Hemodialysis is Not Associated With Pre-prosthetic Inpatient Rehabilitation Outcomes After Dysvascular Lower Extremity Amputation: A Retrospective Cohort Study.

BACKGROUND: Lower extremity amputation due to complications from peripheral vascular disease and/or diabetes are common and these patients often have multiple comorbidities. Patients with end-stage renal disease receiving hemodialysis (ESRD/HD) are a particularly vulnerable group at risk for amputation. After lower extremity amputation (LEA) surgery, many patients undergo post-operative inpatient rehabilitation to improve their pre-prosthetic functional independence. Given the increased complexity of dysvascular patients living with ESRD/HD compared to those without ESRD/HD, the association of HD with pre-prosthetic inpatient functional outcomes warrants further study. OBJECTIVE: The objective of this study was to compare the pre-prosthetic functional outcomes and Length of Stay (LOS) among patients with recent dysvascular LEA with and without ESRD/HD. METHODOLOGY: A retrospective cohort design was used to analyze a group of 167 patients with unilateral, dysvascular limb loss who were admitted to inpatient rehabilitation with 24 of these patients in the ESRD/HD group. Age, gender, amputation level, amputation side, length of stay (LOS), time since surgery, Functional Independence Measure (FIM) scores (admission and discharge), and Charlson Comorbidity Index (CCI) were collected. FINDINGS: There was no difference between patients with dysvascular amputation with and without ESRD/HD in the association of functional outcomes or LOS in this cohort and rehabilitation model. The CCI score was higher in the ESRD/HD group. Multivariate analysis indicated an inverse relationship with age and FIM scores, where increased age was associated with lower Total and Motor FIM at admission and discharge. There were no associations with FIM change. Age was positively associated with LOS. Being female was inversely associated to motor FIM scores at admission and discharge. CONCLUSION: Among patients with recent dysvascular LEA, ESRD/HD is not associated with different functional outcomes or LOS in the pre-prosthetic inpatient rehabilitation setting. This suggests that despite added comorbidity that patients with ESRD/HD may still benefit from inpatient rehabilitation to optimize pre-prosthetic function.

Comorbidity and Non-prosthetic Inpatient Rehabilitation Outcomes After Dysvascular Lower Extremity Amputation.

BACKGROUND: Dysvascular amputations arising from peripheral vascular disease and/or diabetes are common. Patients who undergo amputation often have additional comorbidities that may impact their recovery after surgery. Many individuals undergo post-operative inpatient rehabilitation to improve their non-prosthetic functional independence. Thus far, our characterization of comorbidity in this population and how it is associated with non-prosthetic inpatient functional recovery remains relatively unexplored. OBJECTIVE: The objective of this study was to describe comorbidities, using the Charlson Comorbidity Index (CCI), and to examine associations between comorbidity and functional outcomes in a cohort of patients with dysvascular limb loss undergoing non-prosthetic inpatient rehabilitation. METHODOLOGY: A retrospective cohort design was used to analyze a group of 143 patients with unilateral, dysvascular limb loss who were admitted to inpatient rehabilitation. Age, sex, amputation level, amputation side, length of stay (LOS), time since surgery, Functional Independence Measure (FIM) scores (Total and Motor at admission and discharge), and CCI scores were collected. FINDINGS: The data showed that neither total or specific comorbidities were associated with functional outcomes or LOS in this cohort and rehabilitation model. Multivariate analysis demonstrated an inverse relationship with age and FIM scores, where increased age was associated with lower Total and Motor FIM at admission and discharge. Comorbidities were not associated with functional outcomes. Dementia was negatively associated with FIM scores, however this requires more study given the low number of patients with dementia in this cohort. CONCLUSION: These data suggest that regardless of burden of comorbidity or specific comorbidities that patients with dysvascular limb loss may derive similar functional benefit from post-operative non-prosthetic inpatient rehabilitation.

Return to work after occupational and non-occupational lower extremity amputation.

BACKGROUND: Factors impacting on return to work (RTW) after lower extremity amputation are important in occupational rehabilitation. AIMS: Our objective was to compare RTW in patients who had traumatic work-related amputation with amputations from other causes. METHODS: A retrospective cohort study was conducted with participants employed at the time of amputation and at least 1 year post-discharge from amputee rehabilitation. The primary outcome measure was RTW. RESULTS: One hundred and forty-seven amputees were included with 69% returning to work. Amputation reason did not impact on RTW (odds ratio [OR] 1.83, P = non-significant). Trans-femoral amputees were less likely to RTW (OR 0.22, P < 0.05). Years since amputation (OR 1.20, P = 0.001) and Reintegration to Normal Living Index (OR 1.05, P < 0.001) were predictive of RTW after adjusting for other covariates. CONCLUSIONS: Amputation aetiology did not impact on RTW. Years since amputation, level of amputation and Return to Normal Living Index were associated with RTW which may be important to consider in RTW prognosis and planning.

The frequency of acute kidney injury in patients with chronic hepatitis C virus infection treated with sofosbuvir-based regimens.

BACKGROUND: Guidelines recommend withholding sofosbuvir (SOF) in patients with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min. AIM: To assess the risk of acute kidney injury (AKI) in patients with no renal contraindications for SOF-based treatment. METHODS: This multicenter retrospective observational study included all consecutive patients that were treated with SOF-based or telaprevir/boceprevir (TVR/BOC)-based regimens at two tertiary university centers in North America. AKI was defined as an increase of ≥0.3 mg/dL (≥26.5 µmol/L) in serum creatinine level. Multivariable logistic regression analysis was used to identify risk factors for the occurrence of AKI. RESULTS: In total, 426 patients were included and treated with a SOF-based regimen (n=233, 54.7%) or TVR/BOC-based regimen (n=193, 45.3%). Among patients treated with a TVR/BOC-based regimen 34 (18%) of 193 patients experienced AKI compared to 26 (11%) of 233 patients treated with SOF-based regimens (P=.056). Multivariable logistic regression analysis showed that the presence of ascites (OR: 4.44, 95%CI: 1.46-13.54, P=.009) and the use of NSAIDs (OR: 4.47, 95%CI: 1.32-15.19, P=.016) were associated with a risk of AKI during SOF-based antiviral therapy. Creatinine levels returned to normal at end of follow-up in 23 (88%) of the 26 patients who experienced AKI with a SOF-based regimen and had a creatinine level available during follow-up. CONCLUSIONS: Although the risk for AKI was lower than for patients treated with TVR/BOC-based regimens, AKI was seen during 11% of SOF-based regimens and was mostly reversible. Patients with ascites and patients using NSAIDs have an increased risk for AKI during SOF-based antiviral therapy.

Prevalence and risk factors for viral blipping in chronic hepatitis B patients treated with nucleos (t) ide analogues.

The clinical relevance of viral blipping during nucleos (t) ide analogue (NA) treatment is unclear in chronic hepatitis B (CHB). We investigated the prevalence, risk factors and clinical outcomes for those with viral blipping during NA treatment. A retrospective cohort study investigated consecutively treated CHB patients from May 2008 to February 2015 on the NAs such as entecavir (ETV), tenofovir (TDF) and lamivudine (LAM). Included patients were previously treatment naive. Viral blipping was defined as serum HBV DNA >20 IU/mL on one occasion, and not >200 IU/mL, with subsequent measurement returning to undetectable levels, that is <20 IU/mL. A total of 242 treatment-compliant CHB patients were included with 44 (18.2%) experiencing viral blipping. In multivariable Cox regression, Asian race (HR=7.40, 95% CI 1.01-54.29, P<.049), LAM therapy (vs ETV/TDF, HR=2.53, 95% CI 1.29-4.95, P<.007), higher creatinine (per SD, HR=1.47, 95% CI 1.21-1.79, P<.001), HBeAg positivity (HR=2.68, 95% CI 1.39-5.03, P<.003) and longer time to achieve undetectable HBV DNA (per month, HR=1.05, 95% CI 1.02-1.08, P=.001) were associated with an increased risk of viral blipping. Viral blipping did not show any significant association with viral breakthrough, HBsAg loss, ALT flares or disease progression. Viral blipping is a frequent event during NA therapy; however, it did not lead to any clinically significant outcomes. Thus, it may not require more frequent blood work and patient visits in clinical practice.

Combined ursodeoxycholic acid (UDCA) and fenofibrate in primary biliary cholangitis patients with incomplete UDCA response may improve outcomes.

BACKGROUND: Fibrates appear to improve biochemistry in patients with primary biliary cholangitis (PBC), but it is unclear which factors predict response and whether treatment improves transplant-free survival. AIM: To evaluate biochemical profiles, liver-related outcomes and adverse events following fenofibrate therapy in PBC patients with incomplete response to ursodeoxycholic acid (UDCA). METHODS: A retrospective cohort study was performed at a tertiary centre. Cox regression was used to compare outcomes between patients treated with fibrates and UDCA (FF) or UDCA alone, adjusted for a propensity score to account for treatment selection bias. RESULTS: A total of 120 patients were included (FF group n = 46, UDCA group n = 74, median fenofibrate treatment 11 months); 41% vs. 7% met the Toronto criteria for biochemical response [alkaline phosphatase ≤1.67 times the upper limit of normal] in the FF and UDCA groups, respectively (P = 0.0001). Fenofibrate was also associated with improved decompensation-free and transplant-free survival [hazard ratio (HR) 0.09, 95% CI 0.03-0.32, P = 0.0002]. However, only fenofibrate use, not biochemical response, was independently associated with improved outcomes on multivariable analysis (HR 0.40, 95% CI 0.17-0.93, P = 0.03). Twenty-two percent discontinued fenofibrate due to adverse events (most common: abdominal pain and myalgias). In cirrhotic patients, bilirubin increased more rapidly in the FF group (P = 0.005). CONCLUSIONS: Fenofibrate therapy is associated with significant improvement in alkaline phosphatase, decompensation-free and transplant-free survival in PBC patients with incomplete UDCA response. However, fenofibrate should be used cautiously in cirrhosis, with close monitoring for clinical/biochemical decompensation. Additional studies are required to assess the validity of alkaline phosphatase as an appropriate response criteria for fibrate therapy.

Association of 25-Hydroxyvitamin D status and genetic variation in the vitamin D metabolic pathway with FEV1 in the Framingham Heart Study.

BACKGROUND: Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults. METHODS: We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts. RESULTS: We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P=0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P=0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P<0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P=0.09). CONCLUSIONS: Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.

Polymorphisms in genes within the IGF-axis influence antenatal and postnatal growth.

Two pregnancy cohorts were used to investigate the association between single-nucleotide polymorphisms (SNPs) in genes within the insulin-like growth factor (IGF)-axis and antenatal and postnatal growth from birth to adolescence. Longitudinal analyses were conducted in the Raine pregnancy cohort (n = 1162) using repeated measures of fetal head circumference (HC), abdominal circumference (AC) and femur length (FL) from 18 to 38 weeks gestation and eight measures of postnatal height and weight (1-17 years). Replications of significant associations up to birth were undertaken in the Generation R Study (n = 2642). Of the SNPs within the IGF-axis genes, 40% (n = 58) were associated with measures of antenatal growth (P ⩽ 0.05). The majority of these SNPs were in receptors; IGF-1R (23%; n = 34) and IGF-2R (13%; n = 9). Fifteen SNPs were associated with antenatal growth (either AC or HC or FL) in Raine (P ⩽ 0.005): five of which remained significant after adjusting for multiple testing. Four of these replicated in Generation R. Associations were identified between 38% (n = 55) of the IGF-axis SNPs and postnatal height and weight; 21% in IGF-1R (n = 31) and 9% in IGF-2R (n = 13). Twenty-six SNPs were significantly associated with both antenatal and postnatal growth; 17 with discordant effects and nine with concordant effects. Genetic variants in the IGF-axis appear to play a significant role in antenatal and postnatal growth. Further replication and new analytic methods are required in order to better understand this key metabolic pathway integrating biologic knowledge about the interaction between IGF-axis components.