Delirium in older adults is associated with development of new dementia: a systematic review and meta-analysis.

OBJECTIVES: Observational studies have examined the association between delirium and development of new dementia. However, no recent review has collectively assessed the available evidence quantitatively and qualitatively. We systematically reviewed and critically evaluated the literature regarding the association between delirium and dementia, and calculated the odds of developing new dementia after having delirium. METHODS: This systematic review and meta-analysis was conducted according to Preferred reporting items for systematic reviews and meta-analyses guidelines. MEDLINE, EMBASE and PsycINFO, were searched for English-language articles that compared the incidence of new dementia in older adult (≥65) inpatients with delirium, to inpatients without delirium. A random effects model was used for meta-analysis, and overall effect size was calculated using reported raw data of event counts. The Newcastle-Ottawa Quality Assessment scale assessed risk of bias. RESULTS: Six observational studies met eligibility criteria, with follow-up times ranging from six months to five years. Four looked at hip fracture surgical patients; one was on cardiac surgery patients and one examined geriatric medical patients. All studies excluded patients with pre-existing dementia. Pooled meta-analysis revealed that older adult inpatients who developed delirium had almost twelve times the odds of subsequently developing new dementia compared to non-delirious patients (OR = 11.9 [95% CI: 7.29-19.6]; p < 0.001). CONCLUSIONS: Older adult inpatients who develop delirium are at significant risk of subsequently developing dementia. This emphasises the importance of delirium prevention and cognitive monitoring post-delirium. The included studies mainly examined post-surgical patients-further research on medical and intensive care unit cohorts is warranted. Future studies should assess whether delirium duration, severity and subtype influence the risk of developing dementia.

Advanced Structural Health Monitoring Method by Integrated Isogeometric Analysis and Distributed Fiber Optic Sensing.

Attempts in digital management of structures are among the most popular topics in the trend of Information of Things (IoT). However, the implementation lags behind. This work recognized that Computer Aided Design (CAD) comprises the core of modern engineering; thus, most digital information can be available if CAD is used not only in design but also for life cycle structural health monitoring (SHM). Based on this concept, the newly designed method utilizes the isogeometric analysis (IGA) tool to include the Distributed Fiber Optic Sensing (DFOS) information by proposing a fiber mesh model. The IGA model can be obtained directly from CAD, and the boundary conditions can be provided directly or indirectly from DFOS in real time and remotely. Hence a practical method of SHM is able to achieve highly efficient and accurate numerical model creation, which can even accommodate non-linear constitutive property of materials. The proposed method was applied to a pipe deformation model as an example. The inverse analysis method is also shown to determine the contact force for loading on the pipe, which shows the potential for many engineering applications.

Pharmacokinetics and Efficacy of Ceftazidime-Avibactam in the Treatment of Experimental Pneumonia Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae in Persistently Neutropenic Rabbits.

Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is an emerging global public health threat that causes life-threatening pneumonia and bacteremia. Ceftazidime-avibactam (CZA) represents a promising advance for the treatment of serious infections caused by KPC-Kp We investigated the pharmacokinetics and efficacy of ceftazidime-avibactam in the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits. For single-dose and multidose (administration every 8 h) pharmacokinetics, rabbits received ceftazidime-avibactam intravenous infusions at 60/15, 90/22.5, and 120/30 mg/kg of body weight. Ceftazidime mean area under the concentration-time curves (AUCs) ranged from 287 to 608 µg·h/ml for a single dose and from 300 to 781 µg·h/ml for multiple doses. Avibactam AUCs ranged from 21 to 48 µg·h/ml for a single dose and from 26 to 48 µg·h/ml for multiple doses. KPC-Kp pneumonia was established by direct endotracheal inoculation. Treatments consisted of ceftazidime-avibactam at 120/30 mg/kg every 6 h, a polymyxin B (PMB) loading dose of 2.5 mg/kg followed by 1.5 mg/kg every 12 h q12h, or no treatment (untreated controls [UC]). There were significant reductions in the residual bacterial burden, lung weights, and pulmonary hemorrhage scores in CZA- and PMB-treated rabbits for a 7-day or a 14-day (P ≤ 0.01) course in comparison with those in the UC. These results corresponded to significant decreases in the bacterial burden in bronchoalveolar lavage fluid after a 7-day or a 14-day treatment (P ≤ 0.01). The outcomes demonstrated an improved response at 14 days versus that at 7 days. There was significantly prolonged survival in rabbits treated with CZA for 14 days in comparison with that in the PMB-treated or UC rabbits (P ≤ 0.05). This study demonstrates that ceftazidime-avibactam displays linear dose-proportional exposures simulating those seen from human plasma pharmacokinetic profiles, is active for the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits, and provides an experimental foundation for the treatment of severely immunocompromised patients with this life-threatening infection.

A call to action for delirium research: Meta-analysis and regression of delirium associated mortality.

BACKGROUND: Delirium is an extremely common hospital complication. No study to date has assessed whether a priori defined covariates; type of hospital setting and year of study publication, influence the relationship between delirium and mortality. This is also the first study to examine the longitudinal trend of delirium-associated mortality over recent decades, to analyse the trajectory of our efforts in combating this disease. METHODS: MEDLINE, EMBASE and PsycINFO, were searched from January 1981 to May 2018 for English-language primary articles. Rigorous title and abstract screen and full-text screen were conducted independently by two reviewers. This paper adhered to MOOSE guidelines. Data was extracted independently by one reviewer using standardised data-collection sheets, with a separate reviewer verifying for accuracy. The quality of included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Unadjusted effect sizes and event counts were analysed with a random effects model in primary meta-analysis and meta-regression, whereas a mixed effect model was used in secondary sub-group analysis. Mortality data at longest follow-up and cumulative mortality (hospital mortality combined with mortality at longest follow-up) data were analysed. RESULTS: As part of a larger project, 446 of 6790 articles were retrieved, including 71 studies that measured mortality. Our results demonstrate that elderly inpatients with delirium had significantly greater odds of mortality (OR 3.18 [95%CI: 2.73, 3.70]) compared to non-delirious controls. Patients with delirium in the ICU had the highest odds for mortality (OR: 7.09 [95%CI: 3.60, 14.0]); double the risk compared to the average. Curiously, despite advancements in delirium research, delirium associated in-hospital odds of mortality has not changed in 30 years. CONCLUSION: This is the largest meta-analysis to confirm the association between delirium and mortality, in older (age ≥ 65) hospital inpatients. The current meta-analysis highlights the significant odds of mortality after an episode of delirium, and these odds are much higher for ICU patients. However, in contrast to other medical conditions that have seen a decrease in associated mortality over the past few decades, delirium associated mortality remains unchanged. These findings underscore the urgent need for better delirium treatments. PROSPERO Registration Number: CRD42018098627, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=98627.

Epicardial bridge via the coronary sinus musculatures revealed by ultra-high-definition mapping.

Mapping and ablation of perimitral flutter, a macro-reentrant tachycardia, can be sometimes challenging. We describe a case of perimitral atrial flutter following the pulmonary vein isolation in which mitral isthmus ablation failed to terminate the arrhythmia due to epicardial-endocardial breakthrough via the muscle fibers of coronary sinus. Ultra-high-definition mapping system was utilized to locate the epicardial bridge, and spot ablation of the lesion subsequently terminated the arrhythmia.

Ceftolozane-Tazobactam in the Treatment of Experimental Pseudomonas aeruginosa Pneumonia in Persistently Neutropenic Rabbits: Impact on Strains with Genetically Defined Mechanisms of Resistance.

Ceftolozane-tazobactam (C/T) is a novel cephalosporin with in vitro activity against Pseudomonas aeruginosa that is resistant to extended-spectrum penicillins and antipseudomonal cephalosporins. In order to assess the antimicrobial effect of C/T in treatment of Pseudomonas pneumonia, we investigated the pharmacokinetics and efficacy of C/T in persistently neutropenic rabbits. Pseudomonas pneumonia was established by direct endotracheal inoculation. Treatment groups consisted of C/T, ceftazidime (CAZ), piperacillin-tazobactam (TZP), and untreated controls (UC). Rabbits received a dosage of C/T of 80 mg/kg every 4 h (q4h) intravenously (i.v.) (53 mg/kg ceftolozane/26 mg/kg tazobactam) to match the free drug time above the MIC as well as a comparable plasma area under the concentration-time curve (AUC) (humanized doses of ceftolozane-tazobactam of 3 g [2 g/1 g]) q8h, due to the more rapid elimination of ceftolozane in rabbits (0.75 h) than in humans (2.5 h). Four molecularly characterized clinical P. aeruginosa isolates from patients with pneumonia were studied, including one isolate from each classification group: pan-susceptible (PS), outer membrane porin D (OPRD) porin loss (OPRDPL), efflux pump expression (EPE), and AmpC hyperexpression (ACHE). Treatment was continued for 12 days. Treatment with ceftolozane-tazobactam resulted in a ≥105 reduction in residual pulmonary and bronchoalveolar lavage (BAL) fluid bacterial burdens caused by all 4 strains (P ≤ 0.01). This antibacterial activity coincided with reduction of lung weight (an organism-mediated pulmonary injury marker) (P < 0.05). CAZ was less active in ACHE-infected rabbits, and TZP had less activity against EPE, ACHE, and OPRDPL strains. Survival was prolonged in the C/T and CAZ treatment groups in comparison to the TZP and UC groups (P < 0.001). Ceftolozane-tazobactam is highly active in treatment of experimental P. aeruginosa pneumonia in persistently neutropenic rabbits, including infections caused by strains with the most common resistance mechanisms.

The role of prophylaxis topical antibiotics in cardiac device implantation.

BACKGROUND: Combined systemic and topical antibiotic prophylaxes are used in cardiac electronic implantable device (CEID) procedures, but very few studies have assessed prophylactic use of topical antibiotics after CEID implantation. OBJECTIVE: To evaluate the efficacy of topical antibiotic prophylaxis in the prevention of surgical site infection after CEID implantation procedures. METHODS: This was a prospective randomized, placebo-controlled, single-center, single-operator study. All patients (n = 1,008) received standard systemic antibiotic prophylaxis. Patients were randomized into four groups and received various topical prophylaxes after procedure. All patients were followed for at least 12 months. Surgical site inflammation and infection were graded based on degree of inflammation, discharge, wound culture, and blood culture. RESULT: Fifty-eight patients developed surgical site inflammation and infection. Fourteen patients had culture-positive wound infections. Among them, 13 patients had superficial wound infections with Staphylococcus species. Only one had pocket infection with Pseudomonas bacteremia. The surgical site infection rate was higher in those with longer procedural time, associated with 2.3 times more likelihood of infection (P = 0.01). Patients with an associated malignancy were associated with 3.6 times more likelihood of infection (P < 0.01). CONCLUSIONS: Careful skin preparation prior to incision is important, whereas the use of topical antibiotics after closure has not shown significant benefit. Patients with malignancy and longer procedural times are more likely to develop infection. There is a trend for less infection with cephalic approach. Systemic antibiotics with staphylococcal coverage are needed as most of the wound culture positive infections are caused by Staphylococcus species.

Recurrent acute coronary events in a young adult.

Acute myocardial infarction (MI) in young adults is rare. Clinicopathological conditions such as nephrotic syndrome, antiphospholipid syndrome, spontaneous coronary artery spasms or embolism can be attributed to such events. In this case report, we present a 30-year-old male who had his first MI at the age of 20 years. He received percutaneous intervention as initial treatment. Despite aggressive risk factor management, he continued to have acute coronary events and was later diagnosed with antiphospholipid syndrome (APS). At the same time, he was diagnosed with severe chronic thromboembolic pulmonary hypertension and severe tricuspid regurgitation. He underwent pulmonary endartererectomy, tricuspid annuloplasty and radial artery bypass graft to the first obtuse marginal artery. Warfarin therapy was initiated upon the diagnosis of APS. Despite being therapeutic on warfarin and aggressive risk factor management, he had yet another MI. Coronary angiogram at this time showed fresh occlusion of the right coronary artery at the mid-segment, and the patient received two overlapping stents that achieved a good effect. This case emphasizes the importance of awareness, early recognition and aggressive management of patients with APS presenting chest pain or acute coronary events. Despite appropriate treatment, such as risk factor management and percutaneous interventions, recurrence of an acute coronary event is high. The presentation of younger patients with recurrent coronary events but no significant risk factors of atherosclerosis should evoke the suspicion of APS-related coronary artery disease, and all risk factors should be aggressively managed.

The Impact of Electromagnetic Interference from Charging All-electric Vehicles on Implantable Cardioverter-defibrillator Performance.

Electric vehicles (EVs) are growing in popularity and in general use. The effect of electromagnetic interference (EMI) caused by supercharging all-electric vehicles on implantable cardioverter-defibrillator (ICD) function has not been studied. The objective of this study was to determine the extent of the effect of EMI from charging Tesla all-electric vehicles (Tesla, Inc., Austin, TX, USA) on cardiac implantable electronic device function. A proof-of-concept study was performed to explore the potential effect of EMI from Tesla vehicles while charging the battery using a 220-V wall charger and a 480-V Supercharger. Tesla Model S and Model X vehicles were used for this study. We enrolled 34 patients with stable ICD function for the initial phase using the standard wall charger, followed by an additional 35 patients for the second phase using the Supercharger. Tracings were obtained at nominal and highest sensitivity settings while patients sat in the driver's seat, passenger seat, back seats, and facing the charging port. In each position, the device and the patient were monitored in real time by a certified technician for any inappropriate sensing and/or delivery of therapies. A medical magnet was also available on site. Emergency medical services and physician supervision were available at all times, and patients were contacted the following day to ensure their well-being. No device interactions were identified at both the nominal and highest sensitivity settings of each ICD during exposure to vehicle charging using a Tesla 220-V wall charger and a 480-V Supercharger at any of the five positions in and around each vehicle. Interaction was defined as oversensing, undersensing, mode switch, or upper rate tracking behavior. There was also no damage to any ICD, and no inappropriate shocks were administered to any patient. In conclusion, transvenous ICD function is not interrupted by EMI transmitted while charging Tesla vehicles using either the 220-V wall charger or the 480-V Supercharger.

Bird diversity along an urban to rural gradient in large tropical cities peaks in mid-level urbanization.

The gradient from natural to urban areas strongly associates with the structure of avian communities over that gradient. Most research on urban birds is from temperate areas and knowledge from tropical Southeast Asia is lacking. We examined bird species diversity, relative abundance, and species composition along an urban to rural gradient in three Myanmar cities, and assessed potential environmental factors responsible for the changes. We counted birds within 40 point-count sites with 50-m fixed-radius in three large cities of Myanmar, namely Mandalay, Mawlamyine, and Myeik. We distinguished four urban habitat types (Downtown-urban, University Campus-suburban, Paddy Field-agriculture, Hill-forest). We classified all species into migrant or resident and into major feeding groups and related with several environmental parameters such as 'impervious surface'. We counted 5,423 individuals of 103 species with roughly equal species diversity between the three cities. Rock Pigeon (Columba livia) was the most frequent species. The species composition differed significantly between the four major habitat types. Omnivores were more abundant in the city center than all other functional groups. Interestingly, insectivores were also predominant in the city center. In addition, more generalist' species occurred towards the city center compared to the periphery, indicating that the periphery has increased relevance for specialized birds. We found some marked differences in species composition between the three cities of Mandalay, Mawlamyine, and Myeik. Additionally to species composition, species diversity and relative abundance differed significantly between each of the four major habitat types in all three cities.

Diagnostic Challenges of a Mass in the Left Atrium.

A 61-year-old female former smoker with history of bronchial-associated lymphoid tissue lymphoma presented with increasing dyspnea, cough with white phlegm and significant weight loss. Chest X-ray showed complete opacification of the left hemithorax. A computed tomography (CT) pulmonary angiogram ruled out pulmonary embolism but revealed mass within the left atrium. A transthoracic echocardiography showed an echogenic mass in the left atrium. A cardiac MRI confirmed a bulky left lung mass suggestive of carcinoma invading the left atrium via the left pulmonary veins. CT-guided biopsy of left lung mass was suggestive of non-small cell lung carcinoma (NSCLC, adenocarcinoma). We would like to discuss the challenges and the importance of making the correct diagnosis of intracardiac mass.

Who Watches the "Watchman" and How Often?

Atrial fibrillation (AF) is a common cardiac arrhythmia that is encountered during the hospitalization. Sometimes, many patients cannot be anticoagulated to prevent AF-related cardiovascular accidents because of the risk of bleeding. In these cases, we recommend putting left atrial appendage (LAA) to prevent thrombus formation in the left atrium due to AF. There is no clear time frame of how long we need to follow up with echocardiogram to monitor device-related blood clot formation and continue anticoagulation therapy if there is recurrent thrombus formation after LAA placement. We would like to present a case with AF in which the patient had epistaxis, which required to hold anticoagulation and arterial embolization. The patient agreed to the placement of the Watchman device and subsequently it was complicated by device-related thrombosis (DRT). The patient required prolonged anticoagulation treatment and follow-up echocardiogram to prevent DRT in the future.

Hkakabo Razi landscape as one of the last exemplar of large contiguous forests.

Deforestation and forest degradation around the world endanger the functioning of ecosystems, climate stability, and conservation of biodiversity. We assessed the spatial and temporal dynamics of forest cover in Myanmar's Hkakabo Razi Landscape (HRL) to determine its integrity based on forest change and fragmentation patterns from 1989 to 2016. Over 80% of the HRL was covered by natural areas, from which forest was the most prevalent (around 60%). Between 1989 and 2016, forest cover declined at an annual rate of 0.225%. Forest degradation occurred mainly around the larger plains of Putao and Naung Mung, areas with relatively high human activity. Although the rate of forest interior loss was approximately 2 to 3 times larger than the rate of total forest loss, forest interior was prevalent with little fragmentation. Physical and environmental variables were the main predictors of either remaining in the current land-cover class or transitioning to another class, although remaining in the current land cover was more likely than land conversion. The forests of the HRL have experienced low human impact and still constitute large tracts of contiguous forest interior. To ensure the protection of these large tracts of forest, sustainable forest policies and management should be implemented.

Direct Current Ablation of Deep Substrate Arrhythmia.

Direct-current ablation has been reinvestigated in animal models with considerably good outcomes and safety margins. Its modified version using biphasic energy lowers the current density further, minimizing its complications. We report a first-in-human ablation of ventricular tachycardia using biphasic direct current with short-term success and no procedural complications. (Level of Difficulty: Intermediate.).

Utility of Intracardiac Echocardiography to Diagnose Infective Endocarditis.

Infective endocarditis (IE) can lead to significant morbidity and mortality without appropriate treatment. Modified Duke Criteria are accepted by many professional societies to establish the diagnosis of IE, and cardiac imaging is one of the major diagnostic criteria. Transesophageal echocardiography is an algorithmic escalation to diagnose IE when transthoracic echo does not appreciate a positive finding. In patients with contraindications to transesophageal echocardiography, cardiac magnetic resonance imaging, cardiac computed tomography (CT), cardiac CT angiography, and fluorodeoxyglucose positron emission tomography with CT or CT angiography may be alternative diagnostic tools. However, these imaging modalities have their own limitations such as local unavailability, the presence of non-magnetic resonance imaging compatible implants, or impaired renal function. Intracardiac echocardiography could be a considerable alternative under those circumstances.

Inappropriate Defibrillator Shocks due to Mechanical Inference from an Investigational Device.

Cardiac contractility modulation (CCM) is an investigational device-based therapy to enhance ventricular contractility in systolic heart failure patients who are not candidates for cardiac resynchronization therapy (CRT) owing to the absence of wide QRS complexes or who have failed to respond on CRT. The principal mechanism is based on the stimulation of cardiac muscles by nonexcitatory electrical signals to augment the influx of calcium ions into the cardiomyocytes. The majority of patients receiving CCM therapy have concurrent implantable cardioverter defibrillators, and the manufacturer declares both devices can be used in parallel without any interactions. Nevertheless, proper lead positioning of both devices are crucial, and it is mandatory to check device-device interactions during each and every cardiac electronic implantable device-related procedure to prevent adverse outcomes.

Air Entrapment Causing Inappropriate Shock From a Subcutaneous Implantable Cardioverter Defibrillator.

Subcutaneous implantable cardioverter defibrillator (S-ICD) is an accepted alternative to conventional transvenous devices. Their efficacy in arrhythmia management is comparable to ICDs. However, those devices also have limitations such as lack of anti-tachycardia pacing capability or higher occurrence of device oversensing associated with inappropriate shocks. Air entrapment inside one or more of subcutaneous pockets has been reported as one of uncommon causes of device malfunction. It is important to recognize the wandering or drifting baseline signals during device interrogation for timely diagnosis and appropriate treatment.

A Case of Complete Heart Block With Diagnostic Challenge and Therapeutic Dilemma.

Permanent pacemaker implantation is a class I indication for all symptomatic patients with complete heart block either congenital or acquired. However, certain portions of patients with congenital complete heart block are asymptomatic. Those patients are often very young, and implanting a permanent pacemaker is not always an easy decision. A therapeutic dilemma arises when a select patient population does not meet certain criteria to gain the maximum benefits out of prophylactic pacemaker therapy. Most asymptomatic patients with congenital complete heart block will eventually become symptomatic and require pacemakers at some point in their life but the definitive answer for the ideal time to initiate pacemaker therapy in such population has not been established. We present a case of asymptomatic congenital complete heart block with junctional escape rhythm, which is capable of incrementing the heart rate with physical activity to result in a challenge in diagnosis as well as the treatment strategy.

Therapeutic Dilemma of Natural Watchman: Congenital Absence of the Left Atrial Appendage.

Congenital absence of the left atrial appendage is a rare congenital cardiac anomaly which is usually an incidental finding. We present a rare case of congenital absence of the left atrial appendage in a 77-year-old female patient with atrial fibrillation, and we will discuss the role of anticoagulation in the patient with congenital absence of the left atrial appendage based on the scientific data and theoretic background.