5-Fluorouracil-Loaded Hyaluronic Acid-Coated Niosomal Vesicles: Fabrication and Ex Vivo Evaluation for Skin Drug Delivery.

5-Fluorouracil (5-FU) is one of the most potent drugs against solid tumors. However, its parenteral administration is associated with systemic toxicity, while its topical application has limited percutaneous absorption. To overcome these limitations, the current study undertakes the formulation of 5-FU as niosomal vesicles that were coated with hyaluronic acid to improve its targeting efficiency for cancer cells. The niosomes were prepared by the thin-film hydration method using cholesterol as physiological lipid and nonionic surfactants (Tween 80 and Span 80) in the ratio of 1:1. The niosomal vesicles were characterized for their size, size distribution, viscosity, surface tension, density, and drug entrapment efficiency. The vesicles were within the particle size range of 337-478 nm with relatively homogeneous particle size distribution (PDI ≤ 0.5). The ζ-potential and drug entrapment efficiency of coated formulations (F2 and F4) were comparatively higher than corresponding noncoated formulations (F1 and F3). The release behavior of 5-FU from niosomal vesicles using a dialysis membrane depicts that initial burst drug release was higher for F1 and F3 due to their smaller particle size in comparison to their coated counterparts. However, the release was more controlled for F4 due to the larger particle size, higher viscosity, and entrapped fraction of the formulation. The permeation of the drug through the rat's skin was comparatively higher in the case of noncoated formulations than their coated counterparts (p ≤ 0.05). This could be attributed to their small particle size and lower surface tension. In the case of coated formulations, the hydrophilic hyaluronic acid hinders the permeation of the drug through the lipid bilayer membrane of the skin. The retention of the drug in the skin was found to be in the range of 20-40%, which is sufficient to achieve optimum drug concentration in the tumorous tissue. Overall, the study successfully designed novel niosomal carrier systems for improved 5-FU delivery after topical application.

Combining serum metabolomic profiles with traditional risk factors improves 10-year cardiovascular risk prediction in people with type 2 diabetes.

AIMS: To identify a group of metabolites associated with incident cardiovascular disease (CVD) in people with type 2 diabetes and assess its predictive performance over-and-above a current CVD risk score (QRISK3). METHODS AND RESULTS: A panel of 228 serum metabolites was measured at baseline in 1066 individuals with type 2 diabetes (Edinburgh Type 2 Diabetes Study) who were then followed up for CVD over the subsequent 10 years. We applied 100 repeats of Cox least absolute shrinkage and selection operator to select metabolites with frequency >90% as components for a metabolites-based risk score (MRS). The predictive performance of the MRS was assessed in relation to a reference model that was based on QRISK3 plus prevalent CVD and statin use at baseline. Of 1021 available individuals, 255 (25.0%) developed CVD (median follow-up: 10.6 years). Twelve metabolites relating to fluid balance, ketone bodies, amino acids, fatty acids, glycolysis, and lipoproteins were selected to construct the MRS that showed positive association with 10-year cardiovascular risk following adjustment for traditional risk factors [hazard ratio (HR) 2.67; 95% confidence interval (CI) 1.96, 3.64]. The c-statistic was 0.709 (95%CI 0.679, 0.739) for the reference model alone, increasing slightly to 0.728 (95%CI 0.700, 0.757) following addition of the MRS. Compared with the reference model, the net reclassification index and integrated discrimination index for the reference model plus the MRS were 0.362 (95%CI 0.179, 0.506) and 0.041 (95%CI 0.020, 0.071), respectively. CONCLUSION: Metabolomics data might improve predictive performance of current CVD risk scores based on traditional risk factors in people with type 2 diabetes. External validation is warranted to assess the generalizability of improved CVD risk prediction using the MRS.

This study looked at whether combining a group of new markers found in the blood (called metabolites) with traditional risk factors (such as high blood pressure and obesity) could more accurately predict how likely people with type 2 diabetes are to develop cardiovascular diseases in the next 10 years. Key findingsTwelve metabolites (including amino acids and lipids) showed strong association with 10-year cardiovascular risk in people with type 2 diabetes, and a metabolites-based risk score (MRS) was created by integrating these metabolites.Combining the MRS with traditional risk factors was better at predicting the risk of a person with T2D for developing cardiovascular diseases within the next 10 years than using traditional risk factors alone.

Risk of dementia associated with body mass index, changes in body weight and waist circumference in older people with type 2 diabetes: The Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: To determine the relationship of dementia with preceding body mass index (BMI), changes in body weight and waist circumference in older people with type 2 diabetes. METHODS: In the Edinburgh Type 2 Diabetes Study (1064 men and women with type 2 diabetes, aged 60-75), body weight, waist circumference and BMI were measured at baseline and after 4 years in a subgroup (n = 821). Percentage body weight and waist circumference change over 4 years were calculated. Data on incident dementia was recorded during a median follow-up time of 10.84 years. Survival models considering a range of co-variables and/or death as a competing risk were used to estimate the risks of dementia associated with each weight-related variable. RESULTS: A total of 105 incident dementia events were recorded. When compared with people in the lowest BMI group (<25 kg/m2 ), risk of dementia was lower in intermediate BMI groups (25-29.9 kg/m2 , HR 0.44, p = 0.002; 30-34.9 kg/m2 , HR 0.41, p = 0.001) and the highest BMI group (≧35 kg/m2 , HR 0.35, p = 0.001). In the weight change subgroup, 78 incident dementia events were recorded between years 4 and 10. Body weight loss over 5% (compared with ≦5%) was associated with higher incidence of dementia (HR 2.06, p = 0.010). The association between waist circumference change and dementia was not significant. CONCLUSIONS/INTERPRETATIONS: Both a lower BMI and weight loss over a period of years are indicative of increased dementia risk for older people with type 2 diabetes, while waist circumference changes may be less informative.

Levothyroxine dosages during pregnancy among hypothyroid women. An experience from a tertiary care center of Karachi, Pakistan, based on data from Maternal Hypothyroidism on Pregnancy Outcomes Study (MHPO-5).

OBJECTIVES: The dosage of levothyroxine (LT4) during pregnancy differs among different ethnic groups worldwide. These differences are due to variations in geographical iodine distribution, autoimmunity, and variations in thyrotropin (TSH) targets for pregnancy. To the best of our knowledge, we report the levothyroxine dosage prescribed during pregnancy in hypothyroid women, for the first time from Pakistan. RESULTS: Levothyroxine dosage of 280 hypothyroid women during pregnancy were reviewed. The median LT4 dosages prescribed before conception was 85.7 mcg per day which increased by 14.3 mcg per day in the first trimester (P 0.001). A significant difference in dosage was observed between controlled and uncontrolled TSH groups in the first trimester (P 0.05). Lower LT4 dosage was prescribed for subclinical hypothyroid women as compared to overt hypothyroid cases, whereas dosages did not differ according to autoimmune status in the latter part of gestation.

Translation and validation of the Urdu version of the European organization for research and treatment of cancer core quality of life questionnaire (EORTC QLQ-C30) and brain module (QLQ-BN20) in primary brain tumor patients.

INTRODUCTION: This study translated and validated the Urdu version of the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) and Brain Module (QLQ-BN20) amongst patients with primary brain tumors (PBT) in Pakistan, and assessed the correlation of QoL with resilience, depression, and anxiety. METHODS: Translation of the EORTC QLQ-C30 and QLQ-BN20 was performed as per EORTC guidelines. A survey comprising of Urdu translations of EORTC QLQ-C30, QLQ-BN20, Wagnild and Young Resilience Scale (RS-14) and Hospital Anxiety and Depression Scale was administered to patients with PBT at a tertiary care hospital in Pakistan. Reliability (via Cronbach alpha), content validity index (CVI) scores, construct validity, and inter-scale correlations were assessed. RESULTS: Our sample consisted of 250 patients with PBT, most commonly glioma (46.8%) and meningioma (21.2%). All patients were able to understand the Urdu translations. The Cronbach alphas for the QLQ-C30 and the QLQ-BN20 were 0.860 and 0.880, respectively. The CVI scores for clarity and relevance were high for both the EORTC QLQ-C30 (0.98 and 0.96, respectively) and the QLQ-BN20 tool (0.81 and 0.95, respectively). The global QoL domain (EORTC QLQ-C30) showed significant positive correlations with resilience (r = 0.422), and significant negative correlations with depression (r = - 0.541) and anxiety (r = - 0.502). Strong inter-scale correlations were observed between physical functioning and insomnia (r = - 0.690) and role functioning and insomnia (r = - 0.641). CONCLUSION: Our study confirms the Urdu versions of the EORTC QLQ-C30 and QLQ-BN20 as valid clinical tools for the measurement of QoL in primary brain tumors patients within the cultural and socioeconomic context of Pakistan.

Quality of life (QoL) is an important facet of well-being for patients with primary brain tumors (PBTs), as these individuals face significant distress during the course of their illness and treatment. It is important to have valid and reliable tools to accurately measure the QoL of patients with PBTs. The EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) and its brain tumor-specific module EORTC QLQ-BN20 (EORTC QLQ-Brain Neoplasms 20) are exactly that.However, the use of the EORTC QLQ-C30 and QLQ-BN20 is limited in Pakistan, where the national language is Urdu, and the majority of patients are of low socioeconomic backgrounds. Since no Urdu translations of the EORTC QLQ-C30 and QLQ-BN20 exist, we aimed to translate and validate these tools to enable their applicability in Pakistan.The Urdu versions of the EORTC QLQ-C30 and QLQ-BN20 demonstrated good validity amongst patients with PBTs. Thus, our study confirms the EORTC QLQ-C30 and QLQ-BN20 as valuable clinical tools for the measurement of QoL in primary brain tumors patients within the linguistic, cultural and socioeconomic context of Pakistan.

Resilience and its associated factors in head and neck cancer patients in Pakistan: an analytical cross-sectional study.

INTRODUCTION: The study aimed to assess resilience and its associated factors in head and neck cancer patients, post-treatment in a low middle income country (LMIC) such as Pakistan. METHODS: An analytical cross-sectional study was conducted from November 2019 to May 2020 among head and neck cancer patients aged at least 18 years at the largest private tertiary care hospital, in Karachi, Pakistan. Information regarding their resilience scores was collected through Wagnild and Young's Resilience scale that comprises of 14 items (RS-14). Moreover, depression and anxiety were also assessed via Hospital Anxiety and Depression Scale (HADS) and social support was assessed by Enriched Social Support Instrument (ESSI). RESULTS: The data was analyzed by linear regression modeling. Unadjusted and adjusted beta coefficients with 95% CI were reported. A total of 250 head and neck cancer patients were recruited, 79% of them were males. Mean age of the patients was 51.59 years with 93% having high social support and only 8% having severe depression and 3% having severe anxiety. After adjusting for the covariates in multivariable analysis resilience was associated with severe depression (- 17[- 20.98,-12.93]) or borderline depression (- 4[- 8.41,-0.39]), severe anxiety (- 11 [- 17.88,-4.18]), low social support (- 6[- 9.62,-1.71]), having family members of > 6 in the household (- 2[- 4.31,-0.29), smokeless tobacco users post- treatment (10[5.79, 14.45]), and those who underwent tracheotomy (- 4[- 7.67,-0.21]). There was a significant interaction between education and role in the family (decision maker). CONCLUSION: In Pakistan, a South Asian LMIC, collectivist culture prevails, family ties are greatly promoted thus resilience and social support is highly prevalent in head and neck cancer patients resulting in lower prevalence of depression and anxiety. Our study highlights that higher resilience is prevalent among small families less than six members, as the welfare of the individual is prioritized over multiple needs of the family. Formal Education and role in household/decision making power are effect modifiers in our study, demonstrating its protective effect on the mental health of head and neck cancer patients. High resilience scores were reported among current smokeless tobacco users as compared to quitters post treatment. Resilience-building interventions should be formulated to aid head and neck cancer patients to cope with the disease and its sequel.

Resilience and its associated factors in brain tumor patients in Karachi, Pakistan: An analytical cross-sectional study.

OBJECTIVES: This study assessed resilience in brain tumor patients at a tertiary care hospital in Pakistan (a lower middle-income country; LMIC) and explored its relationship with patients' sociodemographic factors, clinical characteristics, social support, and mental health. METHODS: A cross-sectional survey was conducted amongst adult (≥18 years) patients with brain tumor at the Aga Khan University Hospital, Pakistan. Resilience was assessed by Wagnild and Young's Resilience Scale, and patients' psychosocial characteristics by the Hospital Anxiety and Depression Scale and the Enriched Social Support Instrument. RESULTS: A total of 250 patients were included (mean age: 44 years; 68% males), with majority (97.6%) having high social support and only 4.4% and 2% having symptomatic depression and anxiety, respectively. On multivariable linear regression adjusted for covariates, lower resilience was associated with not being involved in household decision-making (Adjusted Beta Coefficient: 4.58 [95% Confidence Interval:-7.59, -1.56]), not currently working (-2.80 [-4.61, -0.99]), undergoing multiple neurosurgical interventions such as tumor biopsies or resections (-8.64 [-13.11, -4.16]), receiving chemotherapy (-5.17 [-9.51, -0.83]) or combination adjuvant therapy (-2.91 [-5.14, -0.67]), low social support (-7.77 [-13.73, 1.81]), mild depression (-13.00 [-17.00,-8.99]) or symptomatic depression (-19.79 [-24.69, -14.89]), and mild anxiety (-4.24 [-7.98, -0.50]). CONCLUSION: Our study highlights the function of familial/household role and working status in mediating resilience, and demonstrates the well-known protective effect of resilience for mental health in brain tumor patients in Pakistan, a South-Asian LMIC. These findings are of clinical relevance with regards to the development of culture-specific evidence-based resilience-building interventions that may help patients with brain tumors to cope with the psychological distress of cancer.

Feasibility of preoperative tattooing of percutaneously biopsied axillary lymph node: an experimental pilot study.

BACKGROUND: In the last three decades, axillary lymph node dissection (ALND) has been replaced by sentinel lymph node biopsy (SLNB) in all clinically node-negative patients. However, when SLNB alone is performed in clinically node-positive patients who are rendered node-negative by neoadjuvant chemotherapy, the procedure has a high false-negative rate and other complementary procedures have been described to improve its reliability. Preoperative tattooing of the suspicious lymph node with India ink at the time of biopsy, in addition to sentinel lymph node biopsy, is a reasonable alternative. The objective of our study is to determine, in clinically node-positive patients, the feasibility of tattooing suspicious axillary lymph node at the time of percutaneous needle biopsy and its retrieval at the time of surgery. METHODS: A prospective experimental study will be conducted divided into two phases-phases I and II. In phase I, 10 patients committed to undergo upfront surgery (without neoadjuvant chemotherapy) will have a suspicious lymph node tattooed by injecting India ink at the time of core needle biopsy. All patients will undergo a SLNB, during which the axilla will be inspected to determine if the tattooed lymph node can be visualized. Routine microscopic examination will follow, and concordance between the sentinel and tattooed node will also be established. In phase II, the process will be repeated for 30 patients who undergo surgery after neoadjuvant chemotherapy. The analysis will be performed in Stata version 12. DISCUSSION: There is a need to identify and test the techniques for the down-staged axilla in post-neoadjuvant chemotherapy patients, which are not only practical and limit the number of invasive procedures necessary but are representative of the new axillary status and help limit the extent of axillary surgery without negatively impacting outcomes. We propose that, for the patient undergoing neoadjuvant chemotherapy with a biopsy-proven disease in the axilla, this could be achieved by India ink which allows marking, identification, and retrieval of the biopsied lymph node. Retrieval of this previously biopsied lymph node along with sentinel nodes, if found to be representative of the status of the remainder of the axilla, could potentially eliminate the need for routine axillary lymph node dissection and thus limit morbidity. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03939598. Retrospectively registered on 7 May 2019.

Translation and Validation of 10/66 Dementia Diagnostic Battery in Urdu in Karachi, Pakistan.

PURPOSE: The 10/66 dementia research group (DRG) diagnostic tool was devised to diagnose dementia in people with low education in low and middle-income countries. This study aimed to validate the 10/66 DRG tool in Urdu in Pakistan. METHODOLOGY: People older than or equal to 60 years were included: (1) With normal cognition: no/low education, high education, and depression; (2) People with mild and moderate dementia. The diagnostic and statistical manual IV-TR clinician diagnosis was used as the gold standard for dementia. The Clinician Dementia Rating scale was used to rate dementia severity. The geriatric mental status AGECAT stage I output was used to diagnose depression. The 10/66 battery was comprised of CSI-D (cognitive screening instrument for dementia), CERAD (consortium to establish a registry of Alzheimer disease), and animal naming test. RESULT: The sensitivity and specificity of CSI-D COG score for diagnosing dementia was 86.7% and 72.1%, for CSI-D DF score was 71.1% and 96.1%, for CERAD-10 word list delayed recall was 85.9% and 62.2% at a cut point of ≥5 words, and 70.3% and 97.7% for 10/66 diagnostic algorithm. CONCLUSIONS: The 10/66 DRG tool is a valid instrument for diagnosing dementia in the Urdu-speaking population, including with low education and depression, in Pakistan.

Resilience and quality of life (QoL) of head and neck cancer and brain tumour survivors in Pakistan: an analytical cross-sectional study protocol.

BACKGROUND: Cancer is a devastating disease and has detrimental effects on the quality of life (QoL) of cancer survivors and interferes with their treatment compliance. The aim of the study is to assess resilience and QoL among cancer survivors and to evaluate the important factors affecting their resilience and QoL, with respect to the Pakistani cultural context. METHOD AND ANALYSIS: A cross-sectional study will be conducted at a tertiary care hospital in Karachi, Pakistan. A minimum sample size of 250 head and neck cancers and 250 brain tumour survivors with 10% inflation for non-response rate will be required. The SD of QoL and resilience will range from 16.5 to 40.8 for head and neck cancer, and 12.7 to 34.1 for brain tumour, at 5% level of significance, with 2.5 precision. QoL will be assessed by European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-H&N35 and EORTC QLQ-BN20 and resilience will be evaluated by Wagnild and Young's 14-item scale. Mean±SD will be reported for resilience and QoL scores. Unadjusted and adjusted ß-coefficients, with 95% CI, will be reported by using multiple linear regression analysis. Correlation analysis will also be performed using Pearson or Spearman rank correlation coefficients. A p value of <0.05 will be considered significant. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Aga Khan University Pakistan's Ethical Review Committee. Written informed consent will be taken from the participants by trained research assistants. A trained psychologist will provide on-spot counselling to the participants and those identified with severe depression will be referred to a psychiatrist. The study materials will be kept under lock and key and the electronic data base will be password protected and will only be accessed by the research team. The study findings will be disseminated through publications conferences and workshops and research briefs. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov registry (NCT03466762).

Making prescriptions "talk" to stroke and heart attack survivors to improve adherence: Results of a randomized clinical trial (The Talking Rx Study).

BACKGROUND: We developed and tested the effectiveness of a tailored health information technology driven intervention: "Talking Prescriptions" (Talking Rx) to improve medication adherence in a resource challenged environment. METHODS: We conducted a parallel, randomized, controlled, assessor-blinded trial at the Aga Khan University (AKU), Karachi, Pakistan. Adults with diagnosis of cerebrovascular accident (CVA) or coronary artery disease (CAD) diagnosed least one month before enrollment, on anti-platelets and statins, with access to a mobile phone were enrolled. The intervention group received a) Daily Interactive Voice Response (IVR) call services regarding specific statin and antiplatelet b) Daily tailored medication reminders for statin and antiplatelet and c) Weekly lifestyle modification messages for a period of 3 months. We assessed Medication adherence to statin and antiplatelets by a validated version of the 8-item Morisky Medication Adherence scale 8 (MMAS-8) at 3 months by a blinded assessment officer. Analysis was conducted by intention-to-treat principle (ITT). RESULTS: Between April 2015 and December 2015, 197 participants (99 in intervention and 98 in the usual care group) enrolled in the Talking Rx Study. The dropout rate was 9.6%. Baseline group characteristics were similar. At baseline, the mean MMAS-8 was 6.68 (SD = 1.28) in the intervention group and 6.77 (SD = 1.36) in usual care group. At end of follow-up, the mean MMAS-8 increased to 7.41(0.78) in the intervention group compared with 7.38 (0.99) in usual care group with mean difference of 0.03 (S.D 0.13) (95% C.I [-0.23, 0.29]), which was not statistically significant. (P-Value = 0.40) CVA patients showed a relatively greater magnitude of adherence via the MMAS-8 at the end of follow up where the mean MMAS-8 increased to 7.29 (S.D 0.82) in the intervention group as compared to 7.07(S.D 1.24) in usual care group with mean difference of 0.22 (SD = 0.22) 95% C.I (-0.20, 0.65) with (P-value = 0.15). Around 84% of those on intervention arm used the service, calling at least 3 times and listening to their prescriptions for an average of 8 minutes. No user was excluded due to technologic reasons. CONCLUSION: The use of a phone based medication adherence program was feasible in LMIC settings with high volume clinics and low patient literacy. In this early study, with limited follow up, the program did not achieve any statistically significant differences in adherence behavior as self-reported by the MMAS-8 Scale. TRIAL REGISTRATION: Clinical Trials.gov NCT02354040.

Quality of life after stroke in Pakistan.

BACKGROUND: There is very little information about the quality of life (QOL) of stroke survivors in LMIC countries with underdeveloped non communicable health infrastructures, who bear two thirds of the global stroke burden. METHODOLOGY: We used a sequential mix methods approach. First, a quantitative analytical cross-sectional study was conducted on 700 participants, who constituted 350 stroke survivor and their caregiver dyads. QOL of stroke survivor was assessed via Stroke Specific Quality of Life Scale (SSQOLS) whereas QOL of caregivers was assessed through RAND-36. In addition; we assessed complications, psychosocial and functional disability of stroke survivors. Following this quantitative survey, caregivers were qualitatively interviewed to uncover contextually relevant themes that would evade quantitative surveys. Multiple linear regression technique was applied to report adjusted ß-coefficients with 95% C.I. RESULTS: The QOL study was conducted from January 2014 till June 2014, in two large private and public centers. At each center, 175 dyads were interviewed to ensure representativeness. Median age of stroke survivors was 59(17) years, 68% were male, 60% reported depression and 70% suffered post-stroke complications. The mean SSQOLS score was 164.18 ± 32.30. In the final model severe functional disability [adjß -33.77(-52.44, -15.22)], depression [adjß-23.74(-30.61,-16.82)], hospital admissions [adjß-5.51(-9.23,-1.92)] and severe neurologic pain [adjß -12.41(-20.10,-4.77)] negatively impacted QOL of stroke survivors (P < 0.01). For caregivers, mean age was 39.18 ± 13.44 years, 51% were female and 34% reported high stress levels. Complementary qualitative study revealed that primary caregivers were depressed, frustrated, isolated and also disappointed by health services. CONCLUSION: The QOL of Stroke survivors as reported by SSQOLS score was better than compared to those reported from other LMIC settings. However, Qualitative triangulation revealed that younger caregivers felt isolated, depressed, overwhelmed and were providing care at great personal cost. There is a need to develop cost effective holistic home support interventions to improve lives of the survivor dyad as a unit. TRIAL REGISTRATION: NCT02351778 (Registered as Observational Study).

Facilitators and barriers to NCD prevention in Pakistanis-invincibility or inevitability: a qualitative research study.

BACKGROUND: Non-communicable diseases (NCD) are the leading causes of death globally. In Pakistan, they are among the top ten causes of mortality, especially in the productive age group (30-69 years). Evidence suggests that health perceptions and beliefs strongly influence the health behavior of an individual. We performed focus group interviews to delineate the same so as to design the user interface of a non-invasive stroke risk monitoring device. METHODS: It was a qualitative study, designed to explore how health perceptions and beliefs influence behavior for NCD prevention. Four focus group discussions (FGD) were conducted with 30 stable participants who had diabetes mellitus, ischemic heart disease, blood pressure, and stroke. The data was collected using a semi-structured interview guide designed to explore participants' perceptions of their illnesses, self-management behaviors and factors affecting them. The interviews were transcribed and content analysis was done using steps of content analysis by Morse and Niehaus [10]. RESULTS: Medication adherence, self-monitoring of blood sugars and blood pressures, and medical help seeking were the commonly performed self-management behaviors by the participants. Personal experience of illness, familial inheritance of disease, education and fear of premature death when life responsibilities were unfulfilled, emerged as strong facilitators of self-management behaviors. A sense of personal invincibility, Fatalism or inevitability, lack of personal threat realization, limited knowledge, inadequate health education, health care and financial constraints appeared as key barriers to the self-management of chronic disease in participants. CONCLUSIONS: Behavioural interventional messaging will have to engender a sense of personal vulnerability and yet empower self-efficacy solutions at the individual level to deal with both invincibility and inevitability barriers to adoption of healthy behavior.

Using a tailored health information technology- driven intervention to improve health literacy and medication adherence in a Pakistani population with vascular disease (Talking Rx) - study protocol for a randomized controlled trial.

BACKGROUND: Vascular disease, manifesting as myocardial infarction and stroke, is a major cause of morbidity and mortality, especially in low- and middle-income countries. Current estimates are that only one in six patients have good adherence to medications and very few have sufficient health literacy. Our aim is to explore the effectiveness and acceptability of Prescription Interactive Voice Response (IVR) Talking Prescriptions (Talking Rx) and SMS reminders in increasing medication adherence and health literacy in Pakistani patients with vascular disease. METHODS: This is a randomized, controlled, single center trial. Adult participants, with access to a cell phone and a history of vascular disease, taking multiple risk-modifying medications (inclusive of anti-platelets and statins) will be selected from cerebrovascular and cardiovascular clinics. They will be randomized in a 1:1 ratio via a block design to the intervention or the control arm with both groups having access to a helpline number to address their queries in addition to standard of care as per institutional guidelines. Participants in the intervention group will also have access to Interactive Voice Response (IVR) technology tailored to their respective prescriptions in the native language (Urdu) and will have the ability to hear information about their medication dosage, correct use, side effects, mechanism of action and how and why they should use their medication, as many times as they like. Participants in the intervention arm will also receive scheduled SMS messages reminding them to take their medications. The primary outcome measure will be the comparison of the difference in adherence to anti-platelet and statin medication between baseline and at 3-month follow-up in each group measured by the Morisky Medication Adherence Scale. To ascertain the impact of our intervention on health literacy, we will also compare a local content-validated and modified version of Test of Health Literacy in Adults (TOFHLA) between the intervention and the control arm. We estimate that a sample size of 86 participants in each arm will be able to detect a difference of 1 point on the MMAS with a power of 90 % and significance level of 5 %. Accounting for an attrition rate of 15 %, we plan to enroll 100 participants in each arm (total study population = 200). We hypothesize that a linguistically tailored health IT intervention based on IVR and SMS will be associated with an improvement in adherence (to anti-platelet and lipid-lowering medications) and an improvement in health literacy in Pakistani patients with vascular disease. DISCUSSION: This innovative study will provide early data for the feasibility of the use of IT based prescriptions in an lower middle incorme country setting with limited numeracy and literacy skills. TRIAL REGISTRATION: Clinical Trials.gov: NCT02354040 - 2 February 2015.