Palatable Levocetirizine Dihydrochloride Solid Dispersed Fast-Dissolving Films: Formulation and In Vitro and In Vivo Characterization.

One of the most important issues for bitter-tasting drugs such as levocetirizine dihydrochloride (LCD) is the production of palatable dosage forms. LCD also has a delayed onset of action following oral administration. In this study, solid dispersed fast-dissolving films (FDFs) of LCD using the solvent casting method for oral application were prepared and evaluated. The FDF is composed of HPMC as the film forming polymer and different types of superdisintegrants (sodium starch glycolate, croscarmellose sodium, or crospovidone). FDF containing crospovidone showed the highest percentage release of the drug (100.54% ± 1.47 within 3 min.) and was chosen for fabricating into palatable solid dispersed FDFs using different ratios of gelatine. The results of Raman and FTIR revealed that the drug's crystalline structure has been disrupted, and the drug has intermolecular hydrogen bonds with gelatine. The solid dispersed FDF (LF-7), which contained the drug in the form of a 1 : 1 solid dispersion with gelatine, showed a rapid in vitro disintegration (25 seconds) and a burst release of the drug (99.22% ± 2.22 within one min). The in vivo studies were conducted on human participants and showed a significant (p < 0.05) reduction in disintegration time (9.43 ± 2.16 sec.) and higher taste masking ability of the solid dispersed FDF (LF-7) compared to the nonsolid dispersed FDF (LF-4). The stability studies indicated that the prepared FDF remained stable over three months. Overall, FDFs of levocetirizine dihydrochloride with a palatable and rapid onset of action were developed to relieve allergic symptoms.

A hybrid, effectiveness-implementation research study protocol targeting antenatal care providers to provide female genital mutilation prevention and care services in Guinea, Kenya and Somalia.

BACKGROUND: In settings with high prevalence of female genital mutilation (FGM), the health sector could play a bigger role in its prevention and care of women and girls who have undergone this harmful practice. However, ministries of health lack clear policies, strategic plans or dedicated funding to implement anti-FGM interventions. Along with limited relevant knowledge and skills to prevent the practice of FGM and care for girls and women living with FGM, health providers have limited interpersonal communication skills and self-efficacy, while some may have supportive attitudes towards FGM and its medicalization. We propose to test the effectiveness of a health system strengthening intervention that includes training antenatal care (ANC) providers on person-centred communication (PCC) for FGM prevention. METHODS: This will be a two-level, hybrid, effectiveness-implementation research study using a cluster randomized trial design in Guinea, Kenya and Somalia conducted over a 6 months period. In each country, within pre-selected regions/counties, 60 ANC clinics will be randomized to intervention and control arms. At baseline, all clinics will receive the level one intervention involving provision of FGM-related clinical guidelines and handbook as well as anti-FGM policies and posters. At month 3, intervention clinics will receive the level two intervention comprising of a training for ANC providers on PCC to challenge their FGM-related attitudes and build their communication skills to effectively provide FGM prevention counselling. A process evaluation will be conducted to understand 'how' and 'why' the intervention package achieves intended results. Multi-level regression modelling will be used for quantitative data analysis while qualitative data will be assessed using thematic content analysis to determine the effectiveness, feasibility and acceptability of the different intervention levels. DISCUSSION: The proposed study will strengthen the knowledge base regarding how to effectively involve health providers in FGM prevention and care. TRIAL REGISTRATION: Trial registration and date: PACTR201906696419769 (June 3rd, 2019).

Comparison of the diagnostic performance of 2 core biopsy needles for EUS-guided tissue acquisition from solid pancreatic lesions.

BACKGROUND AND AIMS: A new core biopsy needle with a novel tip, opposing bevel, and sheath design has recently been introduced for EUS-guided fine-needle biopsy (FNB). The diagnostic utility of this needle for differentiating solid pancreatic masses is currently unknown. The aim of this study was to compare the diagnostic performance and yield for tissue acquisition from solid pancreatic lesions of the opposing bevel needle with those of a reverse bevel EUS-FNB needle. METHODS: Consecutive patients with solid pancreatic masses undergoing EUS-FNB using the opposing bevel (n = 101) and the reverse bevel (n = 100) core biopsy needles were included in the study. Final diagnosis was based on positive histology or at least 12 months of follow-up in cases with a negative biopsy. The primary outcome was the diagnostic performance of the 2 needles for malignant pancreatic masses. A secondary outcome was the diagnostic yield. RESULTS: Compared with the reverse bevel needle, using strict criteria the opposing bevel needle provided significantly higher sensitivity (71.1% vs 90.1%; P = .0006) and overall accuracy (74% vs 92%; I = 0.0006) for discriminating malignant from benign solid pancreatic masses. The proportion of samples classified as adequate for histologic analysis was 87% for the reverse bevel needle versus 99% for the opposing bevel needle (p = 0.002) Multivariate analysis controlling the needle gauge and site did not show any significant difference in accuracy and sensitivity between the 2 groups. There were no adverse events in either group. CONCLUSIONS: In this first, large, single-center preliminary cohort study, an EUS core biopsy needle with a novel tip, opposing bevel, and sheath design afforded substantially superior tissue yield and diagnostic performance compared with a reverse-bevel needle. If replicated by randomized controlled trials, our findings suggest that similarly designed needles could become the standard of care for EUS-guided tissue acquisition from solid pancreatic masses.

Primary Healthcare Workers' Awareness of Acute Rheumatic Fever & Rheumatic Heart Disease: A Study in Public Health Facilities in South Western Uganda.

Introduction: Timely identification and treatment of a streptococcal throat infection prevents acute rheumatic fever (ARF) and its progression to Rheumatic Heart Disease (RHD). However, children in developing countries still present with established RHD, due to either missed, untreated or sub-optimally treated sore throats and ARF. We aimed to determine the level of knowledge, skills, and practices of primary health workers in South Western Uganda in providing care such children. Methods: We conducted a comparative quantitative cross-sectional study to assess knowledge, practices, and skills regarding the care of a child with a sore throat, ARF, and RHD. The responses were scored against a structured guide. The Fisher's exact test and the chi-squared test with level of significance set at 0.05 were utilized to compare differences in knowledge, skills, and practices among health workers in private and public health facilities about ARF and RHD. Results: Eighty health workers from health facilities were interviewed in Mbarara district with a median age of 29.5 years (IQR 27.34) and median duration in practice of 5 years (IQR: 2, 10). On average, there were at least 3 children with sore throats weekly. At least 95% (CI: 87.25%-98.80%) of the health worker had awareness about ARF and RHD. Only 43.75% (95% CI: 33.18%-54.91%) had good knowledge about ARF and RHD. Majority, 61.25% (95% CI: 50.03%-71.39%) did not know the proper prophylaxis and investigations for a child with ARF. There were no statistically significant differences but a clinically meaningful differentials in the level of knowledge among health workers in public and private facilities. Conclusion: The knowledge and skill level of health workers in primary healthcare facilities about ARF and RHD in South Western Uganda remains low, with no difference between practitioners in public and private facilities.

Cluster randomised trial of a health system strengthening approach applying person-centred communication for the prevention of female genital mutilation in Guinea, Kenya and Somalia.

INTRODUCTION: There is limited evidence on effective health systems interventions for preventing female genital mutilation (FGM). This study tested a two-level intervention package at primary care applying person-centred communication (PCC) for FGM prevention. METHODS: A cluster randomised trial was conducted in 2020-2021 in 180 antenatal care (ANC) clinics in Guinea, Kenya and Somalia. At baseline, all clinics received guidance and materials on FGM prevention and care; at month 3, ANC providers at intervention sites received PCC training. Data were collected from clinic managers, ANC providers and clients at baseline, month 3 and month 6 on primary outcomes, including delivery of PCC counselling, utilisation of level one materials, health facility preparedness for FGM prevention and care services and secondary outcomes related to clients' and providers' knowledge and attitudes. Data were analysed using multilevel and single-level logistic regression models. RESULTS: Providers in the intervention arm were more likely to deliver PCC for FGM prevention compared with those in the control arm, including inquiring about clients' FGM status (adjusted OR (AOR): 8.9, 95% CI: 6.9 to 11.5; p<0.001) and FGM-related beliefs (AOR: 9.7, 95% CI: 7.5 to 12.5; p<0.001) and discussing why (AOR: 9.2, 95% CI: 7.1 to 11.9; p<0.001) or how (AOR: 7.7, 95% CI: 6.0 to 9.9; p<0.001) FGM should be prevented. They were more confident in their FGM-related knowledge (AOR: 7.0, 95% CI: 1.5 to 32.3; p=0.012) and communication skills (AOR: 1.8; 95% CI: 1.0 to 3.2; p=0.035). Intervention clients were less supportive of FGM (AOR: 5.4, 95% CI: 2.4 to 12.4; p<0.001) and had lower intentions of having their daughters undergo FGM (AOR: 0.3, 95% CI: 0.1 to 0.7; p=0.004) or seeking medicalised FGM (AOR: 0.2, 95% CI: 0.1 to 0.5; p<0.001) compared with those in the control arm. CONCLUSION: This is the first study to provide evidence of an effective FGM prevention intervention that can be delivered in primary care settings in high-prevalence countries. TRIAL REGISTRATION AND DATE: PACTR201906696419769 (3 June 2019).

The feasibility, acceptability, appropriateness and impact of implementing person-centered communication for prevention of female genital mutilation in antenatal care settings in Guinea, Kenya and Somalia.

BACKGROUND: There is limited evidence on how to engage health workers as advocates in preventing female genital mutilation (FGM). This study assesses the feasibility, acceptability, appropriateness and impact of a person-centered communication (PCC) approach for FGM prevention among antenatal care (ANC) providers in Guinea, Kenya and Somalia. METHODS: Between August 2020 and September 2021, a cluster randomised trial was conducted in 180 ANC clinics in three countries testing an intervention on PCC for FGM prevention. A process evaluation was embedded, comprising in-depth interviews (IDIs) with 18 ANC providers and 18 ANC clients. A qualitative thematic analysis was conducted, guided by themes identified a priori and/or that emerged from the data. RESULTS: ANC providers and clients agreed that the ANC context was a feasible, acceptable and appropriate entry point for FGM prevention counselling. ANC clients were satisfied with how FGM-related information was communicated by providers and viewed them as trusted and effective communicators. Respondents suggested training reinforcement, targeting other cadres of health workers and applying this approach at different service delivery points in health facilities and in the community to increase sustainability and impact. CONCLUSION: These findings can inform the scale up this FGM prevention approach in high prevalence countries.

Level and determinants of knowledge, attitude, and practice of risky sexual behavior among adolescents in Harar, Ethiopia.

Background: Adolescence is a transition period of advancement from a state of immature sexual characteristics to sexual and reproductive maturity; an improvement in the mental form progressing to the mental maturity of a grown-up adult; and a period of transition from total socioeconomic dependence to relative independence. An adolescent is defined as a person aged between 10 and 19 years. This study assessed the level and determinant factors of knowledge, attitude, and practice of risky sexual behavior among secondary school adolescents in Harar, Eastern Ethiopia, 2022. Methods: A school-based cross-sectional study design was employed. From the total population of adolescents, 387 respondents were sampled. A simple random sampling method was used to select study participants. The data was collected by using a self-administered questionnaire and analyzed using SPSS version 26. Result: Among the participants, 47.3% had good knowledge of risky sexual behavior. 41.9% had a positive attitude toward risky sexual behavior. 36.1% of students had started sexual activity before they reached 18 years old. Out of 9.3% of respondents who have had sexual intercourse, almost 50% of them had multiple partners. Students who live in urban areas were three times (adjusted odds ratio: 3.3, 95% CI: 1.6, 6.6) more likely to have good knowledge about risky sex than their counterparts in rural settings. Conclusion: There is a significant number of risky sexual behaviors, such as having a different sexual partner and having unprotected sex with a non-regular partner. Being female, in urban residence, not having pocket money, and attending parties have significant associations with having good knowledge about risky sex. Harari Regional Educational and Health Bureau should provide repeated tailored information that can specifically address the attitude of the adolescents toward risky sexual behavior using different media, teachers, and school clubs in respect of sexual and reproductive health. The existing adolescent reproductive health program should be strengthened and evaluated to improve the sexual behavior of adolescents.

Distinct Clinical and Prognostic Features of Myelodysplastic Syndrome in Patients from the Middle East, North Africa, and Beyond: A Systemic Review.

Myelodysplastic syndrome (MDS) describes a group of bone marrow malignancies with variable morphologies and heterogeneous clinical features. The aim of this study was to systematically appraise the published clinical, laboratory, and pathologic characteristics and identify distinct clinical features of MDS in the Middle East and North Africa (MENA) region. We conducted a comprehensive search of the PubMed, Web of Science, EMBASE, and Cochrane Library databases from 2000 to 2021 to identify population-based studies of MDS epidemiology in MENA countries. Of 1935 studies, 13 independent studies published between 2000 and 2021 representing 1306 patients with MDS in the MENA region were included. There was a median of 85 (range 20 to 243) patients per study. Seven studies were performed in Asian MENA countries (732 patients, 56%) and six in North African MENA countries (574 patients, 44%). The pooled mean age was 58.4 years (SD 13.14; 12 studies), and the male-to-female ratio was 1.4. The distribution of WHO MDS subtypes was significantly different between MENA, Western, and Far East populations (n = 978 patients, p < 0.001). More patients from MENA countries were at high/very high IPSS risk than in Western and Far East populations (730 patients, p < 0.001). There were 562 patients (62.2%) with normal karyotypes and 341 (37.8%) with abnormal karyotypes. Our findings establish that MDS is prevalent within the MENA region and is more severe than in Western populations. MDS appears to be more severe with an unfavorable prognosis in the Asian MENA population than the North African MENA population.

Comparative analysis of within-host diversity among vaccinated COVID-19 patients infected with different SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly evolving RNA virus that mutates within hosts and exists as viral quasispecies. Here, we evaluated the within-host diversity among vaccinated and unvaccinated individuals (n = 379) infected with different SARS-CoV-2 Variants of Concern. The majority of samples harbored less than 14 intra-host single-nucleotide variants (iSNVs). A deep analysis revealed a significantly higher intra-host diversity in Omicron samples than in other variants (p value < 0.05). Vaccination status and type had a limited impact on intra-host diversity except for Beta-B.1.315 and Delta-B.1.617.2 vaccinees, who exhibited higher diversity than unvaccinated individuals (p values: <0.0001 and <0.0021, respectively). Three immune-escape mutations were identified: S255F in Delta and R346K and T376A in Omicron-B.1.1.529. The latter 2 mutations were fixed in BA.1 and BA.2 genomes, respectively. Overall, the relatively higher intra-host diversity among vaccinated individuals and the detection of immune-escape mutations, despite being rare, suggest a potential vaccine-induced immune pressure in vaccinated individuals.

COVID-19 Vaccine Platforms: Challenges and Safety Contemplations.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic as of March 2020, creating a global crisis and claiming millions of lives. To halt the pandemic and alleviate its impact on society, economy, and public health, the development of vaccines and antiviral agents against SARS-CoV-2 was a dire need. To date, various platforms have been utilized for SARS-CoV-2 vaccine development, and over 200 vaccine candidates have been produced, many of which have obtained the United States Food and Drug Administration (FDA) approval for emergency use. Despite this successful development and licensure, concerns regarding the safety and efficacy of these vaccines have arisen, given the unprecedented speed of vaccine development and the newly emerging SARS-CoV-2 strains and variants. In this review, we summarize the different platforms used for Coronavirus Disease 2019 (COVID-19) vaccine development, discuss their strengths and limitations, and highlight the major safety concerns and potential risks associated with each vaccine type.