Modifiable lifestyle factors associated with fragility hip fracture: a systematic review and meta-analysis.

INTRODUCTION: Among the various hip fracture predictors explored to date, modifiable risk factors warrant special consideration, since they present promising targets for preventative measures. This systematic review and meta-analysis aims to assess various modifiable risk factors. MATERIAL AND METHODS: We searched four online databases in September 2017. We included studies that reported on modifiable lifestyle risk factors for sustaining fragility hip fractures. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). The inclusion criteria consisted of (1) adult patients with osteoporotic hip fracture, (2) original study, (3) availability of full text articles in English, and (4) report of a modifiable lifestyle risk factor. RESULTS: Thirty-five studies, containing 1,508,366 subjects in total, were included in this study. The modifiable risk factors that were significantly associated with an increased risk of hip fracture were the following: weight < 58 kg (128 lbs) (pooled OR 4.01, 95% CI 1.62-9.90), underweight body mass index (BMI) (< 18.5) (pooled OR 2.83, 95% CI 1.82-4.39), consumption of ≥ 3 cups of coffee daily (pooled OR 2.27, 95% CI 1.04-4.97), inactivity (pooled OR 2.14, 95% CI 1.21-3.77), weight loss (pooled OR 1.88, 95% CI 1.32-2.68), consumption of ≥ 27 g (approx. > 2 standard drinks) alcohol per day (pooled OR 1.54, 95% CI 1.12-2.13), and being a current smoker (pooled OR 1.50, 95% CI 1.22-1.85). Conversely, two factors were significantly associated with a decreased risk of hip fracture: obese BMI (> 30) (pooled OR 0.58, 95% CI 0.34-0.99) and habitual tea drinking (pooled OR 0.72, 95% CI 0.66-0.80). CONCLUSION: Modifiable factors may be utilized clinically to provide more effective lifestyle interventions for at risk populations. We found that low weight and underweight BMI carried the highest risk, followed by high coffee consumption, inactivity, weight loss, and high daily alcohol consumption.

Medications as a Risk Factor for Fragility Hip Fractures: A Systematic Review and Meta-analysis.

Fragility hip fractures and their associated morbidity and mortality pose a global healthcare problem. Several pharmaceutical products have been postulated to alter bone architecture and contribute to fragility hip fractures. We searched four electronic databases from inception to September 2017. Inclusion criteria were the following: (1) adult patients with fragility hip fractures, (2) full text in English, (3) minimum one-year follow-up, and (4) reporting of at least one risk factor. To minimize heterogeneity among the studies, we performed subgroup analyses. Whenever heterogeneity remained significant, we employed random effect meta-analysis for data pooling. Thirty-eight studies were included, containing 1,244,155 subjects and 188,966 cases of fragility hip fractures. Following medications were significantly associated with fragility hip fractures: Antidepressants (OR 2.07, 95% CI 1.98-2.17), antiparkinsonian drugs (OR 2.21, 95% CI 1.15-4.24), antipsychotic drugs (OR 2.0, 95% CI 1.50-2.66), anxiolytic drugs (OR 1.44, 95% CI 1.19-1.75), benzodiazepines (OR 1.84, 95% CI 1.26-2.69), sedatives (OR 1.33, 95% CI 1.14-1.54), systemic corticosteroids (OR 1.65, 95% CI 1.37-1.99), H2 antagonists (OR 1.21, 95% CI 1.18-1.24), proton pump inhibitors (OR 1.41, 95% CI 1.16-1.71), and thyroid hormone (OR 1.29, 95% CI 1.13-1.47). Hormone replacement therapy with estrogen (HRT) was associated with decreased risk of hip fracture (OR 0.80, 95% CI 0.65-0.98). There are several medications associated with sustaining a fragility hip fracture. Medical interventions should be considered for patients on these medications, including information about osteoporosis and fracture prevention.

Risk factors for developing acute compartment syndrome in the pediatric population: a systematic review and meta-analysis.

PURPOSE: Acute compartment syndrome (ACS) is often difficult to diagnose in pediatric patients due to their erratic symptomatology. Therefore, it is of paramount importance to identify at-risk patients to facilitate a prompt diagnosis. This study aims to identify risk factors for the development of ACS in the pediatric population. METHODS: We included studies comprised of pediatric patients with traumatic ACS. We excluded studies evaluating compartment syndrome secondary to exertion, vascular insult, abdominal processes, burns, and snake bites. Heterogeneity was addressed by subgroup analysis, and whenever it remained significant, we utilized a random-effects meta-analysis for data pooling. The protocol has been registered at PROSPERO (ID = CRD42019126603). RESULTS: We included nine studies with 380,411 patients, of which 1144 patients were diagnosed with traumatic ACS. The average age was 10 years old, and 67% of patients were male. Factors that were significantly associated with ACS were: open radius/ulna fractures (OR 3.56 CI 1.52-8.33, p = 0.003), high-energy trauma (OR 3.51 CI 1.71-7.21, p = 0.001), humerus fractures occurring concurrently with forearm fractures (OR 3.49 CI 1.87-6.52, p < 0.001), open tibia fractures (OR 2.29 CI 1.47-3.55, p < 0.001), and male gender (OR 2.06 CI 1.70-2.51, p < 0.001). CONCLUSION: In the present study, open fractures, high-energy trauma, concurrent humerus and forearm fractures, and male gender significantly increased the risk of developing ACS in the pediatric population. Clinicians should raise their suspicion for ACS when one or multiple of these factors are present in the right clinical context. TYPE OF STUDY: Systematic review and meta-analysis. LEVEL OF EVIDENCE: III.

Characterization of applicants for residency training in pathology: Does diversity exist?

CONTEXT: A diverse workforce has been shown to improve productivity and innovation. The level of diversity among pathology residency applicants has not previously been reported. OBJECTIVE: This study aims to characterize the applicants at an academic pathology department to gain a better understanding of diversity among them. DESIGN: Between 2015 and 2017, data from a tertiary care center were analyzed for gender, US and international medical school, USMLE scores, and self-identified racial or ethnic group. For 2017, data was compared to that published by the Association of American Medical Colleges (AAMC). RESULTS: There were 1293 pathology applicants with 48-49% being female. The overall underrepresented minority (URM) applicant pool in pathology represented 12.6%, 9.5%, and 11.1% of our applicants for 2015, 2016, and 2017, respectively. URMs from US medical schools alone represented 4.7%, 3.7%, and 4.5% of our applicants for 2015, 2016, and 2017, respectively. The percentage of 2017 US medical school graduates applying to any US pathology training program was 22.2% versus 38.7% applying to pathology at our center (p ≤0.001). URM applicants for pathology from US medical schools were significantly lower than URM applicants to all AAMC medical specialties (p = 0.035). Among our pathology applicants in 2017, USMLE I scores and number of applicants with any publications were higher for non-URMs compared to URMs (p = 0.048 and p = 0.046, respectively). CONCLUSION: No significant difference related to gender was identified among our applicants while racial/ethnic groups remain underrepresented with significantly fewer URM applicants from US medical schools compared to published AAMC data for all medical specialties.

Ubiquinol (reduced Coenzyme Q10) in patients with severe sepsis or septic shock: a randomized, double-blind, placebo-controlled, pilot trial.

INTRODUCTION: We previously found decreased levels of Coenzyme Q10 (CoQ10) in patients with septic shock. The objective of the current study was to assess whether the provision of exogenous ubiquinol (the reduced form of CoQ10) could increase plasma CoQ10 levels and improve mitochondrial function. METHODS: We performed a randomized, double-blind, pilot trial at a single, tertiary care hospital. Adults (age ≥18 years) with severe sepsis or septic shock between November 2012 and January 2014 were included. Patients received 200 mg enteral ubiquinol or placebo twice a day for up to seven days. Blood draws were obtained at baseline (0 h), 12, 24, 48, and 72 h. The primary outcome of the study was change in plasma CoQ10 parameters (total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10). Secondary outcomes included assessment of: 1) vascular endothelial biomarkers, 2) inflammatory biomarkers, 3) biomarkers related to mitochondrial injury including cytochrome c levels, and 4) clinical outcomes. CoQ10 levels and biomarkers were compared between groups using repeated measures models. RESULTS: We enrolled 38 patients: 19 in the CoQ10 group and 19 in the placebo group. The mean patient age was 62 ± 16 years and 47% were female. Baseline characteristics and CoQ10 levels were similar for both groups. There was a significant increase in total CoQ10 levels, CoQ10 levels relative to cholesterol levels, and levels of oxidized and reduced CoQ10 in the ubiquinol group compared to the placebo group. We found no difference between the two groups in any of the secondary outcomes. CONCLUSIONS: In this pilot trial we showed that plasma CoQ10 levels could be increased in patients with severe sepsis or septic shock, with the administration of oral ubiquinol. Further research is needed to address whether ubiquinol administration can result in improved clinical outcomes in this patient population. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01948063. Registered on 18 February 2013.

Factors Associated with Development of Traumatic Acute Compartment Syndrome: A Systematic Review and Meta-analysis.

BACKGROUND: Acute compartment syndrome (ACS) is a devastating condition, further aggravated by delayed diagnosis. Since ACS is a clinical diagnosis, identification of risk factors for individual patients may help with earlier detection. This study aims to identify the risk factors associated with the development of ACS of the extremities. METHODS: We performed a systematic review and meta-analysis of studies with adult patients at risk for and with traumatic ACS of the extremity. Non-traumatic, chronic exertional, vascular and abdominal compartment syndrome were excluded. Technical reports, biomechanical studies, abstracts, studies of non-human subjects, non-English studies, and studies with less than five subjects were excluded. Meta-analysis was performed on a subset of studies including a control group. We addressed cases of substantial heterogeneity among the studies with subgroup analysis, and whenever heterogeneity remained significant, we employed random effect meta-analysis for the data pooling. The study protocol has been registered in PROSPERO (ID = CRD42019126603). RESULTS: There were 19 studies with 48,887 patients investigating risk factors of traumatic ACS. Of these, there were 1,716 patients with the diagnosis of traumatic ACS. Fourteen studies (46,300 controls and 1,358 ACS patients) qualified for meta-analysis. Male to female ratio was 5.5 with an average age of 36 years. Factors that were significantly associated with the development of ACS were: age 18-64 (OR: 1.34, 95% CI: 1.07-1.68), male (OR: 2.18, 95% CI: 1.53-3.10), gunshot wound with fracture and vascular injury (OR: 12.5, 95% CI: 5.69-27.46), combined forefoot and midfoot injury (OR: 3.3, 95% CI: 2.39-4.57), injury severity score (ISS) 0-9 (OR: 1.58, 95% CI: 1.27-1.97), OTA/AO type C fractures (OR: 2.75, 95% CI: 1.04-7.28), vascular injury (OR: 9.05, 95% CI: 6.69-12.26), and high-energy trauma (OR: 3.10, 95% CI: 1.60-5.82). Factors such as tibia fracture and crush injury were reported but were not included in quantitative analysis, due to lack of control groups and/or only one study qualifying for meta-analysis. CONCLUSION: This study reports on the current significant risk factors for developing traumatic ACS. The most common risk factors included age, sex, gunshot wound with a vascular injury, OTA/AO fracture type C and high-energy trauma.

Multivitamins and risk of fragility hip fracture: a systematic review and meta-analysis.

PURPOSE: Hip fracture is a severe complication of osteoporosis and is associated with a significant healthcare burden worldwide. This meta-analysis explores the association between combined multivitamin use and hip fracture risk. Our results provide more patient-centered insight into the impact of supplement use on osteoporosis outcomes. METHODS: We searched three online databases in August 2019 and included studies that reported on multivitamin use in patients with osteoporotic hip fractures. The inclusion criteria were (1) adult patients with osteoporotic hip fractures, (2) availability of full-text articles in English, and (3) at least 1 year of follow-up. No suitable randomized controlled trials could be identified for inclusion in the analysis. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS). RESULTS: Eight studies containing 80,148 subjects in total were included in this study. Among these, 4237 cases of fragility hip fracture were reported. The average age was 69±5.3 years, and 21% of subjects were male. Multivitamin use was found to be significantly associated with a lower risk of sustaining a fragility hip fracture (OR 0.49, 95%CI: 0.32-0.77). The Begg and Mazumdar test and funnel plot indicated that no significant publication bias was present. CONCLUSION: Combined multivitamins are amongst the most widely used supplements and are often preferred over single vitamins. Our meta-analysis indicates that multivitamin use is significantly protective against osteoporotic hip fracture. In the future, randomized controlled trials should be performed to establish multivitamins as effective preventative measures for this injury.

Found Down Extremity Compartment Syndrome Secondary to Substance Use: An Observational Multicenter Study.

With the worsening opioid epidemic in America, more patients are developing found down extremity compartment syndrome (FDECS). The purpose of this study was to describe this patient population, including their presenting symptoms, laboratory test results, and clinical outcomes. METHODS: We performed a 2-center retrospective review of adult patients who developed FDECS secondary to substance use from January 2006 to December 2019. Patients were managed operatively or nonoperatively at the surgeon's discretion. Data on patient demographic characteristics, laboratory values, hospital course, and clinical outcomes were collected from electronic medical records. RESULTS: In this study, 91 patients were included: 85 patients were managed operatively, and 6 patients were managed nonoperatively. Most patients were male, and the mean patient age (and standard deviation) was 37 ± 11 years. Opioids were the most common substance used. Patients managed operatively underwent a mean of 4 ± 3 surgical procedures, 44% received a skin graft, 25% developed a wound infection, and 11% underwent limb amputation. Patients managed nonoperatively did not undergo a subsequent fasciotomy or amputation. At a mean follow-up of 2.3 years, persistent weakness (66%), pain (78%), persistent sensory deficits (53%), and contractures (18%) were common. CONCLUSIONS: Patients who develop FDECS secondary to substance use have high surgical complication rates and poor clinical outcomes. We found high rates of wound infection, revision surgical procedures, and amputation, often leaving young adults with lifelong disability. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Substance-Related Found-Down Compartment Syndrome: A Systematic Review.

OBJECTIVE: To characterize the patient population with substance-related found-down extremity compartment syndrome (FDECS) and report on their treatment and outcome. DATA SOURCE: This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Articles in English language were identified by searching 3 online databases, EMBASE, PubMed Publisher, and Cochrane Central, in September 2019. STUDY SELECTION: Studies involving substance-related FDECS were included. Exclusion criteria were as follows: patient age <18 years, not original studies, no full text available, technical reports, traumatic acute extremity compartment syndrome, chronic exertional compartment syndrome, and vascular acute extremity compartment syndrome. DATA EXTRACTION: There were 61 studies included with 166 cases of FDECS. Two investigators screened and extracted data independently according to a standardized template. Disagreements were addressed by an attempt to reach a consensus, and involvement of a third reviewer. Studies were quality assessed with "Quality Assessment tool for Case Series Studies." DATA SYNTHESIS: Descriptive statistics were reported using Excel. CONCLUSION: Substance-related FDECS is often occurring in young adults. Data from this review found that most of the patients were already diagnosed with substance use disorders and/or psychiatric disorders. There should be a high index of suspicion of FDECS in patients presenting after prolonged immobilization. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Predicting factors of muscle necrosis in acute compartment syndrome of the lower extremity.

BACKGROUND: Acute physiologic compartment syndrome (ACS) is a disorder of increased intra-compartmental pressure leading to decreased tissue perfusion and muscle necrosis. Tissue ischemia can result in irreversible muscle and nerve injury and requires urgent fasciotomy. The aim of this study was to determine the factors associated with the presence of necrotic muscle in patients undergoing leg fasciotomy. METHODS: This is a retrospective cohort study of all patients undergoing fasciotomies for ACS of the leg at two level 1 trauma centers from 2000 to 2015. We found 1,028 patients who underwent leg fasciotomies. We excluded ACS at other sites than the leg, the index fasciotomy performed at an outside institution, prophylactic fasciotomy with no clinical signs of ACS, and patients with inadequate medical records. A total of 357 patients were included in the final analysis. We used bivariate analysis to assess which explanatory variables are associated with the main outcome measure, the presence of necrotic muscle at fasciotomy. We used multivariable regression analysis to determine association accounting for any confounding. RESULTS: Of 357 cases of ACS of the leg, 14.6% of patients presented with an open fracture and 21.3% of patients were multiply injured. Overall, 14.3% of cases had muscle necrosis at the time of fasciotomy. Fifty-nine percent of patients with necrotic muscle required more than 3 debridements. Open fracture was the only statistically significant predictor of muscle necrosis (OR=2.8). Crush injury (OR=3.1) and soft tissue injuries (OR=2.8) were at an increased odds of necrotic muscle, but only marginally significant. CONCLUSION: ACS is a potentially limb threatening condition often associated with poor outcomes, particularly when the diagnosis is delayed. Patients with open fracture have a three-fold increase in odds of necrotic muscle at the time of fasciotomy.

Biomechanical properties of an intramedullary suture anchor fixation compared to tension band wiring in osteoporotic olecranon fractures- A cadaveric study.

INTRODUCTION: The aim of the study is to compare three different fixation techniques for transverse olecranon repair in cadaveric osteoporotic bone: (1) current recommended AO tension band technique with K-wire fixation; (2) Suture anchor fixation and (3) Polyester suture fixation. METHODS: Evaluated with bone densitometry, 7 osteoporotic human elbow specimens were included in the study. A transverse olecranon fracture was reduced anatomically and were fixated first using a K-wire tension band technique, second using two suture anchors, and third using polyester suture. Static simulations of the kinetics associated with active range of motion (AROM) and push up from a chair exercises were performed with cyclic loading using Instron hydraulic testing apparatus. Fracture displacement was measured using videographic analysis. Failure was defined as 2 mm fracture displacement. RESULTS: The biomechanical analysis found no statistical difference in displacements between the three fixation methods when testing AROM. In simulated push-up exercises, polyester suture fixation failed after 17 cycles and had significantly higher displacement compared to the other two methods. No difference between the K-Wire fixation versus Suture anchor fixation was observed, p = 0.162. CONCLUSION: Suture anchor fixation might be a viable surgical treatment option for osteoporotic transverse elbow fractures in geriatric patients.

Diagnostic Modalities for Acute Compartment Syndrome of the Extremities: A Systematic Review.

IMPORTANCE: Acute compartment syndrome (ACS) can cause catastrophic tissue damage leading to permanent muscle and nerve loss. Acute compartment syndrome is a clinical diagnosis, with intracompartmental pressure (ICP) used in equivocal cases. There are no reliable diagnostic methods. The clinical evaluation is impossible to standardize, and the threshold for ICP has been known to be unreliable; thus, guidelines for diagnosis can result in overtreatment or delayed diagnosis. OBJECTIVE: To present and review the advantages and disadvantages of each diagnostic modality and identify gaps that need to be addressed in the future and to review the most used and appropriate animal and human ACS models. EVIDENCE REVIEW: We included clinical studies and animal models investigating diagnostic modalities for ACS of the extremities. A MEDLINE and Web of Science search was performed. The protocol for the study was registered on PROSPERO (CRD42017079266). We assessed the quality of the clinical studies with Newcastle-Ottawa scale and reported level of evidence for each article. FINDINGS: Fifty-one articles were included in this study, reporting on 38 noninvasive and 35 invasive modalities. Near-infrared spectroscopy and direct ICP measurement using a Stryker device were the most common, respectively. Cadaveric studies used saline infusions to create an ACS model. Most studies with human participants included injured patients with acquired ACS or at risk of developing ACS. In healthy human participants, tourniquets formed the most commonly used ACS model. Application of tourniquets and infusion of saline or albumin were the most used ACS models among animal studies. CONCLUSIONS AND RELEVANCE: This article reports on the most common as well as many new and modified diagnostic modalities, which can serve as inspiration for future investigations to develop more effective and efficient diagnostic techniques for ACS. Future studies on diagnostic modalities should include the development of tools for continuous assessment of ICP to better identify the earliest alterations suggestive of impending ACS. With the advent of such technologies, it may be possible to develop far less aggressive and more effective approaches for early detection of ACS.

Rat Model of Adhesive Capsulitis of the Shoulder.

This proposal aims to create an in vivo rat model of adhesive capsulitis for researching potential treatment options for this condition and other etiologies of comparable arthrofibrosis. The model includes extra-articular fixation of the shoulder in rats via scapular to humeral suturing, resulting in a secondary contracture without invading the intra-articular space and resulting in decreased rotational ROM and increased joint stiffness. We used 10 Sprague-Dawley rats for the purpose of this study. Baseline ROM measurements were taken before glenohumeral immobilization. The rats were subjected to 8 weeks of immobilization before the fixation sutures were removed and changes in ROM and joint stiffness were evaluated. To evaluate whether immobilization resulted in a significant reduction in ROM, changes in kinematics were calculated. ROM was measured at each time point in the follow-up period and was compared to the baseline internal and external ROM measurements. In order to evaluate the stiffness, joint kinetics were calculated by determining the differences in torque (text and tint ) needed to reach the initial external rotation of 60° and initial internal rotation of 80°. After the removal of the extra-articular suture fixation on follow-up day 0, we found a 63% decrease in total ROM compared to baseline. We observed continuous improvement until week 5 of follow-up, with the progress slowing down around a 19% restriction. On week 8 of follow-up, there was still an 18% restriction of ROM. Additionally, on follow-up day 0, we found the torque increased by 13.3 Nmm when compared to baseline. On week 8, the total torque was measured to be 1.4 ± 0.2 Nmm higher than initial measurements. This work introduces a rat model of shoulder adhesive capsulitis with lasting reduced ROM and increased stiffness.

The prevalence and significance of abnormal vital signs prior to in-hospital cardiac arrest.

BACKGROUND: Patients suffering in-hospital cardiac arrest often show signs of physiological deterioration before the event. The purpose of this study was to determine the prevalence of abnormal vital signs 1-4h before cardiac arrest, and to evaluate the association between these vital sign abnormalities and in-hospital mortality. METHODS: We included adults from the Get With the Guidelines(®)- Resuscitation registry with an in-hospital cardiac arrest. We used two a priori definitions for vital signs: abnormal (heart rate (HR) ≤ 60 or ≥ 100 min(-1), respiratory rate (RR) ≤ 10 or >20 min(-1) and systolic blood pressure (SBP) ≤ 90 mm Hg) and severely abnormal (HR ≤ 50 or ≥ 130 min(-1), RR ≤ 8 or ≥ 30 min(-1) and SBP ≤ 80 mm Hg). We evaluated the association between the number of abnormal vital signs and in-hospital mortality using a multivariable logistic regression model. RESULTS: 7851 patients were included. Individual vital signs were associated with in-hospital mortality. The majority of patients (59.4%) had at least one abnormal vital sign 1-4h before the arrest and 13.4% had at least one severely abnormal sign. We found a step-wise increase in mortality with increasing number of abnormal vital signs within the abnormal (odds ratio (OR) 1.53 (CI: 1.42-1.64) and severely abnormal groups (OR 1.62 (CI: 1.38-1.90)). This remained in multivariable analysis (abnormal: OR 1.38 (CI: 1.28-1.48), and severely abnormal: OR 1.40 (CI: 1.18-1.65)). CONCLUSION: Abnormal vital signs are prevalent 1-4h before in-hospital cardiac arrest on hospital wards. In-hospital mortality increases with increasing number of pre-arrest abnormal vital signs as well as increased severity of vital sign derangements.