Drivers of malnutrition among late adolescent and young women in rural Pakistan: a cross-sectional assessment of the MaPPS trial.

OBJECTIVE: This study aimed to characterise the burden of malnutrition and assess how underlying determinants at the structural and intermediary levels contributed to malnutrition among late adolescent and young women in rural Pakistan. DESIGN: Cross-sectional enrolment data assessment. SETTING AND PARTICIPANTS: This study was conducted using data from adolescent and young women (n=25 447) enrolled in the Matiari emPowerment and Preconception Supplementation Trial, collected from June 2017 to July 2018 in Matiari District, Pakistan. The WHO-based cut-offs were applied to anthropometric measures to estimate body mass index (BMI) categories (underweight, overweight, obese) and stunting. Hierarchical models were generated to evaluate the association between the determinants with BMI categories and stunting among late adolescent girls and young women, respectively. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcomes of interest were BMI categories and stunting. Explanatory variables included measures of socioeconomic status, education, occupation, health, well-being, food security, empowerment and food practices. RESULTS: Regardless of age group, the prevalence of underweight was high (36.9%; 95% CI 36.3% to 37.5%). More late adolescent girls were underweight, while more young women were overweight/obese (p<0.001). Stunting affected 9.2% (95% CI 8.9% to 9.6%) of participants, of which 35.7% were additionally underweight and 7.3% overweight/obese. Compared with those in the normal weight category, those underweight were more likely to be impoverished and less empowered. Those overweight/obese were more likely to be from a higher wealth quintile and food secure. Increased education level and food security were associated with reductions stunting risk. CONCLUSIONS: This study informs the data gap and need for comprehensive research on adolescent nutritional status. Findings suggest factors related to poverty played an important, underlying role in undernutrition among participants. Commitment to improving the nutritional status of all adolescent and young women in Pakistan will be critical given the observed burden of malnutrition. TRIAL REGISTRATION NUMBER: NCT03287882.

Assessment of Binary Agarose-Carbopol Buccal Gels for Mucoadhesive Drug Delivery: Ex Vivo and In Vivo Characterization.

Agarose (AG) is a naturally occurring biocompatible marine seaweed extract that is converted to hydrocolloid gel in hot water with notable gel strength. Currently, its mucoadhesion properties have not been fully explored. Therefore, the main aim of this study was to evaluate the mucoadhesive potential of AG binary dispersions in combination with Carbopol 934P (CP) as mucoadhesive gel preparations. The gels fabricated via homogenization were evaluated for ex vivo mucoadhesion, swelling index (SI), dissolution and stability studies. The mucoadhesive properties of AG were concentration dependent and it was improved by the addition of CP. Maximum mucoadhesive strength (MS) (27.03 g), mucoadhesive flow time (FT) (192.2 min), mucoadhesive time in volunteers (MT) (203.2 min) and SI (23.6% at 4 h) were observed with formulation F9. The mucoadhesive time investigated in volunteers (MT) was influenced by AG concentration and was greater than corresponding FT values. Formulations containing 0.3%, w/v AG (F3 and F9) were able to sustain the release (~99%) for both drugs till 3 h. The optimized formulation (F9) did not evoke any inflammation, irritation or pain in the buccal cavity of healthy volunteers and was also stable up to 6 months. Therefore, AG could be considered a natural and potential polymer with profound mucoadhesive properties to deliver drugs through the mucosal route.

Practices and predictors of menstrual hygiene management material use among adolescent and young women in rural Pakistan: A cross-sectional assessment.

Background: In low- and middle-income countries (LMICs), women often use inappropriate materials to manage menstruation, which can threaten their health. Improper practices can also have critical downstream consequences beyond physiologic health, including restricting adolescent girls' access to academic pursuits. Methods: We used cross-sectional data collected through a structured questionnaire from the menstruating adolescents and young women 15-23 years of age living in rural Pakistan (n = 25 305). We aimed to describe menstrual hygiene management (MHM) practices and generate a predictive model of the socioeconomic and demographic factors related to the use of MHM materials. Beliefs and barriers around MHM were also summarized. The outcome variable included: those who practiced appropriate and inappropriate MHM practices. Logistic regression was used to generate the predictive model, with results presented as odds ratios (OR) and 95% confidence interval (CI). Results: Inappropriate MHM practices were reported by 75% (n = 19 006) of participants. The majority 61.9% (n = 15 667) reported using old cloths, 12.6% (n = 3191) used nothing, and 0.5% (n = 136) used old cloth with a sanitary pad. One-fourth of participants reported appropriate MHM material use, including 16.2% (n = 4087) sanitary pads, 8.6% (n = 2167) new cloth, and a few reported using sanitary pads with new cloth 0.2% (n = 45). Inappropriate MHM practices were more common in lowest wealth quintile (OR = 4.41; 95% CI = 2.77-7.01, P < 0.0001), followed by those with no education (OR = 3.9; 95% CI = 3.36-4.52, P < 0.0001). Conclusions: The study indicates the need for multi-sectoral efforts to introduce MHM-specific and MHM-sensitive interventions to improve MHM practices, ranging from the availability of low-cost MHM materials to the inclusion of MHM education in school curriculums and within the community platforms.

Age-Based Anthropometric Cutoffs Provide Inconsistent Estimates of Undernutrition: Findings from a Cross-Sectional Assessment of Late-Adolescent and Young Women in Rural Pakistan.

Ambiguity around age ranges for adolescence and adulthood can make the application of age-based nutrition cutoffs confusing. We examined how estimates generated using the age-based anthropometric cutoffs for adolescent girls (10 to <19 y) and women of reproductive age (15-49 y) compared between late-adolescent and young women, and determined how application of both cutoffs affected late-adolescents' estimates. Using cross-sectional data from participants aged 15-23 y in the Pakistan-based Matiari emPowerment and Preconception Supplementation (MaPPS) Trial (n = 25,447), notably large differences in estimates were observed for stunting (30.5% and 7.9% for late-adolescent and young women, respectively; P < 0.001) and thinness (9.3% and 30.8%, respectively; P < 0.001). When both cutoffs were applied to adolescents' data, estimate differences were maintained. With each year of age, the difference for stunting increased and thinness decreased. Given the discrepancies observed both between and within groups, clarity around application of anthropometric cutoffs for youth (aged 15-24 y) is needed. This trial was registered at clinicaltrials.gov as NCT03287882.

Fixed Dose Single Tablet Formulation with Differential Release of Amlodipine Besylate and Simvastatin and Its Pharmacokinetic Profile: QbD and Risk Assessment Approach.

PURPOSE: A differential release fixed dose matrix tablet of amlodipine besylate (AML-B) and simvastatin (SIM) was formulated to enhance patient compliance. MATERIAL AND METHOD: In the first phase, release controlling parameters of AML-B and SIM granules were identified and in the second phase a fixed dose AML-B and SIM tablet formulation was prepared and optimized for a differential release of the drugs using a quality by design (QbD) and risk assessment approach. A validated HPLC method was employed for simultaneous determination of AML-B and SIM for FDC formulation. A pharmacokinetics of the above drugs was studied in healthy dogs in the third phase. RESULTS: In QbD-based optimized formulation, Eudragit® RSPO-dicalcium phosphate (DCP) blend controlled the release of AML-B over 8 h, though this diffusion-controlled release assumed first order kinetics. DCP and Eudragit® RS 100 also retarded release of SIM causing SIM release over 8 h after AML-B release from the optimized FDC tablet formulation. The HPLC retention times of AML-B and SIM were 2.10 and 15.52 min, respectively. Linearity for AML-B was 5.0-50 ng/mL and 0.01-2.0 µg/mL for SIM with percent recoveries of 92.85-101.53% and 94.51-117.75% for AML-B and SIM. AUC0-∞ of AML-B was increased 3 fold, while AUC0-∞ of SIM was decreased 2 fold. The tmax values for AML-B and SIM were 12 and 6 h, respectively. AML-B was absorbed without any lag time (tlag) while tlag was 6.33 ± 0.81 h for SIM, thus met the study objective. CONCLUSION: The pharmacokinetic study showed an immediate absorption of AML-B while that of SIM was withheld for 6 h, close to the desired delay time of 8 h.

Characterizing Micronutrient Status and Risk Factors among Late Adolescent and Young Women in Rural Pakistan: A Cross-Sectional Assessment of the MaPPS Trial.

Nutritional deficiencies are a leading underlying risk factor contributing to the global burden of disease. In Pakistan, late adolescence is considered a nutritionally vulnerable period, as micronutrient requirements are increased to support maturation, and dietary staples are nutrient poor. However, there has been limited evaluation of micronutrient status beyond anemia and its determinants. Using cross-sectional data from late adolescent and young women (15-23 years) at enrolment in the Matiari emPowerment and Preconception Supplementation (MaPPS) Trial, we aimed to describe the prevalence of key micronutrient deficiencies of public health concern, and generate hierarchical models to examine associations with proxies for social determinants of health (SDoH). The prevalence of micronutrient deficiencies was high: 53.6% (95% confidence interval (CI): 53.0-54.3%) had anemia; 38.0% (95% CI: 36.4-39.6%) iron deficiency anemia; 31.8% (95% CI: 30.2-33.3%) vitamin A deficiency; and 81.1% (95% CI: 79.8-82.4%) vitamin D deficiency. At least one deficiency was experienced by 91.0% (95% CI: 90.1-92.0%). Few SDoH were maintained in the final hierarchical models, although those maintained were often related to socioeconomic status (e.g., education, occupation). To improve the micronutrient status of late adolescent and young women in Pakistan, a direct micronutrient intervention is warranted, and should be paired with broader poverty alleviation methods.

The Effect of Nucleus Size on the Cell Dose in Targeted Radionuclide Therapy - A Monte Carlo Study.

BACKGROUND: Nowadays, the use of radiopharmaceuticals in medicine is unavoidable. Depending on the distribution of the radiopharmaceutical in the cells, the nucleus absorbed dose changes by the variations in their geometry size. Therefore, this study aims to investigate the S-value by the variation of nucleus size using Geant4 toolkit. METHODS: Two spherical cells with a variety of nucleus size have been considered as the cancerous cell. Monoenergetic electrons ranging from 5 to 300 keV are distributed uniformly. The S-value for four target-source components (including Nucleus←Cytoplasm, Nucleus←Cell surface, Nucleus←Nucleus, and Nucleus←Nucleus surface) is computed and plotted. Then, the obtained data are compared with analytical Medical Internal Radiation Dose (MIRD) data. RESULTS: In Nucleus←Cytoplasm compartment for electrons below 10 keV, obtained S-values show a slight decrease for the nucleus in the radii of around half of the cell radius and then S-values increase with the increase in the nucleus radii. In the S-value of Nucleus←Cell surface, for all electron energy levels, a slight decrease observed with the increase of nucleus radii. For Nucleus←Nucleus and Nucleus←Nucleus surface cases, with an increase in the size of the cell nucleus, a sharp reduction in the S-values is detected. CONCLUSION: It can be concluded that for the beta emitters with low-energy radiation (<40 keV), the S-value is heavily dependent on the nucleus size which may affect the treatment of small tumors. While for the beta emitters with higher-energy radiation (>100 keV), the size of the nucleus is not very noticeable in the induced S-value.

Factors associated with low birthweight in term pregnancies: a matched case-control study from rural Pakistan.

Low birthweight (LBW) remains a significant public health problem in Pakistan and further understanding of factors associated with LBW is required. We conducted a hospital-based matched case control study to identify risk factors associated with LBW in a rural district of Pakistan. We found that illiteracy (AOR: 2.68; 95% CI: 1.59 - 4.38), nulliparity (AOR: 1.82; 95% CI: 1.26-2.44), having a previous miscarriage/abortion (AOR: 1.22; 95% CI: 1.06-2.35), having < 2 antenatal care (ANC) visits during last pregnancy (AOR: 2.43; 95% CI: 1.34-2.88), seeking ANC in third trimester (AOR: 3.62; 95% CI : 2.14-5.03), non-use of iron folic acid during last pregnancy (AOR: 2.72; 95% CI: 1.75-3.17), having hypertension during last pregnancy (AOR: 1.42; 95% CI: 1.13-2.20), being anemic (AOR: 2.67; 95% CI: 1.65-5.24) and having postpartum weight of <45 kg (AOR: 3.30; 95% CI : 1.97-4.52) were significantly associated with an increased odds of having a LBW baby. Our study identifies modifiable risk factors requiring immediate commitment from the health authorities.

Some weighted inequalities for Hausdorff operators and commutators.

In this paper, we consider the problem of boundedness of Hausdorff operator on weighted central Morrey spaces. In particular, we obtain sharp bounds for Hausdorff operators on power weighted central Morrey spaces. Analogous results for the commutators of Hausdorff operators when the symbol functions belong to weighted central-BMO spaces are obtained as well.

Assessment of computerized treatment planning system accuracy in calculating wedge factors of physical wedged fields for 6 MV photon beams.

Wedge filters are commonly used in external beam radiotherapy to achieve a uniform dose distribution within the target volume. The main objective of this study was to investigate the accuracy of the beam modifier algorithm of Theraplan plus (TPP version 3.8) treatment planning system and to confirm that either the beam hardening, beam softening and attenuation coefficients along with wedge geometry and measured wedge factor at single depth and multiple fields sizes can be the replacement of wedged profile and wedged cross-sectional data or not. In this regard the effect of beam hardening and beam softening was studied with physical wedges for 6 MV photons. The Normalized Wedge Factors (NWFs) were measured experimentally as well as calculated with the Theraplan plus, as a function of depth and field size in a water phantom for 15°, 30°, 45°, and 60° wedge filters. The beam hardening and softening was determined experimentally by deriving the required coefficients for all wedge angles. The TPP version 3.8 requires wedge transmission factor at single depth and multiple field sizes. Without incorporating the hardening and softening coefficients the percent difference between measured and calculated NFWs was as high as 7%. After the introduction of these parameters into the algorithm, the agreement between measured and TPP (V 3.8) calculated NWFs were improved to within 2 percent for various depths. Similar improvement was observed in TPP version 3.8 while calculating NWFs for various field sizes when the required coefficients were adjusted. In conclusion, the dose calculation algorithm of TPP version 3.8 showed good accuracy for a 6 MV photon beam provided beam hardening and softening parameters are taken into account. From the results, it is also concluded that, the beam hardening, beam softening and attenuation coefficients along with wedge geometry and measured wedge factor at single depth and multiple fields sizes can be the replacement of wedged profile and wedged cross-sectional data in the TPS. The study also indicated that by ignoring the beam softening and beam hardening will result in an inaccurate dose to the target volume of the patient.