An observational cohort study to examine SPUR, a patient-reported outcome measure of medication adherence, as a predictor of admission and early readmission in patients living with Type 2 Diabetes

Introduction: Conservative estimates suggest that the cost of poor medication adherence (MA) to healthcare systems in the UK is close to 800Mn annually, however figures may be as high as 920Mn to 224Bn across larger parts of Europe and the US.(1) This may be attributed to the relationship between poor MA and an increased risk of hospital admission.(2) Often, cases are preventable and hence present an opportunity for avoidable costs if appropriately identified and managed, such as in the case of early readmissions (admissions occurring within 30 days of discharge). However, despite the association between MA and admissions, to date no predictive model has been developed that integrates a holistic Patient-Reported Outcome Measure (PROM) of MA. This study evaluated one such PROM, known as SPUR, as a predictor of general admission and early readmission in patients living with Type 2 Diabetes (T2D). Aim(s): This study sought to develop a predictive model of early readmission and general admission risk using the SPUR tool as a PROM of MA in patients living with T2D. Method(s): Using an observational study design, 6-month retrospective and prospective patient monitoring were conducted to assess the number of admissions and early readmissions during the observational period. Outcomes were reported as binary and count variables. Patients were previously recruited from a large London NHS Trust as part of a cross-sectional study to validate SPUR. Covariates of interest included: age, ethnicity, gender, education level, income, the number of medicines and medical conditions, and Covid-19 diagnoses. A Poisson or negative binomial model was employed for count outcomes, with the exponentiated coefficient indicating incident ratios (IR) [95% CI]. For binary outcomes (Coefficient, [95% CI]), a logistic regression model was developed. Result(s): Data were available for 200 patients. The modal age range was 70-79 years (n=74/200, 37.0%). Most participants were GCSE educated (42.5%), white (76.0%), and over a third female (36.0%) identified as female. For general admission risk as a count variable, a higher SPUR score (increased adherence) was significantly associated with a lower number of admissions (IR = 0.98, [0.96, 1.00]). Other factors associated with an increased risk of admission included: age >=80 years (IR = 5.18, [1.01, 26.55]), GCSE education (IR = 2.11, [1.15 - 3.87]), number of medical conditions (IR = 1.07, [1.01, 1.13]), and a positive Covid- 19 diagnosis during follow-up (IR = 1.83, [1.11, 3.02]). SPUR remained significant when modelled as a binary variable (-0.048, [-0.094, -0.003]). For early readmission, only the SPUR score was significantly predictive of the outcome as a binary variable (-0.051, [-0.094, -0.007]), indicating that those with a higher SPUR score were at less risk of an early readmission. Conclusion(s): The study successfully developed a predictive model for both general admission and early readmissions in patients living with T2D using the SPUR tool and several covariates of clinical relevance. However, a small sample size is noted as a limitation. Future work may look to integrate SPUR as a holistic PROM of MA to support the development of tailored interventions to reduce patients' risk of admission.

A cross-sectional study to evaluate the validity of a novel patient-reported outcome measure of medication adherence in Chronic Obstructive Pulmonary Disease

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is a respiratory condition characterised by a progressive and irreversible decline in lung function. COPD prevalence increased by 44.2% between 1990 and 2015, resulting in 3.2 million deaths globally in 2015.(1) Inhalers are an essential treatment for people living with COPD. However, poor adherence to inhaled medicines is associated with worsening symptom severity, increased hospitalisation, comorbidity, and mortality.(2) Patient Reported Outcome Measures (PROMs) have been designed to examine the factors that contribute to poor medication adherence (MA). To date, none provide a holistic assessment that could be used to design tailored MA interventions. This study sought to address this by evaluating a novel PROM that holistically assesses four key factors of MA referred to as Social, Psychological, Usage, and Rationale, in short, SPUR. Aim(s): To explore the validity of the SPUR model as a holistic PROM of MA in patients living with COPD Methods: This cross-sectional study surveyed adults living with COPD from a large London NHS Trust between January and December 2021. Participants were eligible if they had >=1 inhaler prescribed for a minimum of 6 months prior to the study and were able to read and write in English. Participants who were too clinically unwell to independently complete the survey were excluded, which often included those with a Covid-19 diagnoses. Convenience sampling was used to recruit participants from in-patient wards and the acute admissions unit prior to administration of face-to-face surveys. Survey questions related to socio-clinical data, the SPUR tool, and a previously validated PROM known as the Inhaler Adherence Scale (IAS) that was included as a comparator. The Medication Possession Ratio (MPR), a measure of a patient's pill count in a given time period, was used as an objective comparator of MA. MPR, IAS, and SPUR scores were compared using Spearman's rank correlation coefficient (p). Symptom severity was examined using the COPD Assessment Test (CAT), with a Chi-square analysis (chi2) conducted to explore the relationship between the CAT and SPUR. Result(s): From 123 patients approached for this study, 100 participated providing a response rate of 81.3%. The modal age range was 70-79 years. Participants were predominantly white (90%), educated to GCSE level (51%), and identified as female (52%). Over two thirds (67%) were ex-smokers. SPUR was significantly (p<0.01) and positively correlated with IAS (p=0.65) and MPR (p=0.30), demonstrating that SPUR is a valid measure of MA. Chi-Square analysis identified a significant (p<0.01) relationship between CAT and SPUR scores (chi2=8.570);hence SPUR could reliably identify patients with poorer adherence, which was associated with worsening symptom severity. Conclusion(s): A study strength includes the implementation of an objective measure (MPR) and PROM (IAS) as part of validating SPUR. However, the results should be treated cautiously given the small sample size, which was limited due to Covid-19. This study provides early evidence of SPUR as a reliable holistic measure of MA with significant associations to COPD symptom severity, which could be applied in clinical practice to prospectively address patient outcomes linked to poor MA.

PRECISION MEDICINE

Precision Medicine is one of the most impactful global opportunities in healthcare. We can debate the name, whether it is precision, stratified or personal but at the highest strategic level, we all share a common goal to enable a world where healthcare is informed by each person unique clinical, molecular and lifestyle information. Precision Medicine will spur a revolution in healthcare, bringing the prospects of earlier, pre-symptomatic diagnosis, more effective treatment, significant cost savings for the NHS and all the above combined with better patient outcomes. Moreover, Precision Medicine will reach the global market value of £134 billion by 2025 thus contributing to unprecedented developments in Life Sciences industry, including new jobs creation, and a significant economic growth. The UK is in a prime position to lead on Precision Medicine globally due to the NHS facilitating advanced health data management, excellent genomics and other omics, new imaging modalities and major advances in the artificial intelligence applied to diagnostics. All the above is supported by the triple helix approach, which involves close collaborations among academic researchers, the NHS and industry. The Covid-19 pandemic has made a major contribution to the UK molecular diagnostic capability. This legacy includes very high throughput laboratories, which should become key building blocks for the UK cutting edge Precision Medicine strategy for the next decade and beyond.

Conjugate Effects of Covid-19 and Trips on the Pharmaceutical Drug Prices and Marketing Strategies

COVID-19 waves were the deadliest health crisis faced by the residents of planet earth in the 21th century. This outbreak of SARV-CoV-2 virus and its variants has impacted nearly all of the world in a short window of 16 months. Almost all the nations in the world had maintained a complete lockdown in all the spheres to withstand this medical health emergency. Thus, COVID-19 has a deep impact on the global economy and commerce because of lockdowns, and limited movements as defined in COVID-19 protocol guidelines for its prevention. The trade modalities of the pharmaceutical industry, which is already being governed under the TRIPS and WHO agreements, also got effected like other sectors of the economy. The significant setbacks for the pharmaceutical industry were the disruptions in the operations due to clogged supply chains of raw materials and stalled production units. On the contrary, the opportunity for the invention of vaccines provides the spur for research and development. Certainly, the prices of the drugs and marketing strategies have also been adjusted during this period. In this paper, authors have tried to trace and survey the combined effects of COVID-19 and TRIPS on the pharmaceutical industry's marketing manoeuvres and the prices of the drugs. Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

HUMORAL RESPONSE TO THIRD DOSE OF SARS-COV-2 VACCINES IN THE CKD SPECTRUM: THE SENCOVAC STUDY

BACKGROUND AND AIMS: There is incomplete information on the impact of a third dose of the SARS-CoV-2 vaccine in advance chronic kidney disease (CKD). The aim of the present analysis was to evaluate the kinetics of humoral response in the CKD spectrum (KT, HD, PD and ND-CKD) 6 months after completing the initial vaccine schedule. Some patients of each group received a third dose before 6 months, providing a pragmatic insight into real-world responses to different vaccine schedules in patients with advanced CKD not on dialysis, on dialysis or in KT recipients. METHOD: The SENCOVAC study describes the humoral response and safety of different SARS-CoV-2 vaccines in a real-world setting in 3687 CKD patients: 787 kidney transplant (KT), 319 peritoneal dialysis (PD), 2297 haemodialysis (HD) and 284 non-dialysis-CKD (ND-CKD) patients. Anti-Spike antibodies were assessed in an efficacy analysis at 28 days (n = 1755), 3 months (n = 1386), and 6 months (n = 1018, of whom 628 had received a third vaccine dose). Adverse events (AEs) were registered during follow-up, including SARS-CoV-2 infections in the safety analysis. RESULTS: Among the patients included in the efficacy analysis, KT recipients presented lower anti-Spike antibody titers than other CKD cohorts at 28 days and 3 months (P < .001 for all). A total of 943 patients [249 (26%) KT, 108 (11%) PD, 511 (54%) HD and 75 (8%) ND-CKD] had negative baseline anti-Spike antibodies. Again, at 28 days or 3 months, KT recipients developed lower anti-Spike antibody titers than PD (P < .001), HD (P < .001) and ND-CKD (P< .001) patients. At 6 months, patients that had received a third vaccine dose had higher anti-Spike antibody titers than those without the third dose [1837 (507-9726) UI/mL versus 80 (19-409) ml/UI;P < .001] and this was evident in all CKD cohorts. Anti-Spike titers after the third dose were higher in patients boosted with mRNA-1273 than with BNT162b2 [1710 (322-9615) versus 472 (34-2094);P < .001). At 6 months, in patients that had received a third dose, a positive humoral response (anti-Spike antibodies > 36 UI/mL) was achieved in 584 (93%): 94 (80%) of 118 KT recipients, 20 (100%) of 20 patients on PD, 436 (96%) of 455 patients on HD and 34 (97%) of 35 patients with ND-CKD (Fig. 1). Among patients without humoral response 3 months after completing the initial vaccination schedule, 72 (69%) seroconverted after the third dose (62% KT, 76% HD, 100% NDCKD, all PD patients had a positive humoral response at 3 months). Independent predictors of a positive humoral response at 6 months were not-KT (HR for KT 0.26, P = .011), third dose (HR 22.9, P < .001), initial mRNA-1273 (HT 1.78, P = .017) and humoral response at 3 months (HR 26.2, P < .001). Breakthrough SARS-CoV-2 infections occurred in 1.1% of patients, and mortality was 14.6%, none after the third dose. CONCLUSION: In the CKD spectrum, anti-Spike antibody titers continued to decrease from 3 to 6 months after complete vaccination, and KT recipients presented higher rates of negative humoral response at 6 months. A third dose of mRNA vaccine increased anti-Spike antibody titers but was still insufficient to spur a humoral immune response in at least 38% of KT recipients and 24% of patients on HD that lacked anti-SARS-CoV-2 antibodies 3 months post-initial vaccination. New strategies are urgently needed to protect CKD patients that remain negative for anti-SARS-CoV- 2 antibodies, given the high mortality of breakthrough SARS-CoV-2 infections. (Figure Presented).

Extrinsic venous compression secondary to spine osteophytes.

OBJECTIVE: This study aims to report two cases of symptomatic extrinsic compression of the inferior vena cava and left iliac vein caused by vertebral osteophytes. METHODS: We present two case reports of extrinsic venous compression by vertebral osteophytes. Both cases were endovascularly treated, with a successful outcome. A review of the literature of this unusual condition is also presented. RESULTS: The first patient is an 80-year-old woman who presented to the vascular surgery clinic with bilateral lower extremity edema and pain. A computed-tomography angiography (CTA) revealed extrinsic compression of the inferior vena cava from enlarged osteophytes. Venography and intravascular ultrasound were performed, confirming the diagnosis. A self-expanding venous stent was successfully deployed in the inferior vena cava relieving the extrinsic compression. The edema resolved the following day and was discharged without complications. The second patient is a 61-year-old male that presented to the emergency department with a left iliofemoral deep venous thrombosis. CTA showed left iliac vein compression by a lumbar osteophyte. Percutaneous thrombectomy was successfully achieved and an expanding stent was deployed covering the entire lesion. One month after the procedure the patient died from COVID-19-associated respiratory failure. CONCLUSION: Osteophytes must be considered when dealing with extrinsic venous compression, especially in elderly people.