-
PCN Reports : Psychiatry and Clinical... Sep 2023Dementia with Lewy bodies (DLB) is the second most common cause of dementia after Alzheimer's disease. The disease is characterized by many Lewy bodies appearing in the... (Review)
Review
Dementia with Lewy bodies (DLB) is the second most common cause of dementia after Alzheimer's disease. The disease is characterized by many Lewy bodies appearing in the patient's cerebrum. DLB frequently presents with a variety of autonomic symptoms from the early or prodromal stages of the disease, and these are listed as supportive features in the diagnostic criteria. As several useful assessment methods for evaluating autonomic function in DLB have been reported, this review will focus on cardiovascular and respiratory dysfunction and its assessments. Cardiovascular disorders, such as orthostatic hypotension and abnormal heart rate variability, have been reported in DLB patients. Decreased myocardial uptake by metaiodobenzylguanidine myocardial scintigraphy has been added as an indicative biomarker for DLB in the 2017 revision of the diagnostic criteria. We have reported reduced ventilatory response to hypercapnia, abnormal respiratory rhythm, and high frequency of sleep-disordered breathing as abnormalities of the respiratory regulatory system associated with DLB. Since autonomic dysfunction is highly prevalent in DLB from the early or prodromal phase of the disease and is associated with reduced activities of daily living and quality of life, the evaluation of autonomic dysfunction is also useful in the differential diagnosis of DLB from Alzheimer's disease. There are fewer studies on the respiratory regulatory system than on the cardiovascular system, thus further research is needed to explore its role in DLB.
PubMed: 38867816
DOI: 10.1002/pcn5.129 -
JMIR Research Protocols Jun 2024Falls in older patients can lead to serious health complications and increased health care costs. Fall risk-increasing drugs (FRIDs) are a group of drugs that may induce... (Randomized Controlled Trial)
Randomized Controlled Trial
Assessing the Efficacy of the ARMOR Tool-Based Deprescribing Intervention for Fall Risk Reduction in Older Patients Taking Fall Risk-Increasing Drugs (DeFRID Trial): Protocol for a Randomized Controlled Trial.
BACKGROUND
Falls in older patients can lead to serious health complications and increased health care costs. Fall risk-increasing drugs (FRIDs) are a group of drugs that may induce falls or increase the tendency to fall (ie, fall risk). Deprescribing is the process of withdrawal from an inappropriate medication, supervised by a health care professional, with the goal of managing polypharmacy and improving outcomes.
OBJECTIVE
This study aims to assess the effectiveness of a deprescribing intervention based on the Assess, Review, Minimize, Optimize, and Reassess (ARMOR) tool in reducing the risk of falls in older patients and evaluate the cost-effectiveness of deprescribing FRIDs.
METHODS
This is an open-label, parallel-group randomized controlled academic trial. Individuals aged 60-80 years who are currently taking 5 or more prescribed drugs, including at least 1 FRID, will be recruited. Demographic data, medical conditions, medication lists, orthostatic hypotension, and fall history details will be collected. Fall concern will be assessed using the Fall Efficacy Scale, and fall risk will be assessed by the Timed Up and Go test and Tinetti Performance-Oriented Mobility Assessment tool. In this study, all treating physicians will be randomized using a stratified randomization method based on seniority. Randomized physicians will do deprescribing with the ARMOR tool for patients on FRIDs. Participants will maintain diaries, and monthly phone follow-ups will be undertaken to monitor falls and adverse events. Physical assessments will be performed to evaluate fall risk every 3 months for a year. The rationality of prescription drugs will be evaluated using the World Health Organization's core indicators.
RESULTS
The study received a grant from the Indian Council of Medical Research-Safe and Rational Use of Medicine in October 2023. The study is scheduled to commence in April 2024 and conclude by 2026. Efficacy will be measured by fall frequency and changes in fall risk scores. Cost-effectiveness analysis will also include the incremental cost-effectiveness ratio calculation. Adverse events related to deprescription will be recorded.
CONCLUSIONS
This trial will provide essential insights into the efficacy of the ARMOR tool in reducing falls among the geriatric population who are taking FRIDs. Additionally, it will provide valuable information on the cost-effectiveness of deprescribing practices, offering significant implications for improving the well-being of older patients and optimizing health care resource allocation. The findings from this study will be pertinent for health care professionals, policy makers, and researchers focused on geriatric care and fall prevention strategies.
TRIAL REGISTRATION
Clinical Trials Registry - India CTRI/2023/12/060516; https://ctri.nic.in/Clinicaltrials/pubview2.php.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/55638.
Topics: Humans; Accidental Falls; Aged; Deprescriptions; Aged, 80 and over; Female; Male; Middle Aged; Risk Reduction Behavior; Polypharmacy; Cost-Benefit Analysis; Randomized Controlled Trials as Topic
PubMed: 38861709
DOI: 10.2196/55638 -
Acta Cardiologica Jun 2024Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure....
BACKGROUND
Midodrine, an FDA-approved medication for orthostatic hypotension, is also used off-label to manage hypotension in dialysis patients, including those with heart failure. However, in patients with reduced ejection fraction (HFrEF) and/or right heart failure, midodrine is potentially harmful. No known studies examine the safety of midodrine in hospitalised kidney failure patients with HF.
METHODS
The TriNetX database was queried for hospitalised kidney failure patients with HFrEF and/or right heart failure who experienced hypotension (SBP < 110 mm Hg or MAP < 70 mm Hg). Excluding those needing critical care or vasopressors, we compared cohorts based on midodrine use, matching for comorbidities.
RESULTS
Analysis showed patients on midodrine had a higher 6-month mortality risk ratio (RR 1.53, 95% CI 1.037 to 2.246) and Hazard Ratio (HR 1.54, 95% CI 1.022 to 2.317) compared to those not on midodrine, indicating an association with increased mortality.
CONCLUSION
This study illuminates the complexities in treating hospitalised patients with kidney failure and HF. Our findings, drawn from an exploratory analysis, indicate that inpatient midodrine use is associated with increased 6-month mortality. This may reflect deleterious effects from vasoconstriction and/or unmeasured confounders in this vulnerable population. This investigation, utilising TriNetX, was limited by access to deidentified aggregate data, preventing detailed exploration of specifics such as timing, dosage, and indications for midodrine use. Moreover, given its observational nature, cause-effect relationship cannot be established. Our findings indicate an increased mortality associated with midodrine use for hypotension, underscoring the need for further research and consideration of alternative strategies.
PubMed: 38860595
DOI: 10.1080/00015385.2024.2365608 -
Public Health Jun 2024The main objective was to determine the prevalence of falls and associated factors in older adults living in Qatar.
OBJECTIVE
The main objective was to determine the prevalence of falls and associated factors in older adults living in Qatar.
STUDY DESIGN
Cross-sectional study.
METHODS
This is a cross-sectional study of older adults aged ≥60 years with at least one encounter with primary health care corporation (PHCC) in Qatar during the period 2017-2022. Data on documented falls, demographic variables, and medical comorbidities were extracted from all PHCCs in Qatar. Descriptive and inferential statistics were used to address the aim of the study.
RESULTS
A total of 68,194 older adults had at least one encounter with PHCC. The median age was 65.0 years, 58.9% were males, and 32.6% were Qatari nationality. A higher percentage of falls was found in individuals with hypertension (80%), diabetes (74.2%), and dyslipidemia (48.9%), which were also the most prevalent comorbidities. The prevalence of falls was 6.7% (95% CI 6.6-6.9). Compared to individuals aged 60-69 years, individuals aged 70-79, 80-89, and 90-99 had increased odds of falls by 1.6 (95% CI 1.5, 1.8), 2.5 (95% CI 2.2, 2.8), and 2.6 (95% CI 2.0, 3.3), respectively. Females and individuals of Qatari nationality had increased odds of fall by 1.5 (95% CI 1.4, 1.6) and 1.2 (95% CI 1.1, 1.3), respectively. Orthostatic hypotension, syncope, Parkinson's disease, and hip arthritis showed the strongest associations with falls.
CONCLUSIONS
Given the growing population of older adults in the Middle East and North African region, falls is a public health concern. The risk factors identified in this study suggest the need for proactive healthcare strategies tailored to the unique needs of older adult populations.
PubMed: 38848620
DOI: 10.1016/j.puhe.2024.04.011 -
Journal of Alzheimer's Disease : JAD 2024Dementia with Lewy bodies (DLB) presents with various symptoms, posing challenges for early diagnosis challenging. Dopamine transporter (123I-FP-CIT) single-photon...
BACKGROUND
Dementia with Lewy bodies (DLB) presents with various symptoms, posing challenges for early diagnosis challenging. Dopamine transporter (123I-FP-CIT) single-photon emission tomography (SPECT) and 123I-meta-iodobenzylguanidine (123I-MIBG) imaging are crucial diagnostic biomarkers. Hypothesis about body- and brain-first subtypes of DLB indicate that some DLB may show normal 123I-FP-CIT or 123I-MIBG results; but the characteristic expression of these two subtypes remains unclear.
OBJECTIVE
This study aimed to evaluate the diagnostic sensitivity of 123I-FP-CIT and 123I-MIBG imaging alone, combined in patients with DLB and explore symptoms associated with the abnormal imaging results.
METHODS
Demographic data, clinical status, and imaging results were retrospectively collected from patients diagnosed with possible DLB. Both images were quantified using semi-automated software, and the sensitivity of each imaging modality and their combination was calculated. Demographic data, cognition, and motor and non-motor symptoms were compared among the subgroups based on the imaging results. Symptoms related to each imaging abnormality were examined using binomial logistic regression analyses.
RESULTS
Among 114 patients with DLB, 80 underwent 123I-FP-CIT SPECT (sensitivity: 80.3%), 83 underwent 123I-MIBG imaging (68.2%), and 66 both (sensitivity of either abnormal result: 93.9%). Visual hallucinations differed among the four subgroups based on imaging results. Additionally, nocturia and orthostatic hypotension differed between abnormal and normal 123I-MIBG images.
CONCLUSIONS
Overall, 123I-FP-CIT SPECT was slightly higher sensitivity than 123I-MIBG imaging, with combined imaging increasing diagnostic sensitivity. Normal results of a single imaging test may not refute DLB. Autonomic symptoms may lead to abnormal 123I-MIBG scintigraphy findings indicating body-first subtype of patients with DLB.
Topics: Humans; Lewy Body Disease; Male; Female; Aged; Tomography, Emission-Computed, Single-Photon; Dopamine Plasma Membrane Transport Proteins; 3-Iodobenzylguanidine; Retrospective Studies; Tropanes; Aged, 80 and over; Sensitivity and Specificity; Radiopharmaceuticals; Myocardial Perfusion Imaging; Brain; Middle Aged; Dopaminergic Imaging
PubMed: 38848178
DOI: 10.3233/JAD-231395 -
Clinical Autonomic Research : Official... Jun 2024Neurogenic orthostatic hypotension (nOH) results from deficient reflexive delivery of norepinephrine to cardiovascular receptors in response to decreased cardiac venous...
PURPOSE
Neurogenic orthostatic hypotension (nOH) results from deficient reflexive delivery of norepinephrine to cardiovascular receptors in response to decreased cardiac venous return. Lewy body (LB) forms of nOH are characterized by low F-dopamine-derived radioactivity (a measure of cardiac noradrenergic deficiency), olfactory dysfunction by the University of Pennsylvania Smell Identification Test (UPSIT), and increased deposition of alpha-synuclein (α-syn) in dermal sympathetic noradrenergic nerves by the α-syn-tyrosine hydroxylase (TH) colocalization index. This observational, cross-sectional study explored whether combinations of these biomarkers specifically identify LB forms of nOH.
METHODS
Clinical laboratory data were reviewed from patients referred for evaluation at the National Institutes of Health for chronic autonomic failure between 2011 and 2023. The cutoff value for low myocardial F-dopamine-derived radioactivity was 6000 nCi-kg/cc-mCi, for olfactory dysfunction an UPSIT score ≤ 28, and for an increased α-syn-TH colocalization index ≥ 1.57.
RESULTS
A total of 44 patients (31 LB, 13 non-LB nOH) had data for all three biomarkers. Compared to the non-LB group, the LB nOH group had low myocardial F-dopamine-derived radioactivity, low UPSIT scores, and high α-syn-TH colocalization indexes (p < 0.0001 each). Combining the three biomarkers completely separated the groups. Cluster analysis identified two distinct groups (p < 0.0001) independently of the clinical diagnosis, with one cluster corresponding exactly to LB nOH.
CONCLUSION
LB forms of nOH feature cardiac noradrenergic deficiency, olfactory dysfunction, and increased α-syn-TH colocalization in skin biopsies. Combining the data for these variables efficiently separates LB from non-LB nOH. Independently of the clinical diagnosis, this biomarker triad identifies a pathophysiologically distinct cluster of nOH patients.
PubMed: 38844644
DOI: 10.1007/s10286-024-01035-2 -
MedRxiv : the Preprint Server For... May 2024Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial...
BACKGROUND
Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ), an α-1 adrenergic receptor antagonist with a known efficacy in treating benign prostatic hypertrophy and hypertension, has shown potential in addressing energy metabolism deficits associated with PD due to its action on phosphoglycerate kinase 1 (PGK1). This study aimed to investigate the safety, tolerability, bioenergetic target engagement, and optimal dose of TZ in neurologically healthy subjects.
METHODS
Eighteen healthy men and women (60 - 85 years old) were stratified into two cohorts based on maximum TZ dosages (5 mg and 10 mg daily). Methods included plasma and cerebrospinal fluid TZ concentration measurements, whole blood ATP levels, Phosphorous magnetic resonance spectroscopy for brain ATP levels, F-FDG PET imaging for cerebral metabolic activity, and plasma metabolomics.
RESULTS
Our results indicated that a 5 mg/day dose of TZ significantly increased whole blood ATP levels and reduced global cerebral F-FDG PET uptake without significant side effects or orthostatic hypotension. These effects were consistent across sexes. Higher doses did not result in additional benefits and showed a potential biphasic dose-response.
CONCLUSIONS
TZ at a dosage of 5 mg/day engages its metabolic targets effectively in both sexes without inducing significant adverse effects and provides a promising therapeutic avenue for mitigating energetic deficiencies. Further investigation via clinical trials to validate TZ's efficacy and safety in neurodegenerative (i.e., PD) contexts is warranted.
PubMed: 38826433
DOI: 10.1101/2024.05.22.24307622 -
Scientific Reports Jun 2024In recent decades, the trend toward early same-day discharge (SDD) after surgery has dramatically increased. Efforts to develop adequate risk stratification tools to... (Meta-Analysis)
Meta-Analysis
In recent decades, the trend toward early same-day discharge (SDD) after surgery has dramatically increased. Efforts to develop adequate risk stratification tools to guide decision-making regarding SDD versus prolonged hospitalization after total hip arthroplasty (THA) remain largely incomplete. The purpose of this report is to identify the most frequent causes and risk factors associated with SDD failure in patients undergoing THA and total knee arthroplasty (TKA). A systematic search following PRISMA guidelines of four bibliographic databases was conducted for comparative studies between patients who were successfully discharged on the same day and those who failed. Outcomes of interests were causes and risk factors associated with same-day discharge failure. Odds ratios (OR) were calculated for dichotomous variables, whereas mean differences (MD) were calculated for continuous variables. Meta-analysis was performed using RevMan software. Random effects were used if there was evidence of heterogeneity. Eight studies with 3492 patients were included. The most common cause of SDD failure was orthostatic hypotension, followed by inadequate physical condition, nausea/vomiting, pain, and urinary retention. Female sex was a risk factor for failure (OR 0.77, 95% CI 0.63-0.93), especially in the THA subgroup. ASA score IV (OR 0.33, 95% CI 0.14-0.76) and III (OR 0.72, 95% CI 0.52-0.99) were risk factors, as were having > 2 allergies and smoking patients. General anesthesia increased failure risk (OR 0.58, 95% CI 0.42-0.80), while spinal anesthesia was protective (OR 1.62, 95% CI 1.17-2.24). The direct anterior and posterior approaches showed no significant differences. In conclusion, orthostatic hypotension was the primary cause of SDD failure. Risk factors identified for SDD failure in orthopedic surgery include female sex, ASA III and IV classifications, a higher number of allergies, smoking patients and the use of general anesthesia. These factors can be addressed to enhance SDD outcomes.
Topics: Humans; Arthroplasty, Replacement, Knee; Arthroplasty, Replacement, Hip; Risk Factors; Patient Discharge; Female; Male; Length of Stay
PubMed: 38824204
DOI: 10.1038/s41598-024-63353-9 -
Revista Espanola de Medicina Nuclear E... May 2024Myocardial uptake on bone scintigraphy has become useful for the detection of transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to assess the prevalence of...
AIM
Myocardial uptake on bone scintigraphy has become useful for the detection of transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to assess the prevalence of myocardial uptake in patients over 18 years of age with no clinical suspicion of cardiac amyloidosis (CA) who had undergone bone scintigraphy.
METHODS AND RESULTS
This was an observational, retrospective, multicenter study across 21 Spanish hospitals (September-November 2019). Of the 9864 scans analyzed (locally and centrally), incidental cardiac uptake was observed in 71 patients (0.72%), a prevalence that increased with age. A previous diagnosis of heart failure was found in 16.9% of patients with positive uptake, with >50% in NYHA II. ATTR-CA was diagnosed in 10 patients, with a mean delay of 10.4 months (95% CI: 5.1-15.7). All were >70 years old, primarily male, and had greater left ventricular hypertrophy than patients without a confirmed diagnosis (p<0.0001). ATTR-CA patients had higher rates of orthostatic hypotension (30.0% vs. 3.8% in non-ATTR-CA; p=0.025).
CONCLUSIONS
This is the first retrospective, national, multicenter study evaluating the prevalence of incidental cardiac uptake in bone scintigraphy performed for non-cardiac reasons, showing a prevalence of 0.72% in this population. Referral of these patients may facilitate early diagnosis of CA with a resulting benefit for patients.
PubMed: 38821407
DOI: 10.1016/j.remnie.2024.500020