Systematic review of multivariable prognostic models for outcomes at least 30 days after hip fracture finds 18 mortality models but no non-mortality models warranting validation.

OBJECTIVE: Prognostic models have the potential to aid clinical decision-making after hip fracture. This systematic review aimed to identify, critically appraise and summarise multivariable prediction models for mortality or other long-term recovery outcomes occurring at least 30 days after hip fracture. STUDY DESIGN: MEDLINE, Embase, Scopus, Web of Science and CINAHL databases were searched up to May 2023. Studies were included that aimed to develop multivariable models to make predictions for individuals at least 30 days after hip fracture. Risk of bias (ROB) was dual-assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Study and model details were extracted and summarised. RESULTS: From 5,571 records, 80 eligible studies were identified. They predicted mortality in n=55 studies/ 81 models, and non-mortality outcomes (mobility, function, residence, medical and surgical complications) in n=30 studies/ 45 models. Most (n=46; 58%) studies were published since 2020. A quarter of studies (n=19; 24%) reported using 'machine-learning methods', while the remainder used logistic regression (n=54; 68%) and other statistical methods (n=11; 14%) to build models. Overall, 15 studies (19%) presented 18 low ROB models, all predicting mortality. Common concerns were sample size, missing data handling, inadequate internal validation and calibration assessment. Many studies with non-mortality outcomes, (n=11; 37%) had clear data complexities that were not correctly modelled. CONCLUSION: This review has comprehensively summarised and appraised multivariable prediction models for long-term outcomes after hip fracture. Only 15 studies out of 55 predicting mortality were rated as low ROB, warranting further development of their models. All studies predicting non-mortality outcomes were high or unclear ROB. Careful consideration is required for both the methods used and justification for developing further non-mortality prediction models for this clinical population.

Impact of Stroke History on the Risk of Recurrent Hip Fracture or Major Osteoporotic Fractures among Patients with Incident Hip Fracture: A Nationwide Cohort Study.

Considerable uncertainty prevails regarding risk factors for recurrent fracture among older patients with hip fracture. We aimed to investigate the relationship between prefracture stroke history, baseline mobility, and the risk of recurrent hip fracture. This cohort study was based on the Danish Multidisciplinary Hip Fracture Registry, 2011-2018 (n = 48,230). We estimated cumulative incidence (competing risk of death) of recurrent hip fracture and major osteoporotic fractures within 1 and 2 years comparing patients with/without prefracture stroke history. Analyses were performed overall and stratified on baseline mobility status (good mobility: Cumulated Ambulation Score ≥ 5 versus poor mobility: Cumulated Ambulation Score < 5). Using Cox regression, adjusted cause-specific hazard ratios (HRs) with 95% confidence intervals (CIs) were obtained. The 1-year cumulative incidence was 4.6% (95% CI: 3.9-5.4) among patients with stroke history and 4.3% (95% CI: 4.1-4.5) among patients without stroke history. For patients with good mobility, the cumulative incidence of recurrent hip fracture was 5.8% (95% CI: 4.3-7.5) versus 3.7% (95% CI: 3.4-4.0) for patients with versus without stroke history. Corresponding numbers for patients with poor mobility were 4.4% (95% CI: 3.6-5.5) and 5.0% (95% CI: 4.7-5.3). Stroke history was associated with an adjusted HR of 1.55 (95% CI: 1.15-2.10) for recurrent fracture among patients with good mobility. In contrast, no association was observed among patients with poor mobility (adjusted HR 0.88 [95% CI: 0.70-1.10]). The associations were attenuated after 2 years of follow-up and for major osteoporotic fractures. In conclusion, stroke history was associated with slightly higher risk of recurrent fracture among patients with first-time hip fracture in the overall analysis, although the CI included a null result. The association was modified by baseline mobility: Patients with stroke history and good mobility had a markedly higher risk, whereas patients with stroke and poor mobility did not. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The Interaction Effect Between Previous Stroke and Hip Fracture on Postoperative Mortality: A Nationwide Cohort Study.

Purpose: It remains uncertain how a history of stroke impacts the prognosis for patients with hip fracture. This study aimed to evaluate mortality following hip fracture surgery by comparing patients with and without a history of stroke. Patients and Methods: All patients aged 65 years or above in Denmark receiving hip fracture surgery between 2010 and 2018. For every patient, 10 individuals from the general population without hip fracture were sampled. Comparators had a similar stroke history, age, and sex on the date of hip fracture surgery (index date). We established four cohorts: hip fracture patients with/without stroke and non-hip fracture patients with/without stroke. Outcomes were all-cause mortality at 0-30 days, 31-365 days and 1 to 5 years. Direct standardized mortality rates (MR) with 95% confidence intervals (CI) were computed. We calculated the interaction contrast to estimate excess absolute mortality among patients with both hip fracture and stroke. Through a Cox proportional hazards model, we estimated the hazard ratio (HR) and the attributable proportion as a measure of excess relative mortality attributable to interaction. Results: Of the hip fracture patients, 8433 had a stroke history and 44,997 did not. Of the non-hip fracture patients, 84,330 had a stroke history and 449,962 did not. Corresponding 30-day MRs/100 person years were 148.4 (95% CI: 138.8-158.7), 124.3 (95% CI: 120.7-128.1), 14.3 (95% CI: 13.4-15.2) and 8.4 (95% CI: 8.1-8.7). The interaction contrast was 18.2 (95% CI: 7.5-28.8), and the attributable proportion was 9.0% (95% CI: 2.9-15.1). No interaction was present beyond 30 days. Conclusion: We observed excess short-term mortality in patients with stroke and hip fracture, but the effect disappeared at later follow-up periods. Clinicians are encouraged to pay rigorous attention to early complications among hip fracture patients with stroke, as this may serve as a way to reduce mortality.

Comorbidity and Quality of In-Hospital Care for Hip Fracture Patients.

OBJECTIVES: We examined whether the comorbidity burden of patients with hip fracture was associated with quality of in-hospital care reflected by fulfillment of process performance measures. DESIGN: Population-based cohort study using prospectively collected data from the Danish Multidisciplinary Hip Fracture Registry (DMHFR). SETTING AND PARTICIPANTS: Patients aged 65 years or older with an incident hip fracture from 2014 to 2018 registered in the DMHFR (n = 31,443). METHODS: Comorbidity was measured using the Charlson Comorbidity Index based on hospital diagnoses. Quality of in-hospital care was defined as fulfillment of eligible process performance measures, including preoperative optimization, early surgery, early mobilization, pain assessment, basic mobility, nutritional risk, need for anti-osteoporotic medication, fall prevention, and a post-discharge rehabilitation program, reflecting guideline-recommended in-hospital care. The outcomes were (1) an all-or-none composite measure defined as fulfillment of all relevant process performance measures, and (2) fulfillment of the individual process performance measures. Using binary regression, we calculated relative risk (RR) for the association between comorbidity level and outcomes. RESULTS: The overall proportion of patients with hip fracture who fulfilled the all-or-none measure was 31%. Among patients with no comorbidity, 34% fulfilled the all-or-none measure versus 29% among patients with high comorbidity (Charlson ≥ 3). This corresponds to a 15% lower chance (RR = 0.85, 95% confidence interval 0.81-0.89). Increasing comorbidity was also associated with lower fulfillment of the individual process performance measures. The largest difference was seen for preoperative optimization, early surgery, and early mobilization, where patients with high comorbidity had 6% to 11% lower chance of fulfillment of these process performance measures compared with patients without comorbidity. CONCLUSION AND IMPLICATIONS: Increasing level of comorbidity was associated with lower quality of in-hospital care among patients with hip fracture. Our results highlight the need for tailored clinical initiatives to ensure that comorbid patients also benefit from the positive progress in hip fracture care in recent years.

Postoperative complications, mortality, and quality of in-hospital care among hip fracture patients with Parkinson's disease.

AIM: The aim of this study was to investigate the association between Parkinson's disease (PD) and postoperative complications, mortality, and quality of in-hospital care in patients with hip fracture. METHODS: We included patients aged 65+ years with an incident hip fracture from 2004-2017, registered in the Danish Multidisciplinary Hip Fracture Registry. Patients with PD were identified using diagnosis codes prior to hip fracture. Using log-binomial regression, we calculated both 30-day crude and adjusted risk ratios (aRR) with 95% confidence intervals (CIs) for the following outcomes: any hospital-treated infections, pneumonia, urinary tract infection, sepsis, community-treated infections, cardiovascular events, mortality, and fulfilment of quality indicators of in-hospital care. Analyses were adjusted for age, sex and Charlson comorbidity index score. RESULTS: We identified 77,550 hip fracture patients of which 1,915 had PD. Compared to non-PD, patients with PD had higher risk of any hospital-treated - (aRR = 1.27 (CI: 1.10-1.45) and community-treated infection (aRR = 1.22 (CI: 1.13-1.32)), pneumonia (aRR = 1.38 (1.11-1.69)), urinary tract infection (aRR of 1.58 (CI: 1.28-1.92)) and sepsis (aRR = 1.18 (CI: 0.67-1.89)), but a reduced risk of cardiovascular events (aRR = 0.59 (CI: 0.41-0.82)). The aRR for 30-day mortality was 1.11 (CI: 0.97-1.27) for PD vs non-PD patients, and the aHR for 1-year mortality was 1.19 (CI: 1.09-1.30). The aRRs for fulfillment of all relevant quality indicators was about 1 for PD vs non-PD patients. CONCLUSION: Hip fracture patients with PD have a higher risk of infections and mortality within 30 days after surgery after adjustment for sex, age, and comorbidity. They do, however, receive comparable quality of in-hospital care after hip fracture compared to non-PD patients.

Development and validation of a model for predicting mortality in patients with hip fracture.

OBJECTIVE: to develop a user-friendly prediction tool of 1-year mortality for patients with hip fracture, in order to guide clinicians and patients on appropriate targeted preventive measures. DESIGN: population-based cohort study from 2011 to 2017 using nationwide data from the Danish Hip Fracture Registry. SUBJECTS: a total of 28,791 patients age 65 and above undergoing surgery for a first-time hip fracture. METHODS: patient-related prognostic factors at the time of admission were assessed as potential predictors: Nursing home residency, comorbidity (Charlson Comorbidity Index [CCI] Score), frailty (Hospital Frailty Risk Score), basic mobility (Cumulated Ambulation Score), atrial fibrillation, fracture type, body mass index (BMI), age and sex. Association with 1-year mortality examined by determining the cumulative incidence, applying univariable logistic regression and assessing discrimination (area under the receiver operating characteristics curve [AUROC]). The final model (logistic regression) was utilised on a development cohort (70% of patients). Discrimination and calibration were assessed on the validation cohort (remaining 30% of patients). RESULTS: all predictors showed an association with 1-year mortality, but discrimination was moderate. The final model included nursing home residency, CCI Score, Cumulated Ambulation Score, BMI and age. It had an acceptable discrimination (AUROC 0.74) and calibration, and predicted 1-year mortality risk spanning from 5 to 91% depending on the combination of predictors in the individual patient. CONCLUSIONS: using information obtainable at the time of admission, 1-year mortality among patients with hip fracture can be predicted. We present a user-friendly chart for daily clinical practice and provide new insight regarding the interplay between prognostic factors.

Association of CHA2 DS2 -VASc Score with Stroke, Thromboembolism, and Death in Hip Fracture Patients.

OBJECTIVES: Patients undergoing hip fracture surgery have a 10 times increased risk of stroke compared with the general population. We aimed to evaluate the association between the CHA2 DS2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke/TIA [transient ischemic attack]/systemic embolism (2 points), vascular disease, age 65-74 years, and female sex) score and the risk of stroke, thromboembolism, and all-cause mortality in patients with hip fracture with or without atrial fibrillation (AF). DESIGN: Nationwide prospective cohort study. SETTING: Danish hospitals. PARTICIPANTS: Subjects were all incident hip fracture patients in Denmark age 65 years and older with surgical repair procedures between 2004 and 2016 (n = 78,096). Participants were identified using the Danish Multidisciplinary Hip Fracture Registry. MEASUREMENTS: We calculated incidence rates, cumulative incidences, and hazard ratios (HRs) with 95% confidence intervals (CIs) by CHA2 DS2 -VASc score, stratified on AF history. RESULTS: The cumulative incidence of ischemic stroke 1 year after hip fracture increased with ascending CHA2 DS2 -VASc score, and it was 1.9% for patients with a score of 1 and 8.6% for patients with a score above 5 in the AF group. Corresponding incidences in the non-AF group were 1.6% and 7.6%. Compared with a CHA2 DS2 -VASc score of 1, adjusted HRs were 5.53 (95% CI = 1.37-22.24) among AF patients and 4.91 (95% CI = 3.40-7.10) among non-AF patients with a score above 5. A dose-response-like association was observed for all cardiovascular outcomes. All-cause mortality risks and HRs were substantially higher for all CHA2 DS2 -VASc scores above 1 in both the AF group and the non-AF group. CONCLUSION: Among patients with hip fracture, a higher CHA2 DS2 -VASc score was associated with increased risk of stroke, thromboembolism, and death. This finding applied both to patients with and without AF. Patients with high CHA2 DS2 -VASc scores had almost similar absolute risks for cardiovascular outcomes, irrespective of AF. J Am Geriatr Soc 68:1698-1705, 2020.

The Positive Predictive Value of Hip Fracture Diagnoses and Surgical Procedure Codes in the Danish Multidisciplinary Hip Fracture Registry and the Danish National Patient Registry.

AIM: The health-care databases may be a valuable source for epidemiological research in hip fracture surgery, if the diagnoses are valid. We examined the validity of hip fracture diagnoses and surgical procedure codes in the Danish Multidisciplinary Hip Fracture Registry (DMHFR) and the Danish National Patient Registry (DNPR) by calculating the positive predictive value (PPV). METHODS: We identified a random sample of 750 hip fracture patients registered in the DMHFR between 2014 and 2017. Diagnoses have been coded by the 10th revision of the International Classification of Diseases, while procedures have been coded by the Nordic Medico-Statistical Committee classification in the DNPR and directly transferred to the DMHFR. Using the surgical procedure description from the medical record as gold standard, we estimated the PPV of the hip fracture diagnoses and surgical procedure codes in the DMHFR and the DNPR with 95% confidence interval (CIs). RESULTS: The PPV was 90% (95% CI: 86%-93%) for fracture of the neck of femur, 92% (95% CI: 87%-95%) for trochanteric fracture, and 83% (95% CI: 78%-88%) for subtrochanteric fracture. Joining trochanteric and subtrochanteric fracture resulted in a PPV of 97% (95% CI: 95%-98%). Procedure codes had a PPV of 100% for primary prosthetic replacement and internal fixation with intramedullary nail, 96% (95% CI: 85%-99%) for internal fixation using screws alone, 91% (95% CI: 84%-96%) for internal fixation using plates and screws, and 89% (95% CI: 83%-94%) for internal fixation with other or combined methods. Stratifying by age group, gender, hospital type and calendar year of surgery showed similar results as the overall PPV estimates. CONCLUSION: Our findings indicate a high quality of the hip fracture diagnoses and corresponding procedure codes in the DMHFR and the DNPR, with a majority of PPVs above 90%. Thus, the DMHFR and the DNPR are a valuable data source on hip fracture for epidemiological research.

Administration of a Toll-like receptor 9 agonist decreases the proviral reservoir in virologically suppressed HIV-infected patients.

Toll-like receptor (TLR) agonists can reactivate HIV from latently infected cells in vitro. We aimed to investigate the TLR-9 agonist, CPG 7909's in vivo effect on the proviral HIV reservoir and HIV-specific immunity. This was a post-hoc analysis of a double-blind randomized controlled vaccine trial. HIV-infected adults were randomized 1:1 to receive pneumococcal vaccines with or without 1 mg CPG 7909 as adjuvant at 0, 3 and 9 months. In patients on suppressive antiretroviral therapy we quantified proviral DNA at 0, 3, 4, 9, and 10 months (31 subjects in the CPG group and 37 in the placebo-adjuvant group). Furthermore, we measured HIV-specific antibodies, characterized T cell phenotypes and HIV-specific T cell immunity. We observed a mean reduction in proviral DNA in the CPG group of 12.6% (95% CI: -23.6-0.0) following each immunization whereas proviral DNA in the placebo-adjuvant group remained largely unchanged (6.7% increase; 95% CI: -4.2-19.0 after each immunization, p = 0.02). Among participants with additional cryo-preserved PBMCs, HIV-specific CD8+ T cell immunity as indicated by increased expression of degranulation marker CD107a and macrophage inflammatory protein 1ß (MIP1ß) tended to be up-regulated following immunization with CPG 7909 compared with placebo as adjuvant. Further, increasing proportion of HIV-specific CD107a and MIP1ß-expressing CD8+ T cells were strongly correlated with decreasing proviral load. No changes were observed in T cell phenotype distribution, HIV-specific CD4+ T cell immunity, or HIV-specific antibodies. TLR9-adjuvanted pneumococcal vaccination decreased proviral load. Reductions in proviral load correlated with increasing levels of HIV specific CD8+ T cells. Further investigation into the potential effect of TLR9 agonists on HIV latency is warranted.