Patient characteristics and treatment patterns of patients with locally advanced or metastatic HER2-low breast cancer, a single site descriptive study.

PURPOSE: To evaluate the prevalence and characteristics of different HER2 categories among patients with advanced breast cancer (aBC) and describe treatment patterns and outcomes of those with HER2-low disease. METHODS: A retrospective cohort study was conducted via chart review at the Huntsman Cancer Institute, including patients diagnosed with aBC (stages IIIB, IIIC and IV) between 2010 and 2019. All patients with IHC1+ were considered HER2-low unless FISH was positive. Patients with IHC2+ were only classified as HER2-low if a negative FISH was documented. The prevalence and characteristics of each HER2 category were reported. Treatment patterns and survival outcomes of HER2-low patients who received first line treatment in 2017 or later were presented. RESULTS: A total of 240 of 414 patients (58%) with aBC were HER2-low, with the majority of patients (83%) classified as hormone receptor (HR)-positive. In first line, most HR-positive patients received endocrine therapy with chemotherapy for stage IIIB/IIIC (47%) and with CDK4/6 inhibitors for stage IV breast cancer (50%) Most HR-negative patients received chemotherapy alone (92% for stage IIIB/IIIC, 60% for stage IV). In second line, chemotherapy alone was the most common modality (21.4% for HR-positive; 45.5% for HR-negative). Median overall survival was 37.7 months while median progression-free survival from first line was 18.0 months, decreasing to 8.0 months in second line. CONCLUSION: A substantial proportion of patients previously classified as HER2-negative have low but detectable HER2 expression and may benefit from novel HER2-directed agents, which have demonstrated clinical benefit in this population post-chemotherapy.

Impact of Cognitive Rehabilitation on Cognitive and Functional Outcomes in Adult Cancer Survivors: A Systematic Review.

OBJECTIVES: This systematic review (PROSPERO CRD42021275421) synthesized evidence on the efficacy of cognitive rehabilitation on cognitive and functional outcomes in adult cancer survivors. METHODS: Articles were identified though PubMed/MEDLINE, EMBASE, PsycINFO, and Web of Science from inception through June 30, 2023. Studies included participants ≥18 years old, diagnosed with cancer. Primary outcomes were validated measures of subjective and objective cognition. Articles were dual reviewed for eligibility and data extraction. Risk of bias was assessed with the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields. RESULTS: The search yielded 3,811 articles; 65 full-text articles were reviewed; 53 articles (15 cognitive training, 14 strategy-based, 21 combinations, three inpatient rehabilitation), representing 52 unique studies, were included. Positive effects were observed in at least one objective cognitive measure in 93% of strategy training, 81% of cognitive training, 79% of combination rehabilitation interventions. Positive effects were observed in subjective cognition in 100% of strategy training, 55% of cognitive training, and 92% of combination interventions. Among studies with comparator groups, processing speed improved in 60% of cognitive training studies, while strategy training did not improve processing speed; otherwise, cognitive domain effects were similar between intervention types. Impact on functional outcomes was inconclusive. CONCLUSIONS: Cognitive rehabilitation appear beneficial for cancer-related cognitive impairment (CRCI). Differential effects on specific cognitive domains (eg, processing speed) and subjective cognition may exist between intervention types. IMPLICATIONS FOR NURSING PRACTICE: Nurses should increase patient and provider awareness of the benefits of cognitive rehabilitation for CRCI.

Modeling the population health impact of incorporating a multi-cancer early detection (MCED) test to existing cancer screening among immunocompromised individuals.

OBJECTIVE: To assess the screening efficiency of an multi-cancer early detection (MCED) test added to standard of care (SoC) screening, compared to SoC screening alone, among immunocompromised individuals, and to estimate the diagnostic workup costs associated with positive screening results. METHODS: We estimated the potential impact of cancer screening among immunocompromised individuals aged 50-79 years within the University of Utah Health system who underwent a stem cell/solid organ transplant or were diagnosed with a primary or secondary immunodeficiency disorder between January 2000 and February 2018. We derived cancer incidence rates from the Huntsman Cancer Institute Tumor Registry, and screening performance of SoC screening and an MCED test from published literature. Outcomes of screening efficiency included the true-positive to false-positive (TP:FP) ratio, diagnostic yield (DY), and cancer detection rate (CDR) for SoC screening alone and an incremental MCED test. Scenario and probabilistic sensitivity analyses were conducted. RESULTS: Among 4932 immunocompromised individuals aged 50-79 years, we estimated that 2595 tests would be done under SoC screening and assumed that all individuals received an additional MCED test. Adding an MCED test to SoC screening substantially improved screening efficiency (TP:FP = 1:1, DY = 5.15/1000 tests, CDR = 42.0%), compared to SoC screening alone (TP:FP = 1:99, DY = 1.23/1000 tests, CDR = 5.3%), assuming an MCED test with 100% uptake. Our findings were also robust to parameter uncertainty. CONCLUSION: Adding an MCED test to complement existing screening may be a highly efficient strategy to increase the detection of cancers among immunocompromised individuals. These results could help to improve cancer prevention and detection efforts among individuals with multiple cancer risk factors.

The association of weight loss from anti-obesity medications or bariatric surgery and apnea-hypopnea index in obstructive sleep apnea.

INTRODUCTION: Weight loss is recommended for individuals with obstructive sleep apnea (OSA) and overweight or obesity, but there is limited evidence to guide the selection of weight management strategies for patients who do not lose sufficient weight with diet and lifestyle changes. We evaluated the relationship between weight loss caused by pharmacologic or surgical interventions and subsequent improvement in OSA by the apnea-hypopnea index (AHI). METHODS: PubMed, Cochrane CENTRAL, and EMBASE were searched for randomized trials comparing pharmacologic or surgical obesity interventions to usual care, placebo, or no treatment in adults with OSA. The association between percentage weight loss and AHI change between randomization and last follow-up was evaluated using meta-regression. PROSPERO: CRD42022378853. RESULTS: Ten eligible trials (n = 854 patients) were included. Four (n = 211) assessed bariatric surgery, and 6 (n = 643) assessed pharmacologic interventions over a median follow-up of 13 months (interquartile range 6-26 months). The linear best estimate of the change in AHI is 0.45 events per hour (95% Confidence Interval 0.18 to 0.73 events per hour) for every 1% body weight lost. CONCLUSIONS: Weight loss caused by medication or surgery caused a proportionate improvement of the AHI. Providers could consider extrapolating from this relationship when advising patients of the expected effects of other pharmacologic or surgical interventions without direct evidence in OSA.

Holes can be perilous: A rare presentation of intestinal obstruction - Herniation through the broad ligament.

A 57-year-old lady presented with symptoms of intestinal obstruction preceded by a 2-day history of lower abdomen pain. Clinically, she had a distended abdomen with tenderness in her lower abdomen. Laboratory investigations were unremarkable. An abdominal radiograph showed a dilated small bowel with no extensive bowel gas. A computed tomography (CT) scan showed suspected intestinal obstruction secondary to herniation into the right broad ligament. The decision was made to proceed with surgery, and the intraoperative results confirmed the CT results. The literature review is outlined here, and this instance illustrates a surprising discovery.

Spinal medial branch nerve root block (MBNB) intervention compared to standard care-vertebroplasty (VP) for the treatment of painful osteoporotic vertebral fractures in frail, older hospitalised patients: a feasibility study.

Our study aimed to assess the feasibility outcomes comparing spinal medial branch nerve root block intervention to standard care vertebroplasty for the treatment of painful osteoporotic vertebral fractures in frail, hospitalised older patients. We found the study to be feasible and now propose a clinical effectiveness, cost effectiveness and safety evaluation. INTRODUCTION: Vertebroplasty (VP) is a key-hole procedure involving injection of bone cement into a fractured vertebral body, to reduce pain and increase vertebral body stability, although it is associated with a small risk of complications, particularly in frail, older hospitalised patients. Medial branch spinal nerve block (MBNB) may be an alternative treatment to alleviate pain symptoms, with less complications; however, no study has prospectively compared the clinical effectiveness, cost-effectiveness and safety of MBNB to VP, in frail, older hospitalised patients. The aim of our study was to conduct a 1st stage feasibility study, exploring recruitment, retention and several outcomes measures (means and SDs), together with qualitative interviews to assess participant and clinician views, to inform a definitive larger study. METHODS: We conducted a two-arm feasibility randomised controlled trial with participants allocated to continue with routine surgical care-VP or MBNB treatment, with an embedded qualitative study. Data was collected at baseline, week 1, 4, and week 8. RESULTS: Out of 40 eligible patients, 30 (75%) consented to take part in the study. The overall median time from randomisation to intervention was 3 days, IQR 1-7 days, 5 (1-7) days for VP and 2 (1-3) days for MBNB. Median (IQR) length of hospital stay for the VP group was 20 (8) days and for the MBNB 15(22) days. The proportion of completeness of outcome data collection at weeks 1, 4 and 8 was at least 77%: 14 (100%), 12 (85.7%) and 11(78.9%) for VP and 13 (100%), 12 (92.3%) and 10 (76.8%) for MBNB, respectively. There were no significant difference in the clinical outcomes or adverse events between the two groups. DISCUSSION: Our study was feasible in achieving is target recruitment, participants adhered to the randomisation and at least 77% completeness of data at the 8 week end-point (target 75%). We now plan to conduct a definitive clinical effectiveness, cost effectiveness and safety outcome study, comparing VP to MBNB in frail, older patients hospitalised with an acute vertebral osteoporotic fracture.

Systematic in vivo candidate evaluation uncovers therapeutic targets for LMNA dilated cardiomyopathy and risk of Lamin A toxicity.

BACKGROUND: Dilated cardiomyopathy (DCM) is a severe, non-ischemic heart disease which ultimately results in heart failure (HF). Decades of research on DCM have revealed diverse aetiologies. Among them, familial DCM is the major form of DCM, with pathogenic variants in LMNA being the second most common form of autosomal dominant DCM. LMNA DCM is a multifactorial and complex disease with no specific treatment thus far. Many studies have demonstrated that perturbing candidates related to various dysregulated pathways ameliorate LMNA DCM. However, it is unknown whether these candidates could serve as potential therapeutic targets especially in long term efficacy. METHODS: We evaluated 14 potential candidates including Lmna gene products (Lamin A and Lamin C), key signaling pathways (Tgfß/Smad, mTor and Fgf/Mapk), calcium handling, proliferation regulators and modifiers of LINC complex function in a cardiac specific Lmna DCM model. Positive candidates for improved cardiac function were further assessed by survival analysis. Suppressive roles and mechanisms of these candidates in ameliorating Lmna DCM were dissected by comparing marker gene expression, Tgfß signaling pathway activation, fibrosis, inflammation, proliferation and DNA damage. Furthermore, transcriptome profiling compared the differences between Lamin A and Lamin C treatment. RESULTS: Cardiac function was restored by several positive candidates (Smad3, Yy1, Bmp7, Ctgf, aYAP1, Sun1, Lamin A, and Lamin C), which significantly correlated with suppression of HF/fibrosis marker expression and cardiac fibrosis in Lmna DCM. Lamin C or Sun1 shRNA administration achieved consistent, prolonged survival which highly correlated with reduced heart inflammation and DNA damage. Importantly, Lamin A treatment improved but could not reproduce long term survival, and Lamin A administration to healthy hearts itself induced DCM. Mechanistically, we identified this lapse as caused by a dose-dependent toxicity of Lamin A, which was independent from its maturation. CONCLUSIONS: In vivo candidate evaluation revealed that supplementation of Lamin C or knockdown of Sun1 significantly suppressed Lmna DCM and achieve prolonged survival. Conversely, Lamin A supplementation did not rescue long term survival and may impart detrimental cardiotoxicity risk. This study highlights a potential of advancing Lamin C and Sun1 as therapeutic targets for the treatment of LMNA DCM.

Factors Affecting Patient and Caregiver Preferences for Treatment of Myeloma and Indolent Lymphoma.

PURPOSE: Treatment options for myeloma and indolent lymphoma are increasing exponentially, with distinct efficacy, side effects, and cost. We aim to determine the factors influencing patient and caregiver treatment preferences. METHODS: Patients and caregivers of patients with myeloma and indolent lymphoma were recruited from two cancer centers in Singapore. Preferences were elicited using a discrete choice experiment. Attributes and levels were selected based on a previous qualitative study. The relative preference for levels within each attribute (part worth utility values) and the extent to which an attribute would influence decision making (relative importance) were calculated. Patient and caregiver participation in the treatment plan selection process were assessed using the Control Preference Scale. RESULTS: One hundred ninety-nine patients and 169 caregivers were recruited. Patients placed the highest importance on out-of-pocket costs (relative importance = 35%), followed by efficacy (25%), persistent side effects (19%), administration route (8%), treatment duration (7%), and short-term side effects (5%). Caregivers ranked efficacy (27%) as the most important attribute, over out-of-pocket costs (24%). Most patients preferred a collaborative role in the shared decision-making process, while similar proportions of caregivers favored active and collaborative roles. CONCLUSION: Our study demonstrates that both patients and caregivers consider cost seriously when making treatment decisions. Furthermore, as patient and caregiver preferences may differ, there are implications for treatment selection and counseling, especially in cultures where caregivers have more prominent roles in treatment planning.

Brain-derived neurotrophic factor as a biomarker in cancer-related cognitive impairment among adolescent and young adult cancer patients.

Brain-derived neurotrophic factor (BDNF) improves cognitive function by stimulating neurogenesis and neuroplasticity. We hypothesize that higher plasma BDNF levels are protective against cognitive toxicity among adolescent and young adult cancer patients (15-39 years old). In a prospective, longitudinal study, we recruited 74 newly diagnosed cancer and 118 age-matched non-cancer controls who completed the Cambridge Neuropsychological Test Automated Battery (CANTAB), Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog) and blood draws. Plasma BDNF was quantified using an enzyme-linked immunosorbent assay. Genomic DNA from buffy coat was genotyped for BDNF Val66Met. Most cancer participants were diagnosed with breast (24%) and head/neck (22%) cancers. After adjusting for sociodemographic variables (age, gender, race, marital status, education years), cancer participants had lower BDNF levels (ng/mL) at baseline (median: 10.7 vs 21.6, p < 0.001) and 6-months post-baseline (median: 8.2 vs 15.3, p = 0.001) compared to non-cancer controls. Through linear mixed modelling adjusted for sociodemographic variables, baseline cognition, fatigue, psychological distress, and time, we observed that among cancer participants, lower baseline BDNF levels were associated with worse attention (p = 0.029), memory (p = 0.018) and self-perceived cognitive abilities (p = 0.020) during cancer treatment. Met/Met was associated with enhanced executive function compared to Val/Val (p = 0.012). Plasma BDNF may serve as a predictive biomarker of cancer-related cognitive impairment.

Economic and Clinical Outcomes of Pediatric Patients Under Two With Respiratory Syncytial Virus Infection in Thailand: A Real-world Retrospective Cohort Study.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of acute respiratory tract infection in children, including in Thailand. We conducted this study to evaluate the economic and clinical outcomes of patients <2 years old with RSV infection at a tertiary teaching hospital in Thailand. METHODS: This was a retrospective cohort study during 2014-2021. To be eligible, patients had to report at least 1 positive RSV test and were <2 years old. Descriptive statistics were used to describe baseline characteristics, healthcare resource utilization, direct medical costs (1 US dollars [USD] = 31.98 Thai Baht) and clinical outcomes. RESULTS: Among 1370 RSV-positive patients, 49.9% of the patients (n = 683) were hospitalized at or within 3 days of RSV diagnosis with a median length of stay of 6 days (interquartile range [IQR]: 4-9 days), 38.8% were diagnosed with RSV-related respiratory complications (n = 532) and 1.5% died during the hospitalization episode (n = 20). A total of 22.5% of hospitalized patients (n = 154) received critical care during the hospitalization episode. The median cost of each RSV episode was USD539 (IQR: USD167-USD2106) and was higher among hospitalized patients (median: USD2112; IQR: USD1379-USD3182) compared with nonhospitalized patients (median: USD167; IQR: USD112-USD276). CONCLUSIONS: RSV infection represents a potentially important contributor to healthcare resource use and medical costs among children <2 years old in Thailand. Coupled with epidemiologic data, findings from our study will be useful to illustrate the overall economic burden associated with RSV infection among children in Thailand.

Severe midface and maxillary hypoplasia in non-cleft and non-syndromic patients: A 2-stage surgical strategy using distraction osteogenesis and orthognathic surgery.

Severe midface and maxillary hypoplasia can have an impact on an individual, either on the appearance, functions or psychologically. Based on literature review, severe maxillary hypoplasia with more than 25.0 mm reverse overjet in non-cleft and non-syndromic patients is very rare. It is more often seen in cleft lip and palate and syndromic patients. When the magnitude of correction exceeds the limit of what a single orthognathic surgery can achieve, multiple surgeries would be required, involving different surgical techniques. The authors report two rare cases of non-syndromic nor cleft severe hypoplastic midface and maxilla with 26.0 mm and 27.0 mm reverse overjet, respectively, treated with 2-stage surgery involving maxillary distraction osteogenesis and orthognathic surgery. Both cases recorded reasonably clinical and functional outcomes. The significance of both surgical interventions is further discussed.

A Systematic Literature Review of Gaps and Challenges in Value Assessment of Biosimilars: An ISPOR Special Interest Group Report.

OBJECTIVES: This study aims to provide an overview of the gaps and challenges in the value assessment of biosimilars and to identify potential approaches to address them. METHODS: A multidisciplinary, international team of biosimilar experts identified gaps and challenges. A systematic review was conducted of the peer-reviewed literature in PubMed, EMBASE, Web of Science Core Collection, EBSCOhost Business Source Complete; and of the gray literature. Preliminary results were presented at ISPOR conferences and this article benefited from 2 review rounds among ISPOR Biosimilar Special Interest Group members. RESULTS: Given that a biosimilar is highly similar to its reference biologic, health technology assessment agencies should accept the comparability exercise approved by regulatory authorities and, thus, conduct a price comparison when biosimilar reimbursement is requested for the same indication as the reference biologic. If the reference biologic is not reimbursed or is not the standard of care, a full economic evaluation of the biosimilar versus a relevant comparator needs to be conducted. To date, little consideration has been given to specific challenges, such as how biosimilar value assessment can account for the nocebo effect, potential differences between biologic-naive and biologic-experienced patients, the availability of intravenous and subcutaneous administration forms or different administration devices for the same active compound, value-added services, and the contribution of biosimilars for generating health gain at the population level. CONCLUSIONS: There is a need to gather further insights in the methodology of value assessment for biosimilars, and health technology assessment agencies need to develop more elaborate guidance on biosimilar value assessment in specific circumstances.

Cost-effectiveness analysis of the SMART quit clinic program in smokers with cardiovascular disease in Thailand.

INTRODUCTION: The SMART Quit Clinic Program (FAHSAI Clinic) has been implemented in Thailand since 2010; however, it remains unclear whether the benefits gained from this program justify its costs. We assessed its cost-effectiveness compared to usual care in a population of Thai smokers with cardiovascular disease (CVD) from a societal perspective. METHODS: We conducted a cost-utility analysis using a Markov model to simulate lifetime costs and quality-adjusted life years (QALYs) of Thai smokers aged ≥35 years receiving smoking cessation services offered from FAHSAI Clinic or usual care over a horizon of 50 years. The model used a 6-month continuous abstinence rate from a multicenter prospective study of 24 FAHSAI Clinics. A series of sensitivity analyses including probabilistic sensitivity analysis were conducted to assess robustness of study findings. Cost data are presented in US$ for 2020. RESULTS: The FAHSAI Clinic was dominant as it was less costly ($9537.92 vs $10964.19) and more effective (6.06 vs 5.96 QALYs) compared with usual care over the 50-year time horizon. Changes in risks of stroke and coronary heart disease among males had the largest impact on the cost-effectiveness findings. The probability that FAHSAI Clinic was cost-effective was 99.8% at a willingness-to-pay threshold of $5120. CONCLUSIONS: The FAHSAI Clinic smoking cessation program was clinically superior and cost-saving compared to usual care for Thai patients with CVD in all scenarios. A budget impact analysis is needed to estimate the financial impact of adopting this program within the Thai healthcare system.

Comparative effectiveness of psychosocial interventions in adults with harmful use of alcohol: a systematic review and network meta-analysis.

AIMS: Psychosocial approaches are the hallmark of treatment for harmful alcohol use. However, the most effective psychosocial intervention has not been identified. We aimed to compare the effectiveness of psychosocial therapy for harmful alcohol use using a network meta-analysis approach. METHODS: We searched PubMed, Embase, CENTRAL, CINAHL and ProQuest Dissertations and Theses from inception to January 2022. Randomized controlled trials in adults aged > 18 years with harmful alcohol use were included. Psychosocial interventions were classified using the theme, intensity, and provider/platform (TIP) framework. The mean differences (MD) of the alcohol use disorder identification test (AUDIT) score were estimated in the primary analysis using a random-effects model. Surface under the cumulative ranking curve (SUCRA) methods were used to rank different interventions. The certainty of evidence was evaluated using the confidence in network meta-analysis (CINeMA) approach. This review was registered with PROSPERO (CRD42022328972). RESULTS: A total of 4225 records were retrieved from searches; 19 trials (n = 7149) met the inclusion criteria. The most common TIP combination was brief interventions delivered once via face-to-face sessions (six studies) and 11 TIP features were included in the network meta-analysis. A significant difference in AUDIT score was evident among 16 of 55 treatment comparisons, with the highest effect size observed when motivational interviewing plus cognitive behavioral therapy in multiple sessions via face-to-face (MI-CBT/Mult/F2F) was compared with usual care [MD = -4.98; 95% confidence interval (CI) = -7.04, -2.91]. This finding was consistent with SUCRA, which suggested that MI-CBT/Mult/F2F is most likely to be better than other interventions (SUCRA = 91.3). MI-CBT/Mult/F2F remained the highest-ranking intervention in our sensitivity analyses (SUCRA = 64.9, 80.8). However, the certainty of evidence for most treatment comparisons was low. CONCLUSIONS: Combined psychosocial intervention with a more intensive approach may provide greater effect in reducing harmful alcohol consumption behavior.

Comparison of diagnostic accuracy for diabetes diagnosis: A systematic review and network meta-analysis.

Aim: Fasting Plasma Glucose (FPG) and Hemoglobin A1c (HbA1c) are used as diagnostic tests for diagnosing diabetes mellitus, but it is unclear which test has the best diagnostic accuracy. This systematic review and network meta-analysis aimed to estimate the diagnostic accuracy of HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and the combination of HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl (HbA1c| FPG), compared with Oral Glucose Tolerance Test (OGTT) ≥ 200 mg/dl for diagnosis diabetes. Materials and methods: We performed a comprehensive search in PubMed, Embase, Cochrane Library, and Scopus from inception to September 24th, 2021. Inclusion criteria were any study design comparing HbA1c ≥ 6.5%, FPG ≥ 126 mg/dl, and HbA1c ≥ 6.5% or FPG ≥ 126 mg/dl with OGTT ≥ 200 mg/dl as the reference test. Data were independently extracted, risk of bias was assessed using QUADAS-2 by two reviewers. Network meta-analysis was done using a bivariate regression model using the Bayesian framework. The relative ranking of all tests was also assessed. Results: Out of 5,026 studies, 73 were included. The sensitivities of HbA1c, FPG, and HbA1c| FPG were 0.51 [95% Credible Interval (CrI): 0.43, 0.58], 0.49 (95% CrI: 0.43, 0.55), and 0.64 (95% CrI: 0.51, 0.75), while the specificities were 0.96 (95% CrI: 0.94, 0.97), 0.98 (95% CrI: 0.97, 0.98), and 0.95 (95% CrI: 0.88, 0.98), respectively. The corresponding positive likelihood ratios (LR) were 13.36 (95% CrI: 8.91, 20.72), 21.94 (95% CrI: 15.04, 31.88), and 11.78 (95% CrI: 5.48, 26.56). HbA1c| FPG is superior based on sensitivity, whereas FPG is ranked best based on specificity and positive LR. Conclusion: Our findings suggest that FPG ≥ 126 mg/dl should be recommended as the best diagnostic test for diabetes. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021282856.

Cancer incidence in immunocompromised patients: a single-center cohort study.

BACKGROUND: Diminished immune defense plays an important role in cancer development. Cancer risk in immunocompromised patients may differ. Identifying individuals with elevated cancer risk can inform strategies for routine cancer screening. This study aimed to understand and compare cancer incidence and risk in three patient groups: recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT); diagnosis of primary or secondary immunodeficiency disorder (PID/SID); and recipients of tumor necrosis factor inhibitor (TNF-i) therapy. METHODS: This retrospective cohort study used the University of Utah Health System database and Huntsman Cancer Institute tumor registry. Patients aged ≥18 years with SOT/HSCT, PID/SID or ≥ 3 months of TNF-i therapy were included. The date of transplant, diagnosis of PID/SID, or 1st TNF-i medication order date was defined as the index date. We calculated cumulative cancer incidence by Kaplan-Meier method. A Cox-proportional hazard regression model with a stepwise variable selection process was used to identify independent risk factors associated with the time to onset of a new primary cancer. RESULTS: In total, 13,887 patients were included which comprised of 2982 (21%) SOT/HSCT, 7542 (54%) PID/SID and 3363 (24%) patients receiving TNF-i. The mean (SD) age ranged from 46.8 (15) years - 50.4 (18.2) years. The proportion of white patients ranged from 72.3-84.8%. The estimated cumulative cancer incidence was 11.5% in the SOT/HSCT cohort, 14.3% in the PID/SID cohort, and 8.8% in the TNF-i cohort. The multivariable model adjusted for age, benign in-situ disease, Charlson Comorbidity Index, hypertension/cardiovascular disease/end stage renal disease, gender, race/ethnicity, and renal cyst as significant risk factors. The adjusted hazard ratios for cancer development in SOT/HSCT and PID/SID cohorts compared to the TNF-i cohort over the full follow-up period were 1.57 (95% CI: 1.16-2.13) and 2.14 (95% CI: 1.65-2.77), respectively. CONCLUSION: A significantly increased risk of cancer was observed in PID/SID patients and SOT/HSCT patients compared to TNF-i patients. Age ≥ 50 years, male gender, and clinical comorbidities were additional factors impacting cancer risk. PID/SID and SOT/HSCT patients may benefit from more intensive cancer screening.

A 3-year retrospective analysis of patients admitted with clinical vertebral fragility fractures across hospitals in England, UK.

Our database aimed to assess the impact of vertebral fragility fractures (VFFs) on hospitalisation in England. The results showed that admissions secondary to VFF are increasing annually, more significantly in patients aged 75 years and over. Vertebral augmentation has been showed to reduce length of stay in hospital. INTRODUCTION: Vertebral fragility fractures (VFFs) are the most common osteoporotic fracture. VFF can result in significant pain requiring hospitalisation. However, there are little data on patient numbers, hospital bed days, and costs, contributed to by these patients. METHODOLOGY: We report a retrospective analysis of patients aged 55 years and over admitted to hospitals across England from 2017 to 2019. ICD-10 classifications for VFF and OPCS codes were used to identify admissions and patients who had undergone vertebral augmentation (VA). RESULTS: There were 99,370 patients (61% female) admitted during this period, with 64,370 (65%) patients aged over 75 years. There was a 14.3% average increase in admissions annually. Patients aged over 75 years accounted for 1.5 million bed days, costing £465 million (median length of stay (MLOS) 14.4 days). In comparison, those aged 55-74 years, accounted for 659,000 bed days, costing £239 million (MLOS 10.7 days). The majority of patients (84%) were admitted under a non-surgical speciality and were primarily older (median age 76.8 vs 67.6 years, MLOS 8.2 vs 6.0 days), compared to those admitted to surgical wards 1755 patients underwent vertebral augmentation (VA) (1.8% of the total cohort). The median age of patients undergoing VA was 73.3 years, with 775 (44.2%) of these were aged 75 years and over. In comparison, the median age of patients managed conservatively (non-surgically) was 75.7 years, with 63,595 patients (65.1%) aged 75 years and over. The MLOS and cost per patient admission were lower in the VA group compared to those managed non-surgically. CONCLUSION: Hospitalised VFF patients represented a significant number, cost, and use of bed days. Those undergoing VA had a significantly shorter length of stay. Further studies are necessary to define those who may benefit from early VA.

Work Outcomes and Medical Costs Among Singaporean Adolescent and Young Adult Cancer Survivors.

Purpose: To quantify and evaluate trends of work outcomes and medical costs among Singaporean adolescent and young adult (AYA) cancer survivors. Methods: This cross-sectional study was conducted at the National Cancer Centre Singapore between July 2016 and October 2018. Cancer patients who were diagnosed between the age of 15 and 39 years and had completed treatment were eligible. Siblings of cancer patients were recruited as controls. Work outcomes were collected using an investigator-designed questionnaire, while cost data were extracted from the hospital database. Descriptive statistics were used to quantify work and cost outcomes. Mixed-effects logistic regression was used to compare employment rates between survivors and controls. Generalized linear models were used to characterize trends between medical costs and symptom burden. Results: A total of 29 cancer survivors and 23 sibling controls were analyzed. Approximately 80% of survivors and controls were employed at the time of survey; however, more than half of the employed survivors reported impaired work outcomes due to effects from cancer and cancer treatment, including work reallocation, absenteeism, and decreased work ability. Median productivity loss due to absenteeism in the past 3 months was estimated to be U.S. dollar (USD) 110. Total medical cost incurred within the first year after treatment completion remained high at a median of USD6592, with out-of-pocket expenditure between 17.2% and 100.0%. Conclusion: Despite their young age and having completed cancer treatment, Singaporean AYA cancer survivors may continue to experience poor work outcomes even after resuming work. High medical costs may also persist.

Cognitive impairment in adolescent and young adult cancer patients: Pre-treatment findings of a longitudinal study.

BACKGROUND: There is little information about cancer-related cognitive impairment (CRCI) in adolescent and young adults (AYA, 15-39 years old) due to its rare incidence. Here, we present the pre-treatment (before chemotherapy or radiotherapy) evaluation of cognitive function and ability of AYA with cancer (AYAC) in a multicentered cohort study. METHODS: Newly diagnosed AYAC and age-matched healthy controls (HC) were recruited between 2018 and 2021. The primary outcome was the comparison of pre-treatment cognitive impairment defined as 2 standard deviations (SDs) below the HC on ≥1 cognitive test, or >1.5 SDs below on ≥2 tests using CANTAB® between AYAC and HC. Secondary outcomes included self-perceived cognitive ability assessed by FACT-Cog v3 and biomarkers (inflammatory cytokines and brain-derived neurotrophic factor [BDNF]). RESULTS: We recruited 74 AYAC (median age = 34) and 118 HC (median age = 32). On objective cognitive testing, we observed three times more AYAC patients performed poorly on at least 2 cognitive tests compared to HC (40.5% vs. 13.6%, p < 0.001). AYAC self-perceived less degree of cognitive impairment than HC (p < 0.001). However, AYAC perceived a greater impact of cognitive changes on their quality of life compared to HC (p = 0.039). Elevated baseline inflammatory markers (IL-2, IL-4, IL-6, IL-8, IL-10 and IFN-γ) were observed among AYAC compared to HC, and baseline BDNF was lower in AYAC compared to HC. Interaction effects between cancer diagnosis and biomarkers were observed in predicting cognitive function. CONCLUSION: With the pre-existence of CRCI and risk factors of neuroinflammation even prior to systemic therapy, AYAC should receive early rehabilitation to prevent further deterioration of cognitive function after initiation of systemic therapies. (ClinicalTrials.gov Identifier: NCT03476070).

Longitudinal evaluation of dehydroepiandrosterone (DHEA), its sulfated form and estradiol with cancer-related cognitive impairment in early-stage breast cancer patients receiving chemotherapy.

The purpose of this study is to elucidate how patient-reported cognitive symptoms manifest from variations in hormone levels or precursors such as dehydroepiandrosterone (DHEA) and its sulfated form [collectively termed as DHEA(S)] and to investigate their association in breast cancer survivors. Levels of estradiol and DHEA(S) were compared between early-stage breast cancer patients with and without cancer-related cognitive impairment (CRCI) during adjuvant chemotherapy. Data were analyzed from 242 patients (mean age ± SD = 50.8 ± 9.2 years) who had completed FACT-Cog v.3.0, blood draws and questionnaires. Regression model was used to fit the magnitude of change in each respective biomarker levels against overall cognitive impairment status while adjusting for clinically important covariates. There was reduction in mean plasma levels of estradiol and DHEAS during and towards the end of chemotherapy (p-values < 0.001). Compared to non-impaired patients, smaller magnitude of decline was observed in DHEA(S) levels in patients reporting CRCI, with significant association between decline in DHEAS levels and acute onset of CRCI at 6 weeks from baseline (adjusted ß of 0.40, p-value of 0.02). In contrast, patients reporting CRCI showed greater magnitude of decline in estradiol compared to non-impaired patients, although this was not found to be statistically significant. There was an association between magnitude of change in biomarker levels with self-reported CRCI which suggests that the hormonal pathway related to DHEAS may be implicated in acute CRCI for breast cancer survivors. Our findings help to improve biological understanding of the pathway from which DHEAS may correlate with cognitive dysfunction and its impact on cancer survivors.