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Alzheimer's disease and related dementias (ADRD), pain and chronic complex conditions (CCC) often co-occur leading to polypharmacy and with potential inappropriate medications (PIMs) use, are important risk factors for adverse drug reactions and hospitalizations in older adults. Many US veterans are at high risk for persistent pain due to age, injury or medical illness. Concerns about inadequate treatment of pain-accompanied by evidence about the analgesic efficacy of opioids-has led to an increase in the use of opioid medications to treat chronic pain in the Veterans Health Administration (VHA) and other healthcare systems. This study aims to investigate the relationship between receipt of pain medications and centrally (CNS) acting PIMs among veterans diagnosed with dementia, pain intensity, and CCC 90-days prior to hospitalization. The final analytic sample included 96,224 (81.7%) eligible older veterans from outpatient visits between October 2012-30 September 2013. We hypothesized that veterans with ADRD, and severe pain intensity may receive inappropriate pain management and CNS-acting PIMs. Seventy percent of the veterans, and especially people with ADRD, reported severe pain intensity. One in three veterans with ADRD and severe pain intensity have an increased likelihood for CNS-acting PIMs, and/or opioids. Regular assessment and re-assessment of pain among older persons with CCC, patient-centered tapering or discontinuation of opioids, alternatives to CNS-acting PIMs, and use of non-pharmacological approaches should be considered.Biomedical research has, over the past decades, found components of the immune system at the functional center of almost every pathophysiological condition and disease [...].There is international public concern regarding retirement of racehorses, including the reason for retirement and the outcome for horses after racing. However, there are currently no prospective studies investigating these factors. A recent independent inquiry in Queensland, Australia, highlighted that the true outcomes for horses after retirement from racing are largely unknown. see more Furthermore, there are currently no measures to monitor the outcome for racehorses and their welfare once they have left the care of the trainer. This study investigated these gaps in knowledge through a weekly survey conducted over a 13-month period. We aimed to evaluate (1) the incidence of retirement, (2) the reasons and risk factors for retirement and (3) the medium-term (greater than 6 months) outcomes for horses after retirement. Data were collected through personal structured weekly interviews with participating trainers and analysed using negative binomial and logistic regression. There was a low incidence of retirements, namoluntarily (p = 0.03). Whether retirement was voluntary or involuntary did not influence whether horses were used for breeding or pleasure. The primary limitation of this study is that our results reflect retirement in racehorses in South East Queensland, Australia, and may not be globally applicable. Furthermore, we were unable to monitor the long-term outcome and welfare of horses in their new careers. It is vital that the industry is focused on understanding the risks for voluntary rather than involuntary retirement and optimising the long-term repurposing of horses. There is a need for traceability and accountability for these horses to ensure that their welfare is maintained in their new careers.Clinicians often encounter thyroid function tests (TFT) comprising serum/plasma free thyroxine (FT4) and thyroid stimulating hormone (TSH) measured using different assay platforms during the course of follow-up evaluations which complicates reliable comparison and interpretation of TFT changes. Although interconversion between concentration units is straightforward, the validity of interconversion of FT4/TSH values from one assay platform to another with different reference intervals remains questionable. This study aims to establish an accurate and reliable methodology of interconverting FT4 by any laboratory to an equivalent FT4 value scaled to a reference range of interest via linear transformation methods. As a proof-of-concept, FT4 was simultaneously assayed by direct analog immunoassay, tandem mass spectrometry and equilibrium dialysis. Both linear and piecewise linear transformations proved relatively accurate for FT4 inter-scale conversion. Linear transformation performs better when FT4 are converted from a more accurate to a less accurate assay platform. The converse is true, whereby piecewise linear transformation is superior to linear transformation when converting values from a less accurate method to a more robust assay platform. Such transformations can potentially apply to other biochemical analytes scale conversions, including TSH. This aids interpretation of TFT trends while monitoring the treatment of patients with thyroid disorders.Prostate cancer (PCa) has a vast clinical spectrum from the hormone-sensitive setting to castration-resistant metastatic disease. Thus, chemotherapy regimens and the administration of androgen receptor axis-targeted (ARAT) agents for advanced PCa have shown limited therapeutic efficacy. Scientific advances in the field of molecular medicine and technological developments over the last decade have paved the path for immunotherapy to become an essential clinical modality for the treatment of patients with metastatic PCa. However, several immunotherapeutic agents have shown poor outcomes in patients with advanced disease, possibly due to the low PCa mutational burden. Adoptive cellular approaches utilizing chimeric antigen receptor T cells (CAR-T) targeting cancer-specific antigens would be a solution for circumventing the immune tolerance mechanisms. The immunotherapeutic regimen of CAR-T cell therapy has shown potential in the eradication of hematologic malignancies, and current clinical objectives maintain the equivalent efficacy in the treatment of solid tumors, including PCa. This review will explore the current modalities of CAR-T therapy in the disease spectrum of PCa while describing key limitations of this immunotherapeutic approach and discuss future directions in the application of immunotherapy for the treatment of metastatic PCa and patients with advanced disease.

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