Therapies for patients with chronic heart failure caused by left ventricular systolic dysfunction have advanced substantially over recent decades. The cumulative effect of these therapies on ...mortality, mode of death, symptoms, and clinical characteristics has yet to be defined.
This study was a comparison of 2 prospective cohort studies of outpatients with chronic heart failure caused by left ventricular systolic dysfunction performed between 1993 and 1995 (historic cohort: n=281) and 2006 and 2009 (contemporary cohort: n=357). In the historic cohort, 83% were prescribed angiotensin-converting enzyme inhibitors and 8.5% were prescribed β-adrenoceptor antagonists, compared with 89% and 80%, respectively, in the contemporary cohort. Mortality rates over the first year of follow-up declined from 12.5% to 7.8% between eras (P=0.04), and sudden death contributed less to contemporary mortality (33.6% versus 12.7%; P<0.001). New York Heart Association class declined between eras (P<0.001). QTc dispersion across the chest leads declined from 85 ms (SD, 2) to 34 ms (SD, 1) and left ventricular end-diastolic dimensions declined from 65 mm (SD, 0.6) to 59 mm (SD, 0.5) (both P<0.001).
Survival has significantly improved in patients with chronic heart failure caused by left ventricular systolic dysfunction over the past 15 years; furthermore, sudden death makes a much smaller contribution to mortality, and noncardiac mortality is a correspondingly greater contribution. This has been accompanied by an improvement in symptoms and some markers of adverse electric and structural left ventricular remodeling.
AbstractRapid overcorrection of chronic hyponatremia can lead to osmotic demyelination syndrome or central pontine myelinolysis (CPM), a diagnosis often triggered by observing the characteristics of ...neurological abnormalities developed as a result of CPM. However, anyone with chronic hyponatremia and overcorrection of serum sodium is at risk of physiological CPM despite the lack of clinical symptoms. We report an adult patient who presented as post-op delirium, had incidental finding of CPM by magnetic resonance imaging (MRI) of the head after a liver transplant. Despite his non-typical presentation, the patient had the typical risk factors of CPM such as chronic hyponatremia, rapid overcorrection of serum sodium and cirrhosis undergoing a transplant. As hyponatremia and neurological disorder such encephalopathy simultaneously affect patients with cirrhosis, CPM may be more common than once thought in the chronic liver disease population and inappropriate hyponatremia management has important medical consequences that can go unnoticed.
This prospective randomized study examined the acute‐phase response and wound healing, comparing laparoscopic (LA) and open posterior (PA) adrenalectomy in a cushingoid porcine model. Repository ...corticotropin gel was given to 40 pigs for 21 days. Biochemical and tissue parameters of Cushing syndrome were confirmed. The pigs were randomized to undergo LA or PA. In addition to operating time and morbidity, the acute‐phase response was compared by measuring the postoperative white blood cell count, fasting glucose, C‐reactive protein, and nitrogen balance. Wound healing was assessed by (1) scored (1–4) gross appearance at 48 hours and 1 and 2 weeks; (2) histologic examination; and (3) tensile strength. There was no difference in operating time (mean ± SD) (36 ± 9 minutes open vs. 37 ± 7 minutes laparoscopic), perioperative mortality, degree of leukocytosis, fasting glucose, or C‐reactive protein (p > 0.05). Nitrogen balance, wound scores, and tensile strength at 24 hours and 1 week were more favorable in the LA group than in the PA group (p < 0.05). In the cushingoid porcine model, laparoscopic adrenalectomy was less catabolic and was associated with fewer wound complications than the open posterior adrenalectomy. These findings provide support for continued pursuit of laparoscopic methods for adrenalectomy in the clinical setting.
Iron is an irreplaceable component of proteins and enzyme systems required for life. This need for iron is a well-characterized evolutionary mechanism for genetic selection. However, there is limited ...consideration of how iron bioavailability, initially determined by planetary accretion but fluctuating considerably at global scale over geological time frames, has shaped the biosphere. We describe influences of iron on planetary habitability from formation events >4 Gya and initiation of biochemistry from geochemistry through oxygenation of the atmosphere to current host-pathogen dynamics. By determining the iron and transition element distribution within the terrestrial planets, planetary core formation is a constraint on both the crustal composition and the longevity of surface water, hence a planet's habitability. As such, stellar compositions, combined with metallic core-mass fraction, may be an observable characteristic of exoplanets that relates to their ability to support life. On Earth, the stepwise rise of atmospheric oxygen effectively removed gigatons of soluble ferrous iron from habitats, generating evolutionary pressures. Phagocytic, infectious, and symbiotic behaviors, dating from around the Great Oxygenation Event, refocused iron acquisition onto biotic sources, while eukaryotic multicellularity allows iron recycling within an organism. These developments allow life to more efficiently utilize a scarce but vital nutrient. Initiation of terrestrial life benefitted from the biochemical properties of abundant mantle/crustal iron, but the subsequent loss of iron bioavailability may have been an equally important driver of compensatory diversity. This latter concept may have relevance for the predicted future increase in iron deficiency across the food chain caused by elevated atmospheric CO
.
Vertebrate dung is central to the dung beetle life cycle, constituting food for adults and a protective and nutritive refuge for their offspring. Adult dung beetles have soft mandibles and feed ...primarily on nutritionally rich dung particles, while larvae have sclerotized mandibles and consume coarser dung particles with a higher C/N ratio. Here, using the dung beetles Euoniticellus intermedius and E. triangulatus, we show that these morphological adaptations in mandibular structure are also correlated with differences in basic gut structure and gut bacterial communities between dung beetle life stages. Metagenome functional predictions based on 16S rDNA characterization further indicated that larval gut communities are enriched in genes involved in cellulose degradation and nitrogen fixation compared to adult guts. Larval gut communities are more similar to female gut communities than they are to those of males, and bacteria present in maternally provisioned brood balls and maternal ‘gifts’ (secretions deposited in the brood ball along with the egg) are also more similar to larval gut communities than to those of males. Maternal secretions and maternally provisioned brood balls, as well as dung, were important factors shaping the larval gut community. Differences between gut microbiota in the adults and larvae are likely to contribute to differences in nutrient assimilation from ingested dung at different life history stages.
Purpose
Anterior cruciate ligament (ACL) graft failure is a complication that may require revision ACL reconstruction (ACL-R). Non-anatomic placement of the femoral tunnel is thought to be a frequent ...cause of graft failure; however, there is a lack of evidence to support this belief. The purpose of this study was to determine if non-anatomic femoral tunnel placement is associated with increased risk of revision ACL-R.
Methods
After screening all 315 consecutive patients who underwent primary single-bundle ACL-R by a single senior orthopedic surgeon between January 2012 and January 2017, 58 patients were found to have both strict lateral radiographs and a minimum of 24 months follow-up without revision. From a group of 456 consecutive revision ACL-R, patients were screened for strictly lateral radiographs and 59 patients were included in the revision group. Femoral tunnel placement for each patient was determined using a strict lateral radiograph taken after the primary ACL-R using the quadrant method. The center of the femoral tunnel was measured in both the posterior–anterior (PA) and proximal–distal (PD) dimensions and represented as a percentage of the total distance (normal center of anatomic footprint: PA 25% and PD 29%).
Results
In the PA dimension, the revision group had significantly more anterior femoral tunnel placement compared with the primary group (38% ± 11% vs. 28% ± 6%,
p
< 0.01). Among patients who underwent revision; those with non-traumatic chronic failure had statistically significant more anterior femoral tunnel placement than those who experienced traumatic failure (41% ± 13% vs. 35% ± 8%,
p
< 0.03). In the PD dimension, the revision group had significantly more proximal femoral tunnel placement compared with the primary group (30% ± 9% vs 38% ± 9%,
p
< 0.01).
Conclusion
In this retrospective study of 58 patients with successful primary ACL-R compared with 59 patients with failed ACL-R, anterior and proximal (high) femoral tunnels for ACL-R were shown to be independent risk factors for ACL revision surgery. As revision ACL-R is associated with patient- and economic burden, particular attention should be given to achieving an individualized, anatomic primary ACL-R. Surgeons may reduce the risk of revision ACL-R by placing the center of the femoral tunnel within the anatomic ACL footprint.
Level of evidence
Level III.
Next‐generation manufacturing (NGM) has evolved over the past decade to a point where large biopharmaceutical organizations are making large investments in the technology and considering ...implementation in clinical and commercial processes. There are many well‐considered reasons to implement NGM. For the most part, organizations will not fund NGM unless the implementation benefits the funding organization by providing reduced costs, reduced time, or additional needed capabilities. Productivity improvements gained from continuous purification are shown in this work, which used a new system that fully integrates and automates several downstream unit operations of a biopharmaceutical process to provide flexibility and easy implementation of NGM. The equipment and automation needed to support NGM can be complicated and expensive. Biopharmaceutical Process Development considered two options as follows: (1) design its own NGM system or (2) buy a prebuilt system. PAK BioSolutions offers a turn‐key automated and integrated system that can operate up to four continuous purification stages simultaneously, while maintaining a small footprint in the manufacturing plant. The system provides significant cost benefits (~10× lower) compared with the alternative—integration of many different pieces of equipment through a Distributed Control System that would require significant engineering time for design, automation, and integration. Integrated and Continuous Biomanufacturing can lead to significant reductions in facility size, reduced manufacturing costs, and enhanced product quality when compared with the traditional batch mode of operation. The system uses new automation strategies that robustly link unit operations. We present the optimized process fit, sterility and bioburden control strategy, and automation features (such as pH feedback control and in‐line detergent addition), which enabled continuous operation of a 14‐day end‐to‐end monoclonal antibody purification process at the clinical manufacturing scale.
Pregnant women with type 1 diabetes are a high-risk population who are recommended to strive for optimal glucose control, but neonatal outcomes attributed to maternal hyperglycaemia remain ...suboptimal. Our aim was to examine the effectiveness of continuous glucose monitoring (CGM) on maternal glucose control and obstetric and neonatal health outcomes.
In this multicentre, open-label, randomised controlled trial, we recruited women aged 18–40 years with type 1 diabetes for a minimum of 12 months who were receiving intensive insulin therapy. Participants were pregnant (≤13 weeks and 6 days' gestation) or planning pregnancy from 31 hospitals in Canada, England, Scotland, Spain, Italy, Ireland, and the USA. We ran two trials in parallel for pregnant participants and for participants planning pregnancy. In both trials, participants were randomly assigned to either CGM in addition to capillary glucose monitoring or capillary glucose monitoring alone. Randomisation was stratified by insulin delivery (pump or injections) and baseline glycated haemoglobin (HbA1c). The primary outcome was change in HbA1c from randomisation to 34 weeks' gestation in pregnant women and to 24 weeks or conception in women planning pregnancy, and was assessed in all randomised participants with baseline assessments. Secondary outcomes included obstetric and neonatal health outcomes, assessed with all available data without imputation. This trial is registered with ClinicalTrials.gov, number NCT01788527.
Between March 25, 2013, and March 22, 2016, we randomly assigned 325 women (215 pregnant, 110 planning pregnancy) to capillary glucose monitoring with CGM (108 pregnant and 53 planning pregnancy) or without (107 pregnant and 57 planning pregnancy). We found a small difference in HbA1c in pregnant women using CGM (mean difference −0·19%; 95% CI −0·34 to −0·03; p=0·0207). Pregnant CGM users spent more time in target (68% vs 61%; p=0·0034) and less time hyperglycaemic (27% vs 32%; p=0·0279) than did pregnant control participants, with comparable severe hypoglycaemia episodes (18 CGM and 21 control) and time spent hypoglycaemic (3% vs 4%; p=0·10). Neonatal health outcomes were significantly improved, with lower incidence of large for gestational age (odds ratio 0·51, 95% CI 0·28 to 0·90; p=0·0210), fewer neonatal intensive care admissions lasting more than 24 h (0·48; 0·26 to 0·86; p=0·0157), fewer incidences of neonatal hypoglycaemia (0·45; 0·22 to 0·89; p=0·0250), and 1-day shorter length of hospital stay (p=0·0091). We found no apparent benefit of CGM in women planning pregnancy. Adverse events occurred in 51 (48%) of CGM participants and 43 (40%) of control participants in the pregnancy trial, and in 12 (27%) of CGM participants and 21 (37%) of control participants in the planning pregnancy trial. Serious adverse events occurred in 13 (6%) participants in the pregnancy trial (eight 7% CGM, five 5% control) and in three (3%) participants in the planning pregnancy trial (two 4% CGM and one 2% control). The most common adverse events were skin reactions occurring in 49 (48%) of 103 CGM participants and eight (8%) of 104 control participants during pregnancy and in 23 (44%) of 52 CGM participants and five (9%) of 57 control participants in the planning pregnancy trial. The most common serious adverse events were gastrointestinal (nausea and vomiting in four participants during pregnancy and three participants planning pregnancy).
Use of CGM during pregnancy in patients with type 1 diabetes is associated with improved neonatal outcomes, which are likely to be attributed to reduced exposure to maternal hyperglycaemia. CGM should be offered to all pregnant women with type 1 diabetes using intensive insulin therapy. This study is the first to indicate potential for improvements in non-glycaemic health outcomes from CGM use.
Juvenile Diabetes Research Foundation, Canadian Clinical Trials Network, and National Institute for Health Research.
•There is a potential association between BMI and duration of visit for men but not for women.•This analysis failed to identify differences by BMI in patient-centered communication patterns in cancer ...care.•Preliminary data suggest that the care of obese patients in routine cancer care delivery deserves further investigation
To determine the potential relationship between measures of patient-provider communication and patient body mass index (BMI) and gender in cancer care.
We audio-recorded cancer patients’ communication with their clinicians in an academic medical oncology practice from 2012-2014. We coded audio-recordings with the Roter Interaction Analysis System. We then examined whether BMI was associated with patient centeredness, time with doctor, global affect, and patient self-reported communication quality. Univariate associations with BMI were assessed with Chi-square and Kruskal-Wallis tests. A cumulative logit model adjusted for patient and visit characteristics in a multivariable model.
We recorded 327 patient interactions with 37 clinicians. After adjusting for patient sex, and visit characteristics, visit length, patient-centeredness, global affect (patient or clinician) and satisfaction did not differ. However, higher BMI was associated with shorter visit length, and lower Negative Global Affect (p = 0.03 and p = 0.03, respectively) in men only.
In this exploratory analysis, communication characteristics did not vary by patient BMI overall. However, in men, higher BMI was associated with shorter visit length and more negative affect. Those differences did not persist after adjusting for multiple comparisons.
Patient body size may contribute to clinical communication in cancer care, particularly for obese men.
Originally developed for application to ecology courses for undergraduate majors, the Four‐Dimensional Ecology Education (4DEE) Framework offers possibilities for adaptation to courses with ecology ...content for many other audiences. Recognizing the extraordinary range of classroom contexts and constraints, we developed some general, flexible recommendations and approaches to guide instructors in adapting the 4DEE Framework for an array of non‐major audiences and classroom context needs. Our hope is that 4DEE‐aligned courses for non‐majors will provide these students with greater appreciation of ecology and inspire them to use their knowledge to address many critical environmental issues in their personal and professional lives. Many of our recommendations likely apply to natural science, engineering, and math majors as well. We encourage more ecologists to embrace teaching non‐majors courses as a response to the urgent need to improve ecological literacy for everyone.
PDF
