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Table 3 Adjusted hazard ratios for Z-drug prescription and adverse events for people with dementia according to prescribed daily defined dose of Z-drugs

From: Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study

Outcome and daily defined dose prescribeda No. events in the Z-drug cohort Sleep disturbance and no sedative-hypnotic (n = 1833) No Z-drug, proximal GP consultation (n = 10,214)
Age, sex adjusted Fully adjustedb Age, sex adjusted Fully adjustedb
Fracture
 ≤ 0.5 117 1.30 (0.99–1.70) 1.22 (0.90–1.66) 1.33 (1.07–1.65) 1.28 (1.01–1.63)
 0.6–0.9 5 1.28 (0.51–3.20) 1.06 (0.39–2.89) 1.24 (0.50–3.05) 1.08 (0.42–2.76)
 ≥ 1 42 1.70 (1.19–2.42) 1.67 (1.13–2.46)c 1.66 (1.18–2.34) 1.58 (1.09–2.28)c
Hip fracture
 ≤ 0.5 55 1.30 (0.88–1.93) 1.21 (0.78–1.90) 1.42 (1.03–1.97) 1.43 (1.00–2.06)
 0.6–0.9 < 5 1.10 (0.26–4.67) 0.79 (0.15–4.11) 1.27 (0.31–5.22) 1.05 (0.24–4.64)
 ≥ 1 27 2.30 (1.45–3.65) 1.96 (1.16–3.31)c 2.50 (1.61–3.89) 2.36 (1.44–3.87)c
Forearm fracture
 ≤ 0.5 20 1.66 (0.81–3.40) 1.22 (0.48–3.12) 1.28 (0.77–2.15) 1.29 (0.73–2.27)
 ≥ 0.6 9 2.18 (0.98–4.85) 1.91 (0.67–5.47) 1.53 (0.72–3.24) 1.42 (0.59–3.38)
Fall
 ≤ 0.5 335 1.05 (0.90–1.22) 0.95 (0.80–1.13) 1.43 (1.26–1.63) 1.35 (1.17–1.56)c
 0.6–0.9 14 0.84 (0.49–1.44) 0.73 (0.41–1.29) 1.19 (0.70–2.02) 1.07 (0.61–1.87)
 ≥ 1 124 1.42 (1.15–1.74) 1.33 (1.06–1.66)c 1.92 (1.58–2.35) 1.81 (1.46–2.34)c
Mortality
 ≤ 0.5 321 1.49 (1.26–1.77) 1.38 (1.14–1.68)c 1.18 (1.03–1.34) 1.07 (0.93–1.24)
 0.6–0.9 16 1.56 (0.95–2.56) 1.60 (0.96–2.70) 1.25 (0.77–2.02) 1.22 (0.75–1.99)
 ≥ 1 99 1.56 (1.24–1.96) 1.33 (1.03–1.71) 1.26 (1.02–1.55) 1.06 (0.85–1.33)
Acute bacterial infection
 ≤ 0.5 297 1.15 (0.98–1.36) 1.00 (0.83–1.20) 1.37 (1.20–1.57) 1.23 (1.06–1.43)c
 0.6–0.9 13 0.98 (0.56–1.72) 0.86 (0.47–1.57) 1.20 (0.69–2.08) 1.12 (0.63–1.99)
 ≥ 1 106 1.40 (1.12–1.76) 1.25 (0.98–1.60) 1.64 (1.32–2.04) 1.52 (1.21–1.91)c
Ischaemic stroke/transient ischaemic attack
 ≤ 0.5 55 1.04 (0.72–1.51) 1.12 (0.71–1.75) 0.96 (0.71–1.30) 0.95 (0.68–1.31)
 0.6–0.9 5 1.97 (0.78–4.96) 1.98 (0.74–5.28) 1.74 (0.72–4.19) 1.71 (0.74–3.98)
 ≥ 1 33 2.07 (1.36–3.15) 1.88 (1.14–3.10)c 1.90 (1.30–2.79) 1.61 (1.08–2.42)
Venous thromboembolism
 ≤ 0.5 26 2.01 (1.16–3.49) 2.00 (0.90–4.47) 1.35 (0.85–2.13) 1.26 (0.74–2.12)
 ≥ 0.6 < 5 0.78 (0.27–2.25) 0.85 (0.21–3.39) 0.56 (0.21–1.54) 0.66 (0.22–1.95)
  1. Abbreviations: HR hazard ratio, CI confidence interval, GP general practitioner
  2. aThe reference group for all comparisons is no Z-drug prescription. Most patients assigned to the ‘0.6–0.9 DDD’ Z-drug group were prescribed 3.75 mg zopiclone with instructions similar to ‘TAKE ONE OR TWO AT NIGHT’
  3. bAdjusted for all covariates listed in Table 1
  4. cFully adjusted HR remaining statistically significant after controlling the false discovery rate to < 5% (based on 37 tests; 11 outcomes with three dose categories and two outcomes with two dose categories)