Impact of the COVID-19 pandemic on prescription refills for immune-mediated inflammatory disorders: a time series analysis (January 2019 to January 2021) using the English Prescribing Dataset.

OBJECTIVE: To investigate monthly prescription refills for common immunosuppressive/immunomodulatory therapy (sulfasalazine, hydroxychloroquine, azathioprine, methotrexate, leflunomide) prescriptions in England during the complete first wave of the COVID-19 pandemic. Secondary analysis examined unit cost analysis and regional use. DESIGN AND SETTING: A national cohort of community-based, primary care patients who anonymously contribute data to the English Prescribing Dataset, dispensed in the community in England, were included. Descriptive statistics and interrupted time series analysis over 25 months (14 months before, 11 months after first lockdown) were evaluated (January 2019 to January 2021, with March 2020 as the cut-off point). OUTCOME MEASURES: Prescription reimbursement variance in period before the pandemic as compared with after the first lockdown. RESULTS: Fluctuation in monthly medicines use is noted in March 2020: a jump is observed for hydroxychloroquine (Mann-Whitney, SE 14.652, standardised test statistic 1.911, p value=0.059) over the study period. After the first lockdown, medicines use fluctuated, with wide confidence intervals. Unit-cost prices changed substantially: sulfasalazine 33% increase, hydroxychloroquine 98% increase, azathioprine 41% increase, methotrexate 41% increase, leflunomide 20% decrease. London showed the least quantity variance, suggesting more homogeneous prescribing and patient access compared with Midlands and East of England, suggesting that some patients may have received medication over/under requirement, representing potential resource misallocation and a proxy for adherence rates. Changepoint detection revealed four out of the five medicines' use patterns changed with a strong signal only for sulfasalazine in March/April 2020. CONCLUSIONS: Findings potentially present lower rates of adherence because of the pandemic, suggesting barriers to care access. Unit price increases are likely to have severe budget impacts in the UK and potentially globally. Timely prescription refills for patients taking immunosuppressive/immunomodulatory therapies are recommended. Healthcare professionals should identify patients on these medicines and assess their prescription-day coverage, with planned actions to flag and follow-up adherence concerns in patients.

Hypothesis testing for neural cell growth experiments using a hybrid branching process model.

Neuron branching patterns can characterize neural cell types and act as markers for neurodegenerative disease and neural development. We develop a hybrid Markovian model for neural branching that extends previously published models by (i) using a discretized gamma model to account for underdispersion in primary branching, (ii) incorporating both bifurcation and trifurcation branching events to accommodate observed data, and (iii) only requiring branch counts and not branching topology as observations, allowing larger numbers of neurons to be sampled than in previous literature. Inference for primary branching is achieved through a gamma generalized linear model. Due to incomplete data, bifurcation and trifurcation probabilities are estimated using an expectation-maximization algorithm, which is shown to give consistent estimates using simulation studies and theoretical arguments. In simulation studies, comparison of standard errors shows no significant loss of accuracy relative to when topological information is available. A unified methodology for testing hypotheses using likelihood ratio tests (LRTs) is developed. The methodology is applied to an experiment where neurons are cocultured with different treatments: growth factor (GF), hypothalamic-astroglial conditioned medium (HY), and combination. The model provides statistically adequate fit at all branching orders. All treatments cause significantly higher branching at primary and secondary orders relative to control (p-value < 0.01), but not at higher branching orders, suggesting genetic regulation by the treatments. Using a computationally feasible lower bound on the LRT, bifurcation probabilities are shown to decrease exponentially with branching order for all treatments except HY (p-value 0.03).

Levels and temporal trends (1983-2003) of persistent organic pollutants (POPs) and mercury (Hg) in seabird eggs from Northern Norway.

The main objective of this study was to investigate possible temporal trends of persistent organic pollutants (POPs) and mercury in eggs of herring gulls (Larus argentatus), black-legged kittiwakes (Rissa tridactyla), common guillemots (Uria aalge) and Atlantic puffins (Fratercula arctica) in Northern Norway. Eggs were collected in 1983, 1993 and 2003. Egg concentrations of POPs (PCB congeners IUPAC numbers: CB-28, 74, 66, 101, 99, 110, 149, 118, 153, 105, 141, 138, 187, 128, 156, 157, 180, 170, 194, 206, HCB, alpha-HCH, beta-HCH, gamma-HCH, oxychlordane, trans-chlordane, cis-chlordane, trans-nonachlor, cis-nonachlor, p,p'-DDE, o,p'-DDD, p,p'-DDD, o,p'-DDT and p,p'-DDT) and mercury were quantified. Generally, POP levels decreased between 1983 and 2003 in all species. No significant temporal trend in mercury levels was found between 1983 and 2003.