The pharmaceutical productivity gap - Incremental decline in R&D efficiency despite transient improvements.

Rising research and development costs, currently exceeding $3.5 billion per novel drug, reflect a five-decade decline in pharmaceutical R&D efficiency. While recent reports suggest a potential turnaround, this review offers a systems-level analysis to explore whether this marks a structural shift or transient reversal. We analyzed financial data from the 200 largest pharmaceutical firms, novel drug approvals, and more than 80 000 clinical trials between 2012 and 2023. Our analysis revealed that despite recent stabilization, the pharmaceutical industry continues to face challenges, particularly due to elevated late-stage clinical attrition, suggesting that a sustained turnaround in R&D efficiency remains elusive.

Predictors of attrition during acute pharmacotherapy of psychotic depression in a clinical trial.

Little is known about factors that contribute to attrition in clinical trials of the pharmacotherapy of psychotic depression. The purpose of this study was to identify factors associated with attrition during acute pharmacotherapy in the Study of the Pharmacotherapy of Psychotic Depression II (STOP-PD II) clinical trial. Sociodemographic and clinical variables were assessed at baseline in 269 men and women, aged 18-85 years, who were treated with up to 12 weeks of open-label sertraline plus olanzapine. Univariate analyses examined the association of baseline variables with overall non-completion, as well as reasons for non-completion. Logistic regression was used to model the relationship of the significant univariate predictors with non-completion and its reasons. Seventy-four (27.5 %) participants did not complete the acute treatment phase of STOP-PD II. Male gender, younger age, inpatient status, higher Clinical Global Impression (CGI) severity of illness, and higher severity of psychomotor disturbance were associated with non-completion in univariate analyses. In regression models, higher CGI severity of illness score was the only significant independent predictor of non-completion, explained by withdrawal of consent. Our findings have implications for the retention of persons with psychotic depression in clinical trials.

More foreign-accented but more comprehensible: Attrition and amelioration of L1 speech in proficient L2 learners.

Background: There is an increasing interest in cross-linguistic influences of the second language (L2) on the first (L1), but its communicative impact remains to be elucidated. This study investigates how L2 learners' L1 pronunciation is perceived as foreign-accented and (in) comprehensible as a function of their L2 learning experience and proficiency levels. Methods: Read speech of 154 L1 Japanese learners of L2 English in the J-AESOP corpus was examined, where approximately one-third of them had lived in English-speaking countries and the rest had never lived outside of Japan. Their L1 speech was rated by another group of native Japanese listeners for accentedness and comprehensibility (from October 25, 2022 to August 20, 2023), while their L2 speech was previously rated by native American English listeners for nativelikeness or proficiency. The speakers' vowel acoustics were also examined. Results: More proficient L2 speakers were perceived as more foreign-accented in their L1, but only if they had lived overseas; their length of residence abroad predicted the degree of perceived accentedness. In contrast, more proficient L2 speakers were consistently perceived as more comprehensible in the L1, regardless of prior overseas experience. Acoustic analyses indicated that perceived accentedness is associated with a clockwise chain shift of all vowel categories in the vowel space. It was also revealed that the dispersion, rather than compactness, of vowel production contributed to perceived comprehensibility, although the degree of L1 vowel dispersion did not predict L2 proficiency. Conclusions: The overall results suggest two main conclusions. First, perceptible L1 foreign accent likely results from L1 disuse rather than L2 interference, thereby L1 pronunciation differs from native norms at a system-wide rather than category-specific level. Second, L2 learning has a positive influence on perceived L1 comprehensibility, rather than individuals with clearer and more comprehensible L1 speech being inherently better L2 learners.

Attrition, adherence, and compliance to exercise training interventions in persons with traumatic brain injury: a systematic review of training studies.

BACKGROUND: Exercise training (ET) is a promising rehabilitation approach for long-term negative consequences of traumatic brain injury (TBI). However, little is known regarding overall rates of attrition, adherence, and compliance to ET in TBI. OBJECTIVE: The purpose of this systematic review was to estimate average attrition, adherence, and compliance rates in ET studies in persons with TBI. METHODS: Databases were searched from inception to April 15, 2024. Two authors independently extracted data related to attrition, adherence, compliance, and possible moderators identified a priori. RESULTS: The average rate of attrition from 45 studies was 14.4%, although the majority of studies had small sample sizes (i.e. n < 42). Based on hierarchical linear regression, the most influential predictors of attrition were sample size and study design. A minority of studies reported adherence (44.4%) or compliance (22.2%) but those that did reported good average adherence (85.1%) and compliance (77.7%). These studies support the ability of persons with TBI to complete an ET intervention as prescribed. CONCLUSIONS: Researchers can use this information to ensure adequate power to detect a true effect of ET in persons with TBI. Researchers conducting ET studies in persons with TBI should clearly and thoroughly report data on attrition, adherence, and compliance.

Obesity-Senescence-Breast Cancer: Clinical Presentation of a Common Unfortunate Cycle.

There are few convincing studies establishing the relationship between endogenous factors that cause obesity, cellular aging, and telomere shortening. Without a functional telomerase, a cell undergoing cell division has progressive telomere shortening. While obesity influences health and longevity as well as telomere dynamics, cellular senescence is one of the major drivers of the aging process and of age-related disorders. Oxidative stress induces telomere shortening, while decreasing telomerase activity. When progressive shortening of telomere length reaches a critical point, it triggers cell cycle arrest leading to senescence or apoptotic cell death. Telomerase activity cannot be detected in normal breast tissue. By contrast, maintenance of telomere length as a function of human telomerase is crucial for the survival of breast cancer cells and invasion. Approximately three-quarters of breast cancers in the general population are hormone-dependent and overexpression of estrogen receptors is crucial for their continued growth. In obesity, increasing leptin levels enhance aromatase messenger ribonucleic acid (mRNA) expression, aromatase content, and its enzymatic activity on breast cancer cells, simultaneously activating telomerase in a dose-dependent manner. Meanwhile, applied anti-estrogen therapy increases serum leptin levels and thus enhances leptin resistance in obese postmenopausal breast cancer patients. Many studies revealed that shorter telomeres of postmenopausal breast cancer have higher local recurrence rates and higher tumor grade. In this review, interlinked molecular mechanisms are looked over between the telomere length, lipotoxicity/glycolipotoxicity, and cellular senescence in the context of estrogen receptor alpha-positive (ERα+) postmenopausal breast cancers in obese women. Furthermore, the effect of the potential drugs, which are used for direct inhibition of telomerase and the inhibition of human telomerase reverse transcriptase (hTERT) or human telomerase RNA promoters as well as approved adjuvant endocrine therapies, the selective estrogen receptor modulator and selective estrogen receptor down-regulators are discussed.

Reasons for Surgical Attrition Among Nonmetastatic Upper Gastrointestinal Cancer Patients: A Single Institutional Experience.

INTRODUCTION: Upper gastrointestinal (UGI) cancers require multidisciplinary treatment, but surgery provides the only potentially curative option. We sought to understand reasons for attrition before surgery within our regional hospital network. METHODS: We performed chart reviews of patients (age 18-80) with stage I-III UGI cancers (gastroesophageal junction, gastric, and hepatopancreatobiliary adenocarcinomas) in our multihospital cancer registry from 2015 to 2021. Our primary outcome was reasons for surgical attrition. Univariable analysis identified factors related to surgical attrition and the Kaplan-Meier method estimated overall survival based on surgery receipt. RESULTS: Seven hundred and ninety-two patients were included in our analysis, of whom 107 (13.5%) did not undergo curative surgery. Reasons for not undergoing surgery included medical comorbidities (30.8%), patient preference/nonmedical barriers (24.3%, which included: not interested without further explanation, worried about complications, nonadherence to appointments, insurance issues, did not wish for blood transfusion, lack of social support, preferring home care, and worried about recurrence), psychosocial (5.6%), progression while on neoadjuvant therapy or waiting for transplant (15.0% and 7.5%), poor performance status (3.7%), side effects of neoadjuvant therapy (3.7%), and death unrelated to treatment or unknown cause (9.4%). Nonsurgical management was not associated with race, socioeconomic status, or distance traveled for care. Survival was greatly improved for patients who underwent surgery (158 vs. 63 weeks, p < 0.05). CONCLUSION: Nearly one in seven patients (18-80 years old) with UGI cancers evaluated at our academic cancer center did not undergo surgical resection. Reasons for surgical attrition included potentially modifiable issues, and addressing these barriers could help overcome inequities in cancer treatment and survival.

Analysis and comparison of tooth wear in late antiquity and early middle age in populations that lived in continental and coastal Croatia using digitized VistaMetrix method.

BACKGROUND: Tooth wear is a non-pathological loss of hard tissues on the incisal and occlusal tooth surface. In archaeology, the loss of dental tissue through attrition is associated with living opportunities and habits, availability, characteristics and methods of food preparation. In forensics, tooth wear is used to estimate the dental age on cadavers. MATERIAL AND METHODS: For this study, we used an archaeological sample from two sample collections. In this study, tooth wear was compared in archaeological samples of well-preserved maxilla and mandible specimens (n=392) from Croatian coastal and continental populations from Late Antiquity (LA) and the Early Middle Ages (EMA). The computer system VistaMetrix 1.38 was used to analyse the abrasion and attrition of hard dental tissues. The Shapiro-Wilk and chi-square tests were performed for categorical data to test the difference between two historical periods and two geographical locations, while the Kruskal-Wallis test was performed for continuous data. RESULTS: There was a statistically significant difference in the proportion of tooth wear in total teeth area (P < 0.001) when comparing continental and coastal Croatia in LA and coastal Croatia between LA and EMA (P = 0.006 and P < 0.001, respectively). Samples from coastal Croatia from the LA period had the lowest percentage of tooth wear with a median of 8.35%, while samples from coastal Croatia from the EMA had the highest percentage of tooth wear with a median of 18.26%. Our results generally show greater tooth wear in the EMA period in male subjects. CONCLUSION: The results of the tooth wear research obtained with the Vista Metrix software can contribute to the study of life circumstances and changes that the analysed population has experienced in its historical development.

Institutional Culture of Belonging and Attrition Risk Among Women Health Care Professionals.

Objective: Attrition of women health care professionals is high, threatening patient care and advances in health care sciences. Women health care professionals have often reported experiencing challenges in the workplace that lower their sense of belonging and may precipitate their attrition. The current study sought to identify dimensions of workplace belonging in women health care professionals and to determine the relative strength of association of these belonging dimensions with intent to leave (ITL) their institution. Methods: Attendees of a continuing education course on women's leadership skills in health care were surveyed about their ITL and workplace belonging experiences. Dimensions of workplace belonging were identified by factor analysis. The strength of association between ITL and each workplace belonging dimension, as well as their relative strengths of association, were assessed in ordinal regression analyses. Results: Women comprised 99% of survey participants. Three dimensions of workplace belonging were identified: "institutional culture," "interactions with supervisor," and "interpersonal relationships." More frequent experiences of support in any of the three belonging dimensions associated strongly with lower ITL. When all three belonging dimensions were considered simultaneously, ITL remained strongly related with experiences of a supportive "institutional culture" (odds ratio 0.41, p < 0.0001), while it became much less strongly related with supportive experiences in the other two dimensions. Conclusions: These findings suggest a dominant role of institutional culture in attrition risk in women health care professionals. Interventions that foster an institutional culture of diversity, opportunities for career advancement, and inclusivity might be effective in improving retention of women health care professionals.

Incidence and predictors of attrition from HIV treatment among adults living with HIV in high-caseload facilities following implementation of universal test and treat strategy in Ethiopia: A prospective cohort study.

BACKGROUND: The introduction of universal test and treat (UTT) strategy has demonstrated a reduction in attrition in some low-resource settings. UTT was introduced in Ethiopia in 2016. However, there is a paucity of information regarding the magnitude and predictors of attrition from HIV treatment in Ethiopia. This study aims to assess the incidence and predictors of attrition from HIV treatment among adults living with HIV (PLHIV) in high-caseload facilities following the implementation of universal test and treat strategy in Ethiopia from March 2019 to June 2020. METHODS: A prospective cohort of individuals in HIV care from 39 high-caseload facilities in Oromia, Amhara, Tigray, Addis Ababa and Dire Dawa regions of Ethiopia was conducted for 12 months. Participants were adults aged 15 year and older who were first testers recruited for 3 months from March to June 2019. Subsequent follow-up was for 12 months, with data collected on sociodemographic and clinical conditions at baseline, 6 and 12 months and attrition at 6 and 12 months. We defined attrition as discontinuation from follow-up care due to loss to follow-up, dropout or death. Data were collected using Open Data Kit at field level and aggregated centrally. Kaplan-Meier survival analysis was employed to assess survival probability to the time of attrition from treatment. The Cox proportional hazards regression model was used to measure association of baseline predictor variables with the proportion of antiretroviral therapy (ART) patients retained in ART during the follow up period. RESULTS: The overall incidence rate for attrition from HIV treatment among the study participants during 12 months of follow-up was 5.02 cases per 1000 person-weeks [95% confidence interval (CI): 4.44-5.68 per 1000 person-weeks]. Study participants from health facilities in Oromia and Addis Ababa/Dire Dawa had 68% and 51% higher risk of attrition from HIV treatment compared with participants from the Amhara region, respectively [adjusted hazard ratio (AHR) = 1.68, 95% CI: 1.22-2.32 and AHR = 1.51, 95% CI: 1.05-2.17, respectively]. Participants who did not have a child had a 44% higher risk of attrition compared with those who had a child (AHR = 1.44, 95% CI: 1.12-1.85). Individuals who did not own mobile phone had a 37% higher risk of attrition than those who owned a mobile phone (AHR = 1.37, 95% CI: 1.02-1.83). Ambulatory/bedridden functional status at the time of diagnosis had a 44% higher risk of attrition compared with participants with a working functional status (AHR = 1.44, 95% CI: 1.08-1.92) at any time during the follow-up period. CONCLUSION: The overall incidence of attrition among people living with HIV enrolled into HIV treatment was not as high as what was reported by other studies. Independent predictors of attrition were administrative regions in Ethiopia where health facilities are located, not having a child, not owning a mobile phone and being ambulatory/bedridden functional status at the time of diagnosis. Concerted efforts should be taken to reduce the magnitude of attrition from HIV treatment and address its drivers.

The use of ultrasound to predict flexor tendinopathy after anterior locking plating of the distal radius.

This study compares ultrasound to clinical and radiographic measurements for assessing tendon pathology associated with distal radial anterior locking plates. A total of 46 patients undergoing removal of a distal radial plate had a preoperative clinical examination, radiographs and ultrasound evaluation to detect evidence of tendon irritation. Gross changes to the tendon were assessed during plate removal. In total, 32 patients demonstrated clinical abnormality. Soong 2 position was noted in 13 patients. Ultrasound revealed tenosynovitis in nine patients, tendon fibrillation or thickening in four patients and a single case of partial discontinuity. Intraoperative assessment revealed tenosynovitis in 28 patients and tendon fibre discontinuity in eight patients. Ultrasound findings were not predictive of intraoperative tenosynovitis and discontinuity. A relationship was noted between higher Soong grade, especially grade 2, and intraoperative presence of tenosynovitis, as well as Soong grade and amount of soft-tissue coverage. This study negates our hypothesis that ultrasound is useful for identifying tendinopathy after distal radial anterior plate fixation.Level of evidence: II.

Nurturing Longitudinal Samples 2.0.

BACKGROUND: While longitudinal designs can provide significant advantages compared to single measurement/cross sectional designs, they require careful attention to study infrastructure and the risk of attrition among the sample over multiple time points. OBJECTIVE: The strategies used to design and manage an appropriate infrastructure for a longitudinal study and approaches to retain samples are explored using examples from 2 studies, a 25-year study of persons living with multiple sclerosis and a 10-year longitudinal follow-up of breast cancer survivors. RESULTS: Key strategies (developing appropriate infrastructure, minimizing costs to participants, and maximizing rewards of study participation) have helped address the serious threat of attrition in these longitudinal samples. CONCLUSION: Implementation of these strategies can help mitigate some of the disadvantages and leverage the strengths of longitudinal research to produce reliable, insightful, and impactful outcomes.

Medical Educator Perceptions of Faculty Effort and Intent to Stay in Academic Medicine.

Purpose: Core roles of medical school faculty are increasingly diverse, substantial, and evolving. In alignment with this dynamic nature of medical education, faculty effort should be accurately appraised, constantly evaluated, and rewarded to ensure faculty satisfaction and promote a culture of belonging. The study goal was to examine the imbalance in official assignments and perceptions of medical school faculty effort in various educator domains. Materials and Methods: An 80-item survey was designed to collect quantitative and qualitative measures of faculty perceptions of effort. Survey questions collected data on faculty demographics, intent to stay, and perceptions of effort in the following educator domains: teaching, educational leadership and administration, research and scholarship, and service. A mixed methods approach was utilized in data analysis. Results: Eighty-eight complete survey responses were collected between February and May of 2022 from respondents from 27 states. There was a significant disparity between assigned and perceived effort in the educator domains of teaching, research, and service (P < 0.01). Faculty satisfaction with percent effort dedicated to teaching significantly correlated with intent to stay (P < 0.05). Satisfaction with workload assignments was higher with advanced academic rank and male gender. Qualitative analysis identified many key themes in the categories of promotion, workload, resources, and retention. Conclusions: Our study revealed that satisfaction with workload directly correlates with intent to stay, and principles of equitable workload distribution are violated from the perspective of the medical educator. This data provides critical information that can be used to assist medical schools in developing metrics to evaluate faculty performance in medical education and improve retention in academic medicine.

Should I stay or should I go? Nursing and midwifery academics intention to stay in or leave academia: A scoping review.

BACKGROUND: There is a chronic lack of appropriately qualified nurses and midwives being attracted into and remaining in the academic workforce. Reasons for this are not well understood but have been linked to stressful work environments related to balancing multiple roles in sometimes unsupportive environments, resulting in overload and demoralisation. AIM: To illuminate factors associated with nursing and midwifery academics' intention to remain in academia and factors associated with intention to leave. DESIGN: A scoping review was undertaken to provide a comprehensive and broad analysis of the related literature. This was guided by Arksey and O'Malley. A search strategy was developed using a combination of keywords and subject headings and adapted for four electronic databases to search for papers published between 2013 and 2024. METHODS: The review included five steps: (i) identifying the question, (ii) identifying relevant studies, (iii) study selection, (iv) data charting, (v) collating, summarising, and reporting the results. Covidence systematic review software was used. Quality appraisal was undertaken using the Mixed Methods Assessment Tool (MMAT). RESULTS: A total of 2870 papers were identified, 23 were included in the review. Retaining academics includes addressing issues related to promotion positive work environments such teamwork, professional relationships, supporting older academics, and professional development. Preventing attrition includes addressing emotional exhaustion and burnout, and ensuring academics feel valued and are recognised. Notably, there was a lack of research related to the Indigenous nursing and midwifery academic workforce. CONCLUSION: Given the predicted workforce shortages it is imperative for nursing education providers to develop strategies to promote healthy work environments and career pathways, and identify how to develop strong leadership in an ageing nursing and midwifery academic workforce. Importantly, the lack of research related to the Indigenous academic workforce is concerning and must be a priority area for focus.

Rethinking animal attrition in preclinical research: Expressing causal mechanisms of selection bias using directed acyclic graphs.

Animal attrition in preclinical experiments can introduce bias in the estimation of causal treatment effects, as the treatment-outcome association in surviving animals may not represent the causal effect of interest. This can compromise the internal validity of the study despite randomization at the outset. Directed Acyclic Graphs (DAGs) are useful tools to transparently visualize assumptions about the causal structure underlying observed data. By illustrating relationships between relevant variables, DAGs enable the detection of even less intuitive biases, and can thereby inform strategies for their mitigation. In this study, we present an illustrative causal model for preclinical stroke research, in which animal attrition induces a specific type of selection bias (i.e., collider stratification bias) due to the interplay of animal welfare, initial disease severity and negative side effects of treatment. Even when the treatment had no causal effect, our simulations revealed substantial bias across different scenarios. We show how researchers can detect and potentially mitigate this bias in the analysis phase, even when only data from surviving animals are available, if knowledge of the underlying causal process that gave rise to the data is available. Collider stratification bias should be a concern in preclinical animal studies with severe side effects and high post-randomization attrition.

Predictors of attrition in a randomized controlled trial of an electronic nicotine delivery system among people interested in cigarette smoking reduction.

BACKGROUND: Mitigating attrition is a key component to reduce selection bias in longitudinal randomized controlled trials (RCTs). Few studies of electronic nicotine delivery systems (ENDS) allow for the examination of long-term retention. This analysis explores the relationship between attrition, baseline measures, and condition assigned for a RCT involving ENDS differing in nicotine delivery over a 24-week intervention period. METHODS: Participants (N = 520) who smoked ≥10 cigarettes per day [CPD] for ≥1 year and reported interest in reducing but not quitting were randomized to 1 of 4 conditions: an ENDS containing 0, 8, or 36 mg/ml liquid nicotine (administered double-blind) or a cigarette-shaped plastic tube. Cox proportional hazards regression models were fit to examine attrition over time and predictors of attrition including baseline characteristics and condition. A stepwise approach was used to determine the final model; alpha was set at 0.05. RESULTS: Attrition did not differ significantly by condition (223/520), and most (69%) were lost-to-follow-up. Only age, education level, and household income were significantly predictive of attrition. For every additional year of age, attrition risk fell by 3%. Holding a bachelor's degree or higher was associated with reduced attrition risk. Those with the lowest income (<$10 K) were more likely to be withdrawn compared to those earning $10 K-39 K, and those with the highest income ($100 K+) were more likely to be withdrawn compared with the latter bracket and those earning $70-99 K. CONCLUSION: ENDS nicotine content did not drive differential attrition in this trial, and targeted retention efforts are needed for specific subgroups. Trial Registration #: NCT02342795.

Framework Development for Reducing Attrition in Digital Dietary Interventions: Systematic Review and Thematic Synthesis.

BACKGROUND: Dietary behaviors significantly influence health outcomes across populations. Unhealthy diets are linked to serious diseases and substantial economic burdens, contributing to approximately 11 million deaths and significant disability-adjusted life years annually. Digital dietary interventions offer accessible solutions to improve dietary behaviors. However, attrition, defined as participant dropout before intervention completion, is a major challenge, with rates as high as 75%-99%. High attrition compromises intervention validity and reliability and exacerbates health disparities, highlighting the need to understand and address its causes. OBJECTIVE: This study systematically reviews the literature on attrition in digital dietary interventions to identify the underlying causes, propose potential solutions, and integrate these findings with behavior theory concepts to develop a comprehensive theoretical framework. This framework aims to elucidate the behavioral mechanisms behind attrition and guide the design and implementation of more effective digital dietary interventions, ultimately reducing attrition rates and mitigating health inequalities. METHODS: We conducted a systematic review, meta-analysis, and thematic synthesis. A comprehensive search across 7 electronic databases (PubMed, MEDLINE, Embase, CENTRAL, Web of Science, CINAHL Plus, and Academic Search Complete) was performed for studies published between 2013 and 2023. Eligibility criteria included original research exploring attrition in digital dietary interventions. Data extraction focused on study characteristics, sample demographics, attrition rates, reasons for attrition, and potential solutions. We followed ENTREQ (Enhancing the Transparency in Reporting the Synthesis of Qualitative Research) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and used RStudio (Posit) for meta-analysis and NVivo for thematic synthesis. RESULTS: Out of the 442 identified studies, 21 met the inclusion criteria. The meta-analysis showed mean attrition rates of 35% for control groups, 38% for intervention groups, and 40% for observational studies, with high heterogeneity (I²=94%-99%) indicating diverse influencing factors. Thematic synthesis identified 15 interconnected themes that align with behavior theory concepts. Based on these themes, the force-resource model was developed to explore the underlying causes of attrition and guide the design and implementation of future interventions from a behavior theory perspective. CONCLUSIONS: High attrition rates are a significant issue in digital dietary interventions. The developed framework conceptualizes attrition through the interaction between the driving force system and the supporting resource system, providing a nuanced understanding of participant attrition, summarized as insufficient motivation and inadequate or poorly matched resources. It underscores the critical necessity for digital dietary interventions to balance motivational components with available resources dynamically. Key recommendations include user-friendly design, behavior-factor activation, literacy training, force-resource matching, social support, personalized adaptation, and dynamic follow-up. Expanding these strategies to a population level can enhance digital health equity. Further empirical validation of the framework is necessary, alongside the development of behavior theory-guided guidelines for digital dietary interventions. TRIAL REGISTRATION: PROSPERO CRD42024512902; https://tinyurl.com/3rjt2df9.

Proportional Hazards Model on Attrition and its Predictors in Community Antiretroviral Refill Groups among ART Users in Eastern Ethiopia.

BACKGROUND: The HIV epidemic continues to be a major public health challenge worldwide, particularly in sub-Saharan African countries such as Ethiopia. Community-based antiretroviral refill groups are emerging as a patient-centered approach, but there is limited evidence. Therefore, this study aimed to assess attrition and predictors in community antiretroviral refill groups among ART users in Eastern Ethiopia. METHODS: Institutional-based retrospective cohort study was conducted. Systematic random sampling techniques were used. Data were collected via Kobo Collect and exported to Stata. Statistically significant effects were assumed for a P-value < 0.05 at a confidence interval of 95%. RESULTS: The incidence of attrition in community-based ART refill groups was 6.63 (95% CI: 5.78, 7.48) per 100 person-years. The median duration of months in CAGs from the start till the end of the follow-up period was 9 months (IQR = 24). Thus, recruitment level from health facilities, history of LTFU, and stage IV were statistically significant variables. CONCLUSION: The findings of this study highlight the importance of improving the use of community antiretroviral groups in care. Healthcare programs can ultimately improve health outcomes for individuals living with HIV.

Neocortical cholinergic pathology after neonatal brain injury is increased by Alzheimer's disease-related genes in mice.

Hypoxic-ischemic encephalopathy (HIE) in neonates causes mortality and neurologic morbidity, including poor cognition with a complex neuropathology. Injury to the cholinergic basal forebrain and its rich innervation of cerebral cortex may also drive cognitive pathology. It is uncertain whether genes associated with adult cognition-related neurodegeneration worsen outcomes after neonatal HIE. We hypothesized that neocortical damage caused by neonatal HI in mice is ushered by persistent cholinergic innervation and interneuron (IN) pathology that correlates with cognitive outcome and is exacerbated by genes linked to Alzheimer's disease. We subjected non-transgenic (nTg) C57Bl6 mice and mice transgenically (Tg) expressing human mutant amyloid precursor protein (APP-Swedish variant) and mutant presenilin (PS1-ΔE9) to the Rice-Vannucci HI model on postnatal day 10 (P10). nTg and Tg mice with sham procedure were controls. Visual discrimination (VD) was tested for cognition. Cortical and hippocampal cholinergic axonal and IN pathology and Aß plaques, identified by immunohistochemistry for choline acetyltransferase (ChAT) and 6E10 antibody respectively, were counted at P210. Simple ChAT+ axonal swellings were present in all sham and HI groups; Tg mice had more than their nTg counterparts, but HI did not affect the number of axonal swellings in APP/PS1 Tg mice. In contrast, complex ChAT+ neuritic clusters (NC) occurred only in Tg mice; HI increased that burden. The abundance of ChAT+ clusters in specific regions correlated with decreased VD. The frequency of attritional ChAT+ INs in the entorhinal cortex (EC) was increased in Tg shams relative to their nTg counterparts, but HI obviated this difference. Cholinergic IN pathology in EC correlated with NC number. The Aß deposition in APP/PS1 Tg mice was not exacerbated by HI, nor did it correlate with other metrics. Adult APP/PS1 Tg mice have significant cortical cholinergic axon and EC ChAT+ IN pathologies; some pathology was exacerbated by neonatal HI and correlated with VD. Mechanisms of neonatal HI induced cognitive deficits and cortical neuropathology may be modulated by genetic risk, perhaps accounting for some of the variability in outcomes.

The association of systemic condition and medications on alveolar bone loss and tooth attrition.

OBJECTIVE: Periodontal disease is caused by subgingival bacteria that adversely affect the host immune system and create and maintain unmitigated inflammation in gingival and periodontal tissues. The condition is also linked to systemic conditions including cardiovascular disease, diabetes, and arthritis. Periodontitis elevates the bacterial load and spreads systemic inflammation through infection and inflammation. The main radiographic sign of periodontitis is marginal bone loss. Risk factors, including medications, smoking, age, and sex, are known to influence periodontal health. However, there is little information about the impact of systemic conditions and medications on tooth wear. The aim of the present study was to assess the association between systemic conditions and medications and radiographic signs of tooth wear and marginal bone loss. METHOD AND MATERIALS: This retrospective analysis was conducted on a group of 2,223 consecutive patients who came for dental treatment in the clinics of a large Health Maintenance Organization in Israel. Data available for the study included details of concomitant systemic diseases and medication and full-mouth radiographic surveys. Odds ratio and logistic regression analysis were used to detect associations between systemic conditions and medication, and marginal bone loss and tooth wear. RESULTS: The results indicated an elevated odds ratio for tooth wear associated with age, sex, and smoking across all age groups. Among young patients, those using proton pump inhibitors and psychiatric medications had an elevated risk of tooth wear. Age, smoking, and diabetes conditions were associated with an increased odds ratio for marginal bone loss in all age groups. Psychiatric medications and sex elevated the odds ratio for marginal bone loss only among older patients. CONCLUSION: The results highlight the significant impact of age, sex, and smoking on tooth wear, and extend these risks to alveolar bone loss when combined with diabetes and psychiatric conditions.