controlled Study.

BACKGROUND: Exercise intolerance is present even in the early stages of pulmonary arterial hypertension (PAH) and is associated with poorer prognosis. Respiratory muscle dysfunction is common and may contribute to exercise limitation. We sought to investigate the effects of inspiratory muscle training (IMT) to improve exercise capacity in PAH. METHODS: Adults with PAH were prospectively recruited and randomly assigned to either IMT or a control group. At baseline and after 8 weeks, assessment of respiratory muscle function, pulmonary function, neurohormonal activation, 6-minute walk distance and cardiopulmonary exercise testing variables were conducted. Inspiratory muscle strength was assessed by maximal static inspiratory pressure (PImax). The IMT group performed two cycles of 30 breaths at 30-40% of their PImax 5 days a week for 8 weeks. RESULTS: Twelve (12) PAH patients (60±14 years, 10 females) were recruited and randomised (six in the IMT group and six in the control group). After 8 weeks, the IMT group improved PImax by 31 cmH2O compared with 10 cmH2O in controls, p=0.02. Following IMT, 6-minute walk distance improved by 24.5 m in the IMT group and declined by 12 m in the controls (mean difference 36.5 m, 95% CI 3.5-69.5, p=0.03). There was no difference in peak oxygen uptake between-groups (mean difference 0.4 mL/kg/min, 95% CI -2.6 to 3.4, p=0.77). There was no difference in the mean change between-groups in neurohormonal activation or pulmonary function. CONCLUSION: In this pilot randomised controlled study, IMT improved PImax and 6-minute walk distance in PAH patients.

Pulmonary arterial hypertension with below threshold pulmonary vascular resistance.

Pulmonary vascular resistance (PVR) >3 Wood units is a criterion of the haemodynamic definition of pulmonary arterial hypertension (PAH). However, this cut-off is conservative and arbitrarily defined. Data is lacking on the natural history, response to therapy and survival of patients diagnosed with precapillary pulmonary hypertension (PH) with mild or borderline elevation of PVR.In Australia, PAH therapy could be prescribed solely on mean pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) criteria. Using the Australian and New Zealand Pulmonary Hypertension Registry, we aimed to study a population diagnosed with PAH between January 2004 and December 2017 with the pre-defined haemodynamic characteristics of mean PAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wood units.Eighty-two patients met the pre-defined haemodynamic inclusion criteria (mean age 63±11 years; 67 females). Underlying aetiologies included idiopathic disease (n=39), connective tissue disease (CTD; n=42) and HIV infection (n=1). At diagnosis, mean PAP was 27 mmHg (interquartile range (IQR) 25-30 mmHg), PAWP 13 mmHg (IQR 11-14 mmHg) and PVR 2.2 Wood units (IQR 1.9-2.7 Wood units). Baseline 6-min walk distance (6MWD) was 352 m (IQR 280-416 m) and 77% of subjects were in New York Heart Association (NYHA) functional class 3 or 4. All patients were commenced on initial monotherapy with an endothelin receptor antagonist (ERA; n=66) or phosphodiesterase type-5 inhibitor (PDE5i; n=16). At first re-evaluation, 6MWD increased by 46 m (IQR 7-96 m) and 35% of subjects demonstrated improvement in NYHA functional class. After a median follow-up of 65 months (IQR 32-101 months), 18 out of 82 subjects (22.0%) had died, with estimated 1-year and 5-year survival rates of 98% and 84%, respectively. Death attributed to PAH occurred in six out of these 18 patients (33.3%, 7% of total cohort).Patients with precapillary PH and "borderline" PVR falling outside the current definition have adverse outcomes. Such patients appear to respond to PAH therapy; however, this requires further study in randomised trials.

Understanding the Similarities and Differences between Hepatic and Pulmonary Veno-Occlusive Disease.

Hepatic veno-occlusive disease (HVOD), alias sinusoidal obstruction syndrome, may develop as a complication of chemotherapy in the setting of hematopoietic stem cell transplantation. HVOD is less frequently described after exposure to chemotherapy in the nontransplant setting and can also be a complication after ingestion of toxins, such as pyrrolizidine alkaloids. Veno-occlusive disease may also affect the lungs, and it is therefore termed pulmonary veno-occlusive disease (PVOD). Similarly, PVOD can develop after exposure to chemotherapeutic agents in the treatment of solid and hematological malignancies. In addition, PVOD has also been linked to autoimmune disorders and occupational solvent exposure. Finally, the heritable form of PVOD is due to biallelic mutations of the EIF2AK4 gene. Both HVOD and PVOD share common histopathological features and pathophysiologic mechanisms. Both clinical disorders are rare complications that can appear after exposure to the common inciting trigger of chemotherapeutic agents. The present review aims to summarize the current knowledge of HVOD and PVOD and to describe both similarities as well as differences regarding both conditions.

Smoking, air pollution, and lung cancer risk in the Nurses' Health Study cohort: time-dependent confounding and effect modification.

The proportional hazards (PH) model is commonly used in epidemiology despite the stringent assumption of proportionality of hazards over time. We previously showed, using detailed simulation data, that the impact of a modest risk factor cannot be estimated reliably using the PH model in the presence of confounding by a strong, time-dependent risk factor. Here, we examine the same and related issues using a real dataset. Among 97,303 women in the prospective Nurses' Health Study cohort from 1994 through 2010, we used PH regression to investigate how effect estimates for cigarette smoking are affected by increasingly detailed specification of time-dependent exposure characteristics. We also examined how effect estimates for fine particulate matter (PM2.5), a modest risk factor, are affected by finer control for time-dependent confounding by smoking. The objective of this analysis is not to present a credible estimate of the impact of PM2.5 on lung cancer risk, but to show that estimates based on the PH model are inherently unreliable. The best-fitting model for cigarette smoking and lung cancer included pack-years, duration, time since cessation, and an age-by-pack-years interaction, indicating that the hazard ratio (HR) for pack-years was significantly modified by age. In the fully adjusted best-fitting model for smoking including pack-years, the HR per 10-µg/m3 increase in PM2.5 was 1.06 (95% confidence interval (CI) = 0.90, 1.25); the HR for PM2.5 in the full cohort ranged between 1.02 and 1.10 in models with other smoking adjustments, indicating a residual confounding effect of smoking. The HR for PM2.5 was statistically significant only among former smokers when adjusting for smoking pack-years (HR = 1.35, 95% CI = 1.00, 1.82 in the best-fitting smoking model), but not in models adjusting for smoking duration and average packs (pack-years divided by duration). The association between cumulative smoking and lung cancer is modified by age, and improved model fit is obtained by including multiple time-varying components of smoking history. The association with PM2.5 is residually confounded by smoking and modified by smoking status. These findings underscore limitations of the PH model and emphasize the advantages of directly estimating hazard functions to characterize time-varying exposure and risk. The hazard function, not the relative hazard, is the fundamental measure of risk in a population. As a consequence, the use of time-dependent PH models does not address crucial issues introduced by temporal factors in epidemiological data.

Diagnostic delay in pulmonary arterial hypertension: Insights from the Australian and New Zealand pulmonary hypertension registry.

BACKGROUND AND OBJECTIVE: Early diagnosis of PAH is clinically challenging. Patterns of diagnostic delay in Australian and New Zealand PAH populations have not been explored in large-scale studies. We aimed to evaluate the magnitude, risk factors and survival impact of diagnostic delay in Australian and New Zealand PAH patients. METHODS: A cohort study of PAH patients from the PHSANZ Registry diagnosed from 2004 to 2017 was performed. Diagnostic interval was the time from symptom onset to diagnostic right heart catheterization as recorded in the registry. Factors associated with diagnostic delay were analysed in a multivariate logistic regression model. Survival rates were compared across patients based on the time to diagnosis using Kaplan-Meier method and Cox regression. RESULTS: A total of 2044 patients were included in analysis. At diagnosis, median age was 58 years (IQR: 43-69), female-to-male ratio was 2.8:1 and majority of patients were in NYHA FC III-IV (82%). Median diagnostic interval was 1.2 years (IQR: 0.6-2.7). Age, CHD-PAH, obstructive sleep apnoea and peripheral vascular disease were independently associated with diagnostic interval of ≥1 year. No improvement in diagnostic interval was seen during the study period. Longer diagnostic interval was associated with decreased 5-year survival. CONCLUSION: PAH patients experience significant diagnostic interval, which has not improved despite increased community awareness. Age, cardiovascular and respiratory comorbidities are significantly associated with longer time to diagnosis. Mortality rates appear higher in patients who experience longer diagnostic interval.

Projections of Primary TKA and THA in Germany From 2016 Through 2040.

BACKGROUND: Future projections for both TKA and THA in the United States and other countries forecast a further increase of already high numbers of joint replacements. The consensus is that in industrialized countries, this increase is driven by demographic changes with more elderly people being less willing to accept activity limitations. Unlike the United States, Germany and many other countries face a population decline driven by low fertility rates, longer life expectancy, and immigration rates that cannot compensate for population aging. Many developing countries are likely to follow that example in the short or medium term amid global aging. Due to growing healthcare expenditures in a declining and aging population with a smaller available work force, reliable predictions of procedure volume by age groups are requisite for health and fiscal policy makers to maintain high standards in arthroplasty for the future population.Questions/purposes (1) By how much is the usage of primary TKA and THA in Germany expected to increase from 2016 through 2040? (2) How is arthroplasty usage in Germany expected to vary as a function of patient age during this time span? METHODS: The annual number of primary TKAs and THAs were calculated based on population projections and estimates of future healthcare expenditures as a percent of the gross domestic product (GDP) in Germany. For this purpose, a Poisson regression analysis using age, gender, state, healthcare expenditure, and calendar year as covariates was performed. The dependent variable was the historical number of primary TKAs and THAs performed as compiled by the German federal office of statistics for the years 2005 through 2016. RESULTS: Through 2040, the incidence rate for both TKA and THA will continue to increase annually. For TKA, the incidence rate is expected to increase from 245 TKAs per 100,000 inhabitants to 379 (297-484) (55%, 95% CI 21 to 98). The incidence rate of THAs is anticipated to increase from 338 to 437 (357-535) per 100,000 inhabitants (29% [95% CI 6 to 58]) between 2016 and 2040. The total number of TKAs is expected to increase by 45% (95% CI 14 to 8), from 168,772 procedures in 2016 to 244,714 (95% CI 191,920 to 312,551) in 2040. During the same period, the number of primary THAs is expected to increase by 23% (95% CI 0 to 50), from 229,726 to 282,034 (95% CI 230,473 to 345,228). Through 2040, the greatest increase in TKAs is predicted to occur in patients aged 40 to 69 years (40- to 49-year-old patients: 269% (95% CI 179 to 390); 50- to 59-year-old patients: 94% (95% CI 48 to 141); 60- to 69-year-old patients: 43% (95% CI 13 to 82). The largest increase in THAs is expected in the elderly (80- to 89-year-old patients (71% [95% CI 40 to 110]). CONCLUSIONS: Although the total number of TKAs and THAs is projected to increase in Germany between now and 2040, the increase will be smaller than that previously forecast for the United States, due in large part to the German population decreasing over that time, while the American population increases. Much of the projected increase in Germany will be from the use of TKA in younger patients and from the use of THA in elderly patients. Knowledge of these trends may help planning by surgeons, hospitals, stakeholders, and policy makers in countries similar to Germany, where high incidence rates of arthroplasty, aging populations, and overall decreasing populations are present. LEVEL OF EVIDENCE: Level III, economic and decision analysis.

Corrosion Concerns? Trends in Metal-on-Polyethylene Total Hip Arthroplasty Revision Rates and Comparisons Against Ceramic-on-Polyethylene up to 10 Years of Follow-Up.

BACKGROUND: We compared the revision risk between metal-on-polyethylene (MOP) and ceramic-on-polyethylene (COP) total hip arthroplasty patients and evaluated temporal changes in short-term revision risks for MOP patients. METHODS: Primary MOP (n = 9480) and COP (n = 3620) total hip arthroplasties were evaluated from the Medicare data set (October 2005 to December 2015) for revision risk, with up to 10 years of follow-up using multivariate analysis. Temporal change in the short-term revision risk for MOP was evaluated (log-rank and Wilcoxon tests). RESULTS: Revision incidence was 3.8% for COP and 4.3% for MOP. MOP short-term revision risk did not change over time (P ≥ .844 at 1 year and .627 at 2 years). Dislocation was the most common reason for revision (MOP: 23.5%; COP: 24.8%). Overall adjusted revision risks were not different between MOP and COP up to 10 years of follow-up (P ≥ .181). CONCLUSIONS: Concerns with corrosion for metal heads do not appear to result in significantly elevated revision risk for MOP at up to 10 years. Corrosion does not appear as a primary reason for revision compared to other mechanisms.