Article Figures & Data
Figures
- Figure 1.
Sixty-nine thousand, three hundred sixty-eight adults initiating hemodialysis between 2013 and 2014 were selected to be in the study sample. The dialysis initiation cohort was restricted to United States citizens aged 18 years old and older. MPAB, medicare part A and B; MPO, mediare primary, other.
- Figure 2.
Benzodiazepine dispensing differed by geographic region among patients inititiating hemodialysis (n=69,368) between 2013 and 2014.
- Figure 3.
Benzodiazepine dispensing barely changed over time among patients inititiating hemodialysis (n=69,368) between 2013 and 2014. Rates by quarter (Q) are presented as lorazepam milligram equivalent (LME) per 100 person-days.
- Figure 4.
The cumulative incidence of time to first short-acting benzodiazepine prescription dispensed among patients initiating hemodialysis (n=69,368) between 2013 and 2014 differed by race and sex. (A) Cumulative incidence of short-acting benzodiazepine. Approximately 18.1% of white women, 12.5% of white men, 9.5% of nonwhite women, and 6.1% of nonwhite men had used a short-acting benzodiazepine within 6 months of initiating dialysis. (B) Cumulative incidence of long-acting benzodiazepine. Approximately 5.1% of white women, 3.4% of white men, 2.3% of nonwhite women, and 1.8% of nonwhite men had used a long-acting benzodiazepine within 6 months of initiating dialysis.
Tables
- Table 1.
Characteristics of patients who initiated dialysis (n=69,368) between January 2013 and December 2014 by benzodiazepine dispensing within 6 months of initiation
Characteristic Benzodiazepine within 6 mo, n=11,289 No Benzodiazepine within 6 mo, n=58,079 Age, yr, median [IQR] 68 [59–77] 67 [56–76] BMI, kg/m2, median [IQR] 28 [24–34] 28 [24–34] Women, % 54 44 White, % 80 65 Dialysis initiation in 2013, % 59 57 Opioids, % 76 56 Neuropathic pain medication, % Any 68 49 Gabapentin 26 18 Antidepressant, % 56 29 CNS depressant, % 37 18 Comorbidity, % Diabetes 58 60 Cardiovascular disease 57 52 Peripheral vascular disease 14 11 Hypertension 88 89 COPD 16 10 Tobacco use 8 6 Cancer 8 7 Drug use 3 2 Inability to ambulate 20 16 Institutionalized 13 9 No comorbidity 1 2 Cause of kidney failure, % Diabetes 47 49 Hypertensive kidney disease 31 32 GN 6 6 Other 16 13 Dual eligible, % 47 46 Employment status, % Unemployed 19 26 Full time 1 2 Part time 1 2 Retired 46 42 Disabled 29 24 Other 3 4 Medications were ascertained at any point during follow-up. IQR, interquartile range; BMI, body mass index; CNS, central nervous system; COPD, chronic obstructive pulmonary disease.
- Table 2.
Factors associated with short-acting and long-acting benzodiazepines among adults initiating hemodialysis (n=69,368) between 2013 and 2014
Factor Benzodiazepine Short Acting Long Acting aHR (95% CI) P Value aHR (95% CI) P Value Age, per 10-yr older 1.05 (1.03 to 1.07) <0.001 0.90 (0.87 to 0.93) <0.001 Women 1.32 (1.27 to 1.37) <0.001 1.35 (1.26 to 1.45) <0.001 White 1.73 (1.65 to 1.82) <0.001 1.74 (1.59 to 1.89) <0.001 Opioids 1.66 (1.59 to 1.74) <0.001 1.11 (1.03 to 1.20) 0.01 Antidepressant 1.89 (1.81 to 1.96) <0.001 1.59 (1.47 to 1.71) <0.001 CNS depressant 1.73 (1.66 to 1.80) <0.001 1.69 (1.56 to 1.82) <0.001 Year of dialysis initiation 2013 versus 2014 1.11 (1.07 to 1.16) <0.001 1.30 (1.21 to 1.40) <0.001 BMI, per 10-kg/m2 higher 0.95 (0.92 to 0.97) <0.001 0.97 (0.93 to 1.02) 0.24 Comorbidity Diabetes 0.92 (0.88 to 0.97) 0.003 0.99 (0.90 to 1.08) 0.76 Cardiovascular disease 1.06 (1.02 to 1.10) 0.009 0.95 (0.88 to 1.03) 0.22 Peripheral vascular disease 1.03 (0.98 to 1.09) 0.25 1.09 (0.98 to 1.21) 0.13 Hypertension 0.97 (0.91 to 1.03) 0.27 0.99 (0.88 to 1.12) 0.90 COPD 1.20 (1.13 to 1.27) <0.001 1.28 (1.16 to 1.43) <0.001 Tobacco use 1.09 (1.01 to 1.17) 0.02 1.19 (1.05 to 1.35) 0.01 Cancer 1.10 (1.02 to 1.18) 0.01 1.02 (0.88 to 1.17) 0.80 Drug use 1.10 (0.97 to 1.24) 0.14 1.03 (0.83 to 1.28) 0.75 Inability to ambulate 1.09 (1.04 to 1.15) 0.002 1.11 (1.00 to 1.23) 0.06 Institutionalized 1.08 (1.01 to 1.15) 0.03 0.90 (0.79 to 1.02) 0.11 No comorbidity 0.87 (0.73 to 1.04) 0.13 0.91 (0.68 to 1.23) 0.56 Cause of kidney failure Diabetes Reference Reference Hypertensive kidney disease 1.04 (0.99 to 1.09) 0.15 1.03 (0.93 to 1.14) 0.53 GN 1.01 (0.93 to 1.10) 0.78 1.22 (1.05 to 1.42) 0.01 Other 1.06 (0.99 to 1.13) 0.08 1.20 (1.06 to 1.35) 0.005 Employment status Full time Reference Reference Part time 0.95 (0.76 to 1.18) 0.64 1.24 (0.84 to 1.84) 0.28 Unemployed 0.98 (0.84 to 1.14) 0.76 1.31 (0.98 to 1.75) 0.07 Retired 1.05 (0.90 to 1.23) 0.52 1.38 (1.02 to 1.85) 0.04 Disabled 1.13 (0.97 to 1.32) 0.13 1.67 (1.25 to 2.24) 0.001 Other 0.90 (0.75 to 1.08) 0.26 1.22 (0.88 to 1.71) 0.24 Bureau of economic analysis regions Midwest 0.89 (0.80 to 0.99) 0.03 0.73 (0.60 to 0.88) 0.003 Great Lakes 0.96 (0.86 to 1.06) 0.40 0.93 (0.77 to 1.11) 0.41 Plains 0.78 (0.69 to 0.88) <0.001 0.77 (0.62 to 0.96) 0.02 Southeast 1.03 (0.93 to 1.13) 0.59 0.93 (0.78 to 1.11) 0.42 Southwest 0.93 (0.84 to 1.04) 0.20 0.74 (0.61 to 0.89) 0.004 Rocky 0.73 (0.61 to 0.88) 0.002 0.76 (0.55 to 1.04) 0.09 Far West 0.98 (0.88 to 1.09) 0.69 0.70 (0.58 to 0.85) 0.001 All factors were included in a single Cox proportional hazards model with time from hemodialysis initiation to the first dispensed prescription for a short-acting or long-acting benzodiazepines as the outcome. aHR, adjusted hazard ratio; 95% CI, 95% confidence interval.
- Table 3.
Association between benzodiazepines and mortality in patients initiating hemodialysis (n=69,368) between 2013 and 2014
Exposure No. of Deaths Any, aHR (95% CI) Short Acting, aHR (95% CI) Long Acting, aHR (95% CI) Benzodiazepine 16,981 Unadjusted 1.52 (1.41 to 1.64) 1.73 (1.60 to 1.88) 0.83 (0.67 to 1.02) Adjusted 1.31 (1.23 to 1.40) 1.45 (1.35 to 1.56) 0.84 (0.72 to 0.99) LME per milligram higher 1.05 (1.03 to 1.07) 0.98 (0.91 to 1.05) Alprazolam (0.5 LME) 1.33 (1.17 to 1.51) Lorazepam (1.0 LME) 2.06 (1.82 to 2.34) Temazepam (10 LME) 1.48 (1.23 to 1.80) Clonazepam (0.25 LME) 0.73 (0.56 to 0.94) Diazepam (5 LME) 1.00 (0.69 to 1.44) Use of benzodiazepines was treated as time varying, and all models were adjusted. The results below are from three separate models; all models were adjusted for age, sex, race, prescription (antidepressants and CNS depressants), and comorbidities. CNS depressants included sedatives, muscle relaxants, and antipsychotics. Comorbidities included diabetes mellitus, cardiovascular disease, peripheral vascular disease, hypertension, COPD, smoking history, cancer, drug abuse, inability to ambulate, institutionalized, and obesity. In the short-acting benzodiazepine model, those taking long-acting benzodiazepines were treated as unexposed. Similarly, in the long-acting benzodiazepine model, those taking short-acting benzodiazepines were treated as unexposed. LME, lorazepam milligram equivalent.
- Table 4.
Association between benzodiazepines and mortality in patients initiating hemodialysis (n=69,368) between 2013 and 2014 stratified by age, sex, race, and opioid codispensing
Exposure No. of Deaths Follow-Up Time, person-yr Unadjusted aHR (95% CI) Adjusted aHR (95% CI) P Value for Interaction Any benzodiazepine 0.001 No opioid/no benzodiazepine 2556 182,800 Reference Reference No opioid/benzodiazepine 485 41,273 1.32 (1.20 to 1.44) 1.22 (1.13 to 1.32) Opioid/no benzodiazepine 2071 141,526 Reference Reference Opioid/benzodiazepine 190 8105 2.35 (2.04 to 2.71) 1.66 (1.46 to 1.90) Short-acting benzodiazepine <0.001 No opioid/no benzodiazepine 2514 174,636 Reference Reference No opioid/benzodiazepine 420 31,186 1.50 (1.36 to 1.65) 1.34 (1.23 to 1.45) Opioid/no benzodiazepine 2094 143,450 Reference Reference Opioid/benzodiazepine 167 6181 2.74 (2.35 to 3.19) 1.90 (1.65 to 2.18) Long-acting benzodiazepine 0.72 No opioid/no benzodiazepine 2305 157,870 Reference Reference No opioid/benzodiazepine 67 10,280 0.74 (0.58 to 0.94) 0.83 (0.69 to 1.00) Opioid/no benzodiazepine 2238 147,590 Reference Reference Opioid/benzodiazepine 23 2041 1.11 (0.74 to 1.67) 0.89 (0.64 to 1.24) Use of benzodiazepines and other medications was treated as time varying, and all models were adjusted. The results below are from three separate models; all models were adjusted for age, sex, race, prescription (antidepressants and CNS depressants), and comorbidities. CNS depressants included sedatives, muscle relaxants, and antipsychotics. Comorbidities included diabetes mellitus, cardiovascular disease, peripheral vascular disease, hypertension, COPD, smoking history, cancer, drug abuse, inability to ambulate, institutionalized, and obesity.
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