OBJECTIVES: To evaluate the frequency, type and predictors of various types of DTPs among CKD patients at a tertiary-care hospital in Pakistan.

METHODOLOGY: This was a cross-sectional study carried out at Sandeman Provincial Hospital, Quetta between 1-11-2020 and 31-1-2021. It included 303 non-dialysis ambulatory patients of CKD-stage 3 and above. Cipolle et al., criterion was used for classifying the DTPs and a clinician at the study site checked the identified DTPs for accuracy. Data were analyzed by SPSS 23. Multivariate analysis was conducted to find the predictors of individual types of DTPs. A p-value <0.05 was considered statistically significant.

RESULTS: The patients received a total of 2265 drugs with a median of eight drugs per patient (range: 3-15 drugs). A total of 576 DTPs were identified among 86.1% patients with a median of two DTPs (interquartile range 1-3) per patient. Dosage too high (53.5%) was the most common DTP followed by adverse drug reactions (ADRs) (50.5%) and need of additional drug therapy (37.6%). In multivariate analysis, patients' age of >40 years emerged as a predictor of unnecessary drug therapy and dosage too high. The odds of needing a different drug product was significantly high in patients with cardiovascular diseases (CVD) and diabetes mellitus (DM). The dosage too low had significant association with CVD. The risk of ADRs was significantly high in elderly patients (>60 years) and those with CVD. The presence of hypertension, DM and CKD stage-5 emerged as predictors of dosage too high.

METHODS: A cross-sectional observational study was conducted using a convenience sample technique. The translation procedure included five stages: forward translation, revision of translation, backward translation, refinement of translation, and a final test of the pre-final version. The final sets of questionnaires were constructed using an online JotForm platform. The online platform was chosen to automatically calculate the questionnaire's final overall score. Overall, 260 participants were instructed to fill out the English and the Arab-OSDI version twice to conduct the reliability of the translated version and repeatability evaluation.

RESULTS: The mean age of the participants was 33.45 ± 11.74 years old. Cronbach's alpha for all items was greater than 0.80, except for the "blurred vision" and "deteriorating vision" items (0.77 and 0.74, respectively). The mean overall score difference between the English-OSDI and Arab-OSDI was 0.86 based on the Bland-Altman chart. For repeatability, no significant difference in the overall scores between the two repeats of the Arab-OSDI (p = 0.632). The Arab-OSDI overall score (sessions 1 and 2) has a clinical difference (bias) of 0.21. Using the varimax rotation method, only three factors (ocular symptoms, vision-related function, and environmental triggers) had eigenvalues greater than one in the structure of the Arab-OSDI.

METHODS: Male Sprague Dawley rats weighing 200-250 g were grouped into normal rats (N) and diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg body weight) whereas N similarly received citrate buffer. STZ-injected rats with blood glucose of more than 20 mmol/L were considered diabetic and were divided into vehicle-treated (DV) and TRF-treated (DT) groups. N and DV received vehicle, whereas DT received TRF (100 mg/kg body weight) via oral gavage once daily for 12 weeks. Fundus images were captured at week 0 (baseline), week 6 and week 12 post-STZ induction to estimate vascular diameters. At the end of experimental period, rats were euthanized, and retinal tissues were collected for morphometric analysis and measurement of NFκB, phospho-NFκB (Ser536), HIF-1α using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Retinal inflammatory and angiogenic cytokines expression were measured by ELISA and real-time quantitative PCR.

METHODS: Sprague-Dawley rats were divided into normal control rats (N) which received vehicle, and diabetic rats which either received vehicle (DV) or 100 mg/kg of TRF (DT). Diabetes was induced with intraperitoneal injection of STZ (60 mg/kg body weight). Treatments were given orally, once daily, for 12 weeks after confirmation of hyperglycaemia. Fundus photographs were captured at baseline, 6- and 12-week post-STZ injection and average diameter of retinal veins and arteries were measured. At 12-week post-STZ injection, rats were euthanised, and retinae were collected for measurement of Ang-2 and PKC gene and protein expressions.

EXPERIMENTAL APPROACH: The influence of soy lecithin, sodium caseinate and soy lecithin/sodium caseinate at 1:1 ratio on the physicochemical properties and stability of lycopene nanodispersion prepared using the emulsification-evaporation methods before and after treatment at different pH, ionic strength and temperature were investigated. The in vitro bioaccessibility of the nanodispersions was also studied.

RESULTS AND CONCLUSION: Under neutral pH conditions, nanodispersion stabilized with soy lecithin had the highest physical stability and the smallest particle size (78 nm), the lowest polydispersity index (PDI) value (0.180) and highest zeta potential (-64 mV) but the lowest lycopene concentration (1.826 mg/100 mL). Conversely, nanodispersion stabilized with sodium caseinate had the lowest physical stability. Combining the soy lecithin with sodium caseinate at 1:1 ratio resulted in a physically stable lycopene nanodispersion with the highest lycopene concentration (2.656 mg/100 mL). The lycopene nanodispersion produced by soy lecithin also had high physical stability under different pH range (pH=2-8) where the particle size, PDI and zeta potential remained fairly consistent. The nanodispersion containing sodium caseinate was unstable and droplet aggregation occurred when the pH was reduced close to the isoelectric point of sodium caseinate (pH=4-5). The particle size and PDI value of nanodispersion stabilized with soy lecithin and sodium caseinate mixture increased sharply when the NaCl concentration increased above 100 mM, while the soy lecithin and sodium caseinate counterparts were more stable. All of the nanodispersions showed good stability with respect to temperature changes (30-100 °C) except for the one stabilized by sodium caseinate, which exhibited an increased particle size when heated to above 60 °C. The combination of soy lecithin and sodium caseinate was found to increase the bioaccessibility of the lycopene nanodispersion. The physicochemical properties, stability and extent of the lycopene nanodispersion digestion highly depend on the emulsifier type.