Incidence of and risk factors for tenofovir-induced nephrotoxicity: a retrospective cohort study

OBJECTIVES: Despite the recent publication of case reports describing various manifestations of tenofovir-related nephrotoxicity, data regarding the incidence of and risk factors for this adverse effect are currently lacking. METHODS: A retrospective cohort study of patients from four centres in Toronto, Canada, enrolled in the tenofovir expanded access programme with a minimum of 3 months follow up, was carried out. RESULTS: A total of 172 patients receiving tenofovir disoproxil fumarate (TDF) for a median of 16 months (range 3-25 months) were included in the study. Seven (4%) patients developed grade 1 (>44 micromol/L from baseline) increases in serum creatinine (SCr) during follow up; no patient developed grade 2 or higher nephrotoxicity. Fifteen (8.7%) patients had an increase in SCr of greater than 1.5 times baseline values during follow up. Four (2.3%) patients discontinued TDF because of an increase in SCr and/or abnormal urinalysis. Of 62 patients with a urinalysis, grade 1 or higher proteinuria (< 3 g/L) was observed in 27 (43%) patients. Only baseline SCr [odds ratio (OR)=0.51 per 10 micromol/L increase; P=0.0005] and baseline creatinine clearance (1.26 per 10 mL/min increase; P=0.01) were significantly associated with ever having a 1.5-fold increase in serum creatinine. Twenty-eight (16%) and 11 (6%) patients developed grade 1 (serum phosphorus < or = 0.71 mmol/L) and grade 2 (serum phosphorus < or = 0.61 mmol/L) hypophosphataemia during follow-up, respectively. CONCLUSIONS: Although slight increases in SCr did occur after starting TDF, clinically significant nephrotoxicity was rare. The clinical significance of TDF-related hypophosphataemia and proteinuria requires further study.     

Incidence and risk factors for gallstones in patients with inflammatory bowel disease: a large case-control study

The risk for gallstones (GD) in inflammatory bowel diseases and the factors responsible for this complication have not been well established. We studied the incidence of GD in a cohort of Crohn's disease (CD) and ulcerative colitis (UC) patients and investigated the related risk factors. A case-controlled study was carried out. The study population included 634 inflammatory bowel disease (IBD) patients (429 CD, 205 UC) and 634 age-matched, sex-matched, and body mass index (BMI)-matched controls free of GD at enrollment, who were followed for a mean of 7.2 years (range, 5-11 years).The incidence of GD was calculated by dividing the number of events per person-years of follow-up. Multivariate analysis was used to discriminate among the impact of different variables on the risk of developing GD. The incidence rates of GD were 14.35/1,000 persons/year in CD as compared with 7.75 in matched controls (P=0.012) and 7.48/1000 persons/year in UC patients as compared with 6.06 in matched-controls (P=0.38). Ileo-colonic CD location (OR, 2.14), disease duration>15 years (OR, 4.26), >3 clinical recurrences (OR, 8.07), ileal resection>30 cm (OR, 7.03), >3 hospitalizations (OR, 20.7), multiple TPN treatments (OR, 8.07), and long hospital stay (OR, 24.8) were significantly related to GD in CD patients. CONCLUSION: Only CD patients have a significantly higher risk of developing GD than well-matched hospital controls. Site of disease at diagnosis, lifetime surgery, extent of ileal resections, number of clinical recurrences, TPN, and the frequency and duration of hospitalizations are independently associated with GD.     

Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort,IORRA

Abstract

Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case–control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.     

Incidence of and risk factors for interstitial pneumonia in patients with rheumatoid arthritis in a large Japanese observational cohort, IORRA

Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case–control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.     

Incidence and prevalence of acromegaly in a large US health plan database

Purpose

Incidence and prevalence estimates of acromegaly in the United States (US) are limited. Most existing reports are based on European data sources. The objective of this study was to estimate the annual incidence and prevalence of acromegaly in a large US managed care population, overall and stratified by age, sex, and geographic region, using data from 2008 to 2012.

Methods

Using administrative claims data, commercial health plan enrollees were identified with acromegaly if they had two or more medical claims with an acromegaly diagnosis code (ICD-9-CM: 253.0×) or one medical claim with an acromegaly diagnosis code in combination with one other claim for a pituitary tumor or pituitary procedure. The first date for an acromegaly-related claim set the index year. Incidence rates for each year were calculated by dividing the number of new acromegaly cases by the calculated person-time at risk. Annual prevalence estimates were calculated by dividing the number with any evidence of acromegaly by the total number of health plan enrollees enrolled for at least 1 day during each calendar year. Incidence and prevalence estimates were stratified by age (0–17, 18–44, 45–64, 65+ years), sex (male, female), and US geographic region of the health plan (Midwest, Northeast, South, West).

Results

Overall annual incidence rates of acromegaly were relatively constant across 2008–2012 with ~11 cases per million person-years (PMPY). Rates increased with age, ranging from 3–8 cases PMPY among children aged 0–17 years old to 9–18 cases PMPY among adults aged 65 and older. Females had 12 cases PMPY on average compared to 10 cases PMPY among men. On average, the Midwest had the lowest incidence rates (7 cases PMPY) compared to the Northeast, South and West (14, 12, and 10 cases PMPY, respectively). The overall annual prevalence of acromegaly was relatively constant across the 5 years from 2008 to 2012 with approximately 78 cases per million each year. Annual prevalence estimates increased with age, ranging from 29–37 cases per million among children aged 0–17 years old to 148–182 cases per million among adults aged 65 years and older. Males and females were similarly affected; each with approximately 77 cases per million each year. The Northeast and South had the highest prevalence estimates (92 and 89 cases per million, respectively); while the estimates for the West and Midwest were lower (65 and 57 cases per million, respectively) each year.

Conclusion

This study examined 5 years of recent data to estimate the incidence and prevalence of acromegaly in a large geographically-diverse managed care population. The incidence rates were higher on average than published rates outside the US (11 vs. 3.3 PMPY), but prevalence estimates were consistent with previous reports. Incidence and prevalence both increased by age, did not differ for males and females, and varied slightly by US geographic region. The age and sex distribution of the selected population matched the known epidemiology of the disease. Using a claims-based approach, this analysis only captured acromegaly cases with an acromegaly-related medical claim. As a result, these estimates may underestimate the incidence and prevalence of acromegaly in US commercial health plans as they did not include individuals who were undiagnosed, in remission, undertreated, or not monitored during the study period. At the same time, these estimates may be viewed as an upper bound on the incidence of acromegaly in the US as the estimates did not include individuals who were in other health plans or uninsured during the study period. Additional evaluations are needed to identify the full extent of acromegaly in the US.

     

Incidence and risk factors for cholangiocarcinoma in primary sclerosing cholangitis

Cholangiocarcinoma (CCA) is a dreaded complication of primary sclerosing cholangitis (PSC); however, marked variability in the incidence of CCA in PSC is reported. Furthermore, limited information exists on risk factors for the development of CCA in PSC. The aim of this study was to determine the incidence of CCA in patients with PSC and to evaluate baseline risk factors for the later development of CCA. From a previous study of the natural history of PSC, we identified 161 patients with PSC who did not have CCA at study entry. Patients were followed until a diagnosis of CCA was established, liver transplantation was performed, or death occurred. Patients were followed for a median of 11.5 yr (interquartile range 4.0-16.1 yr). Fifty-nine patients (36.6%) died, 50 patients (31.1%) underwent liver transplantation, and 11 patients (6.8%) developed CCA. The rate of CCA developing was approximately 0.6% per year. Compared to the incidence rates of CCA in the general population, the relative risk of CCA in PSC was significantly increased (RR = 1,560; 95%CI = 780, 2,793; p < 0.0001). On univariate analysis, a history of variceal bleeding (p < 0.001), proctocolectomy (p= 0.01), and lack of symptoms (p= 0.02) were significant risk factors for CCA with the Mayo Risk Score being marginally significant (p= 0.051). Multivariate analysis determined only variceal bleeding to be a significant risk factor for CCA (RR 24.2; 95%CI: 3.3-67.1). No association was found between the duration of PSC and the incidence of CCA. In conclusion, approximately 7% of PSC patients later developed CCA over a mean follow-up of 11.5 yr, which is dramatically higher than the rates in the general population. Variceal bleeding is a major risk factor for the later development of CCA.     

Incidence and risk factors for infantile colic in Iranian infants

AIM： To assess the incidence of infantile colic and its association with variable predictors in infants born in a community maternity hospital, Tehran, Iran. METHODS： In this prospective cohort study, mothers who gave birth to live newborns between February 21 and March 20, 2003 at the hospital were invited to join to the study. For every infant-mother dyad data were collected on infant gender, type of delivery, gestational age at birth, birth weight, birth order, and mother＇s reproductive history. Then mothers were given a diary to document the duration of crying/fussiness behav-iors of their infants for the next 12 wk. We scheduled home visits at the time the infants were 3 mo of age to collect the completed diaries and obtain additional information on infants＇ nutritional sources and identify if medications were used for colic relief. Cases of colic were identifi ed by applying Wessel criteria to recorded data. Chi-square and Mann-whitney U tests were used to compare proportions for non-parametric and para-metric variables, respectively. RESULTS： From 413 infants, follow-up was completed for 321 infants. In total, 65 infants （20.24%） satisfi ed the Wessel criteria for infantile colic. No statistical sig-nifi cance was found between colicky and non-colicky infants according to gender, gestational age at birth, birth weight, type of delivery, and, infant＇s feeding pattern. However, fi rstborn infants had higher rate for developing colic （P = 0.03）. CONCLUSION： Colic incidence was 20% in this popu-lation of Iranian infants. Except for birth order status, no other variable was signifi cantly associated with in-fantile colic.     

Incidence and risk factors for cancer after liver transplantation

De novo tumors (DNT) are a serious complication after orthotopic liver transplantation (OLT), showing a higher overall incidence ranging from 4.7% to 15.7% in non-selected series. Skin cancer (SC) is the most frequent malignancy observed, ranging from 6% to 70% of the tumors observed, followed by post-transplant lymphoproliferative disorders (PTLD) (4.3-30%). Different immunosuppressive protocols do not seem to influence DNT appearance. Colon and upper aerodigestive cancer after OLT seems to be more prone to develop when there are associated risk factors, such as primary sclerosing cholangitis (PSC) and alcoholic liver cirrhosis (ALC). Some risk factors, such as age, smoking, alcohol and others seem to play a role in higher risk for malignancy, but the presence of a long-term immunosuppressive state, more than the specific regimen used, is the basis for this higher incidence. Ethnic and demographic factors are also important variables influencing the heterogeneity of the results, especially influencing Kaposi's sarcoma and skin tumors.     

老年骨折患者谵妄的发生率及危险因素分析

目的研究老年骨折患者保守治疗期间谵妄的发生情况,分析其危险因素。方法选择2012年1月~2016年12月住我院南楼的老年骨折保守治疗患者152例,记录基本资料和相关检查指标。采用意识模糊评估法评估患者是否发生谵妄,于骨折后30d内每2d评估1次,分析患者发生谵妄的危险因素。结果 152例患者中62例(40.8%)发生谵妄,58.1%在骨折后10d内发生谵妄,以混合型谵妄为主(46.8%),随时间延长,活动过少型谵妄逐渐增多。谵妄多发于多发肋骨骨折和髋部骨折,多因素回归分析提示,腔隙性脑梗死(OR=0.122,95%CI:0.017~0.887,P=0.038)、美国麻醉医师协会(ASA)分级≥3级(OR=9.061,95%CI:1.484~55.340,P=0.017)、疼痛评分(OR=5.554,95%CI:1.630~18.922,P=0.006)、全身性炎症反应综合征(SIRS,OR=10.640,95%CI:1.401~80.822,P=0.022)、C反应蛋白(OR=1.221,95%CI:1.047~1.425,P=0.011)是老年骨折患者发生谵妄的独立危险因素。结论谵妄是老年多发肋骨骨折或髋部骨折后常见的并发症,骨折后谵妄初发窗口期长,大部分在骨折后10d内,后期以活动过少型谵妄为主。多发腔隙性脑梗死、ASA分级≥3级、剧烈疼痛、SIRS状态、C反应蛋白升高是老年非颅骨骨折患者发生谵妄的独立危险因素。     

Incidence,risk factors and causes of death in an HIV care programme with a large proportion of injecting drug users

Objectives To identify factors influencing mortality in an HIV programme providing care to large numbers of injecting drug users (IDUs) and patients co‐infected with hepatitis C (HCV). Methods A longitudinal analysis of monitoring data from HIV‐infected adults who started antiretroviral therapy (ART) between 2003 and 2009 was performed. Mortality and programme attrition rates within 2 years of ART initiation were estimated. Associations with individual‐level factors were assessed with multivariable Cox and piece‐wise Cox regression. Results A total of 1671 person‐years of follow‐up from 1014 individuals was analysed. Thirty‐four percent of patients were women and 33% were current or ex‐IDUs. 36.2% of patients (90.8% of IDUs) were co‐infected with HCV. Two‐year all‐cause mortality rate was 5.4 per 100 person‐years (95% CI, 4.4–6.7). Most HIV‐related deaths occurred within 6 months of ART start (36, 67.9%), but only 5 (25.0%) non‐HIV‐related deaths were recorded during this period. Mortality was higher in older patients (HR = 2.50; 95% CI, 1.42–4.40 for ≥40 compared to 15–29 years), and in those with initial BMI < 18.5 kg/m² (HR = 3.38; 95% CI, 1.82–5.32), poor adherence to treatment (HR = 5.13; 95% CI, 2.47–10.65 during the second year of therapy), or low initial CD4 cell count (HR = 4.55; 95% CI, 1.54–13.41 for <100 compared to ≥100 cells/μl). Risk of death was not associated with IDU status (P = 0.38). Conclusion Increased mortality was associated with late presentation of patients. In this programme, death rates were similar regardless of injection drug exposure, supporting the notion that satisfactory treatment outcomes can be achieved when comprehensive care is provided to these patients.     

Incidence and risk factors for sternal osteomyelitis after median sternotomy

BackgroundSternal osteomyelitis (OM) after median sternotomy is the rarest form of deep sternal wound infections (DSWIs). A retrospective study was implemented to evaluate the incidence and potential risk factors of sternal OM after median sternotomy.MethodsWe analyzed 3,410 consecutive patients who underwent cardiothoracic surgery via median sternotomy from January 2005 to December 2019 at our institution. A sternal OM and control group without any sign of wound infections after median sternotomy were selected. Comparisons of the variables between the two groups were performed using the Student’s t-test and Fisher’s exact tests. The association of potential risk factors with sternal OM was tested by logistic regression analysis.ResultsA total of 16 patients (0.47%) had sternal OM after median sternotomy. None of the variables were different between the sternal OM patients and the control group including body mass index (BMI), diabetes mellitus (DM), hypertension (HTN), left ventricle (LV) function, transfusion, operation time, cardiopulmonary bypass (CPB) time and intensive care unit and ventilator days. By univariate analysis, none of the variables were associated with an increased risk of sternal OM.ConclusionsThe incidence of sternal OM after median sternotomy in our institution was 0.47% and there was no correlation between the known risk factors of DSWI and sternal OM in our study.     

Incidence and risk factors of the post-thrombotic syndrome

Annually 1-2 in every 1000 adults will develop a deep venous thrombosis of the lower extremity. A third to half of these patients will develop the post-thrombotic syndrome (PTS). However, predicting which patients will develop the PTS remains elusive. Ipsilateral thrombosis recurrence seems to be the most important risk factor. Moreover, residual venous occlusion and valvular reflux seem to predict PTS incidence to some degree. Laboratory parameters, including d-dimers and inflammatory markers, have shown promise in predicting development of the PTS in patients and are currently under investigation. Creating a model based on all combined risk factors and patient characteristics might aid in risk stratification in individual patients.     

Incidence of and risk factors for pulmonary complications after nonthoracic surgery

The prediction of postoperative pulmonary complications is an underinvestigated field. We conducted a prospective cohort study (with postoperative pulmonary complications ascertained by an investigator blinded to perioperative variables) to determine the risk factors for pulmonary complications after elective nonthoracic surgery. Of 1,055 consecutive patients attending the Pre-Admission Clinic of a university hospital (mean age 55 years, 50% men, 15% with history of obstructive airways disease), 28 (2.7%) suffered a postoperative pulmonary complication within 7 days of surgery: 13 patients developed respiratory failure requiring ventilatory support, 9 pneumonia, 5 atelectasis requiring bronchoscopic intervention, and 1 pneumothorax requiring intervention. Mean lengths of stay were substantially prolonged for those patients who developed pulmonary complications within 7 days of surgery: 27.9 days versus 4.5 days, p = 0.006. Eight variables were statistically significantly associated with pulmonary complications on bivariate analyses. Multivariate analyses revealed that four were independently associated with increased risk of pulmonary complications: age (odds ratio [OR] 5.9 for age >/= 65 years, p < 0.001), positive cough test (OR 3.8, P = 0.01), perioperative nasogastric tube (OR 7.7, p < 0.001), and duration of anesthesia (OR 3.3 for operations lasting at least 2.5 hours, p = 0.008). Thus, several perioperative factors predict an increased risk for pulmonary complications after elective nonthoracic surgery.     

Incidence and risk factors for biliary and pancreatic stent migration.

Endoprostheses are commonly used in the treatment of biliary and pancreatic disorders. The frequency of and potential risk factors for stent migration, however, remain largely unknown. From January 1986 to June 1990, 807 biliary and pancreatic stents were placed at our institution. Our study analyzed the occurrence of stent migration among the 589 stents for which follow-up data were available. Results demonstrated incidence rates of 4.9 and 5.9% for proximal (into the duct) and distal (out of the duct) biliary stent migration, respectively. Likewise, incidence rates of 5.2 and 7.5% were observed for proximal and distal pancreatic stent migration, respectively. Malignant strictures, larger diameter stents, and shorter stents were significantly associated with proximal biliary stent migration. Sphincter of Oddi dysfunction and longer stents were associated with proximal pancreatic stent migration. Migration of stents out of the common bile duct occurred more frequently in papillary stenosis. No other significant risk factors for distal migration were found. These results indicate that stent migration is an important complication. Multiple risk factors were associated with stent migration and need to be considered in the development of new stent types.     

Incidence and risk factors for hepatocellular carcinoma in 967 patients with cirrhosis

Purpose: To determine the incidence of hepatocellular carcinoma in cirrhosis and to examine the influence of age and sex, and the contribution of etiological factors. Methods: 967 patients with liver cirrhosis and free of hepatocellular carcinoma were enrolled in this longitudinal, retrospective and observational study. Monitoring for hepatocellular carcinoma was scheduled at 3- to 6-month intervals. The mean (±SD) length of follow-up was 60.3 ± 51.7 months (range 6–258). Results: During the observation period, hepatocellular carcinoma developed in 64 patients. The calculated annual incidence was 2.1%. The probability of being free of liver cancer was 92% at 5 years, 80% at 10 years, and 69% at 15 years. Age was the only independent risk factor for the development of malignancy in the multivariate analysis. There were no differences according to male sex, alcohol abuse, and chronic hepatitis B and C virus infection. Conclusions: The annual incidence of hepatocellular carcinoma was 2.1%. These results, although confirming that age is a risk factor for hepatocellular carcinoma in cirrhosis, indicate that alcohol abuse, male sex, and concurrent hepatitis B and C virus infection do not involve a higher risk of developing liver cancer.