Consequences of Detecting and Pursuing Incidental Findings on Computed Tomographic Colonography Screening in Average-risk Populations

Objective: To weigh the benefits and harms of detecting and pursuing incidental findings on computed tomographic colonography screening in average-risk populations. Data Sources: I searched MEDLINE, EMBASE, ScienceDirect, and the Cochrane Collaboration library from 1996 to present, with all searches limited to English language studies. Study Selection: I developed inclusion and exclusion criteria to examine an average-risk population. Data Extraction: I performed a single data extraction from included studies of fair to good quality for the preparation of evidence tables. I rated the quality of the selected studies using criteria modified from those recommended by the USPSTF for study appraisal. Data Synthesis: Key Question #1: What is the prevalence of all incidental findings detected on CTC? At least one extracolonic finding was detected in 62% of screened patients. 5.9% of patients received additional investigations. One study examined the effects of IV contrast-enhancement. This study reported a lower frequency of patients receiving additional investigation than any of the other studies. Key Question #2: What is the prevalence of specific types of incidental findings? Two studies reported the specific types of findings that were ultimately diagnosed. The most common diagnosed pathologies reported in these studies were nonmalignant tumors (1.5% of screened populations), malignant tumors (0.5% of screened populations) and aortoiliac aneurysms (0.3% of screened populations). Key Question #3: What are the beneficial outcomes of detecting and investigating incidental findings? Three studies reported a total of 114 patients (at least 2.3% of all patients) who received clinical diagnoses. It is uncertain how many of these received treatment, but at least 0.9% of all patients received treatment. The true benefit of pursuing incidental findings is unlikely to include all of the diagnosed and treated pathologies. Key Question #4: What are the harms of detecting and investigating incidental findings? One study reported the number of patients who received additional workup with no reported diagnoses. Underestimated extrapolated values were obtained for two studies. Approximately 3.1% of the patients from these three studies received additional workup with no reported important clinical diagnoses; this value may overestimate the true value. Three studies reported data on invasive procedures that resulted in benign findings. At least 0.5% of patients in these three studies received an invasive procedure that resulted in the diagnosis of a benign finding. All of the patients who receive further investigations with no diagnoses or treatment experience at least some degree of harm. Key Question #5: What are the costs and cost-effectiveness of detection and further investigating incidental findings? The cost of pursuing incidental findings likely falls between $98.56 and$248. Cost-effectiveness analysis cannot be assessed without a more comprehensive evaluation of the benefits and harms. Conclusion: Incidental findings are found in over half of asymptomatic patients who are screened by CTC. The number of patients who receive additional investigations is much fewer. A small percentage of patients receive clinical diagnoses and treatment. Clinical benefit likely results from some, but not all, of these patients receiving diagnoses and treatment. Likewise, a small percentage of screened subjects received additional workup with no reported diagnoses. All of these received at least some degree of harm. The degree of benefit and harm resulting from each diagnoses, treatment, or additional workup remains unclear. This further complicates the task of weighing the benefits versus the harms. Available data is insufficient to appropriately weigh the overall benefits versus the overall harms.Master of Public Healt

CDC Grand Rounds: National Amyotrophic Lateral Sclerosis (ALS) Registry Impact, Challenges, and Future Directions

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a rapidly progressive fatal neurologic disease. Currently, there is no cure for ALS and the available treatments only extend life by an average of a few months. The majority of ALS patients die within 2–5 years of diagnosis, though survival time varies depending on disease progression (1,2). For approximately 10% of patients, ALS is familial, meaning it and has a genetic component; the remaining 90% have sporadic ALS, where etiology is unknown, but might be linked to environmental factors such as chemical exposures (e.g., heavy metals, pesticides) and occupational history (3). Like many other noncommunicable conditions, ALS is a nonnotifiable disease in the United States; therefore, the federal government lacks reliable incidence and prevalence estimates for the United States. During October 2008, Congress passed the ALS Registry Act (4), directing CDC and its sister agency, the Agency for Toxic Substances and Disease Registry, to create a population-based ALS registry for the United States. The main objectives of the National ALS Registry, which was launched in October 2010, are to describe the national incidence and prevalence of ALS; describe the demographics of persons living with ALS; and examine risk factors for the disease (4,5). During January 2017, the Registry launched the National ALS Biorepository, which aims to promote research in areas including biomarkers, genetics, and environmental exposures to heavy metals or organophosphates (6,7)

The influence of delayed light curing on the degree of conversion and polymerization contraction stress in dual-cured resin luting agents

The aim of the study was to assess the effect of delayed photo-initiation on the polymerization contraction stress (PCS) and degree of conversion (DC) of a dual-cure resin-luting agent. Thirty-five disk (6 mm × 1 mm) samples (n = 10 each group) of dual cure resin luting agent for PCS assessment were fabricated and polymerized using two illuminated quartz rods. Based on the delay in photo-initiation, 30 disks were divided among six groups [group A-0 min (min) delay, group B-2 min, group C-4 min, group D-6 min, group E-8 min and group F-10 min]. A non-photoinitiated group (group G – chemical cure – n = 5) was included as control. The PCS for all specimens was assessed using a Tensometer. For DC evaluation thirty-five specimens were divided into seven groups with delays in photo-initiation (group H-0 min, group I-2 min, group J-4 min, group K-6 min, group L-8 min and group M-10 min, group N-chemical cure). DC was assessed using attenuated total reflectance spectroscopic technique. Statistical comparison among groups was performed using analysis of variance (α = 0.05). The maximum and minimum PCS and DC values with delayed photo-initiation was observed in group-C (3.34 MPa) & group-F (2.44 MPa); and group-M (0.78 MPa) and group-H (0.55 MPa) respectively. Chemically cured samples showed the least PCS (group-G, 1.94) and DC (group-N, 0.53) values in their respective categories. PCS significantly decreased with delayed photo-initiation. A significant increase in DC was noticed when photo-initiation was delayed in the dual cure resin luting agent

An Initial Strategy of Intensive Medical Therapy Is Comparable to That of Coronary Revascularization for Suppression of Scintigraphic Ischemia in High-Risk But Stable Survivors of Acute Myocardial Infarction

ObjectivesThe purpose of this study was to determine the relative benefit of intensive medical therapy compared with coronary revascularization for suppressing scintigraphic ischemia.BackgroundAlthough medical therapies can reduce myocardial ischemia and improve patient survival after acute myocardial infarction, the relative benefit of medical therapy versus coronary revascularization for reducing ischemia is unknown.MethodsA prospective randomized trial in 205 stable survivors of acute myocardial infarction was made to define the relative efficacy of an intensive medical therapy strategy versus coronary revascularization for suppressing scintigraphic ischemia as assessed by serial gated adenosine Tc-99m sestamibi myocardial perfusion tomography. All patients at baseline had large total (≥20%) and ischemic (≥10%) adenosine-induced left ventricular perfusion defects and an ejection fraction ≥35%. Imaging was performed during 1 to 10 days of hospital admission and repeated in an identical fashion after optimization of therapy. Patients randomized to either strategy had similar baseline demographic and scintigraphic characteristics.ResultsBoth intensive medical therapy and coronary revascularization induced significant but comparable reductions in total (−16.2 ± 10% vs. −17.8 ± 12%; p = NS) and ischemic (−15 ± 9% vs. −16.2 ± 9%; p = NS) perfusion defect sizes. Likewise, a similar percentage of patients randomized to medical therapy versus coronary revascularization had suppression of adenosine-induced ischemia (80% vs. 81%; p = NS).ConclusionsSequential adenosine sestamibi myocardial perfusion tomography can effectively monitor changes in scintigraphic ischemia after anti-ischemic medical or coronary revascularization therapy. A strategy of intensive medical therapy is comparable to coronary revascularization for suppressing ischemia in stable patients after acute infarction who have preserved LV function

Evidence for ligand- and solvent-induced disproportionation of uranium(IV)

From Springer Nature via Jisc Publications RouterHistory: received 2020-05-14, accepted 2021-07-21, registration 2021-07-28, pub-electronic 2021-08-10, online 2021-08-10, collection 2021-12Publication status: PublishedFunder: RCUK | Engineering and Physical Sciences Research Council (EPSRC); doi: https://doi.org/10.13039/501100000266; Grant(s): EP/K024000/1, EP/M027015/1, EP/P001386/1, EP/S033181/1Funder: Leverhulme Trust; doi: https://doi.org/10.13039/501100000275; Grant(s): RF-2018-545\4Funder: Royal Society; doi: https://doi.org/10.13039/501100000288; Grant(s): UF110005Abstract: Disproportionation, where a chemical element converts its oxidation state to two different ones, one higher and one lower, underpins the fundamental chemistry of metal ions. The overwhelming majority of uranium disproportionations involve uranium(III) and (V), with a singular example of uranium(IV) to uranium(V/III) disproportionation known, involving a nitride to imido/triflate transformation. Here, we report a conceptually opposite disproportionation of uranium(IV)-imido complexes to uranium(V)-nitride/uranium(III)-amide mixtures. This is facilitated by benzene, but not toluene, since benzene engages in a redox reaction with the uranium(III)-amide product to give uranium(IV)-amide and reduced arene. These disproportionations occur with potassium, rubidium, and cesium counter cations, but not lithium or sodium, reflecting the stability of the corresponding alkali metal-arene by-products. This reveals an exceptional level of ligand- and solvent-control over a key thermodynamic property of uranium, and is complementary to isolobal uranium(V)-oxo disproportionations, suggesting a potentially wider prevalence possibly with broad implications for the chemistry of uranium

Frequency of medically attended adverse events following tetanus and diphtheria toxoid vaccine in adolescents and young adults: a Vaccine Safety Datalink study

<p>Abstract</p> <p>Background</p> <p>Local reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td) vaccine and the risk of local reactions may increase with number of prior Td vaccinations.</p> <p>Methods</p> <p>To estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004.</p> <p>Results</p> <p>Overall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations) was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV) in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2). Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics.</p> <p>Conclusion</p> <p>Medically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.</p

Transcriptional Control of Photosynthesis Genes: The Evolutionarily Conserved Regulatory Mechanism in Plastid Genome Function

Chloroplast sensor kinase (CSK) is a bacterial-type sensor histidine kinase found in chloroplasts—photosynthetic plastids—in eukaryotic plants and algae. Using a yeast two-hybrid screen, we demonstrate recognition and interactions between: CSK, plastid transcription kinase (PTK), and a bacterial-type RNA polymerase sigma factor-1 (SIG-1). CSK interacts with itself, with SIG-1, and with PTK. PTK also interacts directly with SIG-1. PTK has previously been shown to catalyze phosphorylation of plastid-encoded RNA polymerase (PEP), suppressing plastid transcription nonspecifically. Phospho-PTK is inactive as a PEP kinase. Here, we propose that phospho-CSK acts as a PTK kinase, releasing PTK repression of chloroplast transcription, while CSK also acts as a SIG-1 kinase, blocking transcription specifically at the gene promoter of chloroplast photosystem I. Oxidation of the photosynthetic electron carrier plastoquinone triggers phosphorylation of CSK, inducing chloroplast photosystem II while suppressing photosystem I. CSK places photosystem gene transcription under the control of photosynthetic electron transport. This redox signaling pathway has its origin in cyanobacteria, photosynthetic prokaryotes from which chloroplasts evolved. The persistence of this mechanism in cytoplasmic organelles of photosynthetic eukaryotes is in precise agreement with the CoRR hypothesis for the function of organellar genomes: the plastid genome and its primary gene products are Co-located for Redox Regulation. Genes are retained in plastids primarily in order for their expression to be subject to this rapid and robust redox regulatory transcriptional control mechanism, whereas plastid genes also encode genetic system components, such as some ribosomal proteins and RNAs, that exist in order to support this primary, redox regulatory control of photosynthesis genes. Plastid genome function permits adaptation of the photosynthetic apparatus to changing environmental conditions of light quantity and quality

Oligomeric states in sodium ion-dependent regulation of cyanobacterial histidine kinase-2

IMI thanks Queen Mary University of London for a graduate teaching studentship. LW thanks the China Scholarship Council (CSC) and Queen Mary University of London for financial support. SP held a Leverhulme Trust early-career post-doctoral research fellowship. JN is grateful for the continued support of the JST CREST Grant Number JPMJCR13M4, Japan. JFA acknowledges the support of research grant F/07 476/AQ and fellowship EM-2015-068 of the Leverhulme Trust