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.

Impact of the COVID-19 pandemic on cardiovascular heart disease medication use: time-series analysis of England's prescription data during the COVID-19 pandemic (January 2019 to October 2020).

BACKGROUND: Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to some routine prescriptions and changed some patient health behaviours. AIM: This study, therefore, retrospectively investigated prescription reimbursement of cardiovascular (CVD) medicines as a proxy measure for patient adherence and access to medicines during the pandemic. METHODS: A cohort study of all primary care patients in England prescribed CVD medicines. The exposure was to the global pandemic. Prescriptions were compared before and after the pandemic's onset. Statistical variation was the outcome of interest. RESULTS: Descriptive statistics show changes to monthly prescriptions, with wide confidence intervals indicating varying underlying practice. Analysis of variance reveals statistically significant differences for bendroflumethiazide, potassium-sparing diuretics, nicorandil, ezetimibe, ivabradine, ranolazine, colesevelam and midodrine. After the pandemic began (March-October 2020), negative parameters are observed for ACE inhibitors, beta-blockers, calcium channel blockers, statins, antiplatelet, antithrombotics, ARBs, loop diuretics, doxazosin, bendroflumethiazide, nitrates and indapamide, indicating decelerating monthly prescription items (statistically significant declines of calcium channel blockers, antithrombotic, adrenoreceptor blockers and diuretics) of CVD medicines within the general population. Many data points are not statistically significant, but fluctuations remain clinically important for the large population of patients taking these medications. CONCLUSION: A concerning decline in uptake of CVD therapies for chronic heart disease was observed. Accessible screening and treatment alongside financial relief on prescription levies are needed. A video abstract is (4 min 51 s) available: https://bit.ly/39gvEHi.

A cross-sectional study on substandard and falsified medicines (fake or counterfeit drugs) in UK pharmacies during the COVID-19 pandemic.

BACKGROUND: Failure of the Falsified Medicines Directive (FMD) in the UK could mean that substandard and falsified medicines (SFs) enter the supply chain. Does this risk patients' health? Readiness to implement FMD, and prevalence of SFs vs. regulator detection were assessed. RESEARCH DESIGN AND METHODS: A total of 12,040 primary care pharmacies across England were invited (April 2021-March 2022). Respondent postcodes were used to extract deprivation scores. Information request was placed with the medicine's agency. Survey findings were used to calculate probability and power of a simulated trial. RESULTS: A total of 208 participants responded: Of the seven who identified SFs, all but one reported it; 61% were ready to implement FMD, 74.1% had adequate resources, 54.8% expected improved patient safety, and 17.8% had ever reported SFs. SFs were prevalent in deprived areas. Bayesian simulation shows 438 (p = 0.030) incidences with a 3% probability of SFs prevalence. The agency identified 15,238 SFs units in the supply chain (2019 and 2020). Results are credible, reliable, and generalisable, with corroborated longitudinal persistence. CONCLUSIONS: FMD or equivalent processes need to be urgently reinstated. Deprived children may be more affected. Pharmacists are worried about liability. All health consultations should assess safety, and effectiveness of medicines. Findings should inform policy, systems planning, surveillance, and evaluations.

Impact of the COVID-19 pandemic on England's national prescriptions of oral vitamin K antagonist (VKA) and direct-acting oral anticoagulants (DOACs): an interrupted time series analysis (January 2019-February 2021).

BACKGROUND: Direct-acting oral anticoagulants (DOACs) were developed as an alternative to warfarin to treat and prevent thromboembolism, including stroke prevention in non-valvular atrial fibrillation patients. The COVID-19 pandemic could increase the risk of stroke and/or the risk of bleeding in patients due to nonadherence or sub/supra-optimal dosing. OBJECTIVE: To investigate DOAC prescription trends in England's community settings during the complete first wave of COVID-19 pandemic. METHODS: Descriptive and interrupted time series (ITS) analyses were conducted to examine the prescription patterns of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) and warfarin for primary care patients in the English Prescribing Dataset from January 2019 to February 2021, with March 2020 as the cut-off point. RESULTS: A 19% increase in mean DOAC's accompanied with 20% warfarin prescriptions decline was observed. ITS modelling showed an increase in DOAC prescription volume in March 2020 (+7 million items, p = 0.008). The pre-existing upward trend in DOAC prescriptions slowed during the period (-427,000 items, p = 0.007). Apixaban was the most frequently used DOAC and had the largest step-change in March 2020 (+5 million items, p = 0.010). The mean monthly combined cost of DOACs and warfarin was higher during the period. DOAC prescription trends were consistent across England's regions. Conclusion: The overall oral anticoagulants use in this period was lower than expected, indicating a medical needs gap, possibly due to adherence issues. The potential clinical and logistical consequences warrant further study to identify contributing factors and mitigate avoidable risks.

Calcineurin inhibitors and related medicines: a cohort study examining England’s primary care prescription changes during the COVID-19 pandemic (January 2019 to March 2021)

Purpose To examine the impact of the COVID-19 pandemic on calcineurin inhibitors and related prescriptions for community patients in England. Methods Data from all primary-care patients who had calcineurin inhibitors prescriptions, dispensed in the community in England were included. Descriptive statistics and interrupted time series analysis over 27 months (15 months before and 12 months after 1st lockdown) was evaluated. Results Descriptive statistics show that mean values have declined since the pandemic’s onset. Over the 27 months: mean Tacrolimus 865,045 doses, standard deviation (SD) 76,147 doses, with 95% CI 834,923, 895,168, (min 567,508, max 1,010,900), ciclosporin 315,496 doses, SD 40,094, 95% CI 299,635, 331,356 (min 191,281, max 382,253) and sirolimus 21,384 doses, SD 2,610, 95% CI 20,352, 22,417 (min 13,022, max 26,156). Analysis of variance between the pre- and post- periods show significant variations in quantities of tacrolimus F 7.432, p = 0.012, ciclosporin F 33.147, p < 0.001 and sirolimus F 18.596, p < 0.001 (1df), mirrored in price analysis. The Interrupted Time Series (ARIMA Modelling) shows declining trends. After the pandemic's onset, a statistically significant downward trend in quantity for tacrolimus p = 0.008 is observed, with an estimated monthly decline of 14,524 doses, ciclosporin p = 0.185, with an estimated decline of 2,161 doses and sirolimus p = 0.002 with an estimated decline of 485 doses, along with declining prices. Conclusion A decrease in prescription medicines use raises concerns for the care of (renal) transplant patients. Patients are encouraged to discuss their planned care with their doctor, secure supplies and remain adherent to their medication. Graphical Supplementary Information The online version contains supplementary material available at 10.1007/s40199-021-00431-7.

Calcineurin inhibitors and related medicines: a cohort study examining England's primary care prescription changes during the COVID-19 pandemic (January 2019 to March 2021).

PURPOSE: To examine the impact of the COVID-19 pandemic on calcineurin inhibitors and related prescriptions for community patients in England. METHODS: Data from all primary-care patients who had calcineurin inhibitors prescriptions, dispensed in the community in England were included. Descriptive statistics and interrupted time series analysis over 27 months (15 months before and 12 months after 1st lockdown) was evaluated. RESULTS: Descriptive statistics show that mean values have declined since the pandemic's onset. Over the 27 months: mean Tacrolimus 865,045 doses, standard deviation (SD) 76,147 doses, with 95% CI 834,923, 895,168, (min 567,508, max 1,010,900), ciclosporin 315,496 doses, SD 40,094, 95% CI 299,635, 331,356 (min 191,281, max 382,253) and sirolimus 21,384 doses, SD 2,610, 95% CI 20,352, 22,417 (min 13,022, max 26,156). Analysis of variance between the pre- and post- periods show significant variations in quantities of tacrolimus F 7.432, p = 0.012, ciclosporin F 33.147, p < 0.001 and sirolimus F 18.596, p < 0.001 (1df), mirrored in price analysis. The Interrupted Time Series (ARIMA Modelling) shows declining trends. After the pandemic's onset, a statistically significant downward trend in quantity for tacrolimus p = 0.008 is observed, with an estimated monthly decline of 14,524 doses, ciclosporin p = 0.185, with an estimated decline of 2,161 doses and sirolimus p = 0.002 with an estimated decline of 485 doses, along with declining prices. CONCLUSION: A decrease in prescription medicines use raises concerns for the care of (renal) transplant patients. Patients are encouraged to discuss their planned care with their doctor, secure supplies and remain adherent to their medication.

Asthma and COPD medicines prescription-claims: A time-series analysis of England's national prescriptions during the COVID-19 pandemic (Jan 2019 to Oct 2020).

BACKGROUND: During the pandemic, there have been disruptions to how patients seek care. RESEARCH DESIGN AND METHODS: To investigate monthly prescription claims for asthma and chronic obstructive pulmonary disease (COPD) medicines during the first UK wave, interrupted time series (ITS) analysis was used. A national cohort of community patients' data were examined. RESULTS: Descriptive statistics show salbutamol, aminophylline, ipratropium, and theophylline remain below pre-pandemic levels.Montelukast showed pre-pandemic monthly increase (Est. 67,151 doses, P = 0.05, 95% CI: 1011, 133,291), followed by a jump of 1.6 million doses at March , followed by monthly declines (Est. -112,098 doses, P = 0.216, 95% CI: -293,499, 69,303).Before the pandemic, tiotropium, salbutamol, aminophylline, and ipratropium (P = 0.003) show monthly declines but theophylline and beclometasone showed increases. In March , salbutamol (P = 0.033) and ipratropium (P = 0.001) show a significant jump. After March , ipratropium continues with a downward trajectory (P = 0.001), with a generalized negative trend for all other agents. Salbutamol confidence bounds become negative after March 2020. Some brands were unavailable. CONCLUSIONS: An 'unmet' medical gap is identified. While it is essential to understand the underlying reasons, urgent action needs to be taken to reassess patients and ensure continuity of care.PLAIN LANGUAGE SUMMARIES (PLS)Asthma and chronic obstructive pulmonary disease (COPD) are long-term lung conditions, affecting 6 million & 1.2 million people respectively and causing breathing difficulties. Sufferers are at a higher risk of chest infections including the coronavirus. Regular use of prescribed medication stabilizes these conditions and prevents them from getting worse. It is common to be prescribed a combination of five to eight oral and inhaled medications.We investigated the impact of the pandemic on the dispensing of these specific medicines across England during the first wave. The English Prescribing Dataset was checked from January 2019 to February 2020 (14 months before the pandemic) and March to October 2020 (8 months after its onset).We find that since March 2020, salbutamol, aminophylline, ipratropium, and theophylline have not returned to their pre-pandemic levels. However, for all agents, there is great variability. Further analysis suggests these trends are not reversing, suggesting that people have not been using their medication as anticipated for 8 months, which is concerning.As a consequence of this work, we recommend that doctors specifically call these patients and discuss their health as a matter of urgency, we encourage patients to continue to take their medication. We advise policy changes to waive the NHS prescription levy for asthma and COPD medication and we seek more granular data for further harm quantification. There are several strengths and weaknesses to our analysis, and we need to conduct more studies to ask patients about their experiences.

Gonadorelins adherence in prostate cancer: A time-series analysis of England's national prescriptions during the COVID-19 pandemic (from Jan 2019 to Oct 2020).

Objective: To examine the effect of the COVID-19 pandemic on gonadorelin analogue prescription for community patients in England. Materials and methods: We included data from all primary-care patients who had relevant prescriptions dispensed in the community in England. Descriptive statistics and interrupted time series analysis over 22 months (15 months before and 7 months after lockdown) was evaluated. Results: A total of 22 months' worth of data were analyzed (or 1 041 638 total items, monthly average 47 347 items). Goserelin; leuprorelin, and triptorelin are the medicines most used by total quantity in the study period. Simple descriptive statistics show that mean values have declined during the pandemic. The Interrupted Time Series (ARIMA Modeling) shows declining trends.After the pandemic's onset, we observe a statistically significant downward trend for goserelin (P = .017) and leuprorelin (P = .014). As these are the major constituents of the model, we interpret this overall data as showing a significant downward category trend. Aside from linearity, a significant step change was noted for leuprorelin (P = .029) showing an increase in prescription items with a similar effect that is close to being statistically significant for goserelin (P = .051).The actual cost of medicines shows minimal variation suggesting that prices of individual medicines have remained stable. The regional data showed variation but this was not statistically significant. In all cases, the Oct-20 figures are lower "year on year." This novel work reports the impact of a global pandemic on prescription volumes of prostate cancer (PCa) medicines. Conclusions: A worrying decrease in prescription medicines raises concerns for the care of PCa patients. We encourage diagnosed patients to discuss their planned care with their doctor.

Acute oxygen therapy: a cross-sectional study of prescribing practices at an English hospital immediately before COVID-19 pandemic.

BACKGROUND: Approximately 14% of UK hospital in-patients receive supplemental oxygen therapy, only 57% have valid prescriptions. Oxygen must be optimally prescribed to ensure maximal therapeutic response whilst minimizing adverse outcomes (including fatality). This study investigates prescription compliance. METHODS: All adults admitted to medical wards (18 February to 3 March 2020) were included. Analyses present proportions, descriptive statistics, and hypothesis testing. Ethical approval was unnecessary for this audit. RESULTS: Of the 636 patients admitted, 66 (10%) were receiving oxygen therapy. Ages ranged from 34 to 100 years with 36 (54.5%) males and 30 (45.5%) females. The prescription was not documented in the oxygen section of the drug chart (n = 37, 56.1%, p = 0.389), nor did it have the physicians signature (n = 40, 60.6%, p = 0.110) nor date (n = 46, 69.7%, p = 0.002). Thirteen chronic obstructive pulmonary disease (COPD) patients (19.7%) were at risk of hypercapnic failure (p = 1.582x10-6). Target oxygen saturation (SpO2) range had been documented for 30 (45.5%) patients. A target SpO2 range of 88-92% was documented for 9 patients (13.6%), a 94-98% range documented for 11 patients (16.7%). All patients had an invalid prescription. CONCLUSION: We present real-world practice in naturalistic settings, immediately before pandemic-lockdown. Enhanced compliance is advocated to reduce risks of harm and mortality.