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Abstract Introduction In 2021, there were 38.4 million people living with HIV (PLHIV) globally, of which 20.6 million (54%) were living in Eastern and Southern Africa. Longitudinal studies, inclusive of community randomized trials (CRTs), provide critical evidence to guide a broad range of health care interventions including HIV prevention. In this study, we have used an individual-level cohort study design to evaluate the association between sex and other baseline characteristics and participant retention in the HPTN 071 (PopART) trial in Zambia and South Africa. Methods HPTN 071 (PopART) was a community randomized trial (CRT) conducted from 2013 to 2018, in 21 communities. The primary outcome was measured in a randomly selected population cohort (PC), followed up over 3 to 4 years at annual rounds. PC retention was defined as completion of an annual follow-up questionnaire. Baseline characteristics were described by study arm and Poisson regression analyses used to measure the association between baseline factors and retention. In addition, we present a description of researcher-documented reasons for study withdrawal by PC participants. Results Of the 38,474 participants enrolled during the first round of the trial (PC0), most were women (27,139, 71%) and 73% completed at least one follow-up visit. Retention was lower in men (adj RR: 0.90; 95% CI: 0.88, 0.91) and higher among older participants (adj RR: 1.23; 95% CI 1.20, 1.26) when comparing ages 35–44 to 18–24 years. Retention was higher among individuals with high socioeconomic status (SES) (adj RR 1.16; 95% CI 1.14, 1.19) and medium SES (adj RR 1.12; 95% CI 1.09, 1.14) compared to low SES. The most common reasons for study withdrawal were study refusal (23%) and relocation outside the CRT catchment area (66%). Conclusion Despite challenges, satisfactory retention outcomes were achieved in PopART with limited variability across study arms. In keeping with other studies, younger age, male sex, and lower SES were associated with lower levels of retention. Relocation outside of catchment area was the most common reason for non-retention in this CRT.

Leg orthosis is one of medical device for fracture bone treatment. Several complications have been reported when patients are wearing the conventional Plaster of Paris or fibreglass leg orthosis. Its including numbness due to tight application, swelling, venous congestion and skin irritation. Therefore, the aim of this study is to develop and biomechanical analyse a customized leg cast that could tackle those complications. First, the leg was scanned using a 3D scanner. The leg cast was constructed from a 3D scanned leg model and designed using 3-Matic software which later simulated in finite element analysis using Marc software. The study focuses on three gait cycles; midstance, heel strike and toe off where stress and deformation were predicted. From the results, the cast only supported the ankle in midstance phase with only 7.297MPa stress and not capable to support the ankle in heel strike and toe off phases with maximum stress of 106.99 MPa and 213.12 MPa, respectively, which are beyond its yield strength of ABS, 23MPa. The average of overall displacement occurred for both skin and cast were less than 1.5mm. In short, the cast could only support the ankle in midstance phase and cannot be used for heel strike.

An introduction to surgical challenges and priorities in rural areas

Rural areas are known to be less well resourced than urban areas. Starting new subspecialty centres in an urban area may be challenging; starting them in rural areas is often even harder. In this article we explore various factors that make starting a tertiary orthopaedics unit difficult. We first discuss the background, followed by general challenges of initiating specialised units in rural areas and then the more specific challenges with regard to orthopaedic surgery, and we finish by discussing some socioeconomic and family issues.

Background. Students’ evaluation of teaching performance is one of the important means of measuring the quality of higher education worldwide. Students are valuable contributors to improvement of the teaching performance of lecturers. For any academic institution, it is very important to receive feedback on teaching quality from students. Objectives. To determine lecturers’ performance as evaluated by undergraduate students in general surgery, with the aim of identifying the lecturers’ strengths and planning tactics for any necessary improvement measures. Methods. This study followed a descriptive research design to evaluate seven lecturers in general surgery by 4th- and 6th-year MB ChB students at the University of Limpopo, Polokwane, South Africa. Results. Seven lecturers were evaluated by the students. From the study results, there is strong evidence that the majority of the participants were satisfied with 5/7 lecturers’ interpersonal skills and communication and presentation style, including an overall rating (p

Background. Emergency general surgery represents illnesses of very diverse pathology, related only by their urgent nature. The burden of general surgery emergency admissions at Pietersburg Hospital in Polokwane, Limpopo Province, South Africa, is currently unknown. Objectives. To describe the demographic characteristics and clinical presentation of general surgical patients admitted to Pietersburg Hospital, as well as their surgical management, in order to plan future resource allocation. Methods. This was a retrospective descriptive audit of patients admitted to the adult general surgery department over the 8-month period April - November 2021. Results. A total of 893 surgical emergency patients treated during the study period were included in the analysis. Of these, 357 were trauma and 536 non-trauma emergency cases. The majority of the patients (61%) were managed non-operatively. Of the 39% who required surgical management, only 24% had their operation performed within the first 24 hours, with the remainder only operated on after a delay owing to unavailability of space in theatre and/or unavailability of an intensive care unit (ICU) bed. Conclusion. The lack of a dedicated surgical emergency theatre and the shortage of ICU beds are burning issues at Pietersburg Hospital and should be addressed as a matter of the greatest urgency.

Background. Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic procedure that is an important treatment modality for the management of hepatic, pancreatic and biliary diseases. The ERCP unit in the Limpopo Academic Complex in Polokwane, South Africa, was established at the end of 2021. Objectives. To identify areas for improvement in the new ERCP unit. Methods. All ERCP procedures were audited in five components: (i) room set-up; (ii) endoscope, guidewires and consumable accessories; (iii) fluoroscopy; (iv) sedation and analgesia; and (v) ERCP endoscopist and staff. These were considered the essential pillars of an ERCP unit. The quality of each component was graded in every ERCP procedure as grade 1 (very poor), grade 2 (below average), grade 3 (average), grade 4 (above average), and grade 5 (highly satisfactory). Results. Nine therapeutic ERCP procedures were performed during the period 10 January - 31 May 2022. Eighteen theatre slots were allocated for ERCP procedures during the study period, but only seven of them were utilised. The quality of ERCP unit components was highest for the sedation and analgesia component (mean grade of 4) and lowest for fluoroscopy (mean 1.8). Conclusion. Establishing a new ERCP service is a task with many challenges. We present the preliminary results of the Limpopo Academic Complex ERCP unit with a view to adding our experience to the current knowledge.

Congenital nasal pyriform aperture stenosis (CNPAS) is a rare cause of upper airway obstruction in infants, with an incidence of 1 in 25 000 live births. Choanal atresia (CA) is a more common cause of upper airway obstruction, with an incidence of 1 in 5 000 - 8 000 live births. These two conditions often occur independently of each other. Radiologists frequently misinterpret CNPAS as CA. We present a case in which unilateral CNPAS and unilateral CA occurred in the same patient on opposite sides of the nose. The patient had none of the associated craniofacial abnormalities or syndromes. The CNPAS was successfully treated with a sub-labial approach and drilling of the stenotic pyriform aperture, while the CA was dilated with Lister dilators.

Abstract Background In a cluster-randomised trial (CRT) of combination HIV prevention (HPTN 071 (PopART)) in 12 Zambian communities and nine South African communities, carried out from 2012 to 2018, the intervention arm A that offered HIV treatment irrespective of CD4 count did not have a significant impact on population level HIV incidence. Intervention arm B, where HIV incidence was reduced by 30%, followed national guidelines that mid trial (2016) changed from starting HIV treatment according to a CD4 threshold of 500 to universal treatment. Using social science data on the 21 communities, we consider how place (community context) might have influenced the primary outcome result. Methods A social science component documented longitudinally the context of trial communities. Data were collected through rapid qualitative assessment, interviews, group discussions and observations. There were a total of 1547 participants and 1127 observations. Using these data, literature and a series of qualitative analysis steps, we identified key community characteristics of relevance to HIV and triangulated these with HIV community level incidence. Results Two interdependent social factors were relevant to communities’ capability to manage HIV: stability/instability and responsiveness/resistance. Key components of stability were social cohesion; limited social change; a vibrant local economy; better health, education and recreational services; strong institutional presence; established middle-class residents; predictable mobility; and less poverty and crime. Key components of responsiveness were community leadership being open to change, stronger history of HIV initiatives, willingness to take up HIV services, less HIV-related stigma and a supported and enterprising youth population. There was a clear pattern of social factors across arms. Intervention arm A communities were notably more resistant and unstable. Intervention arm B communities were overall more responsive and stable. Conclusions In the specific case of the dissonant primary outcome results from the HPTN 071 (PopART) trial, the chance allocation of less stable, less responsive communities to arm A compared to arm B may explain some of the apparently smaller impact of the intervention in arm A. Stability and responsiveness appear to be two key social factors that may be relevant to secular trends in HIV incidence. We advocate for a systematic approach, using these factors as a framework, to community context in CRTs and monitoring HIV prevention efforts. Trial registration ClinicalTrials.gov NCT01900977 . Registered on July 17, 2013.

Abstract Background Following the World Health Organization’s (WHO) 2015 guidelines recommending initiation of antiretroviral therapy (ART) irrespective of CD4 count for all people living with HIV (PLHIV), many countries in sub-Saharan Africa have adopted this strategy to reach epidemic control. As the number of PLHIV on ART rises, maintenance of viral suppression on ART for over 90% of PLHIV remains a challenge to government health systems in resource-limited high HIV burden settings. Non facility-based antiretroviral therapy (ART) delivery for stable HIV+ patients may increase sustainable ART coverage in resource-limited settings. Within the HPTN 071 (PopART) trial, two models, home-based delivery (HBD) or adherence clubs (AC), were offered to assess whether they achieved similar viral load suppression (VLS) to standard of care (SoC). In this paper, we describe the trial design and discuss the methodological issues and challenges. Methods A three-arm cluster randomized non-inferiority trial, nested in two urban HPTN 071 trial communities in Zambia, randomly allocated 104 zones to SoC (35), HBD (35), or AC (34). ART and adherence support were delivered 3-monthly at home (HBD), adherence clubs (AC), or clinic (SoC). Adult HIV+ patients defined as “stable” on ART were eligible for inclusion. The primary endpoint was the proportion of PLHIV with virological suppression (≤ 1000 copies HIV RNA/ml) at 12 months (± 3months) after study entry across all three arms. Viral load measurement was done at the routine government laboratories in accordance with national guidelines, annually. The study was powered to determine if either of the community-based interventions would yield a viral suppression rate drop compared to SoC of no more than 5% in its absolute value. Both community-based interventions were delivered by community HIV providers (CHiPs). An additional qualitative study using observations, interviews with PLHIV, and FGDs with community HIV providers was nested in this study to complement the quantitative data. Discussion This trial was designed to provide rigorous randomized evidence of safety and efficacy of non-facility-based delivery of ART for stable PLHIV in high-burden resource-limited settings. This trial will inform policy regarding best practices and what is needed to strengthen scale-up of differentiated models of ART delivery in resource-limited settings. Trial registration ClinicalTrials.gov NCT03025165 . Registered on 19 January 2017

Noor Nabilah Talik Sisin,1 Khairunisak Abdul Razak,2 Safri Zainal Abidin,3 Nor Fazila Che Mat,1 Reduan Abdullah,1,4 Raizulnasuha Ab Rashid,1 Muhammad Afiq Khairil Anuar,1 Wan Nordiana Rahman1 1Medical Radiation Programme, School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan,Malaysia; 2Material Engineering Programme, School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, Nibong Tebal, Penang, Malaysia; 3Oncological and Radiological Sciences Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia; 4Nuclear Medicine, Radiotherapy and Oncology Department, Hospital of Universiti Sains Malaysia, Kubang Kerian, Kelantan, MalaysiaCorrespondence: Wan Nordiana RahmanSchool of Health Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaTel +6097677811Email wandiana@usm.myPurpose: This study aimed to quantify synergetic effects induced by bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) and baicalein-rich fraction (BRF) natural-based agent on the reactive oxygen species (ROS) generation and radiosensitization effects under irradiation of clinical radiotherapy beams of photon, electron and HDR-brachytherapy. The combined therapeutic responses of each compound and clinical radiotherapy beam were evaluated on breast cancer and normal fibroblast cell line.Methods: In this study, individual BiONPs, Cis, and BRF, as well as combinations of BiONPs-Cis (BC), BiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) were treated to the cells before irradiation using HDR brachytherapy with 0.38 MeV iridium-192 source, 6 MV photon beam and 6 MeV electron beam. The individual or synergetic effects from the application of the treatment components during the radiotherapy were elucidated by quantifying the ROS generation and radiosensitization effects on MCF-7 and MDA-MB-231 breast cancer cell lines as well as NIH/3T3 normal cell line.Results: The ROS generated in the presence of Cis stimulated the most substantial amount of ROS compared to the BiONPs and BRF. Meanwhile, the combination of the components had induced the higher ROS levels for photon beam than the brachytherapy and electron beam. The highest ROS enhancement relative to the control is attributable to the presence of BC combination in MDA-MB-231 cells, in comparison to the BB and BCB combinations. The radiosensitization effects which were quantified using the sensitization enhancement ratio (SER) indicate the highest value by BC in MCF-7 cells, followed by BCB and BB treatment. The radiosensitization effects are found to be more prominent for brachytherapy in comparison to photon and electron beam.Conclusion: The BiONPs, Cis and BRF are the potential radiosensitizers that could improve the efficiency of radiotherapy to eradicate the cancer cells. The combination of these potent radiosensitizers might produce multiple effects when applied in radiotherapy. The BC combination is found to have the highest SER, followed by the BCB combination. This study is also the first to investigate the effect of BRF in combination with BiONPs (BB) and BC (BCB) treatments.Keywords: cisplatin, bismuth oxide, baicalein, radiosensitization, reactive oxygen species

Background: β-thalassaemia is a disorder caused by mutations in the β-globin gene, leading to defective production of haemoglobins (Hb) and red blood cells (RBCs). It is characterised by anaemia, ineffective erythropoiesis, and iron overload. Patients with severe β-thalassaemia require lifelong blood transfusions. Haemoglobin E beta-thalassaemia (HbE/β-thalassaemia) is a severe form of β-thalassaemia in Asian countries. More than 200 alleles have been recognised in the β-globin region. Different geographical regions show different frequencies of allelic characteristics. In this study, the spectrum of β-thalassaemia (β-thal) alleles and their correlation with iron overload, in HbE/β-thalassaemia patients, β-thalassaemia trait, and HbE trait were studied. Methods: Blood samples (n = 260) were collected from 65 β-thalassaemia patients, 65 parents (fathers and/or mothers) and 130 healthy control individuals. Haematological analyses, iron profiles, and serum hepcidin levels were examined for all participants. DNA was extracted from patients’ and their parents’ blood samples, then subjected to PCR amplification. Multiplex amplification refractory mutation system PCR (MARMS-PCR) was conducted for eighteen primers to detect the mutations. Results: There was severe anaemia present in HbE/β-thalassaemia patients compared to their parents and healthy controls. The ferritin and iron levels were significantly increased in patients compared to their parents and healthy controls (p = 0.001). Two common mutations were detected among the patient group and three mutations were detected among their parents, in addition to seven novel mutations in HbE/β-thalassaemia patients (explained in results). Conclusion: Some mutations were associated with severe anaemia in β-thalassaemia patients. The detection of mutations is a prognostic marker, and could enhance the appropriate management protocols and improve the haematological and biochemical statuses of β-thalassaemia patients.

Background: Testing of possibly infected individuals remains cornerstone of containing the spread of SARS-CoV-2. Detection dogs could contribute to mass screening. Previous research demonstrated canines' ability to detect SARS-CoV-2-infections but has not investigated if dogs can differentiate between COVID-19 and other virus infections.Methods: Twelve dogs were trained to detect SARS-CoV-2 positive samples. Three test scenarios were performed to evaluate their ability to discriminate SARS-CoV-2-infections from viral infections of a different aetiology. Naso- and oropharyngeal swab samples from individuals and samples from cell culture both infected with one of 15 viruses that may cause COVID-19-like symptoms were presented as distractors in a randomised, double-blind study. Dogs were either trained with SARS-CoV-2 positive saliva samples (test scenario I and II) or with supernatant from cell cultures (test scenario III).Results: When using swab samples from individuals infected with viruses other than SARS-CoV-2 as distractors (test scenario I), dogs detected swab samples from SARS-CoV-2-infected individuals with a mean diagnostic sensitivity of 73.8% (95% CI: 66.0–81.7%) and a specificity of 95.1% (95% CI: 92.6–97.7%). In test scenario II and III cell culture supernatant from cells infected with SARS-CoV-2, cells infected with other coronaviruses and non-infected cells were presented. Dogs achieved mean diagnostic sensitivities of 61.2% (95% CI: 50.7–71.6%, test scenario II) and 75.8% (95% CI: 53.0–98.5%, test scenario III), respectively. The diagnostic specificities were 90.9% (95% CI: 87.3–94.6%, test scenario II) and 90.2% (95% CI: 81.1–99.4%, test scenario III), respectively.Conclusion: In all three test scenarios the mean specificities were above 90% which indicates that dogs can distinguish SARS-CoV-2-infections from other viral infections. However, compared to earlier studies our scent dogs achieved lower diagnostic sensitivities. To deploy COVID-19 detection dogs as a reliable screening method it is therefore mandatory to include a variety of samples from different viral respiratory tract infections in dog training to ensure a successful discrimination process.

Noor Nabilah Talik Sisin,1 Khairunisak Abdul Razak,2 Safri Zainal Abidin,3 Nor Fazila Che Mat,1 Reduan Abdullah,1,4 Raizulnasuha Ab Rashid,1 Muhammad Afiq Khairil Anuar,1 Nur Hamizah Mohd Zainudin,1 Nashrulhaq Tagiling,1 Norazlina Mat Nawi,5 Wan Nordiana Rahman1 1School of Health Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia; 2School of Materials and Mineral Resources Engineering, Universiti Sains Malaysia, Nibong Tebal, Penang, Malaysia; 3Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, Penang, Malaysia; 4Hospital of Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia; 5School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, MalaysiaCorrespondence: Wan Nordiana RahmanSchool of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaTel +60 97677811Email wandiana@usm.myPurpose: The aim of this study was to investigate the potential of the synergetic triple therapeutic combination encompassing bismuth oxide nanoparticles (BiONPs), cisplatin (Cis), and high dose rate (HDR) brachytherapy with Ir-192 source in breast cancer and normal fibroblast cell line.Methods: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection on the radiosensitization effects and generation of reactive oxygen species (ROS) on three proposed radiosensitizers: BiONPs, Cis, and BiONPs-Cis combination (BC). The optimal, non-cytotoxic concentration of BiONPs (0.5 mM) and the 25% inhibitory concentration of Cis (1.30 μM) were applied. The radiosensitization effects were evaluated by using a 0.38 MeV Iridium-192 HDR brachytherapy source over a prescribed dose range of 0 Gy to 4 Gy.Results: The cellular localization of BiONPs was visualized by light microscopy and accumulation of the BiONPs within the vicinity of the nuclear membrane was observed. Quantification of the sensitization enhancement ratio extrapolated from the survival curves indicates radiosensitization effects for MCF-7 and MDA-MB-231 when treated with BiONPs, Cis, and BC. However, NIH/3T3 cells exhibited contradictive behavior as it only reacted towards the BC combination. Nonetheless, the MCF-7 cell line loaded with BC shows the highest SER of 4.29. ROS production analysis, on the other hand, shows that Cis and BC radiosensitizers generated the highest free radicals in comparison to BiONPs alone.Conclusion: A BiONPs-Cis combination was unveiled as a novel approach that offers promising radiosensitization enhancement that will increase the efficiency of tumor control while preserving the normal tissue at a reduced dose. This data is the first precedent to prove the synergetic implication of BiONPs, Cis, and HDR brachytherapy that will be beneficial for future chemoradiotherapy strategies in cancer care.Keywords: HDR brachytherapy, bismuth oxide nanoparticles, radiosensitization, cisplatin, chemoradiotherapy

Abstract Background Children with cleft lip and/or palate (CL/P) are highly susceptible to malnutrition, which may restrict surgery eligibility and delay repair. Preoperative nutrition programs for children with unrepaired CL/P are an effective treatment to overcome malnutrition for safe surgical intervention in high-resource settings; however, the effectiveness of such programs has not been demonstrated in the setting of low- and middle-income countries (LMICs). We studied the impact of a preoperative nutrition program on improving nutritional status and achieving surgical eligibility for children with CL/P. Methods A retrospective review of patients treated by the Operation Smile (OS) Durgapur Cleft Centre in India from March 2021 to December 2022 was conducted. Patient gender, weight, age, cleft type, parental demographics, and income were recorded. The patients’ malnutrition status was categorized as “mild”, “moderate”, or “severe” based on the Indian Academy of Pediatrics (IAP). Patient IAP classifications were noted at multiple timepoints, where change in nutrition status overtime served as the primary outcome of this study. Whether the child became eligible for surgery was assessed as a secondary outcome. Descriptive statistics used t-tests for continuous variables and chi-squared tests for categorical variables. P-values

Baha Sharaf,1 Faris Tamimi,1 Haneen Al-Abdallat,2 Suhaib Khater,1 Osama Salama,1 Anas Zayed,1 Osama El Khatib,1 Assem Qaddoumi,1 Malek Horani,1 Yosra AL-Masri,1 Wafa Asha,1 Bayan Altalla’,1 Hira Bani Hani,1 Hikmat Abdel-Razeq1,2 1King Hussein Cancer Center, Amman, Jordan; 2School of Medicine, The University of Jordan, Amman, JordanCorrespondence: Hikmat Abdel-Razeq, Department of Internal Medicine, King Hussein Cancer Center, 202 Queen Rania Al Abdullah Street P.O. Box: 1269, Amman, 11941, Jordan, Tel +962-6 5300460, Ext: 1000, Email habdelrazeq@khcc.joIntroduction: The integration of anti-HER2 targeted therapy with chemotherapy has demonstrated an increase in pathologic complete response rates (pCR) in patients with HER2-positive early-stage breast cancer (EBC). This study presents real-world data on the use of trastuzumab with or without pertuzumab, in combination with anthracycline and taxanes-based chemotherapy regimen.Methods: We conducted a retrospective analysis of patients with HER2-positive EBC who underwent neoadjuvant chemotherapy (NACT), treated between January 2014 and September 2021. The regimen included four cycles of doxorubicin and cyclophosphamide (AC), followed by four cycles of docetaxel every three weeks, with anti-HER2 therapy administered alongside docetaxel. Outcomes assessed included pCR, 3-year disease-free survival (DFS), and surgical outcomes.Results: During the study period, 484 consecutive patients with HER2-positive EBC, median age of 47 (range, 21– 80) years, were enrolled. (64.7%) of patients received dual anti-HER2 therapy, while 35.3% received single-agent trastuzumab. The overall pCR rate was 44.2%, with a higher rate (55.6%) in hormone receptor (HR)-negative patients compared to HR-positive patients (39.8%), p=0.002. Although dual therapy resulted in a higher pCR rate (46.6%) compared to trastuzumab alone (39.8%), the difference was not statistically significant (p=0.15). The estimated 3-year DFS was 86.1% with dual therapy and 83.1% with trastuzumab alone (p=0.37). Further stratification revealed superior 3-year DFS in node-negative disease (96.4%) compared to node-positive disease (82.3%), p=0.0021. Patients who achieved pCR had a significantly better 3-year DFS (89.3%) compared to those with residual disease (82.2%), p=0.0177. Rate of breast conserving surgery (BCS) was lower (15.2%) among patients who received trastuzumab alone, compared to 26.5% among those who received dual anti-HER2 [Odds Ratio (OR)= 0.50, 95% Confidence Interval (CI), 0.30– 0.80, p=0.005].Conclusion: Dual anti-HER2 therapy did not significantly enhance DFS but was associated with higher BCS rates, highlighting its potential to improve surgical outcomes.Keywords: dual anti-HER2 regimen, pertuzumab, trastuzumab, breast cancer, neoadjuvant

Rani Septrina,1 Putie Hapsari,2 Irra Rubianti Widarda,1 Ronny Lesmana,3 Reno Rudiman,4 Rizky Abdulah,5 Amelia Febrina6 1Division of Plastic Reconstructive Surgery, Department of Surgery, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, West Java, Indonesia; 2Division of Vascular Surgery, Department of Surgery, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, West Java, Indonesia; 3Department of Physiology, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 4Division of Digestive Surgery, Department of Surgery, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung, West Java, Indonesia; 5Department of Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, West Java, Indonesia; 6Trainee in Plastic Reconstructive and Esthetic Surgery Training Program, Universitas Padjadjaran, Bandung, West Java, IndonesiaCorrespondence: Rani Septrina, Department of Surgery, Universitas Padjadjaran/Hasan Sadikin General Hospital, Jl. Prof Eyckman No. 38, Bandung, West Java, 40161, Indonesia, Email rani.septrina@unpad.ac.idAbstract: Ischemic steal syndrome (ISS) occurs in hemodialysis patients. Hence, it rarely becomes gangrene or disrupts hand function. We reported a patient with an ISS and radial atherosclerosis that presented with infected ulcer. The patient was treated with arterialized venous free flap from the contralateral forearm. Dialysis access can be used as early as 10 days after the flap. The report also describes the long-term functional follow-up after reconstruction. Although there was superficial flap necrosis, this non-physiologic flap can preserve the patient’s hand function.Keywords: Ischemic steal syndrome, hemodialysis access, arterialized venous free flap, hand function

Background: The burden of cancer in India has been rising, yet testing for early detection remains low. This study explored inequalities in the uptake of breast cancer (BC) examination and cervical cancer (CC) among Indian women, focusing on socioeconomic, regional, and educational differences. Methods: Data from the 2019–21 National Family Health Survey (n = 353,518) were used to assess the uptake of BC examination and CC testing. Inequalities were quantified using the slope index of inequality (SII), relative index of inequality (RII), and relative concentration index (RCI). SII measured absolute inequality, while RII and RCI assessed relative inequality between disadvantaged and advantaged groups. Results: The ever uptake of tests for early detection of BC and CC were low at 9 and 20 per 1,000 women, respectively. Higher uptake was observed among women from the richest households compared to the poorest (SII: 1.1 for BC and 1.8 for CC). The magnitude of relative socioeconomic inequalities was more pronounced in rural areas (RCI: 22.5 for BC and 21.3 for CC) compared to urban areas. Similarly, higher-educated women were 4.84 times (RII: 4.84) and 2.12 times (RII: 2.12) more likely to undergo BC examination and CC testing, respectively, compared to non-educated women. The Northeastern region exhibited greater socioeconomic inequality, while the Western region showed more education-based inequality. Conclusion: The lower uptake of BC examination and CC testing and the marked inequalities underscore the need for targeted interventions to improve access and utilization of testing services, especially among lower-educated women, and those in rural areas.

Giuliano Lo Bianco,1 Marinella Pugliesi,2 Giovanni Misseri,1 Sean Li,3 Miles Day,4 Michael E Schatman,5,6 Alaa Abd-Elsayed,7 R Jason Yong,8 Christopher L Robinson8 1Anesthesiology and Pain Department, Foundation G. Giglio Cefalù, Palermo, Italy; 2Anestesia, Rianimazione e Terapia del Dolore, Dipartimento Rizzoli Sicilia di Bagheria, Bagheria, Palermo, Italy; 3National Spine & Pain Centers, Shrewsbury, NJ, USA; 4Traweek-Racz Endowed Professor in Pain Research, Department of Anesthesiology, Texas Tech University HSC, Lubbock, TX, USA; 5Department of Anesthesiology, Perioperative Care, and Pain Medicine, NYU Grossman School of Medicine, New York, NY, USA; 6Department of Population Health-Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USA; 7Department of Anesthesiology, University of Wisconsin-Madison, Madison, WI, USA; 8Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USACorrespondence: Giuliano Lo Bianco, Anesthesiology and Pain Department Fondazione Istituto G, Giglio Cefalù via Pietrapollastra, Cefalù, Palermo, 90015, Italy, Email giulianolobianco@gmail.comBackground: Chronic knee pain from osteoarthritis (OA) affects a significant proportion of adults over 40. Total knee arthroplasty (TKA) remains the standard for advanced OA, yet up to 20% of patients experience chronic postsurgical pain (CPSP). Genicular nerve radiofrequency ablation (GNRFA) can alleviate pain in those unresponsive to conservative treatments or TKA. However, anatomical variability of the genicular nerves may limit treatment durability. This retrospective, single-center observational study investigated whether using a novel V-shaped active tip needle—which creates larger lesions—could improve outcomes.Methods: Fifty patients with symptomatic knee OA or CPSP, who had a ≥ 50% reduction in pain after diagnostic genicular nerve blocks, underwent GNRFA with a V-shaped active tip needle between September 2020 and January 2022. Pain and function were assessed using the visual analogue scale (VAS) at rest and during movement, Western Ontario and McMaster Universities Arthritis Index (WOMAC), Douleur Neuropathique en 4 Questions (DN4), and EuroQol-5 Dimensions (EQ-5D) at baseline and 1, 3, 6, and 9 months post-procedure.Results: By 6 months, 64% of patients showed ≥ 50% reduction in VAS pain scores, sustained at 9 months (p< 0.0001). Median WOMAC scores improved from 62.0 at baseline to 40.0 at 6 months (p< 0.0001). DN4 scores declined from a median of 4.0 at baseline to 2.0 at 6 months and 1.0 at 9 months (p< 0.001). EQ-5D scores demonstrated significant enhancement in quality of life (p< 0.01). Pain intensity differences at rest and during movement remained substantially improved at 9 months (p< 0.0001).Conclusion: GNRFA using a V-shaped active tip needle is a promising intervention for chronic knee pain, offering significant and sustained pain relief and functional improvement. Larger lesions created by the novel needle may overcome anatomical challenges, though further randomized studies are warranted to validate efficacy and safety.Keywords: chronic knee pain, chronic knee osteoarthritis, genicular nerve, pain management, radiofrequency ablation, neuromodulation

Abstract Background Approximately half of all antimicrobial prescriptions in intensive care units (ICUs) may be inappropriate, including those prescribed when not needed, in unnecessary combinations or for longer durations than needed. Inappropriate prescribing is costly, exposes patients to unnecessary side-effects and drives population-level antimicrobial resistance, the prevalence and consequences of which are greatest in low- and middle-income countries. However, the implementation of interventions to improve the appropriateness of antimicrobial prescribing has been variable and requires further study. Methods We propose a type III hybrid implementation/effectiveness interventional cohort trial in 35 ICUs in up to 11 low- and middle- income countries. The study intervention is a structured review of antimicrobial prescriptions as recommended by the World Health Organisation. Strategies to support stakeholder-led implementation include development of local protocols, registry-enabled audit and feedback, and education. Evaluation of implementation, and the determinants of its success, is informed by the RE-AIM framework and the Consolidated Framework for Implementation Research respectively. The primary outcome is a composite measure of fidelity, reach and adoption. Secondary outcomes describe the effectiveness of the intervention on improving antimicrobial prescribing. Qualitative interviews will assess relevant implementation acceptability, adaptations and maintenance. A baseline survey will investigate ICU-level antimicrobial stewardship structures and processes. Discussion This study addresses global policy priorities by supporting implementation research of antimicrobial stewardship, and strengthening associated healthcare professional competencies. It does this in a setting where improvement is sorely needed: low- and middle- income country ICUs. The study will also describe the influence of pre-existing antimicrobial stewardship structures and processes on implementation and improve understanding about the efficacy of strategies to overcome barriers to implementation in these settings. Trial registration This study protocol has been registered with ClinicalTrials.gov (ref NCT06666738) on 31 Oct 2004. https://clinicaltrials.gov/study/NCT06666738?term=NCT06666738&rank=1 .

Mayank Gupta,1 Rany T Abdallah,2 Alaa Abd-Elsayed,3 Krishnan Chakravarthy,4 Miles Day,5 Timothy Deer,6 Sudhir Diwan,7 Nebojsa Nick Knezevic,8 Neel D Mehta,9 Michael E Schatman,10 Amol Soin,11 Peter Staats12 1Kansas Pain Management, Overland Park, KS, USA; 2APICO Pain Management, Bear, DE, USA; 3Anesthesiology Department, University Hospital, Madison, WI, USA; 4Solaris Research Institute, San Diego, CA, USA; 5Department of Anesthesiology, Texas Tech University Health Sciences Center, Lubbock, TX, USA; 6The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 7Advanced Spine on Park Avenue; Department of Anesthesiology, Albert Einstein Medical College, Bronx; Pain Attending, Lenox Hill Hospital/Northwell Health, New York, NY, USA; 8Department of Anesthesiology College of Medicine, University of Illinois at Chicago; Advocate Illinois Masonic Medical Center, Chicago, IL, USA; 9Och Spine at Weill Cornell New York Presbyterian Hospital, New York, NY, USA; 10Department of Anesthesiology, Perioperative Care, and Pain Medicine, NYU Grossman School of Medicine; Department of Population Health, Division of Medical Ethics, NYU Grossman School of Medicine, New York, NY, USA; 11Ohio Pain Clinic, Centerville, OH; Department of Surgery, Wright State University, Dayton, OH, USA; 12National Spine & Pain Centers, Premier Pain Centers, Atlantic Beach, FL, USACorrespondence: Mayank Gupta, Kansas Pain Management, 10995 Quivira Road, Overland Park, KS, USA, Email kansaspaindoctor@gmail.comIntroduction: Ideally, a physical or chemical nonsurgical neurolytic procedure provides targeted neurolysis to relieve pain for a suitable length of time without causing complications. This narrative review focuses on five nonsurgical neurolytic procedures that are well-established and well-documented in the literature for the treatment of refractory neuropathic pain and peripheral neuropathies, in particular: two physical nonsurgical neurolytic techniques (cryoablation and radiofrequency ablation) and three chemoneurolytic agents (alcohol injection, phenol injection, and a high-concentration capsaicin 8% topical system).Methods: Using the definition of nonsurgical physical and chemical neurolytic procedures for neuropathic pain, a focused literature search of the PubMed database for English-language, human studies published through July 2024 included, but was not limited to, the following search terms: “neuropathic pain” AND “cryoablation”, “cryoneurolysis”, “radiofrequency ablation”, “alcohol neurolysis”, “alcohol injection”, “phenol neurolysis”, “phenol injection”, “chemoneurolysis”, “topical capsaicin”, and “TRPV1.” While attempts were made to identify prospective clinical trials for each type of neurolytic procedure, information regarding the conduct and safety and efficacy of some of these nonsurgical neurolytic procedures was primarily limited to case studies and anecdotal evidence.Results: The risk benefit basis of each technique is discussed, and recommendations for proper use based on the literature are summarized. Most techniques require ultrasound or fluoroscopy guidance. Pain relief typically ranges from 3 to 12 months, with repeat neurolytic procedures often required to maintain suitable levels of pain relief.Conclusion: The authors provide their insights as to the best utilization of these identified nonsurgical physical and chemoneurolytic procedures for the treatment of refractory neuropathic pain in different patient populations based on neural targets. Together, these five nonsurgical neurolytic techniques provide patients and physicians with a variety of options for the treatment of refractory neuropathic pain. Keywords: alcohol injection, capsaicin 8%, chemoneurolysis, cryoablation, neuropathic pain, peripheral neuropathy, phenol injection, radiofrequency ablation, topical

Abstract Background Natural killer (NK) cells are crucial constituents of innate immunity, playing a vital role in the early defense against viral infections and cancer. Their antiviral capabilities stem from direct cytotoxic activity against infected cells and immunoregulatory functions that modulate adaptive immune responses. In the context of Coronavirus disease (COVID-19), NK cells contribute to controlling viral replication and limiting excessive inflammatory responses. Aims This review highlights the mechanisms underlying NK cell-mediated antiviral activity, focusing on their interactions with severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2). We discuss potential sources of NK cells for adoptive transfer therapy, critical factors influencing their therapeutic efficacy, and considerations for clinical translation in COVID-19 treatment. Methods Various NK cell sources for adoptive therapy are discussed, including peripheral blood, cord blood, and genetically engineered NK cells. Key factors influencing the therapeutic efficacy and safety of NK cell-based therapies are analyzed, including cytokine modulation, NK cell subset selection, and delivery methods. Conclusion Understanding the mechanisms underlying NK cell-mediated antiviral activity and the factors that influence the success of adoptive NK cell therapy can inform the design of more effective immunotherapies for COVID-19 patients. Strategies for improving NK cell function, such as genetic modification and optimizing therapy protocols, are highlighted to enhance therapeutic outcomes. Graphical Abstract NK cells neutralize SARS-CoV-2 by releasing cytotoxic granules, inhibiting replication, and modulating inflammation. They originate from peripheral blood, cord blood, and genetic engineering. Therapeutic strategies include adoptive transfer, cytokine modulation, and optimized delivery. Inflammation is controlled, reducing excessive immune responses.

Abstract Background Lifestyle changes have meant that it is problematic for many people across the globe to maintain adequate vitamin D concentrations. As UV-catalysed production in the skin, which uses vitamin D-binding protein to facilitate systemic absorption, is the primary source of vitamin D, it is questionable if oral supplementation of this vitamin is the optimal means to replace it. However, supplementing an oil-soluble vitamin via the skin is problematic as it gets stuck in the stratum corneum after topical application. This clinical study will test if a new vitamin D ester, vitamin D phosphate, which is more water-soluble compared to vitamin D, administered via a transdermal patch, can be used to improve vitamin D status. Method This is a two-part study comprising a dose-escalation with the vitamin D phosphate transdermal patch followed by a randomised, double-blind, placebo-controlled, multiarmed, multistage clinical trial. It is a single-centred, 12-week study that will enrol a maximum of 100 participants. The dose escalation study will monitor safety and tolerability using serum calcium and 25(OH)D3 levels. The blinded, randomised trial will test different dose frequencies for 4 weeks compared to a placebo. Then, after an interim analysis, the best dosing frequency will be assessed against a placebo. The primary outcome for the multistage clinical study will be the percentage change in 25(OH)D3 concentration in the serum (ng/mL) at weeks 4 and 8 compared to baseline. The secondary outcome measures include percentage change in serum vitamin D-binding protein levels, skin interstitial fluid biomarker concentrations, and nail appearance after 4 and 8 weeks compared to baseline. Discussion This study will determine if a vitamin D phosphate transdermal patch can improve vitamin D status. In addition, it could provide a better understanding of how vitamin D is absorbed directly into the skin after application by measuring the serum vitamin D-binding protein and skin biomarker responses to transdermal supplementation. Trial registration Clinical Trials.gov NCT06098846, registered on 23rd October 2023.

BACKGROUND: Ischemic stroke remains as a major health problem and one important process in Ischemic Stroke is neuroinflammation which has a principal role to maintain the balance of neurogenesis and neurodegeneration process in the brain. Neuroinflammation can lead to glial scar and inhibit neurogenesis processes which is needed for recovery neuron function. This study was conducted to observe the role of high mobility group box 1 (HMGB1) and tumor necrosis factor-α (TNF-α) as neuroinflammation markers to glial fibrillary acidic protein (GFAP) as glial scar marker and to brain-derived neurotrophic factor (BDNF) as neurogenesis marker in brain tissue following ischemic stroke. METHODS: Fifteen male Wistar rats were randomized to three groups; sham group, rats receiving occlusion and terminated 180 minutes later (group A), and rats receiving occlusion and terminated after 7 days (group B). Expressions of BDNF and BDNF mRNA were examined using immunohistochemistry (IHC) and Reverse Transcription Polymerase Chain Reaction (RT-PCR), respectively. While GFAP, HMGB1, TNF-α were assessed using IHC. RESULTS: Expression of BDNF was found lower in group A and group B than in sham group (5.20±1.924, 5.00±1.581, and 7.80±1.304, respectively; p=0.032). Expression of BNDF mRNA was found lower in group A and B than in sham group as well. While expression of GFAP was found higher in group A and B than in sham group (9.60±1.517, 11.40±2.074, and 5.20±1.48, respectively; p=0.000). Higher level of HMGB1 and TNF-α expressions were also found to in group A and group B than in sham group (9.3±1.528, 11.67±1.528, and 2.00±1.000, respectively; p=0.000 for HMGB1 and 6.33±1.155, 9.33±1.528, and 3.00±1.000, respectively; p=0.002 for TNF-α). CONCLUSION: The presence of low BDNF levels and high levels of GFAP, HMGB1 and TNF-α markers, possibly reflects inhibition of the neurogenesis process by neuroinflammation, and induced glial scar formation in ischemic stroke conditions after than 180 hours until 7 days. KEYWORDS: ischemic stroke, BDNF, GFAP, TNF-α, HMGB1

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a dreadful acute neurological condition with an overwhelmingly high rate of associated morbidities and mortality. Despite leaping advancement in neurosurgical techniques and imaging modalities, there is no substantiative improvement in the overall prognosis for aSAH. Cerebral vasospasm remains the predominant cause of associated morbidities. Human albumin has been used in different neurological conditions, including head trauma, intracerebral hemorrhages, and ischemic strokes, with favorable outcomes. However, its beneficial use in aSAH has not been sufficiently explored until recently a published systematic review by our team. In view of the scarcity of published data and lack of robust evidence, our group has designed the first-ever RCT to compare the use of human albumin-enhanced fluid management versus standard fluid therapy with crystalloids in patients with aSAH. Methods This single-center open-label, prospective, parallel group randomized control trial will be conducted at Hamad General Hospital, Doha, Qatar, from August 2024 to July 2027. A sample size of 84 (42 in each arm) has been calculated to be sufficient to detect a clinically significant difference in the modified Rankin scale good score between two groups (human-albumin induced volume expansion therapy versus crystalloid only) for fluid management in aneurysmal subarachnoid hemorrhage patients. The primary outcome will be based on a dichotomized modified Rankin scale [good grades (0–2) and poor grades (3–6)], while the secondary outcome will include symptomatic vasospasm, transcranial Doppler velocities, and Pulse index Contour Cardiac Output (PiCCO) parameters. Discussion The trial aims to provide firsthand evidence on the beneficial use of human albumin to achieve an optimal fluid management regime to explore its potential role in improving clinical outcomes in patients with aSAH. Trial registration ClinicalTrials.gov NCT06548477. Registered on August 9, 2024. https://clinicaltrials.gov/search?term=NCT06548477 .

Abstract Multimorbidity is characterized by the accrual of two or more long-term conditions (LTCs) in an individual. This state of health is increasingly prevalent and poses public health challenges. Adapting approaches to effectively analyse electronic health records is needed to better understand multimorbidity. We propose a novel unsupervised clustering approach to multiple time-to-event health records denoted as multiple state clustering analysis (MSCA). In MSCA, patients’ pairwise dissimilarities are computed using patients’ state matrices which are composed of multiple censored time-to-event indicators reflecting patients’ health history. The use of state matrices enables the analysis of an arbitrary number of LTCs without reducing patients’ health trajectories to a particular sequence of events. MSCA was applied to analyse multimorbidity associated with myocardial infarction using electronic health records of 26 LTCs, including conventional cardiovascular risk factors (CVRFs) such as diabetes and hypertension, collected from south London general practices between 2005 and 2021 in 5087 patients using the MSCA R library. We identified a typology of 11 clusters, characterised by age at onset of myocardial infarction, sequences of conventional CVRFs and non-conventional risk factors including physical and mental health conditions. Interestingly, multivariate analysis revealed that clusters were also associated with various combinations of socio-demographic characteristics including gender and ethnicity. By identifying meaningful sequences of LTCs associated with myocardial infarction and distinct socio-demographic characteristics, MSCA proves to be an effective approach to the analysis of electronic health records, with the potential to enhance our understanding of multimorbidity for improved prevention and management.

Abstract Background Alogliptin belongs to gliptin family of drugs that inhibits ubiquitous enzyme dipeptidyl peptidase-4 (DPP-4). Gliptins increase the life-span of incretin hormones that appear to benefit functioning of several organs via various signaling pathways. Main body Alogliptin is approved for treatment of type 2 diabetes mellitus (T2DM) in majority of the countries. It is administered orally and efficacious as monotherapy as well as combined therapy with other T2DM drugs, such as pioglitazone and metformin. It has a good safety profile, well-tolerated in elderly patients and in patients with co-morbid conditions including risks of cardiovascular event, renal or hepatic insufficiency. Therefore, alogliptin is incessantly experimented and investigated for its therapeutic benefit. Recent developments have indicated potential of alogliptin in discrete pathological conditions. Emerging evidences suggest prominent cardioprotective, hepatoprotective, reno-protective, anti-inflammatory and lipid-lowering capacity of alogliptin. Apart from inhibiting DPP-4 enzyme, alogliptin also affects several signaling mechanisms to exhibit protective effects in patients with diabetes-induced complications. Conclusion This review highlights the potential role of alogliptin and mechanisms involved in amelioration of several other pathological conditions apart from its role in glucose metabolism. Thus, this may provide insights for better utilization and repurposing of alogliptin as a therapeutic agent.

Saki Suzuki,1– 3 Rintaro Imafuku,3 Chihiro Kawakami,3 Yuriko Abe,1,2 Eric H Jego,2 Chiaki Hidai,1,2 Takuya Saiki3 1Division of Medical Education, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan; 2Medical Education Center, Nihon University School of Medicine, Itabashi-ku, Tokyo, Japan; 3Medical Education Development Center, Gifu University, Yanagido, Gifu, JapanCorrespondence: Saki Suzuki, Division of Medical Education, Nihon University School of Medicine, 30-1 Oyaguchi Kamicho, Itabashi-ku, Tokyo, 173-8610, Japan, Tel +81 3 3972 8111, Email suzuki.saki@nihon-u.ac.jpPurpose: Course evaluations are critical for improving educational practices; however, their results can be influenced by various unexpected factors, including cultural values. Despite several studies on cultural dimensions in course evaluations, Japanese students were rarely the focus of evaluation in the Asian context. Data on Japanese students’ evaluation practices may reveal diverse behavioral patterns in Asian countries, highlighting the value of country-specific studies to uncover unique educational contexts. This study explores, through a cultural lens, how Japanese medical students perceive course evaluations and the factors influencing their participation.Methods: Four Focus Groups were created with 23 third- and fourth-year medical students. The recorded discussion data were analyzed using a thematic analysis approach by applying Hofstede’s model of six cultural dimensions as a theoretical framework.Results: This study identified three main themes influencing student participation in course evaluations: their emotions, insufficient understanding of the evaluations’ significance, and logistics impacting student motivation. Gratitude positively influenced their decision to participate in course evaluations, whereas anger, anxiety about presumptuousness, fear and indifference had a negative impact. Additionally, their willingness to participate was positively influenced by the perceived benefits for future students. Logistics, including the timing of evaluations and the design of the online evaluation form, also contributed to either encouraging or discouraging their participation.Conclusion: This study has illuminated factors shaping medical students’ perceptions and motivations regarding course evaluation through Hofstede’s model. These include “perfectionism” associated with decisiveness, “the attitude of accepting the status” linked to restraint, “teacher-centered education” and “respect for authority” related to power distance, “peer pressure” reflecting collectivism, and “risk avoidance” tied to uncertainty avoidance. Understanding these cultural nuances is crucial for the effective implementation of course evaluations in medical schools, as they offer valuable insights into how cultural contexts influence perceptions and motivations across diverse educational environments.Keywords: course evaluation, medical student, Hofstede, cultural dimensions, Confucian, student attitudes

Wardatul Jannah,1,2 Qisty A Khoiry,1,2 Sofa D Alfian,1,2 Rizky Abdulah1,2 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia; 2Drug Utilization and Pharmacoepidemiology Research Group, Center of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Jatinangor, IndonesiaCorrespondence: Sofa D Alfian, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Jatinangor, KM 21, Jatinangor, Sumedang, Indonesia, Tel/Fax +62-022-7796200, Email sofa.alfian@unpad.ac.idPurpose: To identify the suitability of pharmacy-based measures for determining medication adherence in routine clinical use.Methods: Data were obtained through PubMed and Scopus databases up to December 2023 without publication year restrictions. This review included English studies on assessing medication adherence for hypertension, hyperlipidemia, asthma, chronic obstructive pulmonary disease, and diabetes, using pharmacy databases and providing full-text access. We investigated evidence quality utilizing the Newcastle–Ottawa Scale for non-randomized studies (cohort, case-control, and cross-sectional) and the Risk of Bias Assessment Tool for Non-randomized Studies-2 and JADAD scales for quasi-experiments and randomized control trials, respectively. We determined validity characteristics (completeness, accuracy, reliability, objectivity, continuous adherence history, non-intrusiveness, sensitivity, and specificity) and applicability (cost-effectiveness, ease of use, and interpretability) to evaluate the suitability of pharmacy-based medication adherence measures in clinical settings.Results: This review retrieved 1513 studies, of which 74 met the inclusion criteria. All of the studies, which were published from 2000 to 2023 and mostly utilized a retrospective cohort design (n = 53), included 17.6 million patients. Of the 74 studies, 50 were conducted in the United States. Diabetes mellitus (n = 40) was the most prevalent disease, whereas the medication possession ratio (n = 46) and prescription days covered (n = 31) were the most prevalent pharmacy-based matrix. According to the results, 73 articles demonstrated validity characteristics, whereas 1 article lacked these characteristics. All 74 (100%) articles had applicability characteristics.Conclusion: This systematic review demonstrates that pharmacy-based measures possess valid characteristics, including comprehensive, accurate, objective, reliable, and continuously updated adherence history records. These measures are designed to minimize disruption while offering high sensitivity and specificity. Furthermore, they are characterized by their practicality, being cost-effective, easy to implement, and easy to interpret. These findings suggest that pharmacy-based measures are potentially suitable to assess medication adherence for routine clinical use.Keywords: medication possession ratio, proportion of days covered, pharmacy fill, medication adherence, chronic disease, suitability, validity, applicability, routine clinical use

Objective: Medical students and general practitioners have a vital role in disasters both in the “preparedness and mitigation” and “response and recovery” phases. To prepare students management of disasters as health professionals, the level of disaster preparedness perceptions of the students should be evaluated. So, the undergraduate medical curriculum can be structured to ensure the readiness of the students for disaster. The aim of the study was to determine the level of disaster preparedness perception of medical students. Methods: This descriptive study was conducted in the Faculty of Medicine of a state university. The population of the study consisted of students studying in the fourth, fifth and sixth grades of the medical faculty which had a training on disaster module in the fifth year. The study was completed with the participation of 288 students. In the data collection process, “personal information form” and the “disaster preparedness perception scale of personnel working in prehospital emergency health services” were used. Results: It was found that exposure to disasters, presence of individuals exposed to disasters in the family and environment, participation in disaster exercises, receiving disaster training, willingness to volunteer in disasters, the level of participants' perception of themselves as prepared for disasters, the level of perception of the disaster risk of the region of residence, were effective on the mean total score of the scale. Conclusion: Disaster preparedness perception can be seen as a first step toward competency in disaster management in medical students. Conducting simulation-based well-structured training modules is recommended to improve the disaster preparedness perceptions of the students. Further studies are needed to evaluate the effect of simulation-based training in disaster management.

Purpose: Outcomes of peripheral arterial injury (PAI) depend on various factors, such as warm ischemia time and concomitant injuries. Suboptimal prehospital care may lead to delayed presentation, and a lack of dedicated trauma system may lead to poorer outcome. Also, there are few reports of these outcomes. The study aims to review our experience of PAI management for more than a decade, and identify the predictors of limb loss in these patients. Methods: This is a retrospective analysis of prospectively maintained database of trauma admissions at a level I trauma center from January 2008 to December 2019. Patients with acute upper limb arterial injuries or lower limb arterial injuries at or above the level of popliteal artery were included. Association of limb loss with ischemia time, mechanism of injury, and concomitant injuries was studied using multiple logistic regressions. Statistical analysis was performed using STATA version 15.0 (Stata Corp LLC, Texas). Results: Out of 716 patients with PAI, the majority (91.9%) were young males. Blunt trauma was the most common mechanism of injury. Median ischemia time was 4 h (interquartile range 2–7 h). Brachial artery (28.5%) was the most common injured vessel followed by popliteal artery (17.5%) and femoral artery (17.3%). Limb salvage rate was 78%. Out of them, 158 (22.1%) patients needed amputation, and 53 (7.4%) had undergone primary amputation. The majority (88.6%) of patients who required primary or secondary amputations had blunt trauma. On multivariate analysis, blunt trauma, ischemia time more than 6 h and concomitant venous, skeletal, and soft tissue injuries were associated with higher odds of amputation. Conclusion: Over all limb salvage rates was 77.9% in our series. Blunt mechanism of injury and associated skeletal and soft tissue injury, ischemia time more than 6 h portend a poor prognosis. Injury prevention, robust prehospital care, and rapid referral to specialized trauma center are few efficient measures, which can decrease the morbidity associated with vascular injury.

Abstract Background People who face restricted or uncertain physical and economic access to safe, sufficient, and nutritious food to suit their dietary needs or food choices for a productive, healthy, and active life are said to be in a state or situation of food insecurity. There is a dearth of evidence of individual and community-level factors associated with household-level food insecurity in Ethiopia. Thus, this study aimed to assess individual and community-level factors associated with household-level food insecurity to fill the aforementioned gap. Methods This study analyzed the 2021 Performance Monitoring for Action Ethiopia (PMA-ET) datasets. A total of 24,965 participants in the 2021 Performance Monitoring for Action Ethiopia (PMA-ET) datasets were included in the analysis. STATA version 17.0 was used to analyze the data. A multi-level mixed-effects logistic regression analysis was used to assess the individual and community-level factors associated with household-level food insecurity. An adjusted odds ratio with a 95% confidence interval was used to show the strength and direction of the association, and statistical significance was declared at a P value less than 0.05. Results The prevalence of household-level food insecurity in Ethiopia based on 2021 PMA-ET data was 40.9%. Households who have not been educated (AOR: 5.62 with 95% CI: 2.74, 11.5), having primary educational status (AOR: 2.58 with 95% CI: 1.35, 4.92), having secondary educational status (AOR: 2.20 with 95% CI: 1.17, 4.14), households having middle wealth status (AOR: 3.00 with 95% CI: 1.05, 8.50), households having poor wealth status (AOR: 5.18 with 95% CI: 2.00, 13.4), households doesn’t owned any livestock (AOR: 1.68 with 95% CI: 1.09, 2.84), and complete household income loss since COVID-19 restrictions began (AOR: 3.63 with 95% CI: 1.76, 7.50) were statistically associated with household-level food insecurity. Conclusion The prevalence of household-level food insecurity in Ethiopia was high. Hence, governmental and non-governmental organizations should focus on increasing the literacy status of the community since having low literacy status, including being not educated, has been found to contribute to food insecurity. The link between households that have not owned any livestock and food insecurity is one of our findings, suggesting that there is a need to participate in nonagricultural enterprises, including livestock production. Furthermore, besides government support, households should better to develop an emergency response plan for food security during any emergency including pandemics by increasing their source of income to avert the impact of different socioeconomic derangements.

Ivan Surya Pradipta,1,2,&ast; Kevin Aprilio,1,2,&ast; Yozi Fiedya Ningsih,1,2 Mochammad Andhika Aji Pratama,2 Vesara Ardhe Gatera,3 Sofa Dewi Alfian,1,2 Aulia Iskandarsyah,4 Rizky Abdulah1,2 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 2Drug Utilization and Pharmacoepidemiology Research Group, Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 3Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia; 4Department of Clinical Psychology, Faculty of Psychology, Universitas Padjadjaran, Sumedang, West Java, 45363, Indonesia&ast;These authors contributed equally to this workCorrespondence: Ivan Surya Pradipta, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jalan Ir. Soekarno KM 21, Jatinangor, Sumedang, West Java, 45363, Indonesia, Email ivanpradipta@unpad.ac.idBackground: Chronic disease has become an increasing burden in Indonesia, increasing the importance of treatment adherence to control the disease prognosis. Therefore, we aim to determine the prevalence and characteristics of nonadherence in Indonesian chronic disease population.Methods: We identified 11,408 adult subjects with chronic diseases from the fifth Indonesian Family Life Survey. We defined treatment nonadherence as the outcome variable and characteristics related to the World Health Organization Multidimensional Adherence Model as exposure variables. We used descriptive and multivariable analyses to analyze factors related to treatment nonadherence.Results: We identified that 57% (95% CI 56.1– 57.9) of chronic disease patients were nonadherent to their treatment. Treatment nonadherence was notable in subjects with liver disease (61.8%), tuberculosis (59.8%), digestive diseases (57.9%), other lung diseases (56.8%), psychiatric diseases (51.6%), asthma (51.2%), and hypertension (50%). Treatment nonadherence was associated with socioeconomic-related factors of being aged 15– 65 years, living in rural areas, having history of formal education, and having a household size of 2– 6 people. Furthermore, in patient- and condition-related factors, positive perceptions of their health condition, missing 0– 7 days of their regular activity in the last month, being ex- and non-smokers, having no depression symptoms, and having only one chronic disease were associated with treatment nonadherence.Conclusion: Treatment nonadherence for chronic diseases in Indonesia was found to be prevalent. Further consideration of characteristics associated with treatment nonadherence should be given to ensure optimal control of chronic diseases.Keywords: chronic diseases, adherence, socioeconomic factors, patient-related factors, condition-related factors

Background: The utilization of decellularized extracellular matrix (dECM) derived from animal testis tissue hasdemonstrated potential as a component of tissue-specific scaffolds. Current research is mostly centered arounddECM as a natural resource for culturing testicular cells. This study aimed to assess firstly the comparison ofVoytik-Harbin (VH) and Frytes protocol in creating Ram’s dECM testis hydrogel and secondly the evaluation ofthe best protocol effect on in vitro spermatogenesis.Materials and Methods: In this experimental study, the six testes of mature rams were decellularized and the hydrogelproduction was performed by i. The Frytes protocol utilized a concentration of 1 mg/mL of pepsin, dissolvedin either 0.1 or 0.01 M HCl, and ii. The VH protocol was involved 10 mg of pepsin per 100 mg of ECM in 0.5 M ofacetic acid. Subsequently, mouse testicular cells were cultivated on collagen hydrogel as the control and the moreeffective testicular-derived hydrogel (TDH) to evaluate the early stages of in vitro spermatogenesis.Results: While the Freytes protocol produced a homogeneous pre-gel solution with both HCl concentrations; elevatingthe pH to 7.4 loosened the hydrogel and made gelation problematic. In contrast, the VH protocol solidifiedthe hydrogel and produced a strong hydrogel due to its gelation consistency. Furthermore, the prepared hydrogel byVH with 25 mg of dECM had a significantly higher priority in terms of rheology and structure (P

Abstract Background Undernutrition among children is a public health concern in most low and middle-income countries (LMICs) and is associated with poor child growth and development. Knowledge about child feeding practices is needed for nutritional policies and programs. Hence, this study assessed the status of minimum acceptable diet (MAD) and its associated factors among children aged 6–23 months in Afghanistan. Methods This cross-sectional study was based on a secondary dataset of the 2022–2023 Afghanistan Multiple Indicator Cluster Survey (MICS 2022–23). Complete data from 7,876 children aged 6–23 months were analysed. The outcome variable was MAD and was defined according to the WHO and UNICEF recommendations and indicators for young child feeding practices. Bivariate and multivariate binary logistic regression analyses were used to identify factors associated with MAD. Results About 7.3% of children aged 6–23 months were fed with the recommended MAD. The likelihood of receiving MAD was higher in children aged 13–18 months [adjusted odds ratio (AOR) 2.01 (95%CI: 1.63–2.48)] and 19–23 months [2.11 (95%CI: 1.68–2.66)], in children belonging to households with higher wealth status [1.39 (95%CI: 1.04–1.87), 2.06 (95%CI: 1.51–2.82), and 3.07 (95%CI: 2.14–4.40) for the 3rd, 4th, and 5th quintile of wealth status, respectively], and in children living in rural areas [1.56 (95%CI: 1.21–2.01)]. On the other hand, the maternal age group 30–39 years [0.79 (95%CI: 0.64–0.96)] and non-institutional delivery [0.67 (95%CI: 0.54–0.83)] were associated with reduced odds of MAD. Conclusion Our study revealed that a small percentage (7.3%) of children received MAD in Afghanistan. This emphasizes the need for policies and interventions aimed at the improvement of child feeding practices to ultimately lead to better child nutrition and health in Afghanistan.

Abstract Background Metabolic syndrome (MetS) is a multifaceted disorder that significantly elevates the cardiovascular disease risk. The diversity of the combination of its main components, conditioned by genetics and environmental risk factors, contributes to the complexity of this health condition and increases the difficulty of its diagnosis and treatment. Objective Our study aimed to explore the association between four Alu insertion polymorphisms and the risk of MetS as well as its components in the Doukkala population of Morocco. Methods A case–control study was conducted on 175 cases of MetS and 252 controls. Four Alu insertion polymorphisms (Alu-ACE, Alu-TPA25, Alu-PV92, and Alu-APOA1) were genotyped using Polymerase Chain Reaction followed by direct electrophoresis of its products. Results Our results showed that the Alu-PV92 and Alu-APOA1 Ins/Del polymorphisms are significantly associated with MetS, the patients are characterized by higher frequencies of genotype II (OR = 6.96, 95% CI [4.12–11.75], p

Elhadi Miskeen,1 Jaber Alfaifi,2 Dalal Mohammed Alhuian,3 Mushabab Alghamdi,4 Muffarah Hamid Alharthi,5 Nourah Abdullah Alshahrani,3 Ghala Alosaimi,6 Raydaa Abdullah Alshomrani,3 Abdullah Mohammed Hajlaa,3 Nadir Mohammed Khair,7 Abdullah Mohammed Almuawi,3 Khalifa Haytham Al-Jaber,8 Fath Elrahman Elrasheed,9 Kamal Elhassan,5 Mohammed Abbas10 1Department of Obstetrics and Gynecology, College of Medicine, University of Bisha, Bisha, Saudi Arabia; 2Department of Child Health, College of Medicine University of Bisha, Bisha, Saudi Arabia; 3Medical Student, College of Medicine University of Bisha, Bisha, Saudi Arabia; 4Department of Internal Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia; 5Department of Family and Community Medicine, College of Medicine, University of Bisha, Bisha, Saudi Arabia; 6Medical student, College of Medicine, Taif University, Taif, Saudi Arabia; 7Department of Child Health, Mother and Children Hospital, Bisha, Saudi Arabia; 8Medical student, Royal College of Surgeons, Dublin, Ireland; 9Department of Obstetrics and Gynecology, Faculty of Medicine Najran University, Najran, Saudi Arabia; 10Department of Pediatrics, College of Medicine, Arab Gulf University, Al Manama, BahrainCorrespondence: Elhadi Miskeen, Head Department of Obstetrics and Gynecology, College of Medicine, University of Bisha, P. O. Box 731, Bisha, 61922, Saudi Arabia, Email emiskeen@ub.edu.saIntroduction: With the incorporation of artificial intelligence (AI), significant advancements have occurred in the field of fetal medicine, holding the potential to transform prenatal care and diagnostics, promising to revolutionize prenatal care and diagnostics. This scoping review aims to explore the recent updates in the prospective application of AI in fetal medicine, evaluating its current uses, potential benefits, and limitations.Methods: Compiling literature concerning the utilization of AI in fetal medicine does not appear to modify the subject or provide an exhaustive exploration of electronic databases. Relevant studies, reviews, and articles published in recent years were incorporated to ensure up-to-date data. The selected works were analyzed for common themes, AI methodologies applied, and the scope of AI’s integration into fetal medicine practice.Results: The review identified several key areas where AI applications are making strides in fetal medicine, including prenatal screening, diagnosis of congenital anomalies, and predicting pregnancy complications. AI-driven algorithms have been developed to analyze complex fetal ultrasound data, enhancing image quality and interpretative accuracy. The integration of AI in fetal monitoring has also been explored, with systems designed to identify patterns indicative of fetal distress. Despite these advancements, challenges related to the ethical use of AI, data privacy, and the need for extensive validation of AI tools in diverse populations were noted.Conclusion: The potential benefits of AI in fetal medicine are immense, offering a brighter future for our field. AI equips us with tools for enhanced diagnosis, monitoring, and prognostic capabilities, promising to revolutionize the way we approach prenatal care and diagnostics. This optimistic outlook underscores the need for further research and interdisciplinary partnerships to fully leverage AI’s potential in driving forward the practice of fetal medicine.Keywords: artificial intelligence, fetal medicine, prenatal care, machine learning, fetal monitoring, Bisha, Saudi Arabia

Aftab Ullah,1,&ast; Marina Khan,2,&ast; Yibang Zhang,3 Muhammad Shafiq,4 Mohsan Ullah,1 Azar Abbas,5 Xu Xianxiang,1 Gang Chen,6,7 Yong Diao1 1School of Medicine, Huaqiao University, Quanzhou, Fujian, People’s Republic of China; 2Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat, Pakistan; 3School of Pharmacy, Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of China; 4Research Institute of Clinical Pharmacy, Department of Pharmacology, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China; 5Institute of Medicine, Shenzhen Institute of Advanced Technology, Shenzhen, Guangdong, People’s Republic of China; 6School of Rehabilitation Sciences and Engineering, University of Health and Rehabilitation Sciences, Qingdao, Shandong, People’s Republic of China; 7Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao central Medical Group), Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Diao; Yibang Zhang, Email diaoyong@hqu.edu.cn; zhangyb@ujs.edu.cnAbstract: The effective clinical translation of messenger RNA (mRNA), small interfering RNA (siRNA), and microRNA (miRNA) for therapeutic purposes hinges on the development of efficient delivery systems. Key challenges include their susceptibility to degradation, limited cellular uptake, and inefficient intracellular release. Polymeric drug conjugates (PDCs) offer a promising solution, combining the benefits of polymeric carriers and therapeutic agents for targeted delivery and treatment. This comprehensive review explores the clinical translation of nucleic acid therapeutics, focusing on polymeric drug conjugates. It investigates how these conjugates address delivery obstacles, enhance systemic circulation, reduce immunogenicity, and provide controlled release, improving safety profiles. The review delves into the conjugation strategies, preparation methods, and various classes of PDCs, as well as strategic design, highlighting their role in nucleic acid delivery. Applications of PDCs in treating diseases such as cancer, immune disorders, and fibrosis are also discussed. Despite significant advancements, challenges in clinical adoption persist. The review concludes with insights into future directions for this transformative technology, underscoring the potential of PDCs to advance nucleic acid-based therapies and combat infectious diseases significantly.Keywords: polymer drug conjugates, polymeric therapeutics, nucleic acid

Alicia Christy,1,&ast; Frisca Fernanda,1,&ast; Widya Norma Insani,1,2 Rizky Abdulah1,2 1Department of Pharmacology and Clinical Pharmacy, Universitas Padjadjaran, Sumedang Regency, Jatinangor, Indonesia; 2Centre of Excellence for Pharmaceutical Care Innovation, Universitas Padjadjaran, Sumedang Regency, Jatinangor, Indonesia&ast;These authors contributed equally to this workCorrespondence: Widya Norma Insani, Department of Pharmacology and Clinical Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Jatinangor, West Java, 45363, Indonesia, Email widya.insani@unpad.ac.idAbstract: Digital health interventions have emerged as a promising approach for patient care. The aim of this study was to conduct a systematic review of pharmacist-led digital health interventions for patients with diabetes. The PubMed database was used to select randomized controlled trials that assess the effectiveness of digital health interventions on clinical outcomes among patients with type 1 and 2 diabetes from January 2005 to May 2024. We included randomized controlled trial (RCT) studies on type 1 and 2 diabetes mellitus, analyzing the effects of all digital health interventions by pharmacists, including telephone-based intervention, web-based intervention, and mobile health application, as compared to usual care. The outcomes were a reduction in HbA1c, changes in medication adherence, and reduction of adverse effects. We used the PRISMA reporting standard to implement and report the results. A total of 19 studies were included. Among these, the included digital health interventions were telephone monitoring (n = 15), web-based intervention (n = 2), mobile health application (n = 1), and text-message reminder (n = 1). The findings showed variability: around half of the studies (n = 10, 52.63%) indicated that patients receiving digital health interventions had reduced HbA1c levels compared to those receiving usual care, while five studies (26.31%) found no difference between the intervention and usual care. Five studies (26.31%) showed that such interventions increased medication adherence, while two studies (10.53%) found no difference when compared to standard care. Effectiveness of the intervention is related to several factors, including practicability and patient engagement, frequency of the intervention, and the provision of personalized communication. Tailoring interventions to individual patient profiles and providing adequate support for enhancing practicability of these tools may improve their effectiveness. Further research assessing the cost-effectiveness of such intervention is necessary to inform healthcare policy.Keywords: pharmacist, digital health intervention, diabetes, clinical outcomes, pharmaceutical care

Exercise training in pulmonary arterial hypertension (PAH) has been gaining popularity with guidelines now recommending it as an important adjunct to medical therapy. Despite improvements in function and quality of life, an understanding of metabolic changes and their mechanisms remain unexplored. The objective of this study was therefore to understand the metabolic basis of exercise in a monocrotaline model of PAH.24 male Wistar rats (age: 8–12 weeks and mean body weight: [262.16 ​± ​24.49] gms) were assigned to one of the four groups (i.e., Control, PAH, Exercise and PAH ​+ ​Exercise). The exercise groups participated in treadmill running at 13.3 ​m/min, five days a week for five weeks. Demographic and clinical characteristics were monitored regularly. Following the intervention, LC-MS based metabolomics were performed on blood samples from all groups at the end of five weeks. Metabolite profiling, peak identification, alignment and isotope annotation were also performed. Statistical inference was carried out using dimensionality reducing techniques and analysis of variance.Partial-least-squares discrimination analysis and variable importance in the projection scores showed that the model was reliable, and not over lifting. The analysis demonstrated significant perturbations to lipid and amino acid metabolism, arginine and homocysteine pathways, sphingolipid (p ​

Onychomadesis is the complete removal of the nail’s proximal portion. It affects both the fingernails and toenails and arises following nail matrix arrest. It is a rare childhood ailment, with only a few cases reported worldwide that are not associated with Hand-FootMouth Disease. The first case of onychomadesis diagnosed in Saudi Arabia is presented. A four-year-old girl was clinically diagnosed with the disease. She had no recent history of medication use or trauma, nor a history of periungual dermatitis. Management was conservative. At the 4-month follow-up visit, the damaged nails had improved.