Assessment of non-adherence to cardiovascular medications in Iraq by 8-items Morisky Medication Adherence Scale and analysis of dried blood spots

Medication non-adherence is common in chronic conditions such as cardiovascular diseases (CVD). According to the WHO, over 50% of patients are non-adherent to CVD medications, which results in poor health outcomes, hospital readmissions, high mortality rates and avoidable costs. The aim of this study was to assess medication non-adherence to target CVD medications via the eight-item Morisky Medication Adherence Scale (MMAS-8) and quantification of drug concentrations in blood microsamples collected on Whatman 903 cards and a volumetric absorptive microsampling device (VAMS) for the same patients using liquid chromatography–high resolution mass spectrometry (LCHRMS). Iraqi patients who had been taking one or more of nine commonly prescribed cardiovascular medications (amlodipine, atenolol, atorvastatin, bisoprolol, diltiazem, lisinopril, losartan, simvastatin, and valsartan) for at least six months were enrolled in this study. MMAS-8 scores for individual patients were determined, and whole blood microsamples assessed via LC-HRMS. To estimate overall medication non-adherence, MMAS-8 (score < 6) and the results of quantitative LC-HRMS analysis were compared. 303 patients were recruited for this study (mean age 54) taking an average of four CVD medications. Non-adherence assessed via MMAS-8 was 18.2%, as compared to the 49.2% determined via LC-HRMS analysis of blood microsamples. Both approaches showed no significant correlation between non-adherence and age or gender, but was significantly associated with the number of medications or tablets being taken daily. Quantitative LC-HRMS results obtained via the two microsampling methods (VAMS and 903 cards) were generally consistent and comparable, confirming good reproducibility. MMAS-8 was subject to overestimation and was unable to identify non-adherence to multiple medications in the regimens. Conversely, LC-HRMS gave valuable information about non-adherence to each medication in each patient’s regimen. In subsequent clinician-led patient interviews the main reasons for medication non-adherence were side effects, dose frequencies, complicated regimens, medication cost, patient beliefs, patient knowledge/understanding, and forgetfulness. The impact of using a combination approach of patient MMAS-8 data and objective blood drug concentration data with faceto-face interviews conducted by the specialist in Iraq has the potential to provide Iraqi clinicians with a novel approach to improving patients’ health and reducing the costs of treatment by monitoring and optimising CVD medications in routine clinical practice.Misan Health Directorat

Non-adherence to cardiovascular pharmacotherapy in Iraq assessed using 8-items Morisky questionnaire and analysis of dried blood spot samples

open access journalThe study evaluated the non-adherence to selected cardiovascular medications, atenolol, atorvastatin, bisoprolol, diltiazem, lisinopril, simvastatin and valsartan in Iraqi patients by applying a standardized Morisky questionnaire (8-MMAS) and by measuring therapeutic drug concentrations in dried blood spots (DBS) analyzed by liquid chromatography - high resolution mass spectrometry (LC-HRMS). Sixty-nine patients, on continued use of one or more of the selected drugs, were evaluated. The questionnaire showed that 21.7% of participants were non-adherent whereas DBS analysis showed that 49.3% were non-adherent to their medications. No significant correlation between medication non-adherence and gender was detected, but adherence was negatively correlated with the number of medications in the regimen. The 8-items questionnaire was unable to differentiate non-adherence to multiple medications in the prescribed pharmacotherapy regimens. DBS is an alternative to conventional methods to monitor non-adherence objectively. Agreement between the two approaches was weak (Kappa =0.269, p-value 0.05)

Adherence to cardiovascular pharmacotherapy by patients in Iraq: a mixed methods assessment using quantitative dried blood spot analysis and the 8-item Morisky Medication Adherence Scale

open access articleThis study evaluated the adherence to prescribed cardiovascular therapy medications among cardiovascular disease patients attending clinics in Misan, Amara, Iraq. Mixed methods were used to assess medication adherence comprising the Arabic version of the eight-item Morisky Medication Adherence Scale (MMAS-8) and determination of drug concentrations in patient dried blood spot (DBS) samples by liquid chromatography-high resolution mass spectrometry. Three hundred and three Iraqi patients (median age 53 years, 50.5% female) who had been taking one or more of the nine commonly prescribed cardiovascular medications (amlodipine, atenolol, atorvastatin, bisoprolol, diltiazem, lisinopril, losartan, simvastatin and valsartan) for at least six months were enrolled. For each patient MMAS-8 scores were determined alongside drug concentrations in their dried blood spot samples. Results from the standardized questionnaire showed that adherence was 81.8% in comparison with 50.8% obtained using the laboratory-based microsample analysis. The agreement between the indirect (MMAS-8) and direct (DBS analysis) assessment approaches to assessing medication adherence showed significantly poor agreement (kappa = 0.28, P=0.001). The indirect and direct assessment approaches showed no significant correlation between nonadherence to prescribed cardiovascular pharmacotherapy and age and gender, but were significantly associated with the number of medications in the patient’s treatment regimen (MMAS-8: Odds Ratio (OR) 1.947, 95% CI, P=0.001; DBS analysis: OR 2.164, 95% CI, P=0.001). The MMAS-8 results highlighted reasons for nonadherence to prescribed cardiovascular pharmacotherapy in this patient population whilst the objective DBS analysis approach gave valuable information about nonadherence to each medication in the patient’s treatment regimen. DBS sampling, due its minimally invasive nature, convenience and ease of transport is a useful alternative matrix to monitor adherence objectively in Iraq to cardiovascular pharmacotherapy. This information combined with MMAS-8 can provide clinicians with an evidence-based novel approach to implement intervention strategies to optimise and personalise cardiovascular pharmacotherapy in the Iraqi population and thereby improve patient health outcomes

Volumetric absorptive microsampling (VAMS) coupled with high-resolution, accurate-mass (HRAM) mass spectrometry as a simplified alternative to dried blood spot (DBS) analysis for therapeutic drug monitoring of cardiovascular drugs

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Here, volumetric absorptive microsampling (VAMS), used for the measurement of cardiovascular drugs, is compared against conventional dried blood spot (DBS) card sampling to evaluate adherence to prescribed medication. Volumetric absorptive microsampling (VAMS) is an attractive alternative to plasma sampling for routine drug monitoring and potentially overcomes haematocrit issues associated with quantitative bioanalysis of conventional dried blood spots. A quantitative VAMS-based LC-HRAM MS assay for atenolol, lisinopril, simvastatin and valsartan was developed and validated. The assay demonstrated acceptable linearity, selectivity, accuracy, precision, recovery and insignificant matrix effects with no impact of haematocrit on assay accuracy. Volunteers provided both VAMS and DBS 903 card samples (the current standard) to allow comparison of the two methods and demonstrate the potential utility of VAMS. Analysis of VAMS samples correctly identified drugs in volunteers known to be adherent, and found no false positives from volunteers known to be taking no medication. There was a strong correlation between the two sampling systems confirming the utility of VAMS. Therapeutic drug monitoring (TDM) can assist clinicians in deciding how to proceed with treatment in the event of poor improvement in patient health. VAMS could offer a potentially more efficient method of sample collection, with fewer rejected samples than the DBS approach

LC-HRMS analysis of 133 patient micro-volume blood samples to allow clinical assessment of medication adherence

133 DBS card/VAMS micro-volume blood samples were analysed by LC-HRMS to determine if therapeutic levels of the prescribed cardiovascular (CVD) drugs were present. This research focussed on the top 11 UK prescribed CVD drugs. Calibration samples, prepared from spiked human whole blood, were extracted and analysed by LC-HRMS. This method was validated and applied to volunteer and patient samples. The system successfully identified the prescribed drugs in volunteer’s samples who were known to be adherent. Non-detection of a prescribed drug indicated non-adherence to prescription: a situation identified for 12% of the volunteers and 36% of the patients

Cardiovascular drug monitoring using quantitative LC-HRMS analysis of self-collected micro-volume blood samples

Background Evidence suggests that ˃50% of cardiovascular (CVD) disease patients do not adhere to treatment thus impacting on patient health, additional healthcare costs and medicines wastage. DBS microsampling combined with LC-ToF MS detection has the potential to offer a simple means to monitor drug levels to enable clinicians to personalise optimum treatment for patients. This research compared the use of Whatman 903 dried blood spot (DBS) sample collection cards with volumetric absorptive micro-sampling (VAMS)/Mitra® technology for use as a personal sampling methodology. Methods Recruited volunteers were given demonstrations and information sheets concerning the investigation and sample collection. A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was validated for the determination of the top 11 UK prescribed cardiovascular drugs. For the preparation of DBS and VAMS calibration samples whole blood was spiked with different levels of the 11 target analytes. 8mm DBS discs or the absorptive VAMS tips were extracted with methanol containing the internal standard. The bioanalytical method was applied to fingerprick samples taken from volunteers some of whom were prescribed one or more of the target drugs. Volunteers not prescribed drugs represented blank samples. Results Approximately 17% of the DBS spots were unacceptable for quantification whereas 1 VAMS sample tip was rejected due to incomplete collection. Validation showed comparable quantitative results between the DBS and VAMS microsampling methods for the 11 target drugs. For two study groups anticipated cardiovascular drugs were detected in 83% of the pre-warned group and 73% of the trial group. The latter figure was higher than expected possibly due to the ‘white coat compliance’. The detected drug levels were in line with literature values for the half-life and Cmax for a given drug, Non-adherence was not uniform amongst the cardiovascular drugs. All volunteers preferred the VAMS methodology. Conclusions Both microsampling methods coupled with LC-HRMS analyses facilitate the identification of patients where the prescription apparently failed to produce detectable drug levels in the blood. This information should inform clinicians how to proceed in the healthcare process in the event of poor patient progress

Investigating the antiviral activity of volatile compounds from Nigella sativa against coronaviruses.

The recent emergence of three major coronaviruses and presence of coronaviruses circulating in bats suggests that spillover of new pandemic-potential coronaviruses into humans is likely in future. The development of pan-coronavirus antivirals will be crucial to combat this. Here, we investigated the antiviral activities of Nigella sativa (black cumin) oil extracts from various global locations against seasonal human coronaviruses OC43 and 229E, and SARS-CoV-2 pseudoviruses. Coronavirus-infected cells were directly treated with oil extracts and antiviral activity determined by quantifying viral titres. In diffusion assays, oils were incubated in microwell plates with virus in adjacent wells to investigate the effect of diffused volatile compounds. After incubation over a range of times, infectivity was determined. Our diffusion assay results indicate that volatile compounds present in Nigella sativa extracts show antiviral activities against coronaviruses, with no cytotoxic effect on cells. Significant inhibition of infection was observed after 12 hours incubation, with the most potent oils showing a ≥4 log10 reduction in OC43 infectivity at 24 hours. Interestingly, direct treatment of infected cells with oils showed limited antiviral efficacy, suggesting that the vapour phase may offer higher concentrations of the bioactive compounds without compromising cell viability. We also identified key volatile compounds present in the oil vapour phase; evaluation of the antiviral activity of these volatiles in isolation and in synergy are ongoing. Overall, this work provides a first step towards identifying novel pan-coronavirus antiviral compounds that can be formulated as sprays or inhalers for direct delivery to the site of infection