Review Committee Research Articles

Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non-Small Cell Lung Cancer: The Phase II TRUST-I Study.

Taletrectinib, a highly potent, CNS-active, ROS1 tyrosine kinase inhibitor (TKI), has demonstrated high and durable response rates, high intracranial objective response rate (ORR), prolonged progression-free survival (PFS), and activity against G2032R with a favorable safety profile. We report outcomes from the pivotal TRUST-I study (ClinicalTrials.gov identifier: NCT04395677) of taletrectinib for ROS1+ non-small cell lung cancer in China. TRUST-I evaluated TKI-naїve and crizotinib-pretreated patients. The primary end point was confirmed ORR (cORR) by independent review committee; key secondary end points included duration of response (DOR), PFS, and safety. As of November 2023, 173 patients were enrolled (median age, 55 years; 58% female; 73% never smoked; TKI naїve: n = 106; crizotinib pretreated: n = 67). In TKI-naїve patients, cORR and intracranial cORR were 91% and 88%, respectively, and 52% and 73% in crizotinib-pretreated patients. In TKI-naїve patients, median DOR and median PFS were not reached (NR) with 22.1-month and 23.5-month follow-up, respectively. In crizotinib-pretreated patients, the median DOR was 10.6 months (95% CI, 6.3 months to NR; 8.4-month follow-up), and the median PFS was 7.6 months (95% CI, 5.5 to 12.0 months; 9.7-month follow-up). Eight of 12 patients (67%) with G2032R mutations responded. The most frequent treatment-emergent adverse events (TEAEs) were increased AST (76%), diarrhea (70%), and increased ALT (68%), most of which were grade 1-2. Incidences of neurologic TEAEs were low (dizziness: 23%; dysgeusia: 10%) and mostly grade 1. Discontinuations (5%) and dose reductions (19%) due to TEAEs were low. Taletrectinib continues to show high and durable overall responses, prolonged PFS, robust activity against intracranial lesions and acquired resistance mutations including G2032R, and a favorable safety profile with a low incidence of neurologic TEAEs.

Insights from preventability assessments across 42 state and city maternal mortality reviews in the United States

BackgroundThe rising trend in maternal mortality over the past three decades sets the United States (U.S.) apart from all other high-income countries. Multidisciplinary state and city Maternal Mortality Review Committees (MMRCs) conduct comprehensive reviews of maternal deaths, including assessments of preventability and contributing factors. Objective(s)Assess preventability of and contributing factors to maternal mortality in the U.S. Study DesignThis study is a secondary analysis of cross-sectional, population-based data from the most recent, publicly available MMRC data from 40 state and 2 cities in the U.S. Preventability was analyzed among all deaths during pregnancy or within one year postpartum from any cause (pregnancy-associated deaths, PAD) and deaths during pregnancy or within one year postpartum from causes related to pregnancy or its management, but not from accidental causes (pregnancy-related deaths, PRD). We also explored preventability by cause-of-death and contributing factors grouped as community, patient-family, provider, facility, and health system factors. ResultsOf deaths that occurred after 2010, between 53%-93.8% of PADs and 45%-100% of PRDs were deemed preventable across the 42 states and cities. Across the ten states reporting PRD preventability by cause-of-death, MMRCs deemed preventable >90% of deaths from preeclampsia-eclampsia and mental health conditions, >80% of deaths from hemorrhage and cardiovascular conditions, about 70% of deaths from infection and thrombotic embolism, and about 40% of deaths from amniotic fluid embolism and stroke. A total of 3,345 contributing factors were described in MMRC reports from 14 states in relation to 739 PRDs. While collectively patient-family and provider factors were most frequently noted as contributing to PRDs, the contribution of such factors varied between 6%-56% and 18%-42.3%, respectively, across the states. Based on data from 20 MMRCs with available information, racism or discrimination were noted in relation to 37.7% of PRDs. ConclusionsA large proportion of PADs and PRDs in the U.S. are preventable. However, likely due to differences in MMRC membership, available data, and judgement employed to determine preventability, wide variation exists in the proportion of deaths deemed preventable and factors identified as contributing to such deaths across states. There is need to reevaluate the definitions, structure, and outputs for maternal death preventability assessments currently employed by a majority MMRCs to adequately inform state and national programming and policies.

Anthropometric Measurements of Foot in Undergraduate Medical Students of a Medical College: A Descriptive Cross-sectional Study.

Anthropometry is one of the important parameters for differentiation of sex which varies significantly based on hereditary, geographical, racial, sexual, and other factors. This study was done to provide baseline foot anthropometric data for Nepali medical students to improve the accuracy of stature estimations and enhance forensic and clinical applications. The aim of the study was to calculate anthropometric measurements of foot in undergraduate medical students of a medical college. A descriptive cross-sectional study was conducted on medical students studying at a tertiary care hospital during the period of November 6, 2022 to February 28, 2023 after obtaining ethical clearance from the Institutional Review Committee (Reference number: 06/2022). A total population sampling method was used. The present study was conducted to determine the mean foot index from the right and left foot, mean measurements of the left and right foot, and sex-related dimensions of the foot in Nepalese medical students. Data were collected and analyzed using SPSS. Out of 115 participants, the mean foot index for male and female were 38.34±2.13 and 39.33±2.22 respectively. The mean length of the right foot for males and females were 24.12±0.98 cm and 22.10±1.25 cm respectively. The mean length of the left foot for males and females was 24.20±1.06 cm and 22.07±1.24 cm respectively. This study provides mean values of different measurements of the right and left foot of both sexes of the age group of 18-24 years in the students of a medical college.

Enhancing Nursing Staff Clinical Skills of Pain Assessment: Impact of the Educational Course

Objective: To assess the impact of a newly developed educational course in terms of improvement in post-test scores in clinical skills assessment of patients with patient-controlled intravenous analgesia (PCIA) and epidural analgesia using the Likert scale among nursing staff working in a tertiary care teaching hospital. Introduction: Nurses require certain clinical skills to assess patient’s pain adequately. This can be achieved through regular on-the-job training and educational workshops. This will enhance nurses’ clinical practice regarding pain assessment and improve pain treatment and patient satisfaction. Methods: After getting approval from the Institutional Review Committee an education course was developed and implemented. A total of 86 nursing staff attended the course. Teaching methodologies included online lectures, small group tutorials, and hands-on workshops using demonstrations of locally developed videos. Pain assessment skills were assessed at the start of the workshop and the end of the session using PCIA and Epidural Likert scale assessment forms on simulated patients in this experimental, pre-and post- (single-arm) study. Results: Eighty-six participants completed the course, of which 50 (58.1%) were female. In the clinical skill assessment of patients using PCIA, the mean difference in PCIA assessment scores of participants before and after the workshop was 13.88 (90.79%), which was statistically significant (p=<0.001). In the epidural skills assessment, the mean difference in the score of participants before and after the workshop was 15.09 (79.47%), which was statistically significant (p=<0.001). Conclusion: The educational course had a significant impact on increasing the understanding of pain assessment among nursing staff with statistically significant improvement in their clinical skills.

Pattern of Fine Needle Aspiration Cytology of Head and Neck Swelling in Patients Attending a Tertiary Health Care Center: A Descriptive Cross-sectional Study.

Fine needle aspiration cytology is a simple, rapid, cost-effective method in diagnosis of head and neck swelling with minimal risk of complications. Head and neck swellings include a broad spectrum of diseases with different management for each. Fine needle aspiration cytology is a suitable and useful method for assessment of these swelling. This study was done with the objective to study the frequency and distribution of various head and neck lesions detected by fine needle aspiration cytology. A descriptive cross-sectional study was conducted at the Department of Pathology in a tertiary care center from February 1 to July 31, 2023 after obtaining ethical approval from Institutional Review Committee (Reference number: IRC-PA-191/2078-79). All the patients presenting with head and neck swelling during the study period were included in this study. Total sampling was done. Fine needle aspiration was done and cytological diagnosis was made. Descriptive analysis was done where frequency and percentage were calculated. Out of 112 cases included in the study, 43 (38.40%) were of lymph nodes, 36 (32.14%) of thyroid, 22 (19.64%) of skin and soft tissue and 11 (9.82%) of salivary glands. Among the lymph nodes cases, there were 11 (25.57%) metastases. In thyroid lesions, beingn lesions were seen in 24 (66.68%). This study found that lymph nodes were the most common site for head and neck swellings, frequently involving metastatic lesions.

Preterm Neonates Admitted to the Neonatal Intensive Care Unit of a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

Prematurity is a significant cause of neonatal morbidity and mortality, especially in low-income and middle-income countries like Nepal. However, there is a paucity of data regarding its burden. This study aimed to determine the prevalence and outcomes of preterm neonates admitted to the neonatal intensive care unit of a tertiary care hospital. This descriptive cross-sectional study was conducted among preterm neonates at a tertiary care hospital between July 15, 2022 to July 14, 2023 after obtaining ethical approval from the Institutional Review Committee (Reference number: F-NMC/557/078-079). Neonates with gestational age less than 37 weeks were included in the study. Total sampling method was used. Among 980 neonates admitted to intensive care unit, preterm neonates were 112 (11.43%). A total of 69 (61.61%) preterm neonates were outborn, and 65 (58.04%) were male. The median gestational age and birth weight were 32 weeks (interquartile range: 30- 34 weeks) and 1500 gm (interquartile range: 1300-1800 gm), respectively. There were 60 (53.57%) neonates with sepsis, 51 (45.54%) with neonatal jaundice and 38 (33.93%) with respiratory distress. Death occurred in 12 (10.71%) preterm neonates in the hospital. The prevalence of preterm neonates was similar to other studies done in similar settings.

Development and Use of Suicide Registry for Recording Patient Profile with Self-harm Visiting Tertiary Hospital of Nepal: A Descriptive Cross-sectional Study.

Suicide is a major public health concern globally as well as in Nepal. It is important to have baseline data regarding suicide attempts to develop a prevention strategy. This study aims to describe the methodology used to develop a suicide registry and use it to collect data from patient visiting emergency or psychiatric outpatient department with suicide attempts in a tertiary care hospital. This is a descriptive cross-sectional study conducted retrospectively after obtaining ethical approval (Reference number: drs2005211371) from institutional review committee. Total sampling was done from the database covering the period from October 1, 2017, to September 30, 2023. The database was in the form of suicide registry that was developed after reviewing the existing data of primary health care centres, private hospitals, and tertiary care centers and a series of discussions among mental health experts. Data was entered in Microsoft Excel and analysis was done. Among the 248 patients, there were 109 (43.95%) male and 139 (56.05%) female. There were 209 (84.27%) patients who attempted suicide inside home, poisoning was seen in 90 (36.29%) and 183 (73.79%) had impulsive intention. Out of total patients, 59 (23.79%) had prior communication and 84 (33.87%) had previous attempts, 109 (43.95%) patients had impulsive attempts as diagnosis and 75 (30.24%) had depression. As per the suicide registry, most of the patients attempted suicide inside home and the most common method used was ingestion of poison.

Clinical Outcome of Posterior Instrumented Stabilization and Transpedicular Decompression in Patients Presenting with Thoracic or Lumbar Spinal Tuberculosis in a Tertiary Care Center: A Descriptive Cross-sectional Study.

Posterior instrumented stabilization is a commonly done surgery in spinal tuberculosis. This study aims to evaluate the clinical, radiological, and neurological outcomes of posterior instrumented stabilization and transpedicular decompression in thoracic and lumbar spinal tuberculosis. A descriptive cross-sectional study was conducted for one and a half years with at least six months of follow-up in a tertiary care center. The study was approved by the Institutional Review Committee (Reference number: 119 (6-11-5) 2/075-076). Total sampling was done and the study included patients over 18 years of age with spinal tuberculosis of the thoracic or lumbar regions. These patients underwent posterior instrumented stabilization and transpedicular decompression at the tertiary care center. The age, site of involvement, Visual Analog Scale score for back pain, neurological status as per Frankel Neurology grading, and local kyphotic angle in X-ray were recorded. The median, interquartile range and percentage were calculated. The data was entered in Microsoft Excel 2016 and analysis was done using Epi Info software version 7.2. Thoracic level was most commonly involved in 14 (46.68%) cases. The median back pain as assessed by the Visual Analogue Scale score improved from 8 to 2 at the 6-month follow-up. There was improvement in the neurological grading of all cases and there was no loss of correction in the local kyphotic angle till the final follow-up. The median age of cases was 48 years (interquartile range: 28-62.50). Posterior instrumented stabilization and transpedicular decompression in adult patients with thoracic or lumbar spinal tuberculosis achieves improvements in clinical, radiological, and neurological outcomes.

Turkish cross-cultural adaptation, construct validity, and reliability of the treatment expectations in chronic pain scale.

Measuring treatment expectations using the Treatment Expectations in Chronic Pain (TEC) scale has the potential to help clinicians and researchers better understand the role that treatment expectations play within the framework of multimodal pain management settings. The purpose of this study is to determine the cross-cultural adaptation, construct validity and reliability of the TEC Scale in the Turkish language. The study included 191 volunteers aged 22-65 with chronic musculoskeletal diseases. This study composed of a six-stage cross-cultural adaptation process, which included translation, translation synthesis, back-translation, expert committee review, pre-testing and documentation submission. The Positivity Scale and Illness Cognition Questionnaire were used to measure convergent validity while the Hospital Anxiety and Depression Scale was used to test divergent validity. The psychometric properties of the Turkish version of the TEC scale was examined by confirmatory factor analysis (CFA). Scale's internal consistency was examined using Cronbach's alpha. Pearson correlation coefficients were utilized to evaluate both convergent and divergent validity. The significance level was set at p < .05. The results of the CFA showed that factor structure of predicted subscale fitted well the data (x2/df = 3,07;CFI = 0,91,IFI = 0,91 TLI = 0,87,RMSEA = 0,10). The results of the CFA indicated that factor structure of ideal subscale fitted well with the data (x2/df = 2,38;CFI = 0,92,IFI = 0,93,TLI = 0,90,RMSEA = 0,08). Both subscales of the TEC were strongly correlated. The predicted subscale had moderate relationships to depression, anxiety, and positivity (r=-0.37 to r = 0.55) but poor correlations with measures of acceptance, perceived benefits and helplessness (r=-0.24 to 0.35). The ideal subscale had moderate correlations with measures of positivity (r = 0.36) and depression (r=-0.38) but poor correlations with measures of acceptance, perceived benefits helplessness and anxiety (r = 0.14). The Turkish version of the TEC scale is acceptable, valid, and reliable for use in Turkish patients with chronic musculoskeletal pain in physiotherapy outpatient practice.

Befotertinib for patients with pretreated EGFR T790M mutated locally advanced or metastatic NSCLC: Final overall survival results from a phase 2 trial

BackgroundIn the initial analysis of a pivotal phase 2 single-arm study (NCT03861156), befotertinib (D-0316) showed clinical benefit with a manageable safety profile in pretreated patients with EGFR T790M mutated non-small cell lung cancer (NSCLC), including those with brain metastases. MethodsEligible patients received oral befotertinib of 50 mg (cohort A) or 75–100 mg (cohort B) once daily until disease progression, withdrawal of informed consent, or death. The primary endpoint for the initial analysis was objective response rate (ORR) assessed by an independent review committee. OS and safety were secondary endpoints. Herein, we present the final OS and safety data. ResultsA total of 176 patients in cohort A and 290 patients in cohort B were finally enrolled. At data cutoff (May 31, 2023), the median duration of follow-up was 47.9 months (95 % CI: 47.1–48.3) in cohort A and 36.7 months (35.9–37.9) in cohort B. The median OS was 23.9 months (95 % CI: 21.1–27.2) in cohort A and 31.5 months (26.8–35.3) in cohort B. The median OS for patients with and without brain metastasis in cohort A was 18.6 months (95 % CI: 14.9–26.3) and 26.4 months (95 % CI: 23.0–29.0), respectively. In cohort B, these data was 23.0 months (95 % CI: 18.6–29.1) and 35.5 months (95 % CI: 29.3–NE), respectively. The safety profile of befotertinib remained consistent with previous data. Grade 3 or higher treatment-emergent adverse events were 38.1 % in the cohort A and 50.3 % in the cohort B, and 22.2 % and 31.7 % were related to the study drug. ConclusionBefotertinib demonstrated a more profound OS benefit compared to other 3rd-generation EGFR TKI, despite that cross trial data comparison should be interpreted with caution. The safety profile was manageable and consistent with previously report data in pretreated patients with confirmed T790M mutation-positive NSCLC.

Vebreltinib for Advanced Non-Small Cell Lung Cancer Harboring c-Met Exon 14 Skipping Mutation: A Multicenter, Single-Arm, Phase II KUNPENG Study.

The KUNPENG study aimed to evaluate the efficacy and safety of vebreltinib (also known as bozitinib, APL-101, PLB-1001, and CBT-101), a potent and highly selective inhibitor of c-mesenchymal-epithelial transition (MET), in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring c-Met alterations. This multicenter, multicohort, open-label, single-arm, phase II trial enrolled patients with c-Met dysregulated, locally advanced or metastatic NSCLC from January 2020 to August 2022 across 17 centers. Cohort 1 included patients with MET exon 14 skipping (METex14)-mutant NSCLC who had not previously received MET inhibitors. Participants were administered vebreltinib at a dosage of 200 mg twice a day in 28-day cycles. The primary end point was the objective response rate (ORR), and the key secondary end point was the duration of response (DoR), both evaluated by a blinded independent review committee according to the RECIST version 1.1. As of August 9, 2022, 52 patients had been enrolled in cohort 1, of whom 35 (67.3%) were treatment-naïve. The ORR reached 75% (95% CI, 61.1 to 86). Among treatment-naïve patients, the ORR was 77.1% (95% CI, 59.9 to 89.6), and in previously treated patients, it was 70.6% (95% CI, 44.0 to 89.7). The disease control rate was 96.2%, with a median DoR of 15.9 months, a median progression-free survival of 14.1 months, and a median overall survival of 20.7 months. The most common treatment-related adverse events were peripheral edema (82.7%), QT prolongation (30.8%), and elevated serum creatinine (28.8%). Vebreltinib has shown promising efficacy and a favorable safety profile in patients with METex14-mutant NSCLC.

Consideration of Sustainability When Approving Human Medical Research-A Scoping Review.

This article attempts to highlight the importance of including research sustainability as imperative when assessing human medical research in terms of ethical principles. Using a scoping review of recent literature, the complexity of research sustainability is highlighted with key themes and concepts surrounding this important topic being recognized and discussed. An overall paucity of guidance documents was identified and recommendations have been made to practically address this deficiency. An example of a research sustainability evaluation tool which is currently being piloted has been provided for possible adaptation and use by Ethics Committees and Institutional Review Boards to bolster the concept and inclusion of sustainability during the research approval process.

Bintrafusp Alfa for Recurrent or Metastatic Cervical Cancer After Platinum Failure

Cervical cancer is a common and lethal cancer worldwide. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (or transforming growth factor β trap) fused via a flexible linker to the C-terminus of each heavy chain of an immunoglobulin G1 antibody blocking programmed cell death 1 ligand 1. To evaluate the safety and response rates of bintrafusp alfa in patients with recurrent or metastatic cervical cancer. This phase 2 nonrandomized controlled trial evaluated bintrafusp alfa monotherapy in patients with recurrent or metastatic cervical cancer with disease progression during or after platinum-based chemotherapy. Data were collected from March 2020 to February 2022. Patients received bintrafusp alfa, 1200 mg, intravenously once every 2 weeks. The primary end point was confirmed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by an independent review committee. At data cutoff, 146 of 203 screened patients received 1 or more doses of bintrafusp alfa; of these, the median (range) age was 53 (24-79) years. The study met its primary end point of a 95% CI above the objective response rate benchmark of 15%, with a confirmed objective response rate of 21.9% (95% CI, 15.5-29.5) per the independent review committee. Of these patients, 19 (59.4%) had a durable response of 6 months or more. At data cutoff, responses were ongoing in 13 of 32 responders (40.6%). The most common treatment-related adverse events were anemia (25 [17.1%]), rash (21 [14.4%]), hypothyroidism (15 [10.3%]), and pruritus (15 [10.3%]). Any-cause adverse events of special interest included anemia (82[56.2%]), bleeding events (81 [55.5%]), and immune-related adverse events (49 [33.6%]). This phase 2 nonrandomized controlled trial of bintrafusp alfa met its primary end point, which may support the potential of a bispecific therapy targeting transforming growth factor β and programmed cell death 1 ligand 1 in patients with recurrent or metastatic cervical cancer. ClinicalTrials.gov Identifier: NCT04246489.

Closing the loop: Strengthening course quality of Pharm.D. program via applying a comprehensive four-step review approach

This study explores the course review process implemented by the College of Pharmacy at King Saud University for its Pharm.D. program. Through a qualitative research design, a dedicated course review committee was established to oversee the evaluation process. The committee gathered and analyzed data from various sources, including course reports, student evaluations, and exam center reports, to achieve a holistic understanding of each course’s effectiveness. The evaluation process was structured into a Four-Step Course Evaluation Approach: data collection, data review and recommendations, taking appropriate action, and communicating the outcomes. The “closing the loop” stage ensured that recommendations were effectively implemented, and course evaluation data were systematically archived for future reference. The results of this study, based on the evaluation of 25 courses, revealed significant improvements in course quality, alignment with program learning outcomes, and adherence to accreditation standards. Key findings included the identification of gaps and discrepancies, leading to targeted interventions and enhanced course content. Overall, this study highlights the effectiveness of a structured course review process in enhancing the quality of education and ensuring continuous improvement within the college. The committee focuses on refining evaluation criteria, conducting workshops, and providing training to stay current with emerging accreditation standards and best practices. This systematic course review process demonstrates the College’s commitment to providing high-quality education and preparing students for successful careers in pharmacy, with significant implications for the improvement of pharmacy education and the overall student learning experience.

Foritinib in advanced ROS1-rearranged non-small-cell lung cancer in China: a multicentre, open-label, single-arm, phase 2 study

Currently approved targeted treatment for ROS1-rearranged non-small-cell lung cancer (NSCLC) has either inadequate intracranial activity or CNS-related toxicities. We evaluated the efficacy and safety of foritinib, a novel ALK and ROS1 inhibitor, in patients with advanced ROS1-rearranged NSCLC. This two-part (phase 2a and 2b), multicentre, single-arm, open-label, phase 2 study was done in 29 centres in China. Eligible participants were adults (aged ≥18 years) with histologically or cytologically confirmed ROS1-rearranged, locally advanced or metastatic stage IIIB-IV NSCLC, with an Eastern Cooperative Oncology Group performance status of 2 or less. Patients who had previously received no or one ROS1 inhibitor were enrolled into phase 2a, and patients who were naive to ROS1 inhibitor therapy were enrolled into phase 2b cohort 1. Participants in phase 2a received 80, 120, 160, or 210 mg foritinib succinate (foritinib) orally once daily over 21-day cycles; patients in phase 2b received the recommended phase 2 dose of 160 mg. The primary endpoint was objective response rate, assessed by the independent review committee in the full analysis set (ie, all participants who received at least one dose of study treatment). The safety analysis set included all participants who received at least one dose of study treatment and had available safety assessments. This study is ongoing and is registered with ClinicalTrials.gov, NCT04237805. Between March 26, 2020, and Dec 29, 2022, 104 patients were enrolled and treated. Six patients who had previously received more than one ROS1 inhibitor were enrolled in phase 2a before a protocol amendment stating that patients in this phase should have received no more than one ROS1 inhibitor; these patients were included in the safety analysis but excluded from the efficacy analysis of the ROS1-inhibitor-pretreated cohort. Therefore, the efficacy analysis set (n=98) included 42 patients from phase 2a (17 who were ROS1 inhibitor naive and 25 who had previously received ROS1 inhibitor) and 56 patients from phase 2b cohort 1. In phase 2a, the objective response rate was 94% (95% CI 71-100; 16 of 17 patients) in patients who were ROS1 inhibitor naive and 40% (21-61; ten of 25) in patients who had previously received ROS1 inhibitor. In phase 2b cohort 1, the objective response rate was 88% (95% CI 76-95; 49 of 56 patients). In a prespecified exploratory analysis in 41 patients with CNS metastases at baseline, the objective response rate was 100% (95% CI 48-100; five of five patients) in patients in phase 2a who were ROS1 inhibitor naive, 40% (16-68; six of 15) in patients in phase 2a who had previously received ROS1 inhibitor, and 90% (70-99; 19 of 21) in patients in phase 2b cohort 1. Grade 3-4 treatment-related adverse events occurred in 33 (32%) of 104 patients; the most common were hyperglycaemia (12 [12%] patients) and electrocardiogram prolonged QT interval (six [6%]). Serious treatment-related adverse events occurred in 11 (11%) patients, with hyperglycaemia (six [6%]) being most common. No treatment-related adverse events led to death. Foritinib showed systemic and intracranial antitumour activity and good tolerability in ROS1-inhibitor-naive patients with ROS1-rearranged NSCLC. Foritinib represents a promising treatment for these patients, especially in those with CNS metastases. Fosun Pharma, Wanbang Biopharmaceuticals, and Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer.

Assessment of antimicrobial stewardship programmes and antibiotic use among children admitted to two hospitals in Sierra Leone: a cross-sectional study

IntroductionAntimicrobial resistance (AMR) is a global public health concern and irrational use of antibiotics in hospitals is a key driver of AMR. Even though it is not preventable, antimicrobial stewardship (AMS) programmes will reduce or slow it down. Research evidence from Sierra Leone has demonstrated the high use of antibiotics in hospitals, but no study has assessed hospital AMS programmes and antibiotic use specifically among children. We conducted the first-ever study to assess the AMS programmes and antibiotics use in two tertiary hospitals in Sierra Leone.MethodsThis was a hospital-based cross-sectional survey using the World Health Organization (WHO) point prevalence survey (PPS) methodology. Data was collected from the medical records of eligible patients at the Ola During Children’s Hospital (ODCH) and Makeni Regional Hospital (MRH) using the WHO PPS hospital questionnaire; and required data collection forms. The prescribed antibiotics were classified according to the WHO Access, Watch, and Reserve (AWaRe) classification. Ethics approval was obtained from the Sierra Leone Ethics and Scientific Review Committee. Statistical analysis was conducted using the SPSS version 22.ResultsBoth ODCH and MRH did not have the required AMS infrastructure; policy and practice; and monitoring and feedback mechanisms to ensure rational antibiotic prescribing. Of the 150 patients included in the survey, 116 (77.3%) were admitted at ODCH and 34 (22.7%) to MRH, 77 (51.3%) were males and 73 (48.7%) were females. The mean age was 2 years (SD=3.5). The overall prevalence of antibiotic use was 84.7% (95% CI: 77.9% – 90.0%) and 77 (83.8%) of the children aged less than one year received an antibiotic. The proportion of males that received antibiotics was higher than that of females. Most (58, 47.2 %) of the patients received at least two antibiotics. The top five antibiotics prescribed were gentamycin (100, 27.4%), ceftriaxone (76, 20.3%), ampicillin (71, 19.5%), metronidazole (44, 12.1%), and cefotaxime (31, 8.5%). Community-acquired infections were the primary diagnoses for antibiotic prescription.ConclusionThe non-existence of AMS programmes might have contributed to the high use of antibiotics at ODCH and MRH. This has the potential to increase antibiotic selection pressure and in turn the AMR burden in the country. There is need to establish hospital AMS teams and train health workers on the rational use of antibiotics.

Clinical profile and complications seen in the patients in the later stages of chronic kidney disease presenting to the Emergency Department in a tertiary care center in Nepal: a cross-sectional study.

Chronic kidney disease (CKD) has an estimated prevalence of 6% in Nepal, which has resulted in a huge public health and socioeconomic burden for the country. People with different stages of CKD come to the Emergency Department (ED) with various clinical features and complications, which if detected and managed early can result in a decreased need for renal replacement therapy and thus decreased medical cost. The authors conducted a cross-sectional analysis taking nonprobability convenience sampling in the ED of a tertiary-level hospital of Nepal, after getting approval from the Institutional Review Committee and obtaining informed consent from the patient. Kruskal-Wallis test and χ 2 test of homogeneity were conducted to determine if there were differences in the continuous variables and categorical variables of three stages of CKD. Pairwise comparisons with a Bonferroni correction was done for both variables. Among 291 patients of CKD, 25 were in stage 3, 15 in stage 4, and 251 in stage 5. Significant differences between groups were found in continuous variables of SBP, pulse, temp, TLC, platelet, sodium, potassium, urea, and creatinine. Similarly, a significant difference was found for the categorical variables of hyperkalemia, hyponatremia, thrombocytopenia, leukocytosis, and high creatinine levels. Patients with CKD commonly present to the ED due to electrolyte imbalances, uremia, shortness of breath, and high SBP. Hyperkalemia, thrombocytopenia are more frequently observed in stage 5 CKD, whereas the incidence of hypertension significantly increase from stage 4 onwards. Hyponatremia, on the other hand, is more prevalent in stage 3 than in the later stages.

Pre-existing cardiovascular disease in the intensive care population: a national data study in scotland

Abstract Introduction/Background Each year, nearly 17,000 patients are admitted to Intensive Care Units (ICU) in Scotland. Forty percent of these patients suffer from one or more pre-existing co-morbidity. Pre-existing co-morbid disease is a known risk factor for readmission to ICU, increased healthcare use, protracted recovery and reduced health-related quality of life. Nonetheless, it is unknown which group of patients is most affected. Given the heterogeneity of the ICU population and in consideration of more "targeted" care, understanding the influence of co-morbidities and identification of specific patient groups is necessary. In tandem, the association between cardiovascular disease and critical illness is under researched. Yet it is known that 20% of ICU patients suffer from cardiovascular disease (CVD), with some evidence to suggest CVD is linked to increased 5-year mortality in this group of patients. Purpose To understand the prevalence of pre-existing CVD and other pre-existing co-morbidities in the critically ill population and to determine the influence of pre-existing CVD on hospital readmission rates (within one year of index hospital discharge). Methods This study is a retrospective cohort analysis using routinely collected data on ICU admissions between 2010 and 2019 in Scotland. Following public benefit and privacy panel (PBPP) approval and university integrity committee review, data was accessed via a secure National Safe Haven platform. Demographic data are presented alongside correlation analysis. Results More than 100,000 patients were admitted to ICU between 2010 and 2019. Of these patients, around 10% suffered from pre-existing CVD, with 30% suffering from any co-morbid disease, as defined by Charlson Co-morbidity index. It was identified that around 10% of ICU patients were readmitted to ICU within one year and a further 20% readmitted to hospital within one year. Of those patients readmitted to ICU, 10% suffer from pre-existing CVD. Conclusion This study identified that CVD is prevalent amongst the critically ill population with many experiencing a further admission to ICU. Despite this, little is known about the follow-up care provided to these patients with regards to managing CVD.

Maternal mental health as a major contributor to maternal mortality

Perinatal mental health conditions affect up to 20 % of pregnant or postpartum individuals, and nearly 15 % of pregnant individuals meet criteria for substance use disorder (SUD). All providers taking care of pregnant or postpartum individuals will encounter patients in these scenarios. Maternal Mortality Review Committees (MMRCs) have determined maternal mental health conditions, including SUD, to be the leading cause of preventable maternal death during pregnancy or in the first year postpartum. Lessons learned from MMRCs to prevent these deaths include the recommendation that screening and identification of mental health conditions need to be linked with evidence-based, patient-centered, and accessible treatments. Obstetricians and gynecologists, midwives, family medicine providers, and pediatricians, are in unique positions not only to screen and diagnose, but also to treat individuals with mental health concerns, including SUD, during pregnancy and postpartum.

A randomized phase 2 study of HLX22 plus trastuzumab biosimilar HLX02 and XELOX as first-line therapy for HER2-positive advanced gastric cancer

Gastric cancer is the fifth most common cancer and the fourth most common cause of cancer death worldwide, yet the prognosis of advanced disease remains poor. This was a randomized, double-blinded, phase 2 trial (ClinicalTrials.gov: NCT04908813). Patients with locally advanced/metastatic HER2-positive gastric/gastroesophageal junction cancer and no prior systemic antitumor therapy were randomized 1:1:1 to 25mg/kg HLX22 (a novel anti-HER2 antibody)+ HLX02 (trastuzumab biosimilar)+ oxaliplatin and capecitabine (XELOX) (group A), 15mg/kg HLX22+ HLX02+ XELOX (group B), or placebo+ HLX02+ XELOX (group C) in 3-week cycles. Primary endpoints were progression-free survival (PFS) and objective response rate (ORR) assessed by independent radiological review committee (IRRC). Between November 29, 2021, and June 6, 2022, 82 patients were screened; 53 were randomized to group A (n= 18), B (n= 17), and C (n= 18). With 14.3months of median follow-up, IRRC-assessed median PFS was prolonged with the addition of HLX22 (A vs. C, 15.1 vs. 8.2months, hazard ratio [HR] 0.5 [95% confidence interval (CI) 0.17-1.27]; B vs. C, not reached vs. 8.2months, HR 0.1 [95% CI 0.04-0.52]). Confirmed ORR was comparable among groups (A vs. B vs. C, 77.8% vs. 82.4% vs. 88.9%). Treatment-related adverse events (TRAEs) were observed in 18 (100%), 16 (94.1%), and 17 (94.4%) patients, respectively. One (5.6%) patient in group C reported a grade 5 TRAE. Adding HLX22 to HLX02 and XELOX prolonged PFS and enhanced antitumor response in the first-line treatment of HER2-positive gastric cancer, with manageable safety. Shanghai Henlius Biotech, Inc.