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Journal of Experimental & Clinical... May 2024SMYD3 has been found implicated in cancer progression. Its overexpression correlates with cancer growth and invasion, especially in gastrointestinal tumors. SMYD3...
BACKGROUND
SMYD3 has been found implicated in cancer progression. Its overexpression correlates with cancer growth and invasion, especially in gastrointestinal tumors. SMYD3 transactivates multiple oncogenic mechanisms, favoring cancer development. Moreover, it was recently shown that SMYD3 is required for DNA restoration by promoting homologous recombination (HR) repair.
METHODS
In cellulo and in vivo models were employed to investigate the role of SMYD3 in cancer chemoresistance. Analyses of SMYD3-KO cells, drug-resistant cancer cell lines, patients' residual gastric or rectal tumors that were resected after neoadjuvant therapy and mice models were performed. In addition, the novel SMYD3 covalent inhibitor EM127 was used to evaluate the impact of manipulating SMYD3 activity on the sensitization of cancer cell lines, tumorspheres and cancer murine models to chemotherapeutics (CHTs).
RESULTS
Here we report that SMYD3 mediates cancer cell sensitivity to CHTs. Indeed, cancer cells lacking SMYD3 functions showed increased responsiveness to CHTs, while restoring its expression promoted chemoresistance. Specifically, SMYD3 is essential for the repair of CHT-induced double-strand breaks as it methylates the upstream sensor ATM and allows HR cascade propagation through CHK2 and p53 phosphorylation, thereby promoting cancer cell survival. SMYD3 inhibition with the novel compound EM127 showed a synergistic effect with CHTs in colorectal, gastric, and breast cancer cells, tumorspheres, and preclinical colorectal cancer models.
CONCLUSIONS
Overall, our results show that targeting SMYD3 may be an effective therapeutic strategy to overcome chemoresistance.
Topics: Humans; Animals; Mice; Drug Resistance, Neoplasm; DNA Damage; DNA Repair; Histone-Lysine N-Methyltransferase; Cell Line, Tumor; Xenograft Model Antitumor Assays; Antineoplastic Agents; Female
PubMed: 38812026
DOI: 10.1186/s13046-024-03078-9 -
PloS One 2024The dispensation of medicines in some low- and middle-income countries is often carried out by private vendors operating under constrained conditions. The aim of this...
INTRODUCTION
The dispensation of medicines in some low- and middle-income countries is often carried out by private vendors operating under constrained conditions. The aim of this study was to understand the challenges reported by employees of dispensaries, specifically, chemical and herbal shops and pharmacies in Accra, Ghana. Our objectives were twofold: (1) to assess challenges faced by medicine vendors related to dispensing antimicrobials (antibiotic and antimalarial medications), and (2) to identify opportunities for improving their stewardship of antimicrobials.
METHODS
Data were collected in 79 dispensaries throughout Accra, in 2021, using a survey questionnaire. We used open-ended questions, grounded on an adapted socioecological model of public health, to analyze these data and determine challenges faced by respondents.
RESULTS
We identified multiple, interlocking challenges faced by medicine vendors. Many of these relate to challenges of antimicrobial stewardship (following evidence-based practices when dispensing medicines). Overall, medicine vendors frequently reported challenges at the Customer and Community levels. These included strained interactions with customers and the prohibitive costs of medications. The consequences of these challenges reverberated and manifested through all levels of the socioecological model of public health (Entity, Customer, Community, Global).
DISCUSSION
The safe and effective distribution of medications was truncated by strained interactions, often related to the cost of medicines and gaps in knowledge. While addressing these challenges requires multifaceted approaches, we identified several areas that, if intervened upon, could unlock the great potential of antimicrobal stewardship. The effective and efficient implementation of key interventions could facilitate efforts spearheaded by medicine vendors and leverage the benefits of their role as health educators and service providers.
CONCLUSION
Addressing barriers faced by medicine vendors would provide an opportunity to significantly improve the provision of medications, and ultimately population health. Such efforts will likely expand access to populations who may otherwise be unable to access medications and treatment in formal institutions of care such as hospitals. Our findings also highlight the broad range of care provided by shopkeepers and vendors at dispensaries. These findings suggest that the meaningful engagement of dispensaries as valued conduits of community health is a promising pathway for interventions aiming to improve antimicrobial stewardship.
Topics: Ghana; Humans; Pharmacies; Surveys and Questionnaires; Antimicrobial Stewardship; Anti-Infective Agents; Commerce; Anti-Bacterial Agents; Antimalarials; Public Health
PubMed: 38809832
DOI: 10.1371/journal.pone.0281699 -
Nursing Research and Practice 2024The clinical learning environment (CLE) is critical for developing the practical skills needed in healthcare professions. This study aimed to evaluate healthcare...
BACKGROUND
The clinical learning environment (CLE) is critical for developing the practical skills needed in healthcare professions. This study aimed to evaluate healthcare students' perceptions of the quality of the CLE using the Arabic version of the Clinical Learning Environment, Supervision and Nurse Teacher (ar. CLES + T) scale. The study also aimed to evaluate the tool's measurement invariance and compare perceptions among student groups.
METHODS
This cross-sectional study was carried out at two health education institutes in Morocco throughout the academic year 2018-2019 among 1550 undergraduate students who had just finished a clinical practicum in a hospital or primary healthcare facility. Data were gathered using the ar. CLES + T scale. Confirmatory factor analysis (CFA) and multigroup CFA were performed. The measurement invariance of the ar. CLES + T scale was assessed across gender, study year, and clinical practicum duration, using configural invariance, metric invariance, scalar invariance, and strict invariance. The -test and analysis of variance were used to compare the mean scores of the student groups.
RESULTS
Students expressed positive perceptions toward the CLE. The "Pedagogical atmosphere on the ward" dimension scored the highest, while the "Role of the nurse teacher" dimension received the lowest scores. The measurement invariance of the ar. CLES + T scale by gender, study year, and clinical practicum duration was established. First-year students and those with an extended practicum period were the most satisfied.
CONCLUSION
To promote effective learning in the clinical environment, nurse teachers might use innovative teaching approaches tailored to their evolving role in these settings. Moreover, extending the duration of clinical practicum can further enhance student learning outcomes.
PubMed: 38808270
DOI: 10.1155/2024/7849334 -
PloS One 2024Community pharmacists play an important role in increasing vaccination rates especially in countries where they offer vaccination services and administration. However,...
BACKGROUND
Community pharmacists play an important role in increasing vaccination rates especially in countries where they offer vaccination services and administration. However, little is known about community pharmacist's willingness to provide vaccination services in Saudi Arabia. The objective of this study was to assess knowledge, attitudes, willingness and beliefs of community pharmacists in Saudi Arabia towards providing vaccines at pharmacies.
METHODS
A cross-sectional, online questionnaire-based study using convenience sampling (Snowball technique) was used to obtain responses from community pharmacists across Saudi Arabia. The survey collected information on participants' demographics, knowledge about vaccine, attitude towards vaccine and their attitude to be immunization providers. Bivariate analysis and multiple linear regression models were employed to assess the relationships between demographic variables and outcomes.
RESULTS
The study sample consisted of 384 community pharmacists. More than half of participants had poor knowledge about vaccines (54%). Only 8.4% of participants had good knowledge about vaccines. The results indicated that community pharmacists in the study sample have positive attitude toward vaccines and are willing to provide vaccination services. There was a significant relationship between knowledge about vaccine and attitude toward vaccines. Pharmacists with poor knowledge about vaccines had negative attitude toward vaccines as compared to those with high knowledge (β = -1.743; P-value = 0.024). Additionally, there was a significant relationship between knowledge about vaccine and attitude to be immunization providers. Pharmacists with poor knowledge about vaccines had negative attitude to be immunization providers as compared to those with high knowledge (β = -2.631; P-value = 0.002). Furthermore, a significant number of the community pharmacists reported facing critical barriers to provide vaccines including legal liability, lack of personal resources and lack of appropriate training.
CONCLUSION
Comprehensive training and certification programs for pharmacists are crucial to improve their competencies in handling and administering vaccines to increase the rate of vaccinations in Saudi Arabia.
Topics: Humans; Saudi Arabia; Pharmacists; Male; Female; Health Knowledge, Attitudes, Practice; Adult; Vaccination; Cross-Sectional Studies; Surveys and Questionnaires; Middle Aged; Attitude of Health Personnel; Young Adult; Vaccines
PubMed: 38805488
DOI: 10.1371/journal.pone.0304287 -
Substance Use & Addiction Journal Jul 2024The United States is grappling with an unprecedented overdose crisis, exacerbated by the proliferation of potent synthetic opioids like illicitly manufactured fentanyl....
Methadone's Resurgence in Bridging the Treatment Gap in the Overdose Crisis: Position Statement of AMERSA, Inc (Association for Multidisciplinary Education, Research, Substance Use, and Addiction).
BACKGROUND
The United States is grappling with an unprecedented overdose crisis, exacerbated by the proliferation of potent synthetic opioids like illicitly manufactured fentanyl. Despite the efficacy of methadone treatment in managing opioid use disorder, regulatory barriers hinder its widespread utilization. This article examines the complex landscape of methadone regulation across federal, state, and local levels, highlighting disparities and opportunities for reform.
ISSUE
The COVID-19 public health emergency prompted temporary flexibility in methadone regulations, including expanded take-home doses and telehealth counseling, leading to improved treatment experiences and retention. Permanent revisions to federal guidelines have since been introduced by the Substance Abuse and Mental Health Services Administration, reflecting a progressive shift toward patient-centered care and streamlined access. State regulations, managed by Single State Agencies and State Opioid Treatment Authorities, vary widely, often imposing additional restrictions that impede access to methadone treatment. Local OTP clinics further exacerbate barriers through stringent policies, despite federal and state guidelines advocating for flexibility.
RECOMMENDATIONS
Coordinated efforts among policymakers, healthcare providers, and communities are needed to promote the development of accountability measures, incentives, and community involvement to ensure equitable access and quality of care. To truly meet the demand needed to end the existing overdose crisis and enhance accessibility and comprehensive healthcare services, methadone treatment expansion beyond traditional OTP settings into primary care offices and community pharmacies should take place.
Topics: Humans; Methadone; Opiate Substitution Treatment; United States; Opioid-Related Disorders; COVID-19; Drug Overdose; Analgesics, Opioid; Health Services Accessibility
PubMed: 38804606
DOI: 10.1177/29767342241255480 -
Journal of Multidisciplinary Healthcare 2024Providing accurate and sufficient information is a crucial requirement for delivering effective diabetes care, making it essential for community pharmacists to possess...
BACKGROUND
Providing accurate and sufficient information is a crucial requirement for delivering effective diabetes care, making it essential for community pharmacists to possess adequate knowledge of diabetes mellitus (DM) and its management.
OBJECTIVE
To investigate community pharmacists' level of expertise and engagement in providing counseling and health promotion services for individuals with DM in the United Arab Emirates (UAE).
METHODS
A cross-sectional study design was used. The community Pharmacies were chosen via random sampling and researchers then conducted face-to-face interviews with them using the structured questionnaire. The questionnaire included demographic data, 14 questions on the knowledge and 9 questions about the practice concerning pharmaceutical care for Diabetes Mellitus.
RESULTS
The average age ± SD was 31 ± 6.3. Of the total 516 community pharmacists recruited in the study, 37.2% (n=192) were male and 62.8% (n=324) were female. The average knowledge score about DM prevention and management was 9.7 with a 95% confidence interval (CI) [9.5, 9.9] and the average practice score about DM prevention and management was 7.1 with a 95% confidence interval (CI) [6.9, 7.2]. Better knowledge scores were observed in chief pharmacists (OR 1.29; 95% CI 1.08-1.56), pharmacists with 6-10 Years of experience (OR 6.92; 95% CI 3.43-8.86), pharmacist with > 10 years of experience (OR 1.99; 95% CI 1.67-2.36), when the number of patients the pharmacist serve is 5-10 (OR 1.27; 95% CI 1.06-1.53) and being trained on DM prevention and management (OR 2.18; 95% CI 1.92-2.47). Similarly, better practice scores were observed in older participants (OR1.02; 95% CI 1.001-1.03), chain pharmacies (OR 1.42; 95% CI 1.20-1.68), chief pharmacists (OR 1.56; 95% CI 1.18-2.06), when the number of patients the pharmacists serve was 5-10 (OR 12.26; 95% CI 7.26-16.19), when the number of patients the pharmacists serve was 11-20 (OR 4.23; 95% CI 3.54-5.06) and being trained on DM prevention and management (OR 1.33; 95% CI 1.11-1.59). The most commonly reported barriers to providing counseling and health promotion services for diabetes mellitus (DM) in community pharmacies include a lack of coordination with other healthcare professionals (77%) and insufficient knowledge or clinical skills (68.7%).
CONCLUSION
Our study revealed that community pharmacy staff members displayed a noteworthy level of involvement in providing pharmaceutical care services for patients with diabetes mellitus. Based on these findings, it is recommended to enhance pharmacy education by incorporating more advanced, evidence-based training and curricula focusing on disease management and appropriate therapies, particularly for diabetes.
PubMed: 38803617
DOI: 10.2147/JMDH.S447450 -
Laryngoscope Investigative... Jun 2024Currently, diagnosis of cerebrospinal fluid (CSF) rhinorrhea relies on a multimodal approach, increasing costs and ultimately delaying diagnosis. In the United States...
OBJECTIVE
Currently, diagnosis of cerebrospinal fluid (CSF) rhinorrhea relies on a multimodal approach, increasing costs and ultimately delaying diagnosis. In the United States and internationally, the crux of such a diagnosis relies on confirmation testing (via biomarkers) and localization (e.g., imaging). Biomarker testing may require analysis at an outside facility, resulting in delays diagnosis and treatment. In addition, specialized imaging may be nonspecific and often requires an active leak for diagnosis. There remains a clear need for innovative new technology.
METHODS
A comprehensive review was conducted on both foundational and innovative scholarly articles regarding current and emerging diagnosis modalities for CSF.
RESULTS
Current modalities in CSF rhinorrhea diagnosis and localization include laboratory tests (namely, B2T immunofixation), imaging (CT and/or MRI) with or without intrathecal administration, and surgical exploration. Each of these modalities carry flaws, risks, and benefits, ultimately contributing to delays in diagnosis and morbidity. Promising emerging technologies include lateral flow immunoassays (LFI) and biologically functionalized field-effect transistors (BioFET). Nevertheless, these carry some drawbacks of their own, and require further validation.
CONCLUSION
CSF rhinorrhea remains a challenging diagnosis, requiring a multimodal approach to differentiate from nonpathologic causes of rhinorrhea. Current methods in diagnosis are imperfect, as the ideal test would be a readily accessible, inexpensive, rapid, highly accurate point-of-care test without the need for excess fluid or specialized processing. Critical work is being done to develop promising, new, improved tests, though a clear successor has not yet emerged.
LEVEL OF EVIDENCE
N/A.
PubMed: 38803458
DOI: 10.1002/lio2.1272 -
BMJ Open May 2024This study identifies the most common recorded reason for attendance to primary care for children under 5 years old, including a breakdown via age, ethnicity,...
OBJECTIVES
This study identifies the most common recorded reason for attendance to primary care for children under 5 years old, including a breakdown via age, ethnicity, deprivation quintile and sex.
DESIGN
Cross-sectional.
SETTING
39 of 40 general practices in Lambeth, London, UK.
PARTICIPANTS
22 189 children under 5 years who had attended primary care between the 1 April 2017 and 31 March 2020 and had not opted out of anonymous data sharing within Lambeth DataNet.
OUTCOME MEASURE
The primary objective was to identify the most frequently recorded complaint in general practice for children under 5 years old. The secondary objective was to understand how presenting complaint differs by age, ethnicity, sex and deprivation level. The third objective was to create a multivariate logistic regression with frequent attendance as the outcome variable.
RESULTS
Nine conditions formed over 50% of all patient interactions: the most common reason was upper respiratory tract infections (14%), followed by eczema (8%) and cough (7%). While there was some variation by ethnicity and age, these nine conditions remained dominant. Children living in the most deprived area are more likely to be frequent attenders than children living in the least deprived area (adjusted OR (AOR) 1.27 (95% CI 1.14 to 1.41)). Children of Indian (AOR 1.47 (1.04 to 2.08)), Bangladeshi (AOR 2.70 (1.95 to 3.74)) and other white (AOR 1.18 (1.04 to 1.34)) ethnicities were more likely to be frequent attenders, compared with those of white British ethnicity.
CONCLUSIONS
Most reasons for attendance for children under 5 years to primary care are for acute, self-limiting conditions. Some of these could potentially be managed by increasing access to community care services, such as pharmacies. By focusing on the influence of the broader determinants of health as to why particular groups are more likely to attend, health promotion efforts have the opportunity to reduce barriers to healthcare and improve outcomes.
Topics: Humans; Cross-Sectional Studies; Male; Female; Infant; Child, Preschool; London; Primary Health Care; General Practice; Infant, Newborn; Respiratory Tract Infections; Logistic Models
PubMed: 38803264
DOI: 10.1136/bmjopen-2023-082253 -
BMC Health Services Research May 2024In 2016, Uganda added Hydroxyurea (HU) to the list of essential drugs to treat sickle cell disease SCD. However, Hydroxyurea utilization has been low for several...
Understanding patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, Uganda, a qualitative study.
BACKGROUND
In 2016, Uganda added Hydroxyurea (HU) to the list of essential drugs to treat sickle cell disease SCD. However, Hydroxyurea utilization has been low for several countries in sub-Saharan Africa. This study examined patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, in Uganda.
METHODS
To understand the patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease, we conducted a parallel convergent mixed methods study at outpatient departments of two national referral hospitals in Uganda from October 2022 to January 2023. The cross-sectional mixed-methods study employed both quantitative and qualitative methods. We collected survey data from a systematic sample of 259 participants and conducted individual interviews with a purposive sample of 40 participants (20 adolescents or their caregivers and 20 adult patients with SCD) and interviewed them individually on their knowledge, perceptions, barriers, and facilitators of HU utilization. Descriptive data were analyzed using Stata 16, whereas qualitative data were analyzed thematically using an inductive approach supported by NVivo 12 software. We triangulated data to determine the concordance of qualitative and quantitative data.
RESULTS
The study enrolled 40 participants for qualitative interviews and 259 patients for quantitative, with an average age of 16, over half being female, 46% having secondary education, and 96% unmarried. The prevalence of HU use was 78%. The study identified three themes as follows: Patient barriers at the individual including Inadequate knowledge about HU, Persistent pain, Poor adherence to HU, Poor communication with health care workers, and Psychosocial and emotional challenges. At the facility level, long queues and poor quality of care, drug-related side effects that affect HU, and drug stock-outs were reported. Myths, rumors, and misconceptions about HU, and gender-related barriers were reported to affect HU utilization at a community level. Facilitators for the use of HU and recommendations for improvement. Facilitators included perceived benefits, long duration on HU, information sharing by healthcare workers, availability of complementary drugs, confirmation of diagnosis, and availability of medication at public health facilities or private pharmacies. Patients suggested continuous adherence support, encouragement from healthcare workers, sensitization about benefits and risks, a peer-to-peer approach, and financial support for adolescents and women to start businesses to resolve financial problems.
CONCLUSION
Implementing the use of HU has been challenging in Uganda and needs improvement. Facilitators to hydroxyurea use have been highlighted, though Patient-identified barriers at individual, facility, and community levels that need to be resolved. The experiences and insights shared by our participants provide invaluable guidance for increasing the uptake of HU. Further studies are needed to establish validated instruments to assess patients' pain communication and adherence to the HU regimen.
Topics: Humans; Hydroxyurea; Uganda; Anemia, Sickle Cell; Female; Male; Adult; Adolescent; Qualitative Research; Cross-Sectional Studies; Antisickling Agents; Young Adult; Health Knowledge, Attitudes, Practice; Middle Aged
PubMed: 38802815
DOI: 10.1186/s12913-024-11125-6 -
Frontiers in Health Services 2024The digitalisation of the German healthcare system enables a wide range of opportunities to utilize healthcare data. The implementation of the EHR in January 2021 was a...
Implementation of the electronic health record in the German healthcare system: an assessment of the current status and future development perspectives considering the potentials of health data utilisation by representatives of different stakeholder groups.
INTRODUCTION
The digitalisation of the German healthcare system enables a wide range of opportunities to utilize healthcare data. The implementation of the EHR in January 2021 was a significant step, but compared to other European countries, the implementation of the EHR in the German healthcare system is still at an early stage. The aim of this paper is to characterise the structural factors relating to the adoption of the EHR in more detail from the perspective of representatives of stakeholders working in the German healthcare system and to identify existing barriers to implementation and the need for change.
METHODS
Qualitative expert interviews were conducted with one representative from each of the stakeholder groups health insurance, pharmacies, healthcare research, EHR development and panel doctors.
RESULTS
The interviews with the various stakeholders revealed that the implementation process of the EHR is being delayed by a lack of a viable basis for decision-making, existing conflicts of interest and insufficient consideration of the needs of patients and service providers, among other things.
DISCUSSION
The current status of EHR implementation is due to deficiency in legal regulations as well as structural problems and the timing of the introduction. For instance, the access rights of various stakeholders to the EHR data and the procedure in the event of a technical failure of the telematics infrastructure are remain unclear. In addition, insufficient information and communication measures have not led to the desired acceptance of EHR use among patients and service providers.
PubMed: 38800500
DOI: 10.3389/frhs.2024.1370759