How to optimize the systematic review process using AI tools.

Systematic reviews are a cornerstone for synthesizing the available evidence on a given topic. They simultaneously allow for gaps in the literature to be identified and provide direction for future research. However, due to the ever-increasing volume and complexity of the available literature, traditional methods for conducting systematic reviews are less efficient and more time-consuming. Numerous artificial intelligence (AI) tools are being released with the potential to optimize efficiency in academic writing and assist with various stages of the systematic review process including developing and refining search strategies, screening titles and abstracts for inclusion or exclusion criteria, extracting essential data from studies and summarizing findings. Therefore, in this article we provide an overview of the currently available tools and how they can be incorporated into the systematic review process to improve efficiency and quality of research synthesis. We emphasize that authors must report all AI tools that have been used at each stage to ensure replicability as part of reporting in methods.

Chronic high-dose dimenhydrinate use contributing to early multifactorial cognitive impairment.

Dimenhydrinate is an over-the-counter antihistaminergic medication with anticholinergic properties used to treat nausea or motion sickness worldwide. There is a well-established correlation between the use of anticholinergic medications and dementia, however, it is unclear if a causal role exists. We report a case of minor neurocognitive disorder in a woman in her 40s with several years of high-dose daily dimenhydrinate abuse who subsequently developed significant delusional beliefs. Her clinical presentation was confounded by numerous other factors that could have impacted her cognition, such as a longstanding presumed learning disability, ankylosing spondylitis with adalimumab treatment, extensive cannabis use or potential development of a primary psychotic disorder. Her workup was within normal limits, and she has not responded to first-line antipsychotic medications to date. This case report adds to the growing evidence supporting concerns about potentially irreversible cognitive deficits in chronic misuse of anticholinergic agents, an association previously observed only in the elderly population.

Cultural and regulatory factors influence distribution and trajectory of invasive species in the United States: A wild pig case study.

Since 2012, control of invasive wild pigs (Sus scrofa) in the United States (US) has become a state and national priority due to their propensity to damage agricultural commodities and infrastructure, transmit disease, detrimentally affect ecological processes, and compete with native wildlife for resources. While several life-history characteristics certainly aided their proliferation, the recreational value of wild pigs was likely the stimulus for translocation and subsequent establishment of populations in ≥35 states, causing an annual economic burden of $1.5 billion in the US. Consequently, state-level legislative procedures regarding wild pigs are expanding in scope and priority, but policy among states lacks uniformity. States vary in their treatment of wild pig control based on differing resource appropriations and stakeholder interests. We conducted an evaluation to determine if policy was associated with state-level 1) presence of wild pigs, 2) spatial extent of wild pig population occupancy, and 3) trajectory of wild pig population occupancy. Our results suggest the presence of wild pigs in various states was influenced by hunting preserves and the sale of hunting opportunities. In occupied states, the spatial extent of wild pigs was again associated with the sale of hunting opportunities and a wild pig hunting culture. Finally, the trajectory of state-level wild pig spatial occupancy was positively influenced by the sale of hunting opportunities, and negatively influenced by transportation policies. Based on these findings, we propose state governments standardize transportation policy and fenced hunting regulations across regions of the US in a more prohibitive fashion to diminish range expansion through illegal and negligent introductions via transportation, release, and escapes from game farms. Moreover, in states where wild pigs have yet to establish, we strongly recommend states proactively prohibit transportation through intra- and interstate movement.

Knowledge and Use of Novel Psychoactive Substances in an Italian Sample with Substance Use Disorders.

This study aims to determine prevalence and frequency of use of novel psychoactive substances (NPS) and to identify the factors associated with NPS use in an Italian sample of patients diagnosed with substance use disorder (SUD). Prevalence and correlates of NPS knowledge and use were assessed in 185 patients with SUD in three addiction services (Padova, Belluno, Feltre) in the Veneto region with an ad-hoc designed survey. Two thirds of the samples reported knowing NPS and one third reported using them. NPS were considered by them less dangerous than "regular" substances of abuse (t = 6.06 mean 0.78, p < 0.001). Factors associated with NPS use were youth (OR = 4.81; p < 0.001), studentship (OR = 4.99; p = 0.004), subsequent mental disorders diagnosis (OR = 2.49; p = 0.027), suicide attempt history (OR = 11.67; p < 0.001), home detention (OR = 2.30; p = 0.040), residential care (OR = 5.66; p = 0.002), and polysubstance abuse (t = 8.99 mean 2.65 p < 0.001). NPS use in patients with SUD is highly prevalent, particularly in the youngest age group, and associated with psychiatric comorbidity and worse prognosis. It is crucial to systematically assess NPS use and inform addiction service users with SUD of the toxic and potentially lethal side effects. Mental healthcare professionals working in addiction services should receive education and training. Cohort and longitudinal studies are needed.

Diverting ß-Hydride Elimination of a π-Allyl PdII Carbene Complex for the Assembly of Disubstituted Indolines via a Highly Diastereoselective (4 + 1)-Cycloaddition.

A Pd0-catalyzed formal (4 + 1)-cycloaddition approach to 2,3-disubstituted dihydroindoles is described. The diastereoselective formation of dihydroindoles that is highlighted by a carbene migratory insertion/reductive elimination sequence proceeding via a π-allyl PdII-species compliments existing methods of indoline assembly.

Validating patient prioritization in the 2018 Revised United Network for Organ Sharing Heart Allocation System: A single-center experience.

The 2018 Revised United Network for Organ Sharing Heart Allocation System (HAS) was proposed to reclassify status 1A candidates into groups of decreasing acuity; however, it does not take into account factors such as body mass index (BMI) and blood group which influence waitlist (WL) outcomes. We sought to validate patient prioritization in the new HAS at our center. We retrospectively evaluated patients listed for heart transplantation (n = 214) at Emory University Hospital from 2011 to 2017. Patients were reclassified into the 6-tier HAS. Multistate modeling and competing risk analysis were used to compare outcomes of transplantation and WL death/deterioration between new tiers. Additionally, a stratified sensitivity analysis by BMI and blood group was performed. Compared with tier 4 patients, there was progressively increasing hazard of WL death/deterioration in tier 3 (HR: 2.52, 95% CI: 1.37-4.63, P = .003) and tier 2 (HR: 5.03, 95% CI: 1.99-12.70, P < .001), without a difference in transplantation outcome. When stratified by BMI and blood group, this hierarchical association was not valid in patients with BMI ≥30 kg/m2 and non-O blood groups in our cohort. Therefore, the 2018 HAS accurately prioritizes the sickest patients in our cohort. Factors such as BMI and blood group influence this relationship and iterate that the system can be further refined.

Obstructive sleep apnea, sleep symptoms, and their association with cardiovascular disease.

OBJECTIVES: To determine the frequency of obstructive sleep apnea (OSA), insomnia, restless legs, and other sleep symptoms in patients with cardiovascular disease and the association of these sleep disorders with quantitative cardiovascular measures. METHODS: Study design was a cross-sectional survey and retrospective chart review. A questionnaire containing validated sleep symptoms was distributed to 202 patients with cardiovascular disease at a tertiary referral cardiology clinic. Following a focused review of these patients' medical charts, their questionnaire responses were examined for associations with clinical cardiovascular parameters. RESULTS: Twenty-one percent of patients reported a prior diagnosis of OSA. A total of 115 patients (60%) had at least one additional sleep symptom. Clinically significant insomnia was significantly associated with heart disease (relative risk [RR] = 1.5, confidence interval [CI] = 1.1 to 2.1), prior myocardial infarction or cerebrovascular accident (RR = 2.1, CI = 1.2 to 3.6), and heart failure (RR = 2.2, CI = 1.3 to 3.8). Left ventricular ejection fraction was significantly associated with insomnia by Insomnia Severity Index (ß = -0.52, CI = -0.89 to -0.13). CONCLUSION: The frequency of OSA in patients in this tertiary cardiology clinic was higher than the general population in the United States, with the majority of patients experiencing at least one sleep symptom. Insomnia symptoms were shown to be associated with multiple cardiovascular measures, including left ventricular ejection fraction. These findings imply an interwoven relationship between cardiovascular and sleep symptoms as captured by validated sleep questionnaires. LEVEL OF EVIDENCE: IV Laryngoscope, 130:1595-1602, 2020.

Pregnancy and multiple sclerosis: Risk of unplanned pregnancy and drug exposure in utero.

BACKGROUND: Multiple sclerosis is a central nervous system demyelinating disease that affects women of reproductive potential. It is important to identify the frequency and risk factors of unplanned or disease-modifying therapy-exposed pregnancies to create interventions to reduce these. METHODS: This retrospective, single-center, observational chart review study aims to identify risk factors for unplanned pregnancy to identify a target population for family counseling. RESULTS: In total, 63 live births in 45 patients (20 unplanned and 43 planned) were analyzed. The percentage of unplanned pregnancy was 32%. The proportion of those receiving family planning counseling was lower in the patients with unplanned pregnancies (p < 0.001). The main risk factors for unplanned pregnancy were younger age (p = 0.004), disease-modifying therapy exposure (p < 0.001), and being unmarried (p < 0.001). Overall, 16 pregnancies had disease-modifying therapy exposure and in a subsequent study the risk for disease-modifying therapy exposure was unplanned status (p < 0.001). Birth outcomes were not different between groups. There were more enhancing lesions in the post-partum magnetic resonance imaging of women with planned pregnancy (p < 0.04). CONCLUSION: Prevention of unplanned pregnancy could lead to less disease-modifying therapy exposed pregnancies. This study suggests a targeted intervention of family planning counseling in younger, unmarried multiple sclerosis patients could potentially lead to less unintended in utero disease-modifying therapy exposure.

Left Ventricular Assist Device Infections and the Potential Role for Dalbavancin: A Case Report.

Left ventricular assist device infections (LVADIs) are common but challenging to treat, often requiring prolonged courses of intravenous antibiotics. Dalbavancin could have a role in treating patients with chronic LVADIs given its less frequent dosing requirements. Here, we illustrate a case in which dalbavancin was used as suppressive therapy for an LVADI for greater than 7 months.

Decisional regret in left ventricular assist device patient-caregiver dyads.

BACKGROUND: The objective of this study was to investigate decisional regret among left ventricular assist device (LVAD) patients and their caregivers. METHODS: This study was a single center, cross-sectional survey of patients after LVAD implantation and their caregivers. Subjects were recruited at their outpatient heart failure appointments. Patients and caregivers at least three months from LVAD implantation completed a 5-item, validated decisional regret scale. Summative scores on a 0-100 point scale were determined for patient and caregivers (0 = no regret). Subgroup analysis included gender, LVAD indication (bridge to transplant (BTT) or destination therapy (DT)), time from LVAD implantation, and caregiver relationship. Dyad discordance was defined as a patient-caregiver difference of ≥2 points on any regret scale question. RESULTS: Fifty patients were approached for participation. Thirty-three LVAD patient-caregiver dyads were enrolled in the study (19 male, 14 female patients; 8 male, 25 female caregivers). Patients had a mean age of approximately 50 years. Caregivers had a mean age of approximately 54 years. Patients had a median regret score of 10 (Interquartile range (IQR): 0-30), while caregivers had a median regret score of 20 (IQR: 0-25). Median regret scores of female patients were significantly higher than that of male patients (27.5 vs 0, p = 0.0038). BTT patients had numerically lower regret than DT patients, but this was not statistically significant. Patients who had been implanted for greater than three years had the highest regret scores. Discordance in at least one domain of the regret scale was present in 19 out of 33 (57.6%) dyads. CONCLUSIONS: While decisional regret was reasonably low in this population, comparatively, there was significantly increased decisional regret among female patients and patients further from LVAD implantation. Differences between patients and caregivers were also observed. These findings highlight the need for robust support and continual attention to expectations before and after LVAD implantation.

Mortality in status 2 patients listed for heart transplantation in the United States: Will understanding cause of death help justify implantation of left ventricular assist devices into less sick patients?

OBJECTIVE: It remains unclear whether left ventricular assist device (LVAD) implantation in non-inotrope dependent patients is of clinical benefit. This study sought to evaluate cause of death in patients listed for heart transplant (HT) to determine the relative risks and benefits of implanting LVAD into patients who are less sick than those included in the original clinical trials. METHODS: We examined death as the primary outcome in 23,098 patients listed for HT from 2006 to 2014 using proportional subdistribution hazards modeling. Cause of death was examined as a secondary outcome using χ2 tests. RESULTS: 1859 (8.1%) patients were removed from the wait list for death, including 229 (2.7%) status 1A, 349 (4.6%) status 1B, 246 (13.2%) status 2, and 1035 (26.0%) status 7 patients (P < 0.0001). Status 2 patients who received LVAD while listed had a higher risk of death compared to those who did not (adjusted HR 1.68; 95% CI 1.09-2.59; P = 0.02), while there was no increased risk of death in status 1A (HR 1.02; 95% CI 0.68-1.51; P = 0.9) and status 1B (HR 0.89; 95% CI 0.65-1.23; P = 0.5) who received LVAD. Status 2 patients who received LVAD were more likely to die cerebrovascular causes (0.6% vs. 0.1%, P = 0.009) and organ failure (70.6% vs. 29.4%, P = 0.003). CONCLUSIONS: LVAD implantation in status 2 patients listed for HT is associated with a higher risk of death. More research is needed to determine the impact LVAD implantation will have on mortality in patients with ambulatory, non-inotrope dependent HF.

Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial.

Importance: There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF. Objective: To determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, 2-treatment, crossover trial of 105 patients with HFpEF. Participants were enrolled from July 22, 2016, to September 12, 2017, at 17 US sites, with final date of follow-up of January 2, 2018. Interventions: Inorganic nitrite or placebo administered via micronebulizer device. During each 6-week phase of the crossover study, participants received no study drug for 2 weeks (baseline/washout) followed by study drug (nitrite or placebo) at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks. Main Outcomes and Measures: The primary end point was peak oxygen consumption (mL/kg/min). Secondary end points included daily activity levels assessed by accelerometry, health status as assessed by the Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability. Outcomes were assessed after treatment for 4 weeks. Results: Among 105 patients who were randomized (median age, 68 years; 56% women), 98 (93%) completed the trial. During the nitrite phase, there was no significant difference in mean peak oxygen consumption as compared with the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95% CI, -0.56 to 0.16]; P = .27). There were no significant between-treatment phase differences in daily activity levels (5497 vs 5503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P = .91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P = .39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P = .43), echocardiographic E/e' ratio (16.4 vs 16.6; difference, 0.1 [95% CI, -1.2 to 1.3]; P = .93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, -53 to 75]; P = .74). Worsening heart failure occurred in 3 participants (2.9%) during the nitrite phase and 8 (7.6%) during the placebo phase. Conclusions and Relevance: Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity. Trial Registration: ClinicalTrials.gov Identifier: NCT02742129.

Progression to Stage D Heart Failure Among Outpatients With Stage C Heart Failure and Reduced Ejection Fraction.

OBJECTIVES: This study sought to estimate the rate of progression to Stage D heart failure (HF) among outpatients with Stage C HF and to identify risk factors for progression. BACKGROUND: The pool of patients who may be candidates for advanced HF therapies is growing. METHODS: We estimated 3-year progression to clinically determined Stage D HF and competing mortality among 964 outpatients with Stage C heart failure with reduced ejection fraction (HFrEF), where ejection fraction is ≤40%. RESULTS: The mean age of patients was 62 ± 15 years; 35% were women; 47% were white; 46% were black, and 7% were of other races; median baseline ejection fraction was 28% (25th to 75th percentile: 20% to 35%); and 47% had ischemic heart disease. After 3.0 years (25th to 75th percentile: 1.7 to 3.2 years), 112 patients progressed to Stage D (3-year incidence: 12.2%; 95% confidence interval [CI]: 10.2% to 14.6%; annualized: 4.5%; 95% CI: 3.8% to 5.5%), and 116 patients died before progression (3-year competing mortality: 12.9%; annualized: 4.7%; 95% CI: 3.9% to 5.6%). By 3 years, 25.1% of patients (95% CI: 22.2% to 28.1%) had either progressed to Stage D or died (annualized: 9.2%; 95% CI: 8.1% to 10.5%). Annualized progression rates were higher in black versus white patients (6.3% vs. 2.7%, respectively; p < 0.001), nonischemic versus ischemic patients (6.1% vs. 2.9%, respectively; p < 0.001), and in New York Heart Association functional class III to IV versus I to II patients (7.5% vs. 1.9%, respectively; p < 0.001) but were similar for men and women (4.7% vs. 4.2%, respectively; p = 0.53). Lower ejection fraction and blood pressure, renal and hepatic dysfunction, and chronic lung disease rates were additional predictors of progression. Predictors of competing mortality were different from those of disease progression. CONCLUSIONS: Among patients with Stage C HFrEF receiving care in a referral center, 4.5% progressed to Stage D HF each year, with earlier progression among black and nonischemic patients. These findings have implications for healthcare planning and resource allocation for these patients.

Therapeutic Targets for Multiple Sclerosis: Current Treatment Goals and Future Directions.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and the most common cause of nontraumatic disability in young adults. Most patients have a relapsing-remitting course, and roughly half of them will eventually enter a degenerative progressive phase, marked by gradual accrual of disability over time in the absence of relapses. Early initiation of treatment has delayed the onset of disability progression. Thus, there is increased interest in treating to target in MS, particularly targeting no evidence of disease activity. This review will describe the most common treatment goals in MS: the Rio scores, disease-free survival, and no evidence of disease activity. We will also cover how well current disease-modifying therapies achieve no evidence of disease activity, and discuss future options for improving MS treatment targets.

A Multisensor Algorithm Predicts Heart Failure Events in Patients With Implanted Devices: Results From the MultiSENSE Study.

OBJECTIVES: The aim of this study was to develop and validate a device-based diagnostic algorithm to predict heart failure (HF) events. BACKGROUND: HF involves costly hospitalizations with adverse impact on patient outcomes. The authors hypothesized that an algorithm combining a diverse set of implanted device-based sensors chosen to target HF pathophysiology could detect worsening HF. METHODS: The MultiSENSE (Multisensor Chronic Evaluation in Ambulatory Heart Failure Patients) study enrolled patients with investigational chronic ambulatory data collection via implanted cardiac resynchronization therapy defibrillators. HF events (HFEs), defined as HF admissions or unscheduled visits with intravenous treatment, were independently adjudicated. The development cohort of patients was used to construct a composite index and alert algorithm (HeartLogic) combining heart sounds, respiration, thoracic impedance, heart rate, and activity; the test cohort was sequestered for independent validation. The 2 coprimary endpoints were sensitivity to detect HFE >40% and unexplained alert rate <2 alerts per patient-year. RESULTS: Overall, 900 patients (development cohort, n = 500; test cohort, n = 400) were followed for up to 1 year. Coprimary endpoints were evaluated using 320 patient-years of follow-up data and 50 HFEs in the test cohort (72% men; mean age 66.8 ± 10.3 years; New York Heart Association functional class at enrollment: 69% in class II, 25% in class III; mean left ventricular ejection fraction 30.0 ± 11.4%). Both endpoints were significantly exceeded, with sensitivity of 70% (95% confidence interval [CI]: 55.4% to 82.1%) and an unexplained alert rate of 1.47 per patient-year (95% CI: 1.32 to 1.65). The median lead time before HFE was 34.0 days (interquartile range: 19.0 to 66.3 days). CONCLUSIONS: The HeartLogic multisensor index and alert algorithm provides a sensitive and timely predictor of impending HF decompensation. (Evaluation of Multisensor Data in Heart Failure Patients With Implanted Devices [MultiSENSE]; NCT01128166).

Impact of Insurance Precertification on Discharge of Stroke Patients to Acute Rehabilitation or Skilled Nursing Facility.

BACKGROUND AND PURPOSE: The purpose of this study is to determine if the common insurance practice of requiring precertification before a medically ready stroke patient can be discharged to a skilled nursing facility (SNF) or inpatient rehabilitation facility (IRF) causes a delay in discharge. Eliminating delays in discharge of stroke patients is important given the increasing demands for health-care efficiency after the passage of the Affordable Health Care Act. METHODS: A retrospective chart review of 1007 patients who were admitted to our comprehensive stroke center with the primary diagnosis of stroke over a 12-month period was performed. Out of the patient pool, 289 patients met the inclusion criterion of a primary diagnosis of stroke that required discharge to a SNF or IRF. All 289 patients were medically cleared for discharge to a SNF or IRF by a board-certified vascular neurologist. RESULTS: Of the 289 patients who met the inclusion criteria, 118 required insurance precertification and 171 did not require precertification before being discharged to a SNF or IRF. All 118 patients who required precertification had private health insurance. The patients who required insurance precertification had an average delay of discharge (DOD) of 1.5 days, and those patients who did not require precertification had an average DOD of .8 days (P value <.0001). After removing the outliers, the difference in the length of stay (LOS) between the 2 groups became statistically significant (P value < .04). CONCLUSION: The results of this study demonstrate that insurance precertification leads to delay in discharge, increased LOS, and increased hospital costs for stroke patients.

Rapid-Deployment Versus Conventional Bio-Prosthetic Aortic Valve Replacement.

BACKGROUND: The use of rapid-deployment aortic valve replacement (RD-AVR) has burgeoned in recent years. There are few studies comparing RD-AVR to conventional aortic valve replacement (cAVR) and no studies where both were inserted via full sternotomy. As such, we reviewed our experience and compared the two approaches. METHODS: From 2008 to 2015, 597 patients underwent isolated aortic valve replacement ± coronary artery bypass grafting (CABG) at a single centre. During this period, 41 (7%) patients received RD-AVR and 556 (93%) received cAVR. Of those receiving RD-AVR, surgical access was via full median sternotomy in 40 (98%). Propensity score matching yielded 41 matched pairs. Perioperative outcomes were compared. RESULTS: After propensity score matching, the RD-AVR group had shorter aortic cross clamp (X-clamp) (RD-AVR: 71±33min vs. cAVR: 106±42min, p<0.01) and cardiopulmonary bypass (CPB) times (95±42min vs. 134±47min, p<0.01). There was no difference in 30-day mortality (RD-AVR: 2% vs. cAVR: 2%, p>0.99). RD-AVR patients required shorter mean ventilation (17±25 vs. 63±131hrs, p<0.01) and intensive care unit (ICU) stay (51±45 vs. 108±157hrs, p=0.03) times. RD-AVR also had reduced rates of new postoperative atrial arrhythmias (8% vs. 20%, p=0.02). Total length of postoperative hospital stay was similar. Haemodynamic performance for the RD-AVR was within acceptable limits. CONCLUSIONS: The use of RD-AVR results in shorter X-clamp and CPB times and is associated with reductions in perioperative morbidity. RD-AVR is becoming a valuable component of the surgeon's armamentarium in selected patients. Long-term follow-up will reveal the full potential of these devices.