The Effects of Removing the Requirement for Prior Reimbursement Approval on Anticoagulant Use in Ireland: A Cross-Sectional Study.

PURPOSE: Prior approval for reimbursement is a policy of cost containment while ensuring oversight and governance of medicines. It has been employed in Ireland to address financial challenges due to the shift from warfarin to direct oral anticoagulants (DOACs). Studies assessing the effectiveness of this policy are limited. Thus, we aimed to examine the effectiveness of prior approval for reimbursement of DOACs (apixaban, rivaroxaban) as a cost containment policy in Ireland. METHODS: The Irish Health Service Executive-Primary Care Reimbursement Service database was used in this cross-sectional study. We examined the prescribing frequencies and associated costs of the oral anticoagulants; [(OACs) apixaban, rivaroxaban and warfarin] listed in the top 100 most frequently prescribed drugs, between 2018 and 2021. Time series negative binomial regression was used to assess the impact of removing the approval requirement of apixaban in September 2019 followed by the other DOACs in November 2020. RESULTS: The prescribing frequency of OACs increased by almost 20% from 2018 to 2021. This study showed there were significant differences in the proportion of OACs prescribed among the Community Drug Schemes. A statistically significant decreased use of apixaban (< 1%, p < 0.05) occurred when prior approval was removed for all DOACs. CONCLUSIONS: The removal of prior approval for reimbursement of DOACs in Ireland had a minimal impact on the prescribing frequency trends of the OACs. Future use of these potentially useful policies by healthcare systems requires careful consideration of drug type, approval criteria and length of time the policy remains in place to minimise any negative effects associated with their use.

Impact of coronavirus disease 2019 on head and neck urgent suspected cancer referral pathways in rural Wales.

OBJECTIVE: To assess the impact of the coronavirus disease 2019 pandemic on head and neck urgent suspected cancer referral pathways in rural areas of Wales. METHOD: A retrospective audit was conducted of 2234 head and neck urgent suspected cancer referrals received from January 2019 to November 2020. RESULTS: The referrals dropped by 35 per cent in 2020 compared to the same period in 2019. The time from general practitioner referral to the first ENT appointment improved during the pandemic (8.0 vs 10.0 days; p < 0.001). Of referrals, 92.1 per cent were seen within a 14-day period in 2020, compared with 79.6 per cent in 2019 (p < 0.001). There were no differences between 2020 and 2019 in terms of: the (confirmed cancer) conversion rate (10.6 per cent vs 9.7 per cent; p = 0.60), general practitioner referral to multidisciplinary team discussion time (35.5 vs 41.5 days; p = 0.40) or general practitioner referral to initiation of treatment time (68.0 vs 78.0 days; p = 0.16). CONCLUSION: Whilst coronavirus disease 2019 reduced the number of overall head and neck urgent suspected cancer referrals, the pathways were generally unchanged, if not slightly improved, in rural Wales.

Model studies of DNA photorepair: enthalpy of cleavage of a pyrimidine dimer measured by photothermal beam deflection calorimetry.

The enzyme DNA photolyase mediates the repair of pyrimidine dimers. This repair step, a net retro [2 + 2] reaction, proceeds through either the cation or anion radical of the pyrimidine dimer. In order to understand how electron transfer makes the repair process possible, its energetics have been examined by photothermal beam deflection calorimetry, fluorescence quenching and quantum yield studies. The enthalpy for the cleavage reaction of cis-syn 1,3-dimethylthymine dimer itself was found to be -19 kcal/mol. In addition, from the redox potentials, the enthalpies for the cleavage reactions of the dimer cation radical and the anion radical were determined to be -19 kcal/mol and -28 kcal/mol, respectively.

Changes in concentrations of lysergol in urine and prolactin in plasma, rectal temperature and respiration rate in sheep selected for resistance or susceptibility to ryegrass staggers and fed ergovaline.

AIM: To determine the effects of feeding ryegrass seed containing ergovaline to sheep selected for resistance or susceptibility to ryegrass staggers on concentration of lysergol (a metabolite of ergovaline) in urine, prolactin in plasma, rectal temperature and respiration rate. METHODS: Two experiments were carried out using 12 Romney crossbred ewe lambs aged 9 months, comprising animals resistant (n=4), susceptible (n=4) or outcross (n=4) to ryegrass staggers. In Experiment 1, sheep were given either a single (Part A) or six (Part B) feed (s) of endophyte-infected seed containing ergovaline at 30 mg/kg dry matter (DM), at 42 µg ergovaline/kg bodyweight (BW), to simulate acute and chronic exposure to ergovaline, respectively. The concentration and excretion of lysergol in urine and concentration of prolactin in plasma were measured over 3 and 12 days, for Parts A and B respectively. In Experiment 2, after a recovery period of 7 days, the same sheep were fed with ergovaline at 67 µg/kg of BW for 7 days. Soon after the seventh feed the sheep were moved to a hothouse at 36.5°C and 60% humidity, and 3 h later their rectal temperatures and respiration rates were measured. RESULTS: The concentration of lysergol and excretion in urine increased to a peak between 6 and 9 h after exposure to ergovaline whereas the concentration of prolactin in plasma was markedly reduced. Differences in concentration and rate of excretion of lysergol in urine between animals resistant, outcross and susceptible to ryegrass staggers were not significant (p>0.1). The animals resistant to ryegrass staggers had a lower rectal temperature (p<0.05) and a faster respiration rate than the outcross and susceptible groups when exposed to high ambient temperature and high humidity. CONCLUSIONS: This study showed that excretion of lysergol in urine increased with each exposure of sheep to ergovaline. Animals genetically resistant to ryegrass staggers exhibited a lower rectal temperature and a faster respiration rate than those susceptible, demonstrating the possible cross resistance of sheep to ergovaline in a population originally selected for resistance to ryegrass staggers. Hence potential exists to select animals resistant to ryegrass staggers that are also resistant to ergovaline.

The S-alkyl chain length as a determinant of the anti-leukemic activity of cysteine chloromethyl ketone compounds.

A series of cysteine chloromethyl ketone compounds with a systematic variation of the S-alkyl chain length have been synthesized in order to gauge the effect of the alkyl chain length on the cytotoxicity of these compounds against human acute lymphoblastic leukemia cells. Comparable activities were observed for compounds with S-alkyl chains ranging from pentyl to dodecyl, with the best being undecyl (IC50= 1.7 microM) and dodecyl (IC50=2.0 microM) against B-lineage leukemia cells and hexyl (IC50 = 0.7 microM) against T-lineage leukemia cells.