Recent applications of three-dimensional bioprinting in drug discovery and development.

The ability of three-dimensional (3D) bioprinting to fabricate biomimetic organ and disease models has been recognised to be promising for drug discovery and development as 3D bioprinted models can better mimic human physiology compared to two-dimensional (2D) cultures and animal models. This is useful for target selection where disease models can be studied to understand disease pathophysiology and identify disease-linked compounds. Lead identification and Preclinical studies also benefit from 3D bioprinting as 3D bioprinted models can be utilised in high-throughput screening (HTS) systems and produce efficacy and safety data that closely resembles clinical observations. Although no published applications of 3D bioprinting in clinical trials were found, there were two clinical trials planning to evaluate the predictive ability of 3D bioprinted models by comparing human and model responses to the same chemotherapy. Overall, this review provides a comprehensive summary of the latest applications of 3D bioprinting in drug discovery and development.

Melatonin Use in School-Aged Children and Adolescents: An Exploration of Caregiver and Pharmacist Perspectives.

OBJECTIVE: This study aims to explore the perspectives and experiences of Australian caregivers and community pharmacists about pediatric melatonin use. METHODS: A convenience sample of caregivers with children (aged 11-16 years) using melatonin as a sleep aid and community pharmacists (including pharmacist interns) were recruited. Participants first completed an online survey followed by an online semi-structured interview. Interviews were guided by a schedule of questions for the respective participant groups, broadly exploring their beliefs about melatonin, experiences in using/supplying melatonin, and perceived facilitators/barriers for melatonin use. Interviews were digitally recorded, transcribed verbatim, and analyzed using the Framework Approach. RESULTS: Fourteen caregivers of predominantly neurodiverse adolescents and 24 community pharmacists were interviewed. While melatonin was perceived by caregivers of both typically developing and neurodiverse dependants as safer than pharmacological sleep aids, treatment was only initiated after trialling non-pharmacological strategies first. Pharmacists expressed concerns around the ambiguities in practice and the limited scope of existing resources for guiding pediatric melatonin use. Caregivers frequently deferred to the information available online to procure products or self-adjust doses and dosing schedules. Both pharmacists and caregivers emphasized the need for more affordable and age-appropriate proprietary formulations that are readily accessible. CONCLUSION: Melatonin is administered predominantly by caregivers of neurodiverse adolescents to address their sleep disturbances. The findings underscore the need for reliable, evidence-based information to guide safe and appropriate use of melatonin in pediatric populations. Patient education is also warranted to address maladaptive medication-administration practices. Lastly, there is a need for stronger regulatory oversight of melatonin products to ensure their quality and safety of use.

Antidementia and Psychotropic Drug Use in Older People with Dementia in Australia: A National Data Linkage Study.

OBJECTIVES: To estimate the national prevalence of antidementia and psychotropic medication use, and sociodemographic factors associated with their use, in Australians living with dementia. DESIGN: Retrospective cross-sectional study. SETTING AND PARTICIPANTS: Nationwide data linkage study using 2021 Census and Pharmaceutical Benefits Scheme (PBS) data. All people aged 65 or older with dementia (self-reported in the Census or dispensed an antidementia drug subsidized by the PBS) were included. METHODS: Medication use was defined as at least 1 dispensing during the 3-month period following the Census (August-October 2021). Prevalence of antidementia and psychotropic medication use, including antipsychotics, benzodiazepines and Z-drugs, antiepileptics, opioids, and psychostimulants, was calculated. Sociodemographic factors associated with medication use were explored using multivariable logistic regression models. RESULTS: Of the 177,809 older people living with dementia included, 58.6% were using at least 1 psychotropic medication. Antidepressants were the most commonly used psychotropics (41%), followed by opioids (20%) and antipsychotics (13%). Antidementia medications were used by a quarter of people with dementia (26%). People with dementia living in the highest socioeconomic area were more likely to use antidementia medications [adjusted odds ratio (OR), 1.22; 95% CI, 1.17-1.28] and less likely to use psychotropics (OR, 0.91; 95% CI, 0.88-0.95) compared with people living in the lowest socioeconomic area. Conversely, those living in inner regional areas were more likely to use psychotropics (OR, 1.06; 95% CI, 1.03-1.10) and less likely to use antidementia medications (OR, 0.79; 95% CI, 0.77-0.82) compared with people living in metropolitan areas. CONCLUSIONS AND IMPLICATIONS: Psychotropics were commonly used in people with dementia in Australia. Disparities in access to health care due to socioeconomic status or remoteness may have influenced the use of antidementia and psychotropic medications. Further strategies to allow more equitable access to resources and medications are needed.

A need to integrate pharmacological management for multimorbidity into dementia guidelines in Australia.

Introduction: Pharmacological management is a vital aspect of dementia care. Suboptimal medication prescribing and adverse drug reactions are major causes for ongoing concerns for the quality of care. This review aims to investigate the existence and comprehensiveness of Australian guidelines dedicated to supporting dementia care in the context of pharmacological management. Methods: Guideline registries and databases (EMBASE and CINAHL) were searched to identify Australian guidelines addressing pharmacological management in dementia care and to uncover barriers and considerations associated with guideline implementation. Results: Seven Australian guidelines were identified. Barriers to effective implementation were identified at individual, provider, and system levels. None of the identified guidelines provided comprehensive guidance on management of multimorbidity and polypharmacy. Discussion: Although Australian guidelines are available to guide pharmacological management in dementia, several barriers impede their effective implementation. There is an urgent need for updated guidelines that address the management of multimorbidity and polypharmacy in people living with dementia.

A Comparison of an Australian Observational Longitudinal Alzheimer's Disease Cohort to Community-Based Australian Data.

Background: Observational Alzheimer's disease (AD) cohorts including the Australian, Biomarkers, Imaging and Lifestyle (AIBL) Study have enhanced our understanding of AD. The generalizability of findings from AIBL to the general population has yet to be studied. Objective: We aimed to compare characteristics of people with AD dementia in AIBL to 1) the general population of older Australians using pharmacological treatment for AD dementia, and to 2) the general population of older Australians who self-reported a diagnosis of dementia. Methods: Descriptive study comparing people aged 65 years of over (1) in AIBL that had a diagnosis of AD dementia, (2) dispensed with pharmacological treatment for AD in Australia in 2021 linked to the Australian census in 2021 (refer to as PBS/census), (3) self-reported a diagnosis of dementia in the 2021 Australian census (refer to as dementia/census). Baseline characteristics included age, sex, highest education attainment, primary language, and medical co-morbidities. Results: Participants in AIBL were younger, had more years of education, and had a lower culturally and linguistically diverse (CALD) population compared to the PBS/census cohort and dementia/census cohort (mean age±standard deviation - AIBL 79±7 years, PBS/census 81±7, p < 0.001, dementia/census 83±8, p < 0.001; greater than 12 years of education AIBL 40%, PBS/census 35%, p = 0.020, dementia/census 29%, p < 0.001; CALD - AIBL 3%, PBS/census 20%, p < 0.001, dementia/census 22%, p < 0.001). Conclusions: Our findings suggest that care should be taken regarding the generalizability of AIBL in CALD populations and the interpretation of results on the natural history of AD.

The association between patient-reported experiences with hospital food services and recovery outcomes - A population survey of patients from 75 public hospitals.

BACKGROUND: The quality of food service is vital to patients' experiences in care and recovery in hospitals. This study aimed to identify opportunities for improving hospital food services to enhance overall patient experiences and outcomes. METHODS: This retrospective cross-sectional study uses the Adult Admitted Patient Survey in 2019. Adult patients discharged from acute or rehabilitation care across 75 public hospitals were surveyed about their in-hospital experiences, including ratings of hospital food services, overall ratings of hospital care, complications acquired, and delayed discharge due to feeling unwell. Population weighting was applied in descriptive and multivariable logistic regression analyses. We used adjusted odds ratios (AORs) and 95% confidence intervals (CIs) to estimate the association between hospital food service and the overall rating of hospital care and two recovery outcomes. RESULTS: Eight in ten participants (weighted, 16,919/21,900) consumed food in a hospital [mean age: 60.6 years (SE:0.5; SD: 18.3), 53% female]. Compared to a fair rating, adults who rated "poor/very poor" of hospital food service were 2.7 times more likely to report dissatisfaction with overall care in the hospital [Adjusted Odds Ratio (AOR) (95% CI): 2.73 (1.49, 4.99)], 1.4 times more likely to report complications [AOR:1.43 (1.11, 1.83)] and 1.9 times more likely to report delayed discharge [AOR 1.85 (1.30, 2.62)]. More moderate ratings were associated with attenuation of risk for these outcomes. Furthermore, the magnitude of the effect for these associations was more substantial among patients from non-English-speaking backgrounds (n = 1,759) after controlling for patient characteristics. Food service attributes, including received food as ordered, food delivered within reach, the taste of the meals, and meal interruption, were significant factors for the outcomes assessed. CONCLUSION: These findings underscore the importance of patients' positive experiences of hospital food service in recovery outcomes and identify several food service indicators that can be used to monitor and improve patient experiences and recovery outcomes in hospitals.

A systematic review of diet and medication use among centenarians and near-centenarians worldwide.

Centenarians represent a phenomenon of successful aging. This systematic review aimed to understand lifestyles and health practices, focusing on diet and medication use for healthy longevity in community-based adults 95 years or over. Medline, CINAHL, Scopus, and gray literature were searched from 1 January 2000 to 10 December 2022. Study quality was assessed using the Modified Newcastle-Ottawa Scale (mNOS). Pooled prevalence [%; 95% confidence interval] for categorical variables and pooled mean for continuous variables were estimated for demographics, weight status, lifestyle factors, medications, and health conditions. Of 3392 records screened, 34 studies were included in the review, and 71% (24/34) met the 6/8 criteria in mNOS. Centenarians/near-centenarians' ages ranged from 95 to 118 years, with 75% (71-78%) female and 78% (68-88%) living in rural areas. They had an overall healthy lifestyle: current smoking (7%; 5-9%), drinking (23%; 17-30%), normal weight (52%; 42-61%), overweight (14%; 8-20%), physical activity (23%; 20-26%), and sleep satisfaction (68%; 65-72%). Diet averaged 59.6% carbohydrate, 18.5% protein, and 29.3% fat; over 60% consumed a diverse diet, and < 20% preferred salty food, contributing to lower mortality risks and functional decline. About half used antihypertensives (49%; 14-84%) or other cardiovascular drugs (48%; 24-71%), with an average of 4.6 medications. Common health issues included impaired basic activities of daily living (54%; 33-74%), hypertension (43%; 21-65%), and dementia (41%; 23-59%). The findings of this systemic review underscore the pivotal role of dietary practice and weight management in healthcare strategies to promote healthy ageing. It also recognises rural living styles and sleep hygiene as potential factors contributing to healthy longevity.

Raised body mass index and reduced muscle bulk reduces the incidence of Popeye's deformity post tenotomy of long head of biceps brachii.

OBJECTIVES: The development of the Popeye's deformity is a known complication of long head of the biceps tendon (LHBT) tenotomy. Incidence of developing Popeye's deformity after LHBT tenotomy ranges between 13% and 70%. While this complication is well tolerated, it can be avoided with proper patient selection. We aim to study patient and clinical factors resulting in the development of the Popeye's deformity after LHBT tenotomy so as to better identify suitable surgical candidates. METHODS: 91 patients underwent unilateral rotator cuff repairs and concomitant LHBT tenotomy between March 2013 and March 2017. Assessment of patient factors contributing to Popeye's deformity included patient demographics, and physical attributes were analyzed and correlated. Patients also completed a questionnaire regarding their overall postoperative satisfaction. Prospectively collated Visual Analog Pain Scale (VAS), Constant-Murley shoulder score (CSS), University of California, Los Angeles Shoulder Score (UCLA), and Oxford Shoulder Score (OSS) were compared at 6 and 24 months post operation between patients who developed Popeye's deformity and those who did not. RESULTS: The incidence of post-tenotomy Popeye's sign was 58.9%. Majority of patients were satisfied with their procedure, postoperative function, and cosmesis. Patients who developed Popeye's sign had a statistically significant lower body mass index (BMI) (24.9 â€‹± â€‹4.2 â€‹kg/m2 versus 27.3 â€‹± â€‹4.3 â€‹kg/m2, p â€‹= â€‹0.048) (rpb â€‹= â€‹- 0.210, p â€‹> â€‹0.05) and had a greater biceps-circumference-(in flexion)-to-wrist-circumference ratio (1.91 â€‹± â€‹0.16 versus 1.83 â€‹± â€‹0.13, p â€‹= â€‹0.012) (rpb â€‹= â€‹0.319, p â€‹< â€‹0.05) than those who did not. Nevertheless, the development of Popeye's sign did not affect clinical outcomes (VAS, CSS, UCLA, and OSS; p â€‹> â€‹0.05) at 24 months. CONCLUSIONS: The incidence of Popeye's deformity is high post LHBT tenotomy. There was a greater incidence in patients with lower BMI and greater biceps brachii muscle bulk. However, this complication is well tolerated. By better selecting our patients, we can achieve better outcomes and minimize potential complications. LEVEL OF EVIDENCE: Level-III evidence. TYPE OF STUDY: Retrospective comparative study.

Elucidating the Link Between Anxiety/Depression and Alzheimer's Dementia in the Australian Imaging Biomarkers and Lifestyle (AIBL) Study.

BACKGROUND: The associations between mood disorders (anxiety and depression) and mild cognitive impairment (MCI) or Alzheimer's dementia (AD) remain unclear. METHODS: Data from the Australian Imaging, Biomarker & Lifestyle (AIBL) study were subjected to logistic regression to determine both cross-sectional and longitudinal associations between anxiety/depression and MCI/AD. Effect modification by selected covariates was analysed using the likelihood ratio test. RESULTS: Cross-sectional analysis was performed to explore the association between anxiety/depression and MCI/AD among 2,209 participants with a mean [SD] age of 72.3 [7.4] years, of whom 55.4% were female. After adjusting for confounding variables, we found a significant increase in the odds of AD among participants with two mood disorders (anxiety: OR 1.65 [95% CI 1.04-2.60]; depression: OR 1.73 [1.12-2.69]). Longitudinal analysis was conducted to explore the target associations among 1,379 participants with a mean age of 71.2 [6.6] years, of whom 56.3% were female. During a mean follow-up of 5.0 [4.2] years, 163 participants who developed MCI/AD (refer to as PRO) were identified. Only anxiety was associated with higher odds of PRO after adjusting for covariates (OR 1.56 [1.03-2.39]). However, after additional adjustment for depression, the association became insignificant. Additionally, age, sex, and marital status were identified as effect modifiers for the target associations. CONCLUSION: Our study provides supportive evidence that anxiety and depression impact on the evolution of MCI/AD, which provides valuable epidemiological insights that can inform clinical practice, guiding clinicians in offering targeted dementia prevention and surveillance programs to the at-risk populations.

Controlled release of vancomycin from PEGylated fibrinogen polyethylene glycol diacrylate hydrogel.

Surgical site infection (SSI) is a common issue post-surgery which often prolongs hospitalization and can lead to serious complications such as sternal wound infection following cardiac surgery via median sternotomy. Controlled release of suitable antibiotics could allow maximizing drug efficacy and safety, and therefore achieving a desired therapeutic response. In this study, we have developed a vancomycin laden PEGylated fibrinogen-polyethylene glycol diacrylate (PF-PEGDA) hydrogel system that can release vancomycin at a controlled and predictable rate to be applied in SSI prevention. Two configurations were developed to study effect of the hydrogel on drug release, namely, vancomycin laden hydrogel and vancomycin solution on top of blank hydrogel. The relationship between the rigidity of the hydrogel and drug diffusion was found to comply with a universal power law, i.e., softer hydrogels result in a greater diffusion coefficient hence faster release rate. Besides, vancomycin laden hydrogels exhibited burst release, whereas the vancomycin solution on top of blank hydrogels exhibited lag release. A mathematical model was developed to simulate vancomycin permeation through the hydrogels. The permeation of vancomycin can be predicted accurately by using the mathematical model, which provided a useful tool to customize drug loading, hydrogel thickness and stiffness for personalized medication to manage SSI. To evaluate the potential of hydrogels for bone healing applications in cardiovascular medicine, we performed a proof-of-concept median sternotomy in rabbits and applied the hydrogels. The hydrogel formulations accelerated the onset of osteo-genetic processes in rabbits, demonstrating its potential to be used in human.

Exploring the link between comorbidities and Alzheimer's dementia in the Australian Imaging, Biomarker & Lifestyle (AIBL) study.

INTRODUCTION: Mounting evidence suggests that certain comorbidities may influence the clinical evolution of Alzheimer's dementia (AD). METHODS: We conducted logistic regression analyses on the medical history and cognitive health diagnoses of participants in the Australian Imaging, Biomarker & Lifestyle study (n = 2443) to investigate cross-sectional associations between various comorbidities and mild cognitive impairment (MCI)/AD. RESULTS: A mixture of associations were observed. Higher comorbidity of anxiety and other neurological disorders was associated with higher odds of AD, while arthritis, cancer, gastric complaints, high cholesterol, joint replacement, visual defect, kidney and liver disease were associated with lower odds of AD. DISCUSSION: This study underscores the links between specific comorbidities and MCI/AD. Further research is needed to elucidate the longitudinal comorbidity-MCI/AD associations and underlying mechanisms of these associations. Highlights: Comorbidities that significantly increased AD odds included anxiety and other neurological disorders.Arthritis, cancer, gastric complaints, high cholesterol, joint replacement, visual defect, kidney and liver disease were associated with lower odds of AD.Alcohol consumption had the most significant confounding effect in the study.Visual-AD association was modified by age, sex, and APOE ε4 allele status.Anxiety-AD and depression-AD associations were modified by sex.

Exploring the association between cancer and cognitive impairment in the Australian Imaging Biomarkers and Lifestyle (AIBL) study.

An inverse association between cancer and Alzheimer's disease (AD) has been demonstrated; however, the association between cancer and mild cognitive impairment (MCI), and the association between cancer and cognitive decline are yet to be clarified. The AIBL dataset was used to address these knowledge gaps. The crude and adjusted odds ratios for MCI/AD and cognitive decline were compared between participants with/without cancer (referred to as C+ and C- participants). A 37% reduction in odds for AD was observed in C+ participants compared to C- participants after adjusting for all confounders. The overall risk for MCI and AD in C+ participants was reduced by 27% and 31%, respectively. The odds of cognitive decline from MCI to AD was reduced by 59% in C+ participants after adjusting for all confounders. The risk of cognitive decline from MCI to AD was halved in C+ participants. The estimated mean change in Clinical Dementia Rating-Sum of boxes (CDR-SOB) score per year was 0.23 units/year higher in C- participants than in C+ participants. Overall, an inverse association between cancer and MCI/AD was observed in AIBL, which is in line with previous reports. Importantly, an inverse association between cancer and cognitive decline has also been identified.

Immigration and access to dementia diagnostics and treatment: A nationwide study in Sweden.

•Compared to Swedish-born people, foreign-born people were less likely to receive dementia diagnostic tests.•Being born in Africa or Europe was associated with lower chance of receiving cholinesterase inhibitors.•Asian-born people had higher chance of receiving cholinesterase inhibitors, but were less likely to receive memantine.•Disparities existed in dementia diagnostics and treatment between Swedish-born and foreign-born people, but were not consistent after adjusting for MMSE scores.

Prevalence of and Risk Factors for Drug-Related Readmissions in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Older adults are at an increased risk of drug-related problems, especially following discharge from hospital. Drug-related readmissions place a large burden on the patient and the healthcare system. However, previous studies report inconsistent results on the prevalence and associated risk factors for drug-related hospital readmissions in older adults. OBJECTIVES: We aimed to assess the prevalence of drug-related readmissions in older adults aged 65 years and older and investigate the drug classes, preventability and risk factors most associated with these readmissions. METHODS: A systematic review and meta-analysis were undertaken to answer our objectives. A search of four databases (MEDLINE, Embase, CINAHL and Scopus) was conducted. Three authors independently performed title and abstract screening, full-text screening and data extraction of all included studies. A meta-analysis was conducted to calculate the pooled prevalence of drug-related readmissions across all studies, and a subgroup analysis was performed to explore heterogeneity among studies reporting on adverse drug reaction-related readmissions. RESULTS: A total of 1978 studies were identified in the initial search, of which four studies were included in the final synthesis. Three studies focused on readmissions due to adverse drug reactions and one study focused on readmissions due to drug-related problems. A pooled prevalence of 9% (95% confidence interval 2-18) was found for drug-related readmissions across all studies, and a pooled prevalence of 6% (95% confidence interval 4-10) was found for adverse drug reaction-related readmissions. Three studies explored the preventability of readmissions and 15.4-22.2% of cases were deemed preventable. The drug classes most associated with adverse drug reaction readmissions included anticoagulants, antibiotics, psychotropics and chemotherapy agents. Polypharmacy (the use of five or more medications) and several comorbidities such as cancer, liver disease, ischaemic heart disease and peptic ulcer disease were identified as risk factors for drug-related readmissions. CONCLUSIONS: Almost one in ten older adults discharged from hospital experienced a drug-related hospital readmission, with one fifth of these deemed preventable. Several comorbidities and the use of polypharmacy and high-risk drugs were identified as prominent risk factors for readmission. Further research is needed to explore possible causes of drug-related readmissions in older adults for a more guided approach to the development of effective medication management interventions.

The outcomes of considering goals of care in medication reviews for older adults: a systematic review.

INTRODUCTION: This is a systematic review of prescribing, clinical, patient-reported, and health utilization outcomes of goal-directed medication reviews in older adults. METHODS: A systematic review was conducted using MEDLINE, EMBASE, SCOPUS and CINAHL databases to identify studies examining outcomes of goal-directed medication reviews in humans, with mean/median age ≥ 60 years and in English. RESULTS: Seventeen out of 743 articles identified were included. Whilst there were inconsistent findings regarding changes in the number of medications between groups or post-intervention in one group (n = 6 studies), studies found reductions in drug-related problems (n = 2) and potential to reduce anticholinergics and sedatives (n = 2). Two out of seven studies investigating clinical outcomes found improvements, such as reduced hospital readmissions and improved depression severity. One study found 75% of patients achieved ≥ 1 goals and another found 43% of goals were achieved at six months. Four out of five studies found significant improvements in patient-reported quality of life between groups (n = 2) or post-intervention in one group (n = 2). Both studies investigating cost-effectiveness reported the intervention was cost-effective. CONCLUSIONS: There is evidence of positive impact on medication rationalization, quality of life and cost-effectiveness, supporting goal-directed medication reviews. Larger, longitudinal studies, exploring patient-focused outcomes may provide further insights into the ongoing impact of goal-directed medication reviews.

The Impact of Educational Attainment and Income on Long-Term Care for Persons with Alzheimer's Disease and Other Dementias: A Swedish Nationwide Study.

BACKGROUND: Long-term care improves independence and quality of life of persons with dementia (PWD). The influence of socioeconomic status on access to long-term care was understudied. OBJECTIVE: To explore the socioeconomic disparity in long-term care for PWD. METHODS: This registry-based study included 14,786 PWD, registered in the Swedish registry for cognitive and dementia disorders (2014-2016). Education and income, two traditional socioeconomic indicators, were the main exposure. Outcomes were any kind of long-term care, specific types of long-term care (home care, institutional care), and the monthly average hours of home care. The association between outcomes and socioeconomic status was examined with zero-inflated negative binomial regression and binary logistic regression. RESULTS: PWD with compulsory education had lower likelihood of receiving any kind of long-term care (OR 0.80, 95% CI 0.68-0.93), or home care (OR 0.83, 95% CI 0.70-0.97), compared to individuals with university degrees. Their monthly average hours of home care were 0.70 times (95% CI 0.59-0.82) lower than those of persons with university degrees. There was no significant association between education and the receipt of institutional care. Stratifying on persons with Alzheimer's disease showed significant association between lower education and any kind of long-term care, and between income and the hours of home care. CONCLUSIONS: Socioeconomic inequalities in long-term care existed in this study population. Lower-educated PWD were less likely to acquire general long-term care, home care and had lower hours of home care, compared to their higher-educated counterparts. Income was not significantly associated with the receipt of long-term care.

Poisonings in Older People with Dementia: A Systematic Scoping Review and Meta-Analysis.

BACKGROUND: Older people with dementia are at a particularly high risk of poisonings and their subsequent harms. OBJECTIVE: This review aimed to describe the key agents, incidence, risk factors, and disposition of poisonings in people with dementia reported in the literature. METHODS: Medline, Embase, CINAHL, and PsycINFO databases were searched from 1 September 2001 to 1 September 2021. Terms for dementia, poisonings, and older adults formed the search concepts. Quantitative studies published in English, describing poisonings in older people with dementia, including Alzheimer's disease, were included. Two investigators independently assessed articles for eligibility and extracted relevant data. A meta-analysis of the incidence of poisonings in people with dementia across studies was performed. RESULTS: Of 4,579 articles, 18 were included for final synthesis. Nervous system medications were implicated in over half of all medicinal poisonings, with anti-dementia agents, benzodiazepines, and opioids the most common classes. The non-medicinal agents frequently associated with poisonings were personal care and household products. The yearly incidence of poisoning varied across definitions of poisoning from 3% for International Classification of Disease-defined poisonings to 43% for adverse drug event-defined poisonings. Several risk factors were identified, including multimorbidity, psychotropic medication use, and living in residential care. Where described, up to one in five poisonings resulted in hospitalisation and in death. CONCLUSIONS: Poisonings are common in people with dementia, involving commonly prescribed medications or easily accessible substances. Given the significant outcomes associated, further research is required to better understand these poisonings and improve public health strategies to reduce the occurrence of this preventable harm.

Targeting Solid Cancers with a Cancer-Specific Monoclonal Antibody to Surface Expressed Aberrantly O-glycosylated Proteins.

The lack of antibodies with sufficient cancer selectivity is currently limiting the treatment of solid tumors by immunotherapies. Most current immunotherapeutic targets are tumor-associated antigens that are also found in healthy tissues and often do not display sufficient cancer selectivity to be used as targets for potent antibody-based immunotherapeutic treatments, such as chimeric antigen receptor (CAR) T cells. Many solid tumors, however, display aberrant glycosylation that results in expression of tumor-associated carbohydrate antigens that are distinct from healthy tissues. Targeting aberrantly glycosylated glycopeptide epitopes within existing or novel glycoprotein targets may provide the cancer selectivity needed for immunotherapy of solid tumors. However, to date only a few such glycopeptide epitopes have been targeted. Here, we used O-glycoproteomics data from multiple cell lines to identify a glycopeptide epitope in CD44v6, a cancer-associated CD44 isoform, and developed a cancer-specific mAb, 4C8, through a glycopeptide immunization strategy. 4C8 selectively binds to Tn-glycosylated CD44v6 in a site-specific manner with low nanomolar affinity. 4C8 was shown to be highly cancer specific by IHC of sections from multiple healthy and cancerous tissues. 4C8 CAR T cells demonstrated target-specific cytotoxicity in vitro and significant tumor regression and increased survival in vivo. Importantly, 4C8 CAR T cells were able to selectively kill target cells in a mixed organotypic skin cancer model having abundant CD44v6 expression without affecting healthy keratinocytes, indicating tolerability and safety.

Melatonin use in children and adolescents: A scoping review of caregiver perspectives.

Despite melatonin's popularity as a pediatric sleep-aid, little has been investigated around caregivers' understanding and perception of melatonin use for their dependent. This scoping review analyzes the current literature on pediatric melatonin use, to understand how caregivers' perceptions around melatonin are shaped by their illness/medication-related beliefs, treatment experience and preferences. A literature search was conducted across Embase, Medline, PsycINFO, PubMed and Scopus, generating 184 results for screening against the inclusion criteria. Nineteen studies were retrieved, comprising of 1561 children and adolescents, aged 8.7 ± 2.3 years (range: 0-44 years), conducted primarily in the United States of America (n = 6), Canada (n = 3) and the Netherlands (n = 3). Studies were evaluated for their study design and caregiver-centered outcomes, encompassing: 1) illness/treatment-related beliefs, 2) treatment satisfaction/effectiveness, 3) treatment preference/acceptability, and 4) impact of child's sleep disturbance on caregivers' quality-of-life. Sleep disturbances necessitating melatonin use occurred alongside congenital/neurodevelopmental comorbidities in 18 studies (95%). Melatonin was commonly associated with "naturalness" and "safety". Concepts of treatment satisfaction versus effectiveness were minimally differentiated within included studies. Caregivers preferred concurrent use of melatonin and behavioral interventions for management of their dependents' sleep. Improved sleep in the dependent generally led to better quality-of-life for caregivers and their family.

Changes in medication regimen complexity index following medication-related hospital admissions: A retrospective single-centre study.

BACKGROUND: Medication-related hospitalisations present an opportunity for de-prescribing and simplification of medication regimens. The Medication Regimen Complexity Index (MRCI) is a tool for measuring the complexity of medication regimens. OBJECTIVES: To evaluate whether MRCI changes following medication-related hospitalisations, and to evaluate the relationship between MRCI, length of stay (LOS) in hospital, and patient characteristics. METHODS: A retrospective medical record review of patients admitted to a tertiary referral hospital in Australia for medication-related problems, January 2019 to August 2020. MRCI was calculated using pre-admission medication lists and discharge medication lists. RESULTS: There were 125 patients who met inclusion criteria. The median (IQR) age was 64.0 years (45.0-75.0) and 46.4% were female. Median MRCI decreased by 2.0 following hospitalisation: from median (IQR) 17.0 (7.0-34.5) on admission vs 15.0 (3.0-29.0) on discharge (p < 0.001). Admission MRCI predicted LOS ≥2 days (OR 1.03, 95%CI 1.00-1.05, p = 0.022). Allergic reaction-related hospitalisations were associated with lower admission MRCI. CONCLUSIONS: There was a decrease in MRCI following medication-related hospitalisation. Targeted medication reviews for high-risk patients (e.g., those with medication-related hospitalisations) could further reduce the burden of medication complexity following discharge from hospital and possibly prevent readmissions.