Predictors of Adverse Drug Reaction-Related Hospitalisations Among People with Dementia: A Retrospective Case-Control Study.

INTRODUCTION: Adverse drug reactions (ADRs) are common among people with dementia; however, little is known about the magnitude and predictors associated with ADR-related hospitalisation among these individuals. This study aimed to determine the magnitude, types, drugs implicated and predictors of ADRs associated with hospitalisation among people with dementia. METHODS: This retrospective case-control study analysed medical records of individuals aged ≥ 65 years with dementia admitted to major public hospitals in Tasmania, Australia, from July 2010 to July 2021. Adverse drug reactions and implicated drugs were identified using administrative data and cross-checked with hospital medical records, with consensus reached among the research team. RESULTS: Of the 7928 people admitted to hospital at least once within the study period, 1876 (23.7%) experienced at least one ADR-related hospitalisation. Of these, 300 case patients with 311 ADRs and 300 control patients were randomly selected. The most common types of ADRs were renal (acute kidney injury; AKI) (36.0%), followed by neuropsychiatric (17.6%), cardiovascular (16.0%) and haematological (13.1%). Diuretics, renin-angiotensin system (RAS) inhibitors and anti-thrombotics constituted the main implicated drug classes. The ADR-related hospitalisation was associated with: chronic kidney disease (CKD) (OR 8.00, 95% CI 2.63-24.28, p < 0.001), Australian-born (OR 1.62, 95% CI 1.08-2.43, p = 0.019), hypertension (OR 1.48, 95% CI 1.01-2.17, p = 0.044) and the number of medicines (OR 1.06, 95% CI 1.00-1.12, p = 0.022). Potentially inappropriate medication use and anticholinergic burden did not predict ADR-related hospitalisation. CONCLUSIONS: These predictors could help identify the individuals at the highest risk and enable targeted interventions to be designed.

Adverse clinical outcomes associated with drug-related hospitalizations in people with dementia.

BACKGROUND: This study aimed to determine the clinical impact associated with adverse drug reactions (ADRs) in patients with dementia. RESEARCH DESIGN AND METHODS: This case-control, propensity score-matched study utilized administrative data of people with dementia admitted to major public hospitals in Tasmania, Australia, from July 2010 to December 2019. RESULTS: Acute renal failure constituted the most common ADR. The length of hospital stay was greater for people with an ADR index admission, versus non-ADR index admission (median [IQR]: 9 [4-18] versus 6 [2-12]; p < 0.001). In-hospital mortality and combined in-hospital and post-hospital mortality within 30, 60 and 90 days were higher for those whose index admission was ADR-related (in-hospital: HR 1.40, 95% CI 1.11-1.77, p-value <0.001; 30 days: HR 1.25, 95% CI 1.05-1.49, p-value <0.001; 60 days: HR 1.27, 95% CI 1.08-1.49, p-value <0.001; 90 days: HR 1.29, 95% CI 1.10-1.50, p-value <0.001). Subsequent ADR admission within 30, 60 and 90 days of index discharge was 9 to 10 times greater for people with dementia (30 days: OR 10.0, 95% CI 6.04-16.8, p-value <0.001; 60 days: OR 8.96, 95% CI 5.57-14.4, p-value <0.001; 90 days: OR 9.31, 95% CI 5.79-14.9, p-value <0.001). CONCLUSION: Safe prescribing and vigilant monitoring of ADRs is pivotal to mitigate adverse outcomes in people with dementia.

Single- and Multilayered Perovskite Thin Films for Photovoltaic Applications.

Organic-inorganic lead halide perovskites materials have emerged as an innovative candidate in the development of optoelectronic and photovoltaic devices, due to their appealing electrical and optical properties. Herein, mix halide single-layer (~95 nm) and multilayer (average layer ~87 nm) CH3NH3PbIBr2 thinfilms were grown by a one-step spin coating method. In this study, both films maintained their perovskite structure along with the appearance of a pseudo-cubic phase of (200) at 30.16°. Single-layer and multilayer CH3NH3PbIBr2 thinfilms displayed leaky ferroelectric behavior, and multilayered thinfilm showed a leakage current of ~5.06 × 10-6 A and resistivity of ~1.60 × 106 Ω.cm for the applied electric field of 50 kV/cm. However, optical analysis revealed that the absorption peak of multilayered perovskite is sharper than a single layer in the visible region rather than infrared (IR) and near-infrared region (NIR). The band gap of the thinfilms was measured by Tauc plot, giving the values of 2.07 eV and 1.81 eV for single-layer and multilayer thinfilms, respectively. The structural analysis has also been performed by Fourier transform infrared spectroscopy (FTIR). Moreover, the fabricated CH3NH3PbIBr2 as an absorber layer for photoelectric cell demonstrated a power conversion efficiency of 7.87% and fill factor of 72%. Reported electrical, optical and photoelectric efficiency-based results suggest that engineered samples are suitable candidates for utilization in optoelectronic and photovoltaic devices.

Boosting of Magnetic, Ferroelectric, Energy Storage Efficiency, and Piezoelectric Properties of Zn Intercalated SrBi4Ti4O15-Based Ceramics.

An appropriate amount of Zn-ions are incorporated into the high Curie temperature bismuth layer-structure ferroelectric material to fabricate Sr0.2Na0.4Pr0.4Bi4Ti4O15:xwt%ZnO; (SNPBT:xZn), with x = 0, 0.10, 0.15, and 0.20 ceramic series to investigate the magnetic, ferroelectric, and energy storage efficiency and piezoelectric properties. Pure SNPBT and SNPBT:xZn ceramics have maintained their structure even after the intercalation of Zn-ions at the lattice sites of SNPBT. The addition of ZnO in SNPBT has improved the multifunctional properties of the material at x = 0.15. At room temperature, SNPBT:0.15Zn has shown a high relative density of 96%, exhibited weak ferromagnetic behavior along with a low saturation magnetization (Ms) of 0.028 emu/g with a low coercive field of 306 Oe, a high remnant polarization (Pr) of 9.04 µC/cm2, a recoverable energy density (Wrec) of ~0.5 J/cm3, an energy conversion efficiency (η) of ~41%, a high piezoelectric co-efficient (d33) of 21 pC/N, and an impedance of 1.98 × 107 Ω, which are much improved as compared to pure SBT or pure SNPBT ceramics. Dielectric Constant (ɛr) versus temperature plots present the sharp peak for SNPBT:0.15Zn ceramic at a Curie temperature (TC) ~ 605 °C, confirming the strong ferroelectric nature of the ceramic. Moreover, SNPBT:0.15Zn ceramic has shown strong, piezoelectric, thermally stable behavior, which remains at 76% (16 pC/N) of its initial value even after annealing at 500 °C. The achieved results clearly indicate that SNPBT:0.15Zn ceramic is a promising candidate for future wide-temperature pulse power applications and high-temperature piezoelectric devices.

Ten-year trends in adverse drug reaction-related hospitalizations among people with dementia.

Aim: Trends in the incidence of adverse drug reaction (ADR)-related hospitalizations have been studied in the general population, but not specifically in people with dementia. This study aimed to investigate trends in the incidence of ADR-related hospitalizations among people with dementia, and identify the most commonly implicated drugs and diagnoses in these admissions. Methods: This study utilized the administrative data of all adults admitted to the four major public hospitals of Tasmania, Australia, with a primary or secondary diagnosis of dementia from July 2010 to December 2019. ADR-related hospitalizations were identified by using diagnosis-based and external cause codes. The Cochran-Armitage test was used to examine trends in the incidence of ADR-related hospitalizations. Results: Of the 7552 people with dementia admitted to the hospital at least once within the study period, 1775 (23.5%) experienced at least one ADR-related hospitalization. The estimated annual incidence of ADR-related hospitalizations increased 18% (1484-1760 per 100,000 population with dementia, p for trend <0.05) from 2010 to 2019. For those ADR-related admissions with a drug code recorded, 19.3% were due to antithrombotics and 11.5% to antihypertensives. The most frequent ADR-related admission diagnoses were renal diseases (72.9%). Length of hospital stay and in-hospital mortality were both significantly greater for ADR-related, relative to non-ADR-related, admissions (median 7 versus 5 days and 11% versus 6.7%, respectively; p < 0.001). Conclusion: The annual incidence of ADR-related hospitalizations in people with dementia increased between 2010 and 2019. Antithrombotics were the most commonly implicated drug class. The ADR-related hospitalizations were associated with increased length of stay and greater mortality. Plain Language Summary: Adverse drug reaction-related hospitalizations among people with dementia. Introduction: This study aimed to investigate trends in hospitalizations associated with medication problems among people with dementia, and identify the most commonly implicated drugs and diagnoses in these admissions. Methods: This study utilized the administrative data of all adults admitted to the four major public hospitals of Tasmania, Australia, with dementia from July 2010 to December 2019. Results: The annual incidence of hospitalizations associated with medication problems among people with dementia increased nearly 20% over 10 years. The length of hospital stay and in-hospital mortality were significantly greater for hospitalizations related to medication problems. Conclusion: The incidence of hospitalizations associated with medication problems in people with dementia increased between 2010 and 2019.

Outcomes of Medication Misadventure Among People With Cognitive Impairment or Dementia: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate mortality and hospitalization outcomes associated with medication misadventure (including medication errors [MEs], such as the use of potentially inappropriate medications [PIMs], and adverse drug events [ADEs]) among people with cognitive impairment or dementia. DATA SOURCES: Ovid MEDLINE, Ovid EMBASE, Ovid International Pharmaceutical Abstracts, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials were searched from inception to December 2019. STUDY SELECTION AND DATA EXTRACTION: Relevant studies using any study design were included. Reviewers independently performed critical appraisal and extracted relevant data. DATA SYNTHESIS: The systematic review included 10 studies that reported the outcomes of mortality or hospitalization associated with medication misadventure, including PIMs (n=5), ADEs (n=2), a combination of MEs and ADEs (n=2), and drug interactions (n=1). Five studies examining the association between PIMs and mortality/hospitalization were included in the meta-analyses. Exposure to PIMs was not associated with either mortality (odds ratio [OR]=1.36; 95%CI=0.79-2.35) or hospitalization (OR=1.02; 95%CI=0.83-1.26). In contrast, single studies indicated that ADEs with cholinesterase inhibitors were associated with mortality and hospitalization. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Individuals with cognitive impairment or dementia are at increased risk of medication misadventure; based on relatively limited published data, this does not necessarily translate to increased mortality and hospitalization. CONCLUSIONS: Overall, medication misadventure was not associated with mortality or hospitalization in people with cognitive impairment or dementia, noting the limited number of studies, difficulty in controlling potential confounding variables, and that most studies focus on PIMs.

Multi-faceted proteomic characterization of host protein complement of Rift Valley fever virus virions and identification of specific heat shock proteins, including HSP90, as important viral host factors.

Rift Valley fever is a potentially fatal disease of humans and domestic animals caused by Rift Valley fever virus (RVFV). Infection with RVFV in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. To elucidate the roles that host proteins play during RVFV infection, proteomic analysis of RVFV virions was conducted using complementary analytical approaches, followed by functional validation studies of select identified host factors. Coupling the more traditional Gel LC/MS/MS approach (SDS PAGE followed by liquid chromatography tandem mass spectrometry) with an alternative technique that preserves protein complexes allowed the protein complement of these viral particles to be thoroughly examined. In addition to viral proteins present within the virions and virion-associated host proteins, multiple macromolecular complexes were identified. Bioinformatic analysis showed that host chaperones were among over-represented protein families associated with virions, and functional experiments using siRNA gene silencing and small molecule inhibitors identified several of these heat shock proteins, including heat shock protein 90 (HSP90), as important viral host factors. Further analysis indicated that HSP inhibition effects occur during the replication/transcription phase of the virus life cycle, leading to significant lowering of viral titers without compromising the functional capacity of released virions. Overall, these studies provide much needed further insight into interactions between RVFV and host cells, increasing our understanding of the infection process and suggesting novel strategies for anti-viral development. In particular, considering that several HSP90 inhibitors have been advancing through clinical trials for cancer treatment, these results also highlight the exciting potential of repurposing HSP90 inhibitors to treat RVF.