A sequence symmetry analysis of the interrelationships between statins, diabetes and skin infections

Abstract

Aims To determine statins' impact on skin infection risk in view of conflicting literature: that statins may reduce infection risk, but are also associated with diabetes mellitus, a risk factor for skin and soft tissue infections (SSTIs). Methods Sequence symmetry analysis was performed on prescription claims (2001–2011) from the Australian Department of Veterans' Affairs to determine the interrelationships between: (i) statins and SSTIs; (ii) statins and diabetes; and (iii) diabetes and SSTIs; as well as whether statins increased the risk of SSTIs, independent of diabetes status. Chi‐square tests were performed to detect differences in Index of Relative Socio‐economic Advantage and Disadvantage scores of patients within each interrelationship. Prescriptions for statins, antidiabetic medication, and antistaphylococcal antibiotics were evaluated using nonidentifiable client numbers, prescription dates filled, residential electorates, and pharmaceutical codes. Adjusted sequence ratio and confidence interval were calculated at intervals of 91, 182 and 365 days for sequence symmetry analysis studies. Results Statins were associated with: (i) significant SSTI risk (adjusted sequence ratio > 1; confidence interval >1), (ii) significant diabetes risk, and (iii) diabetic patients had increased risk of SSTIs. Diabetic and nondiabetic statin users had significantly increased risks of SSTIs, while the influence from socioeconomic status was not significant for each of the 3 relationships. Conclusions Statins are associated with increased risk of SSTIs via direct and indirect mechanisms, probably independent of diabetes or socioeconomic statuses. We believe that clinicians should be aware of the association between statins and SSTIs, and, where appropriate, monitor blood glucose levels of statin users.

High‐throughput screening for prescribing cascades among real world statin initiators

“…As previously noted, we also had similar findings with acetylcholinesterases (e.g., donepezil, N06DA) compared to an analysis using Korean National Health Insurance Service data (aSRs of 1.30 vs. 1.44) 15 . We identified a strong signal for skin infections (cephalosporins [e.g., cephalexin]; J01DB) however, found no signal for beta‐lactamase resistant penicillins (e.g., dicloxacillin; J01CF) somewhat contrasting findings from the Australian Department of Veterans' Affairs data 17 . Additionally, we classified signals involving medications used to treat diabetes mellitus as a potential prescribing cascade (Combinations of oral blood glucose lowering drugs [e.g.…”

“…Cardiovascular‐related prescribing cascades are considered high priority targets for deprescribing 9 . To date, seven statin‐related prescribing cascades have been described (Table S1 in the supplement) 10–17 . However, many of these cascades reflect known adverse events observed in large clinical trials or from spontaneous adverse event reporting and thus may have been expected.…”

“…9 To date, seven statin-related prescribing cascades have been described (Table S1 in the supplement). [10][11][12][13][14][15][16][17] However, many of these cascades reflect known adverse events observed in large clinical trials or from spontaneous adverse event reporting and thus may have been expected. Although these hypothesis-driven approaches provide clinically important insight into the presence and magnitude of prescribing cascades, they are not designed to discover new cascades, particularly those unrelated to previously known statin adverse events.…”

Prescribing cascades in community‐dwelling adults: A systematic review

“…Most studies ( n = 88) were retrospective cohort studies, 5 , 7 , 18 , 21 , 23 , 24 , 25 , 26 , 27 , 29 , 30 , 31 , 32 , 33 , 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , …”

“…Most studies ( n = 88) were retrospective cohort studies, 5,7,18,21,23–27,29–34,36–44,47–113 three of which incorporated a case–control study within the study design 49,85,110 and one that conducted a preliminary cross‐sectional study 112 . Five were case–control studies, 19,20 five cross‐sectional studies, 6,46,114–116 and three case‐crossover studies 45,117,118 .…”