We used services rendered rather than registration data to determine whether patients were resident in the province, because individuals beginning to live abroad might not immediately cancel their provincial medical plan coverage. To ensure that new or temporary residents in the province were not filling renewal prescriptions, which would appear as new prescriptions in the drug database, we required evidence that patients had obtained at least 2 years of medical services in the province before the start of treatment with quinine. We also limited our analysis to patients aged 50 years or older at the time of prescription, because nocturnal leg cramps are uncommon in younger adults and hence young patients with leg cramps might have a higher proportion of cramp-associated disease (e.g., motor neuron disease, radiculopathy or hereditary cramp syndromes) that would make them atypical. To help ensure that patients were prescribed quinine for nocturnal leg cramps, we excluded records with physician diagnostic codes or procedural billing indicating malaria, dialysis or amyotrophic lateral sclerosis. We excluded quinine renewals from our analysis because the timing of a new prescription was presumed to be more strongly associated with disease activity than prescription renewals, which might be triggered as much by running out of pills as by fluctuations in symptom burden. 31, 2007, as the last search date for eligible quinine prescriptions. This resulted in a precipitous drop in quinine use, which stayed suppressed for several months. 22), both with provincewide distribution, warned about the health risks of quinine. 16) and a linked radio broadcast ( Almanac, CBC Radio One, Nov. In November 2007, a newspaper article ( Vancouver Sun, Nov. To ensure that new quinine prescriptions were not renewals of over-the-counter (previously unrecorded) quinine purchases, we limited our analysis to new prescriptions dispensed at least 1 year after the date that prescriptions for quinine were required (i.e., Dec. 30, 2000, quinine (previously available over the counter) became a prescription-only drug. We linked these data to hospital, physician services and registration records using encrypted patient identifiers. PharmaNet data, excluding the 4% of the population who are federally insured (e.g., military personnel, First Nations people and inmates in federal penitentiaries), were available for the period Jan. 10, 11 The database is linkable to data from hospital and physician services and registration data for the publicly funded provincial Medical Services Plan. This database contains data on drug use by the 4.2 million residents in the province, with minimal underreporting and misclassification. Pharmacists in the province of British Columbia are required to enter all prescriptions dispensed at community pharmacies, independent of payer, into the provincial PharmaNet database. 7 We also looked for evidence of seasonality more generally (i.e., all forms of leg cramps) by using the Google Trends search engine to look for seasonal variation in the volume of Internet searches for the term “leg cramps.” 8, 9 We did not use International Classification of Diseases diagnostic codes to identify patients with leg cramps, because their accuracy for this condition has not been validated (in our experience, the codes used by family physicians for leg cramps vary widely). 6 Therefore, new quinine prescriptions are an excellent marker for new or escalating treatment of leg cramps, and we previously used these data to assess the potential cramp-promoting effects of commonly used medications. Because the only indication approved by Health Canada (acute malaria) is uncommon, its use is almost exclusively off label for the prevention of nocturnal leg cramps. We looked for seasonality in new quinine prescriptions within the provincial prescribing databases of British Columbia, Canada.
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