Journal: JAMA

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Abstract

Glaucoma in Adults-Screening, Diagnosis, and Management: A Review.

Stein JD, Khawaja AP, Weizer JS
Importance
Glaucoma is the most common cause of irreversible blindness worldwide. Many patients with glaucoma are asymptomatic early in the disease course. Primary care clinicians should know which patients to refer to an eye care professional for a complete eye examination to check for signs of glaucoma and to determine what systemic conditions or medications can increase a patient\'s risk of glaucoma. Open-angle and narrow-angle forms of glaucoma are reviewed, including a description of the pathophysiology, risk factors, screening, disease monitoring, and treatment options.
Observations
Glaucoma is a chronic progressive optic neuropathy, characterized by damage to the optic nerve and retinal nerve fiber layer, that can lead to permanent loss of peripheral or central vision. Intraocular pressure is the only known modifiable risk factor. Other important risk factors include older age, nonwhite race, and a family history of glaucoma. Several systemic medical conditions and medications including corticosteroids, anticholinergics, certain antidepressants, and topiramate may predispose patients to glaucoma. There are 2 broad categories of glaucoma, open-angle and angle-closure glaucoma. Diagnostic testing to assess for glaucoma and to monitor for disease progression includes measurement of intraocular pressure, perimetry, and optical coherence tomography. Treatment of glaucoma involves lowering intraocular pressure. This can be achieved with various classes of glaucoma medications as well as laser and incisional surgical procedures.

Conclusions:
and relevance
Vision loss from glaucoma can be minimized by recognizing systemic conditions and medications that increase a patient\'s risk of glaucoma and referring high-risk patients for a complete ophthalmologic examination. Clinicians should ensure that patients remain adherent with taking glaucoma medications and should monitor for adverse events from medical or surgical interventions used to treat glaucoma.



JAMA: 11 Jan 2021; 325:164-174
Stein JD, Khawaja AP, Weizer JS
JAMA: 11 Jan 2021; 325:164-174 | PMID: 33433580
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Impact:
Abstract

Neonatal Abstinence Syndrome and Maternal Opioid-Related Diagnoses in the US, 2010-2017.

Hirai AH, Ko JY, Owens PL, Stocks C, Patrick SW
Importance
Substantial increases in both neonatal abstinence syndrome (NAS) and maternal opioid use disorder have been observed through 2014.
Objective
To examine national and state variation in NAS and maternal opioid-related diagnoses (MOD) rates in 2017 and to describe national and state changes since 2010 in the US, which included expanded MOD codes (opioid use disorder plus long-term and unspecified use) implemented in International Classification of Disease, 10th Revision, Clinical Modification.
Design, setting, and participants
Repeated cross-sectional analysis of the 2010 to 2017 Healthcare Cost and Utilization Project\'s National Inpatient Sample and State Inpatient Databases, an all-payer compendium of hospital discharge records from community nonrehabilitation hospitals in 47 states and the District of Columbia.
Exposures
State and year.
Main outcomes and measures
NAS rate per 1000 birth hospitalizations and MOD rate per 1000 delivery hospitalizations.
Results
In 2017, there were 751 037 birth hospitalizations and 748 239 delivery hospitalizations in the national sample; 5375 newborns had NAS and 6065 women had MOD documented in the discharge record. Mean gestational age was 38.4 weeks and mean maternal age was 28.8 years. From 2010 to 2017, the estimated NAS rate significantly increased by 3.3 per 1000 birth hospitalizations (95% CI, 2.5-4.1), from 4.0 (95% CI, 3.3-4.7) to 7.3 (95% CI, 6.8-7.7). The estimated MOD rate significantly increased by 4.6 per 1000 delivery hospitalizations (95% CI, 3.9-5.4), from 3.5 (95% CI, 3.0-4.1) to 8.2 (95% CI, 7.7-8.7). Larger increases for MOD vs NAS rates occurred with new International Classification of Disease, 10th Revision, Clinical Modification codes in 2016. From a census of 47 state databases in 2017, NAS rates ranged from 1.3 per 1000 birth hospitalizations in Nebraska to 53.5 per 1000 birth hospitalizations in West Virginia, with Maine (31.4), Vermont (29.4), Delaware (24.2), and Kentucky (23.9) also exceeding 20 per 1000 birth hospitalizations, while MOD rates ranged from 1.7 per 1000 delivery hospitalizations in Nebraska to 47.3 per 1000 delivery hospitalizations in Vermont, with West Virginia (40.1), Maine (37.8), Delaware (24.3), and Kentucky (23.4) also exceeding 20 per 1000 delivery hospitalizations. From 2010 to 2017, NAS and MOD rates increased significantly for all states except Nebraska and Vermont, which only had MOD increases.

Conclusions:
and relevance
In the US from 2010 to 2017, estimated rates of NAS and MOD significantly increased nationally and for the majority of states, with notable state-level variation.



JAMA: 11 Jan 2021; 325:146-155
Hirai AH, Ko JY, Owens PL, Stocks C, Patrick SW
JAMA: 11 Jan 2021; 325:146-155 | PMID: 33433576
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Impact:
Abstract

Effect of Out-of-Hospital Sodium Nitrite on Survival to Hospital Admission After Cardiac Arrest: A Randomized Clinical Trial.

Kim F, Maynard C, Dezfulian C, Sayre M, ... May S, Nichol G
Importance
Therapeutic delivery of sodium nitrite during resuscitation improved survival in animal models of cardiac arrest, but efficacy has not been evaluated in clinical trials in humans.
Objective
To determine whether parenteral administration of sodium nitrite given by paramedics during resuscitation for out-of-hospital cardiac arrest improved survival to hospital admission.
Design, setting, and participants
Double-blind, placebo-controlled, phase 2 randomized clinical trial including 1502 adults in King County, Washington, with out-of-hospital cardiac arrest from ventricular fibrillation or nonventricular fibrillation. Patients underwent resuscitation by paramedics and were enrolled between February 8, 2018, and August 19, 2019; follow-up and data abstraction were completed by December 31, 2019.
Interventions
Eligible patients with out-of-hospital cardiac arrest were randomized (1:1:1) to receive 45 mg of sodium nitrite (n = 500), 60 mg of sodium nitrite (n = 498), or placebo (n = 499), which was given via bolus injection by the paramedics as soon as possible during active resuscitation.
Main outcomes and measures
The primary outcome was survival to hospital admission and was evaluated with 1-sided hypothesis testing. The secondary outcomes included out-of-hospital variables (rate of return of spontaneous circulation, rate of rearrest, and use of norepinephrine to support blood pressure) and in-hospital variables (survival to hospital discharge; neurological outcomes at hospital discharge; cumulative survival to 24 hours, 48 hours, and 72 hours; and number of days in the intensive care unit).
Results
Among 1502 patients with out-of-hospital cardiac arrest who were randomized (mean age, 64 years [SD, 17 years]; 34% were women), 99% completed the trial. Overall, 205 patients (41%) in the 45 mg of sodium nitrite group and 212 patients (43%) in the 60 mg of sodium nitrite group compared with 218 patients (44%) in the placebo group survived to hospital admission; the mean difference for the 45-mg dose vs placebo was -2.9% (1-sided 95% CI, -8.0% to ∞; P = .82) and the mean difference for the 60-mg dose vs placebo was -1.3% (1-sided 95% CI, -6.5% to ∞; P = .66). None of the 7 prespecified secondary outcomes were significantly different, including survival to hospital discharge for 66 patients (13.2%) in the 45 mg of sodium nitrite group and 72 patients (14.5%) in the 60 mg of sodium nitrite group compared with 74 patients (14.9%) in the placebo group; the mean difference for the 45-mg dose vs placebo was -1.7% (2-sided 95% CI, -6.0% to 2.6%; P = .44) and the mean difference for the 60-mg dose vs placebo was -0.4% (2-sided 95% CI, -4.9% to 4.0%; P = .85).

Conclusions:
and relevance
Among patients with out-of-hospital cardiac arrest, administration of sodium nitrite, compared with placebo, did not significantly improve survival to hospital admission. These findings do not support the use of sodium nitrite during resuscitation from out-of-hospital cardiac arrest.
Trial registration
ClinicalTrials.gov Identifier: NCT03452917.



JAMA: 11 Jan 2021; 325:138-145
Kim F, Maynard C, Dezfulian C, Sayre M, ... May S, Nichol G
JAMA: 11 Jan 2021; 325:138-145 | PMID: 33433575
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Impact:
Abstract

Association of Fresh Embryo Transfers Compared With Cryopreserved-Thawed Embryo Transfers With Live Birth Rate Among Women Undergoing Assisted Reproduction Using Freshly Retrieved Donor Oocytes.

Insogna IG, Lanes A, Lee MS, Ginsburg ES, Fox JH
Importance
In in vitro fertilization cycles using autologous oocytes, data have demonstrated higher live birth rates following cryopreserved-thawed embryo transfers compared with fresh embryo transfers. It remains unknown if this association exists in cycles using freshly retrieved donor oocytes.
Objective
To test the hypothesis that in freshly retrieved donor oocyte cycles, a fresh embryo transfer is more likely to result in a live birth compared with a cryopreserved-thawed embryo transfer.
Design, setting, and participants
Retrospective cohort study using national data collected from the Society for Assisted Reproductive Technology for 33 863 recipients undergoing fresh donor oocyte cycles in the US between January 1, 2014 and December 31, 2017.
Exposures
Fresh embryo transfer and cryopreserved-thawed embryo transfer.
Main outcomes and measures
The primary outcome was live birth rate; secondary outcomes were clinical pregnancy rate and miscarriage rate. Analyses were adjusted for donor age, day of embryo transfer, use of a gestational carrier, and assisted hatching.
Results
Recipients of fresh and cryopreserved-thawed embryos had comparable median age (42.0 [interquartile range {IQR}, 37.0-44.0] years vs 42.0 [IQR, 36.0-45.0] years), gravidity (1 [IQR, 0-2] vs 1 [IQR, 0-3]), parity (0 [IQR, 0-1] vs 1 [IQR, 0-1]), and body mass index (24.5 [IQR, 21.9-28.7] vs 24.4 [IQR, 21.6-28.7]). Of a total of 33 863 recipients who underwent 51 942 fresh donor oocyte cycles, there were 15 308 (29.5%) fresh embryo transfer cycles and 36 634 (70.5%) cryopreserved-thawed embryo transfer cycles. Blastocysts were transferred in 92.4% of fresh embryo transfer cycles and 96.5% of cryopreserved-thawed embryo transfer cycles, with no significant difference in the mean number of embryos transferred. Live birth rate following fresh embryo transfer vs cryopreserved-thawed embryo transfer was 56.6% vs 44.0% (absolute difference, 12.6% [95% CI, 11.7%-13.5%]; adjusted relative risk [aRR], 1.42 [95% CI, 1.39-1.46]). Clinical pregnancy rates were 66.7% vs 54.2%, respectively (absolute difference, 12.5% [95% CI, 11.6%-13.4%]; aRR, 1.34; [95% CI, 1.31-1.37]). Miscarriage rates were 9.3% vs 9.4%, respectively (absolute difference, 0.2% [95% CI, -0.4% to 0.7%]); aRR, 0.98 [95% CI, 0.91-1.07]).

Conclusions:
and relevance
In this retrospective cohort study of women undergoing assisted reproduction using freshly retrieved donor oocytes, the use of fresh embryo transfers compared with cryopreserved-thawed embryo transfers was associated with a higher live birth rate. However, interpretation of the findings is limited by the potential for selection and confounding bias.



JAMA: 11 Jan 2021; 325:156-163
Insogna IG, Lanes A, Lee MS, Ginsburg ES, Fox JH
JAMA: 11 Jan 2021; 325:156-163 | PMID: 33433574
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Impact:
Abstract

Effect of Oral Moxifloxacin vs Intravenous Ertapenem Plus Oral Levofloxacin for Treatment of Uncomplicated Acute Appendicitis: The APPAC II Randomized Clinical Trial.

Sippola S, Haijanen J, Grönroos J, Rautio T, ... Paajanen H, Salminen P
Importance
Antibiotics are an effective and safe alternative to appendectomy for managing uncomplicated acute appendicitis, but the optimal antibiotic regimen is not known.
Objective
To compare oral antibiotics with combined intravenous followed by oral antibiotics in the management of computed tomography-confirmed uncomplicated acute appendicitis.
Design, setting, and participants
The Appendicitis Acuta (APPAC) II multicenter, open-label, noninferiority randomized clinical trial was conducted from April 2017 until November 2018 in 9 Finnish hospitals. A total of 599 patients aged 18 to 60 years with computed tomography-confirmed uncomplicated acute appendicitis were enrolled in the trial. The last date of follow-up was November 29, 2019.
Interventions
Patients randomized to receive oral monotherapy (n = 295) received oral moxifloxacin (400 mg/d) for 7 days. Patients randomized to receive intravenous antibiotics followed by oral antibiotics (n = 288) received intravenous ertapenem (1 g/d) for 2 days followed by oral levofloxacin (500 mg/d) and metronidazole (500 mg 3 times/d) for 5 days.
Main outcomes and measures
The primary end point was treatment success (≥65%) for both groups, defined as discharge from hospital without surgery and no recurrent appendicitis during 1-year follow-up, and to determine whether oral antibiotics alone were noninferior to intravenous and oral antibiotics, with a margin of 6% for difference.
Results
Among 599 patients who were randomized (mean [SD] age, 36 [12] years; 263 [44%] women), 581 (99.7%) were available for the 1-year follow-up. The treatment success rate at 1 year was 70.2% (1-sided 95% CI, 65.8% to ∞) for patients treated with oral antibiotics and 73.8% (1-sided 95% CI, 69.5% to ∞) for patients treated with intravenous followed by oral antibiotics. The difference was -3.6% ([1-sided 95% CI, -9.7% to ∞]; P = .26 for noninferiority), with the confidence limit exceeding the noninferiority margin.

Conclusion:
and relevance
Among adults with uncomplicated acute appendicitis, treatment with 7 days of oral moxifloxacin compared with 2 days of intravenous ertapenem followed by 5 days of levofloxacin and metronidazole resulted in treatment success rates greater than 65% in both groups, but failed to demonstrate noninferiority for treatment success of oral antibiotics compared with intravenous followed by oral antibiotics.
Trial registration
ClinicalTrials.gov Identifier: NCT03236961; EudraCT Identifier: 2015-003633-10.



JAMA: 10 Jan 2021; epub ahead of print
Sippola S, Haijanen J, Grönroos J, Rautio T, ... Paajanen H, Salminen P
JAMA: 10 Jan 2021; epub ahead of print | PMID: 33427870
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Impact:
Abstract

Management of Crohn Disease: A Review.

Cushing K, Higgins PDR
Importance
Crohn disease, a chronic gastrointestinal inflammatory disease, is increasing in incidence and prevalence in many parts of the world. Uncontrolled inflammation leads to long-term complications, including fibrotic strictures, enteric fistulae, and intestinal neoplasia. Therefore, early and effective control of inflammation is of critical importance.
Observations
The optimal management approach for Crohn disease incorporates patient risk stratification, patient preference, and clinical factors in therapeutic decision-making. First-line therapy generally consists of steroids for rapid palliation of symptoms during initiation of anti-tumor necrosis factor α therapy. Other treatments may include monoclonal antibodies to IL-12/23 or integrin α4β7, immunomodulators, combination therapies, or surgery. Effective control of inflammation reduces the risk of penetrating complications (such as intra-abdominal abscesses and fistulae), although more than half of patients will develop complications that require surgery. Adverse reactions to therapy include antibody formation and infusion reactions, infections, and cancers associated with immune modulators and biologics and toxicity to the bone marrow and the liver. Both Crohn disease and corticosteroid use are associated with osteoporosis. Vaccinations to prevent infections, such as influenza, pneumonia, and herpes zoster, are important components of health maintenance for patients with Crohn disease, although live vaccines are contraindicated for patients receiving immune suppression therapy.

Conclusions:
and relevance
The treatment of patients with Crohn disease depends on disease severity, patient risk stratification, patient preference, and clinical factors, including age of onset and penetrating complications, and includes treatment with steroids, monoclonal antibody therapies, immunomodulators, and surgery. Physicians should be familiar with the advantages and disadvantages of each therapy to best counsel their patients.



JAMA: 04 Jan 2021; 325:69-80
Cushing K, Higgins PDR
JAMA: 04 Jan 2021; 325:69-80 | PMID: 33399844
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Impact:
Abstract

Prevalence of Pulmonary Embolism Among Patients With COPD Hospitalized With Acutely Worsening Respiratory Symptoms.

Couturaud F, Bertoletti L, Pastre J, Roy PM, ... Leroyer C,
Importance
The prevalence of pulmonary embolism in patients with chronic obstructive pulmonary disease (COPD) and acutely worsening respiratory symptoms remains uncertain.
Objective
To determine the prevalence of pulmonary embolism in patients with COPD admitted to the hospital for acutely worsening respiratory symptoms.
Design, setting, and participants
Multicenter cross-sectional study with prospective follow-up conducted in 7 French hospitals. A predefined pulmonary embolism diagnostic algorithm based on Geneva score, D-dimer levels, and spiral computed tomographic pulmonary angiography plus leg compression ultrasound was applied within 48 hours of admission; all patients had 3-month follow-up. Patients were recruited from January 2014 to May 2017 and the final date of follow-up was August 22, 2017.
Exposures
Acutely worsening respiratory symptoms in patients with COPD.
Main outcomes and measures
The primary outcome was pulmonary embolism diagnosed within 48 hours of admission. Key secondary outcome was pulmonary embolism during a 3-month follow-up among patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulant treatment. Other outcomes were venous thromboembolism (pulmonary embolism and/or deep vein thrombosis) at admission and during follow-up, and 3-month mortality, whether venous thromboembolism was clinically suspected or not.
Results
Among 740 included patients (mean age, 68.2 years [SD, 10.9 years]; 274 women [37.0%]), pulmonary embolism was confirmed within 48 hours of admission in 44 patients (5.9%; 95% CI, 4.5%-7.9%). Among the 670 patients deemed not to have venous thromboembolism at admission and who did not receive anticoagulation, pulmonary embolism occurred in 5 patients (0.7%; 95% CI, 0.3%-1.7%) during follow-up, including 3 deaths related to pulmonary embolism. The overall 3-month mortality rate was 6.8% (50 of 740; 95% CI, 5.2%-8.8%). The proportion of patients who died during follow-up was higher among those with venous thromboembolism at admission than the proportion of those without it at admission (14 [25.9%] of 54 patients vs 36 [5.2%] of 686; risk difference, 20.7%, 95% CI, 10.7%-33.8%; P < .001). The prevalence of venous thromboembolism was 11.7% (95% CI, 8.6%-15.9%) among patients in whom pulmonary embolism was suspected (n = 299) and was 4.3% (95% CI, 2.8%-6.6%) among those in whom pulmonary embolism was not suspected (n = 441).

Conclusions:
and relevance
Among patients with chronic obstructive pulmonary disease admitted to the hospital with an acute worsening of respiratory symptoms, pulmonary embolism was detected in 5.9% of patients using a predefined diagnostic algorithm. Further research is needed to understand the possible role of systematic screening for pulmonary embolism in this patient population.



JAMA: 04 Jan 2021; 325:59-68
Couturaud F, Bertoletti L, Pastre J, Roy PM, ... Leroyer C,
JAMA: 04 Jan 2021; 325:59-68 | PMID: 33399840
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Impact:
Abstract

Gastroesophageal Reflux Disease: A Review.

Maret-Ouda J, Markar SR, Lagergren J
Importance
Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries.
Observations
GERD can influence patients\' health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, which usually is omeprazole 20 mg once daily, the aim is to use the lowest effective dose. Observational studies have suggested several adverse effects after long-term PPI, but these findings need to be confirmed before influencing clinical decision making. Surgery with laparoscopic fundoplication is an invasive treatment alternative in select patients after thorough and objective assessments, particularly if they are young and healthy. Endoscopic and less invasive surgical techniques are emerging, which may reduce the use of long-term PPI and fundoplication, but the long-term safety and efficacy remain to be scientifically established.

Conclusions:
and relevance
The clinical management of GERD influences the lives of many individuals and is responsible for substantial consumption of health care and societal resources. Treatments include lifestyle modification, PPI medication, and laparoscopic fundoplication. New endoscopic and less invasive surgical procedures are evolving. PPI use remains the dominant treatment, but long-term therapy requires follow-up and reevaluation for potential adverse effects.



JAMA: 21 Dec 2020; 324:2536-2547
Maret-Ouda J, Markar SR, Lagergren J
JAMA: 21 Dec 2020; 324:2536-2547 | PMID: 33351048
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Impact:
Abstract

Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.

Kotecha D, Bunting KV, Gill SK, Mehta S, ... Kirchhof P,
Importance
There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure.
Objective
To compare low-dose digoxin with bisoprolol (a β-blocker).
Design, setting, and participants
Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019.
Interventions
Digoxin (n = 80; dose range, 62.5-250 μg/d; mean dose, 161 μg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d).
Main outcomes and measures
The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting.
Results
Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group.

Conclusions:
and relevance
Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points.
Trial registration
ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.



JAMA: 21 Dec 2020; 324:2497-2508
Kotecha D, Bunting KV, Gill SK, Mehta S, ... Kirchhof P,
JAMA: 21 Dec 2020; 324:2497-2508 | PMID: 33351042
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Impact:
Abstract

Association of First Primary Cancer With Risk of Subsequent Primary Cancer Among Survivors of Adult-Onset Cancers in the United States.

Sung H, Hyun N, Leach CR, Yabroff KR, Jemal A
Importance
The number of cancer survivors who develop new cancers is projected to increase, but comprehensive data on the risk of subsequent primary cancers (SPCs) among survivors of adult-onset cancers are limited.
Objective
To quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types and sex.
Design, setting, and participants
A retrospective cohort study from 12 Surveillance, Epidemiology, and End Results registries in the United States, that included 1 537 101 persons aged 20 to 84 years diagnosed with FPCs from 1992-2011 (followed up until December 31, 2017) and who survived at least 5 years.
Exposures
First primary cancer.
Main outcomes and measures
Incidence and mortality of SPCs per 10 000 person-years; standardized incidence ratio (SIR) and standardized mortality ratio (SMR) compared with those expected in the general population.
Results
Among 1 537 101 survivors (mean age, 60.4 years; 48.8% women), 156 442 SPC cases and 88 818 SPC deaths occurred during 11 197 890 person-years of follow-up (mean, 7.3 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 18 of the 30 FPC types, and risk of dying from any SPCs was statistically significantly higher for 27 of 30 FPC types as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 21 of the 31 FPC types, and risk of dying from any SPCs was statistically significantly higher for 28 of 31 FPC types as compared with risks in the general population. The highest overall SIR and SMR were estimated among survivors of laryngeal cancer (SIR, 1.75 [95% CI, 1.68-1.83]; incidence, 373 per 10 000 person-years) and gallbladder cancer (SMR, 3.82 [95% CI, 3.31-4.39]; mortality, 341 per 10 000 person-years) among men, and among survivors of laryngeal cancer (SIR, 2.48 [95% CI, 2.27-2.72]; incidence, 336 per 10 000 person-years; SMR, 4.56 [95% CI, 4.11-5.06]; mortality, 268 per 10 000 person-years) among women. Substantial variation existed in the associations of specific types of FPCs with specific types of SPC risk; however, only a few smoking- or obesity-associated SPCs, such as lung, urinary bladder, oral cavity/pharynx, colorectal, pancreatic, uterine corpus, and liver cancers constituted considerable proportions of the total incidence and mortality, with lung cancer alone accounting for 31% to 33% of mortality from all SPCs.

Conclusions:
and relevance
Among survivors of adult-onset cancers in the United States, several types of primary cancer were significantly associated with greater risk of developing and dying from an SPC, compared with the general population. Cancers associated with smoking or obesity comprised substantial proportions of overall SPC incidence and mortality among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.



JAMA: 21 Dec 2020; 324:2521-2535
Sung H, Hyun N, Leach CR, Yabroff KR, Jemal A
JAMA: 21 Dec 2020; 324:2521-2535 | PMID: 33351041
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Impact:
Abstract

Screening for Hepatitis B Virus Infection in Adolescents and Adults: US Preventive Services Task Force Recommendation Statement.

, Krist AH, Davidson KW, Mangione CM, ... Tseng CW, Wong JB
Importance
An estimated 862 000 persons in the US are living with chronic infection with hepatitis B virus (HBV). Persons born in regions with a prevalence of HBV infection of 2% or greater, such as countries in Africa and Asia, the Pacific Islands, and parts of South America, often become infected at birth and account for up to 95% of newly reported chronic infections in the US. Other high-prevalence populations include persons who inject drugs; men who have sex with men; persons with HIV infection; and sex partners, needle-sharing contacts, and household contacts of persons with chronic HBV infection. Up to 60% of HBV-infected persons are unaware of their infection, and many remain asymptomatic until onset of cirrhosis or end-stage liver disease.
Objective
To update its 2014 recommendation, the USPSTF commissioned a review of new randomized clinical trials and cohort studies published from 2014 to August 2019 that evaluated the benefits and harms of screening and antiviral therapy for preventing intermediate outcomes or health outcomes and the association between improvements in intermediate outcomes and health outcomes. New key questions focused on the yield of alternative HBV screening strategies and the accuracy of tools to identify persons at increased risk.
Population
This recommendation statement applies to asymptomatic, nonpregnant adolescents and adults at increased risk for HBV infection, including those who were vaccinated before being screened for HBV infection.
Evidence assessment
The USPSTF concludes with moderate certainty that screening for HBV infection in adolescents and adults at increased risk for infection has moderate net benefit.
Recommendation
The USPSTF recommends screening for HBV infection in adolescents and adults at increased risk for infection. (B recommendation).



JAMA: 14 Dec 2020; 324:2415-2422
, Krist AH, Davidson KW, Mangione CM, ... Tseng CW, Wong JB
JAMA: 14 Dec 2020; 324:2415-2422 | PMID: 33320230
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Impact:
Abstract

Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Chou R, Blazina I, Bougatsos C, Holmes R, ... Grusing S, Jou J
Importance
A 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited.
Objective
To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF.
Data sources
Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020.
Study selection
Randomized clinical trials (RCTs) on screening and antiviral therapy; cohort studies on screening, antiviral therapy clinical outcomes, and the association between achieving intermediate outcomes after antiviral therapy and clinical outcomes.
Data extraction and synthesis
One investigator abstracted data; a second investigator checked accuracy. Two investigators independently assessed study quality. Random-effects profile likelihood meta-analysis was performed.
Results
Thirty trials and 20 cohort studies, with a total of 94 168 participants, were included. No study directly evaluated the effects of screening for HBV infection vs no screening on clinical outcomes such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high-prevalence countries and demographic and behavioral risk factors would identify nearly all HBV infection cases. In 1 study (n = 21 008), only screening immigrants from high-prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (n = 2972), antiviral therapy compared with placebo or no treatment was associated with greater likelihood of achieving intermediate outcomes, such as virologic suppression and hepatitis B e-antigen (HBeAg) or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virologic suppression to 17 for HBeAg seroconversion. Based on 12 trials (n = 4127), first-line antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (n = 4809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (n = 3893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes but were heterogeneous (hazard ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events vs placebo or no antiviral therapy.

Conclusions:
and relevance
There was no direct evidence for the clinical benefits and harms of HBV screening vs no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes.



JAMA: 14 Dec 2020; 324:2423-2436
Chou R, Blazina I, Bougatsos C, Holmes R, ... Grusing S, Jou J
JAMA: 14 Dec 2020; 324:2423-2436 | PMID: 33320229
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Impact:
Abstract

Association Between Depressive Symptoms and Incident Cardiovascular Diseases.

Harshfield EL, Pennells L, Schwartz JE, Willeit P, ... Davidson KW,
Importance
It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVDs).
Objective
To characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood.
Design, setting, and participants
A pooled analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 162 036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and the UK Biobank (401 219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline.
Exposures
Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Center for Epidemiological Studies Depression (CES-D) scale (range, 0-60; ≥16 indicates possible depressive disorder). The UK Biobank recorded the 2-item Patient Health Questionnaire 2 (PHQ-2; range, 0-6; ≥3 indicates possible depressive disorder).
Main outcomes and measures
Primary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the 2). Hazard ratios (HRs) per 1-SD higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported.
Results
Among 162 036 participants from the ERFC (73%, women; mean age at baseline, 63 years [SD, 9 years]), 5078 CHD and 3932 stroke events were recorded (median follow-up, 9.5 years). Associations with CHD, stroke, and CVD were log linear. The HR per 1-SD higher depression score for CHD was 1.07 (95% CI, 1.03-1.11); stroke, 1.05 (95% CI, 1.01-1.10); and CVD, 1.06 (95% CI, 1.04-1.08). The corresponding incidence rates per 10 000 person-years of follow-up in the highest vs the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs 1) were 36.3 vs 29.0 for CHD events, 28.0 vs 24.7 for stroke events, and 62.8 vs 53.5 for CVD events. Among 401 219 participants from the UK Biobank (55% were women, mean age at baseline, 56 years [SD, 8 years]), 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1 years). The HR per 1-SD higher depression score for CHD was 1.11 (95% CI, 1.08-1.14); stroke, 1.10 (95% CI, 1.06-1.14); and CVD, 1.10 (95% CI, 1.08-1.13). The corresponding incidence rates per 10 000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher vs 0 were 20.9 vs 14.2 for CHD events, 15.3 vs 10.2 for stroke events, and 36.2 vs 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors.

Conclusions:
and relevance
In a pooled analysis of 563 255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.



JAMA: 14 Dec 2020; 324:2396-2405
Harshfield EL, Pennells L, Schwartz JE, Willeit P, ... Davidson KW,
JAMA: 14 Dec 2020; 324:2396-2405 | PMID: 33320224
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Impact:
Abstract

Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.

Antoszyk AN, Glassman AR, Beaulieu WT, Jampol LM, ... Sun JK,
Importance
Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown.
Objective
To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy.
Design, setting, and participants
Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020.
Interventions
Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria.
Main outcomes and measures
The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years.
Results
Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept.

Conclusions:
and relevance
Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation.
Trial registration
ClinicalTrials.gov Identifier: NCT02858076.



JAMA: 14 Dec 2020; 324:2383-2395
Antoszyk AN, Glassman AR, Beaulieu WT, Jampol LM, ... Sun JK,
JAMA: 14 Dec 2020; 324:2383-2395 | PMID: 33320223
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Impact:
Abstract

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment: The SYSUCC-001 Randomized Clinical Trial.

Wang X, Wang SS, Huang H, Cai L, ... Yuan ZY,
Importance
Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed.
Objective
To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer.
Design, setting, and participants
Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy.
Interventions
Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy.
Main outcomes and measures
The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events.
Results
Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event.

Conclusions:
and relevance
Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival.
Trial registration
ClinicalTrials.gov Identifier: NCT01112826.



JAMA: 09 Dec 2020; epub ahead of print
Wang X, Wang SS, Huang H, Cai L, ... Yuan ZY,
JAMA: 09 Dec 2020; epub ahead of print | PMID: 33300950
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Impact:
Abstract

Effect of High-Dose Trivalent vs Standard-Dose Quadrivalent Influenza Vaccine on Mortality or Cardiopulmonary Hospitalization in Patients With High-risk Cardiovascular Disease: A Randomized Clinical Trial.

Vardeny O, Kim K, Udell JA, Joseph J, ... Solomon SD,
Importance
Influenza is temporally associated with cardiopulmonary morbidity and mortality among those with cardiovascular disease who may mount a less vigorous immune response to vaccination. Higher influenza vaccine dose has been associated with reduced risk of influenza illness.
Objective
To evaluate whether high-dose trivalent influenza vaccine compared with standard-dose quadrivalent influenza vaccine would reduce all-cause death or cardiopulmonary hospitalization in high-risk patients with cardiovascular disease.
Design, setting, and participants
Pragmatic multicenter, double-blind, active comparator randomized clinical trial conducted in 5260 participants vaccinated for up to 3 influenza seasons in 157 sites in the US and Canada between September 21, 2016, and January 31, 2019. Patients with a recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor were eligible.
Interventions
Participants were randomly assigned to receive high-dose trivalent (n = 2630) or standard-dose quadrivalent (n = 2630) inactivated influenza vaccine and could be revaccinated for up to 3 seasons.
Main outcomes and measures
The primary outcome was the time to the composite of all-cause death or cardiopulmonary hospitalization during each enrolling season. The final date of follow-up was July 31, 2019. Vaccine-related adverse events were also assessed.
Results
Among 5260 randomized participants (mean [SD] age, 65.5 [12.6] years; 3787 [72%] men; 3289 [63%] with heart failure) over 3 influenza seasons, there were 7154 total vaccinations administered and 5226 (99.4%) participants completed the trial. In the high-dose trivalent vaccine group, there were 975 primary outcome events (883 hospitalizations for cardiovascular or pulmonary causes and 92 deaths from any cause) among 884 participants during 3577 participant-seasons (event rate, 45 per 100 patient-years), whereas in the standard-dose quadrivalent vaccine group, there were 924 primary outcome events (846 hospitalizations for cardiovascular or pulmonary causes and 78 deaths from any cause) among 837 participants during 3577 participant-seasons (event rate, 42 per 100 patient-years) (hazard ratio, 1.06 [95% CI, 0.97-1.17]; P = .21). In the high-dose vs standard-dose groups, vaccine-related adverse reactions occurred in 1449 (40.5%) vs 1229 (34.4%) participants and severe adverse reactions occurred in 55 (2.1%) vs 44 (1.7%) participants.

Conclusions:
and relevance
In patients with high-risk cardiovascular disease, high-dose trivalent inactivated influenza vaccine, compared with standard-dose quadrivalent inactivated influenza vaccine, did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations. Influenza vaccination remains strongly recommended in this population.
Trial registration
ClinicalTrials.gov Identifier: NCT02787044.



JAMA: 03 Dec 2020; epub ahead of print
Vardeny O, Kim K, Udell JA, Joseph J, ... Solomon SD,
JAMA: 03 Dec 2020; epub ahead of print | PMID: 33275134
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Impact:
Abstract

Hearing Loss in Children: A Review.

Lieu JEC, Kenna M, Anne S, Davidson L
Importance
Hearing loss in children is common and by age 18 years, affects nearly 1 of every 5 children. Without hearing rehabilitation, hearing loss can cause detrimental effects on speech, language, developmental, educational, and cognitive outcomes in children.
Observations
Consequences of hearing loss in children include worse outcomes in speech, language, education, social functioning, cognitive abilities, and quality of life. Hearing loss can be congenital, delayed onset, or acquired with possible etiologies including congenital infections, genetic causes including syndromic and nonsyndromic etiologies, and trauma, among others. Evaluation of hearing loss must be based on suspected diagnosis, type, laterality and degree of hearing loss, age of onset, and additional variables such as exposure to cranial irradiation. Hearing rehabilitation for children with hearing loss may include use of hearing aids, cochlear implants, bone anchored devices, or use of assistive devices such as frequency modulating systems.

Conclusions:
and relevance
Hearing loss in children is common, and there has been substantial progress in diagnosis and management of these cases. Early identification of hearing loss and understanding its etiology can assist with prognosis and counseling of families. In addition, awareness of treatment strategies including the many hearing device options, cochlear implant, and assistive devices can help direct management of the patient to optimize outcomes.



JAMA: 30 Nov 2020; 324:2195-2205
Lieu JEC, Kenna M, Anne S, Davidson L
JAMA: 30 Nov 2020; 324:2195-2205 | PMID: 33258894
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Impact:
Abstract

Behavioral Counseling Interventions to Promote a Healthy Diet and Physical Activity for Cardiovascular Disease Prevention in Adults With Cardiovascular Risk Factors: US Preventive Services Task Force Recommendation Statement.

, Krist AH, Davidson KW, Mangione CM, ... Tseng CW, Wong JB
Importance
Cardiovascular disease (CVD) is a leading cause of death in the US. Known modifiable risk factors for CVD include smoking, overweight and obesity, diabetes, elevated blood pressure or hypertension, dyslipidemia, lack of physical activity, and unhealthy diet. Adults who adhere to national guidelines for a healthy diet and physical activity have lower cardiovascular morbidity and mortality than those who do not. All persons, regardless of their CVD risk status, benefit from healthy eating behaviors and appropriate physical activity.
Objective
To update its 2014 recommendation, the USPSTF commissioned a review of the evidence on behavioral counseling to promote a healthy diet and physical activity for CVD prevention in adults with cardiovascular risk factors.
Population
This recommendation statement applies to adults 18 years or older with known hypertension or elevated blood pressure, those with dyslipidemia, or those who have mixed or multiple risk factors such as metabolic syndrome or an estimated 10-year CVD risk of 7.5% or greater. Adults with other known modifiable cardiovascular risk factors such as abnormal blood glucose levels, obesity, and smoking are not included in this recommendation.
Evidence assessment
The USPSTF concludes with moderate certainty that behavioral counseling interventions have a moderate net benefit on CVD risk in adults at increased risk for CVD.
Recommendation
The USPSTF recommends offering or referring adults with CVD risk factors to behavioral counseling interventions to promote a healthy diet and physical activity. (B recommendation).



JAMA: 23 Nov 2020; 324:2069-2075
, Krist AH, Davidson KW, Mangione CM, ... Tseng CW, Wong JB
JAMA: 23 Nov 2020; 324:2069-2075 | PMID: 33231670
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Impact:
Abstract

Bladder Cancer: A Review.

Lenis AT, Lec PM, Chamie K, Mshs MD
Importance
Bladder cancer is a common malignancy in women and is the fourth most common malignancy in men. Bladder cancer ranges from unaggressive and usually noninvasive tumors that recur and commit patients to long-term invasive surveillance, to aggressive and invasive tumors with high disease-specific mortality.
Observations
Advanced age, male sex, and cigarette smoking contribute to the development of bladder cancer. Bladder tumors can present with gross or microscopic hematuria, which is evaluated with cystoscopy and upper tract imaging depending on the degree of hematuria and risk of malignancy. Non-muscle-invasive tumors are treated with endoscopic resection and adjuvant intravesical therapy, depending on the risk classification. Enhanced cystoscopy includes technology used to improve the detection of tumors and can reduce the risk of recurrence. Patients with high-risk non-muscle invasive tumors that do not respond to adjuvant therapy with the standard-of-care immunotherapy, bacille Calmette-Guérin (BCG), constitute a challenging patient population to manage and many alternative therapies are being studied. For patients with muscle-invasive disease, more aggressive therapy with radical cystectomy and urinary diversion or trimodal therapy with maximal endoscopic resection, radiosensitizing chemotherapy, and radiation is warranted to curb the risk of metastasis and disease-specific mortality. Treatment of patients with advanced disease is undergoing rapid changes as immunotherapy with checkpoint inhibitors, targeted therapies, and antibody-drug conjugates have become options for certain patients with various stages of disease.

Conclusions:
and relevance
Improved understanding of the molecular biology and genetics of bladder cancer has evolved the way localized and advanced disease is diagnosed and treated. While intravesical BCG has remained the mainstay of therapy for intermediate and high-risk non-muscle-invasive bladder cancer, the therapeutic options for muscle-invasive and advanced disease has expanded to include immunotherapy with checkpoint inhibition, targeted therapies, and antibody-drug conjugates.



JAMA: 16 Nov 2020; 324:1980-1991
Lenis AT, Lec PM, Chamie K, Mshs MD
JAMA: 16 Nov 2020; 324:1980-1991 | PMID: 33201207
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Impact:
Abstract

Association Between Adherence to Fractional Flow Reserve Treatment Thresholds and Major Adverse Cardiac Events in Patients With Coronary Artery Disease.

Sud M, Han L, Koh M, Austin PC, ... Fang J, Ko DT
Importance
Fractional flow reserve (FFR) is an invasive measurement used to assess the potential of a coronary stenosis to induce myocardial ischemia and guide decisions for percutaneous coronary intervention (PCI). It is not known whether established FFR thresholds for PCI are adhered to in routine interventional practice and whether adherence to these thresholds is associated with better clinical outcomes.
Objective
To assess the adherence to evidence-based FFR thresholds for PCI and its association with clinical outcomes.
Design, setting, and participants
A retrospective, multicenter, population-based cohort study of adults with coronary artery disease undergoing single-vessel FFR assessment (excluding ST-segment elevation myocardial infarction) from April 1, 2013, to March 31, 2018, in Ontario, Canada, and followed up until March 31, 2019, was conducted. Two separate cohorts were created based on FFR thresholds (≤0.80 as ischemic and >0.80 as nonischemic). Inverse probability of treatment weighting was used to account for treatment selection bias.
Exposures
PCI vs no PCI.
Main outcomes and measures
The primary outcome was major adverse cardiac events (MACE) defined by death, myocardial infarction, unstable angina, or urgent coronary revascularization.
Results
There were 9106 patients (mean [SD] age, 65 [10.6] years; 35.3% female) who underwent single-vessel FFR measurement. Among 2693 patients with an ischemic FFR, 75.3% received PCI and 24.7% were treated only with medical therapy. In the ischemic FFR cohort, PCI was associated with a significantly lower rate and hazard of MACE at 5 years compared with no PCI (31.5% vs 39.1%; hazard ratio, 0.77 [95% CI, 0.63-0.94]). Among 6413 patients with a nonischemic FFR, 12.6% received PCI and 87.4% were treated with medical therapy only. PCI was associated with a significantly higher rate and hazard of MACE at 5 years compared with no PCI (33.3% vs 24.4%; HR, 1.37 [95% CI, 1.14-1.65]) in this cohort.

Conclusions:
and relevance
Among patients with coronary artery disease who underwent single-vessel FFR measurement in routine clinical practice, performing PCI, compared with not performing PCI, was significantly associated with a lower rate of MACE for ischemic lesions and a higher rate of MACE for nonischemic lesions. These findings support the performance of PCI procedures according to evidence-based FFR thresholds.



JAMA: 12 Nov 2020; epub ahead of print
Sud M, Han L, Koh M, Austin PC, ... Fang J, Ko DT
JAMA: 12 Nov 2020; epub ahead of print | PMID: 33185655
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Impact:
Abstract

Screening for High Blood Pressure in Children and Adolescents: US Preventive Services Task Force Recommendation Statement.

, Krist AH, Davidson KW, Mangione CM, ... Tseng CW, Wong JB
Importance
Prevalence of hypertension (both primary and secondary) in children and adolescents in the US ranges from 3% to 4%. Primary hypertension in children and adolescents occurs primarily in children older than 13 years and has no known cause but is associated with several risk factors, including family history and higher body mass index. Secondary hypertension occurs primarily in younger children and is most commonly caused by genetic disorders, renal disease, endocrine disorders, or cardiovascular abnormalities.
Objective
To update its 2013 recommendation, the USPSTF commissioned a review of the evidence on the benefits and harms of screening, test accuracy, the effectiveness and harms of treatment, and the association between hypertension and markers of cardiovascular disease in childhood and adulthood.
Population
This recommendation statement applies to children and adolescents aged 3 to 18 years not known to have hypertension or who are asymptomatic.
Evidence assessment
The USPSTF concludes that the evidence to support screening for high blood pressure in children and adolescents is insufficient and that the balance of benefits and harms cannot be determined.
Recommendation
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents. (I statement).



JAMA: 09 Nov 2020; 324:1878-1883
, Krist AH, Davidson KW, Mangione CM, ... Tseng CW, Wong JB
JAMA: 09 Nov 2020; 324:1878-1883 | PMID: 33170248
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Impact:
Abstract

Diagnosis and Treatment of Lower Extremity Venous Thromboembolism: A Review.

Chopard R, Albertsen IE, Piazza G
Importance
Incidence rates for lower extremity deep vein thrombosis (DVT) range from 88 to 112 per 100 000 person-years and increase with age. Rates of recurrent VTE range from 20% to 36% during the 10 years after an initial event.
Observations
PubMed and Cochrane databases were searched for English-language studies published from January 2015 through June 2020 for randomized clinical trials, meta-analyses, systematic reviews, and observational studies. Risk factors for venous thromboembolism (VTE), such as older age, malignancy (cumulative incidence of 7.4% after a median of 19 months), inflammatory disorders (VTE risk is 4.7% in patients with rheumatoid arthritis and 2.5% in those without), and inherited thrombophilia (factor V Leiden carriers with a 10-year cumulative incidence of 10.9%), are associated with higher risk of VTE. Patients with signs or symptoms of lower extremity DVT, such as swelling (71%) or a cramping or pulling discomfort in the thigh or calf (53%), should undergo assessment of pretest probability followed by D-dimer testing and imaging with venous ultrasonography. A normal D-dimer level (ie, D-dimer <500 ng/mL) excludes acute VTE when combined with a low pretest probability (ie, Wells DVT score ≤1). In patients with a high pretest probability, the negative predictive value of a D-dimer less than 500 ng/mL is 92%. Consequently, D-dimer cannot be used to exclude DVT without an assessment of pretest probability. Postthrombotic syndrome, defined as persistent symptoms, signs of chronic venous insufficiency, or both, occurs in 25% to 50% of patients 3 to 6 months after DVT diagnosis. Catheter-directed fibrinolysis with or without mechanical thrombectomy is appropriate in those with iliofemoral obstruction, severe symptoms, and a low risk of bleeding. The efficacy of direct oral anticoagulants-rivaroxaban, apixaban, dabigatran, and edoxaban-is noninferior to warfarin (absolute rate of recurrent VTE or VTE-related death, 2.0% vs 2.2%). Major bleeding occurs in 1.1% of patients treated with direct oral anticoagulants vs 1.8% treated with warfarin.

Conclusions:
and relevance
Greater recognition of VTE risk factors and advances in anticoagulation have facilitated the clinical evaluation and treatment of patients with DVT. Direct oral anticoagulants are noninferior to warfarin with regard to efficacy and are associated with lower rates of bleeding, but costs limit use for some patients.



JAMA: 02 Nov 2020; 324:1765-1776
Chopard R, Albertsen IE, Piazza G
JAMA: 02 Nov 2020; 324:1765-1776 | PMID: 33141212
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Impact:

This program is still in alpha version.