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The role of low-dose thrombolysis in the reduction of pulmonary artery pressure in moderate pulmonary embolism (PE) has not been investigated. Because the lungs are very sensitive to thrombolysis, we postulated that effective and safe thrombolysis might be achieved by a lower dose of tissue plasminogen activator. The purpose of the present study was to evaluate the role of this “safe dose” thrombolysis in the reduction of pulmonary artery pressure in moderate PE. During a 22-month period, 121 patients with moderate PE were randomized to receive a “safe dose” of tissue plasminogen activator plus anticoagulation (thrombolysis group [TG], n = 61 patients) or anticoagulation alone (control group [CG], n = 60). The primary end points consisted of pulmonary hypertension and the composite end point of pulmonary hypertension and recurrent PE at 28 months. Pulmonary hypertension and the composite end point developed in 9 of 58 patients (16%) in the TG and 32 of 56 patients (57%) in the CG (p <0.001) and 9 of 58 patients (16%) in the TG and 35 of 56 patients (63%) in the CG (p <0.001), respectively. The secondary end points were total mortality, the duration of hospital stay, bleeding at the index hospitalization, recurrent PE, and the combination of mortality and recurrent PE. The duration of hospitalization was 2.2 ± 0.5 days in the TG and 4.9 ± 0.8 days in the CG (p <0.001). The combination of death plus recurrent PE was 1 (1.6%) in TG and 6 (10%) in the CG (p = 0.0489). No bleeding occurred in any group, and despite a positive trend in favor of a “safe dose” thrombolysis, no significant difference was noted in the rate of individual outcomes of death and recurrent PE when assessed independently. In conclusion, the results from the present prospective randomized trial suggests that “safe dose” thrombolysis is safe and effective in the treatment of moderate PE, with a significant immediate reduction in the pulmonary artery pressure that was maintained at 28 months.

The goal of emergency airway management is first pass success without adverse events (FPS-AE). Anatomically difficult airways are well appreciated to be an obstacle to this goal. However, little is known about the effect of the physiologically difficult airway with regard to FPS-AE. This study evaluates the effects of both anatomically and physiologically difficult airways on FPS-AE in patients undergoing rapid sequence intubation (RSI) in the emergency department (ED). We analyzed prospectively recorded intubations in a continuous quality improvement database between July 1, 2014-June 30, 2018. Emergency medicine (EM) or emergency medicine/pediatric (EM-PEDS) residents recorded patient, operator, and procedural characteristics on all consecutive adult RSIs performed using a direct or video laryngoscope. The presence of specific anatomically and physiologically difficult airway characteristics were also documented by the operator. Patients were analyzed in four cohorts: 1) no anatomically or physiologically difficult airway characteristics; 2) one or more anatomically difficult airway characteristics; 3) one or more physiologically difficult airway characteristics; and 4) both anatomically and physiologically difficult airway characteristics. The primary outcome was FPS-AE. We performed a multivariable logistic regression analysis to determine the association between anatomically difficult airways or physiologically difficult airways and FPS-AE. A total of 1513 intubations met inclusion criteria and were analyzed. FPS-AE for patients without any difficult airway characteristics was 92.4%, but reduced to 82.1% (difference = -10.3%, 95% confidence interval (CI), -14.8% to -5.6%) with the presence of one or more anatomically difficult airway characteristics, and 81.7% (difference = -10.7%, 95% CI, -17.3% to -4.0%) with the presence of one or more physiologically difficult airway characteristics. FPS-AE was further reduced to 70.9% (difference = -21.4%, 95% CI, -27.0% to -16.0%) with the presence of both anatomically and physiologically difficult airway characteristics. The adjusted odds ratio (aOR) of FPS-AE was 0.37 [95% CI, 0.21 - 0.66] in patients with anatomically difficult airway characteristics and 0.36 [95% CI, 0.19 - 0.67] for patients with physiologically difficult airway characteristics, compared to patients with no difficult airway characteristics. Patients who had both anatomically and physiologically difficult airway characteristics had a further decreased aOR of FPS-AE of 0.19 [95% CI, 0.11 - 0.33]. FPS-AE is reduced to a similar degree in patients with anatomically and physiologically difficult airways. Operators should assess and plan for potential physiologic difficulty as is routinely done for anatomically difficulty airways. Optimization strategies to improve FPS-AE for patients with physiologically difficult airways should be studied in randomized controlled trials.

Streptococcus pneumoniae is the main cause of invasive bacterial disease in children aged younger than 2 years. Navajo and White Mountain Apache children have some of the highest rates of invasive pneumococcal disease documented in the world. We aimed to assess the safety and efficacy of a seven-valent polysaccharide protein conjugate pneumococcal vaccine (PnCRM7) against such disease. In a group-randomised study, we gave this vaccine to children younger than 2 years from the Navajo and White Mountain Apache Indian reservations; meningococcal type C conjugate vaccine (MnCC) served as the control vaccine. Vaccine schedules were determined by age at enrolment. We recorded episodes of invasive pneumococcal disease and serotyped isolates. Analyses were by intention to treat and per protocol. 8292 children enrolled in the trial. In the per protocol analysis of the primary efficacy group (children enrolled by 7 months of age) there were eight cases of vaccine serotype disease in the controls and two in the PnCRM7 group; in the intention-to-treat analysis we noted 11 cases of vaccine serotype disease in the MnCC control group and two in the PnCRM7 group. After group randomisation had been controlled for, the per protocol primary efficacy of PnCRM7 was 76·8% (95% CI −9·4% to 95·1%) and the intention-to-treat total primary efficacy was 82·6% (21·4% to 96·1%). PnCRM7 vaccine prevents vaccine serotype invasive pneumococcal disease even in a high risk population. Other regions with similar disease burden should consider including this vaccine in the routine childhood vaccine schedule.

The BNT162b2 (Pfizer-BioNTech) mRNA COVID-19 vaccine has demonstrated high efficacy in preventing infection with SARS-CoV-2 (the virus that causes COVID-19) in randomized placebo-controlled Phase III trials in persons aged 12-17 years (referred to as adolescents in this report) (1); however, data on real-word vaccine effectiveness (VE) among adolescents are limited (1-3). As of December 2021, the Pfizer-BioNTech vaccine is approved by the Food and Drug Administration (FDA) for adolescents aged 16-17 years and under FDA emergency use authorization for those aged 12-15 years. In a prospective cohort in Arizona, 243 adolescents aged 12-17 years were tested for SARS-CoV-2 by reverse transcription-polymerase chain reaction (RT-PCR) each week, irrespective of symptoms, and upon onset of COVID-19-like illness during July 25-December 4, 2021; the SARS-CoV-2 B.1.617.2 (Delta) variant was the predominant strain during this study period. During the study, 190 adolescents contributed fully vaccinated person-time (≥14 days after receiving 2 doses of Pfizer-BioNTech vaccine), 30 contributed partially vaccinated person-time (receipt of 1 dose or receipt of 2 doses but with the second dose completed <14 days earlier), and 66 contributed unvaccinated person-time. Using the Cox proportional-hazards model, the estimated VE of full Pfizer-BioNTech vaccination for preventing SARS-CoV-2 infection was 92% (95% CI = 79%-97%), adjusted for sociodemographic characteristics, health information, frequency of social contact, mask use, location, and local virus circulation. These findings from a real-world setting indicate that 2 doses of Pfizer-BioNTech vaccine are highly effective in preventing SARS-CoV-2 infection among Arizona adolescents. CDC recommends COVID-19 vaccination for all eligible persons in the United States, including persons aged 12-17 years.

Clinical presentation, outcomes, and duration of COVID-19 has ranged dramatically. While some individuals recover quickly, others suffer from persistent symptoms, collectively known as long COVID, or post - acute sequelae of SARS-CoV-2 (PASC). Most PASC research has focused on hospitalized COVID-19 patients with moderate to severe disease. We used data from a diverse population-based cohort of Arizonans to estimate prevalence of PASC, defined as experiencing at least one symptom 30 days or longer, and prevalence of individual symptoms. There were 303 non-hospitalized individuals with a positive lab-confirmed COVID-19 test who were followed for a median of 61 days (range 30–250). COVID-19 positive participants were mostly female (70%), non-Hispanic white (68%), and on average 44 years old. Prevalence of PASC at 30 days post-infection was 68.7% (95% confidence interval: 63.4, 73.9). The most common symptoms were fatigue (37.5%), shortness-of-breath (37.5%), brain fog (30.8%), and stress/anxiety (30.8%). The median number of symptoms was 3 (range 1–20). Amongst 157 participants with longer follow-up (≥60 days), PASC prevalence was 77.1%.

Background Obesity rates are recognized to be at epidemic levels throughout much of the world, posing significant threats to both the health and financial security of many nations. The causes of obesity can vary but are often complex and multifactorial, and while many contributing factors can be targeted for intervention, an understanding of where these interventions are needed is necessary in order to implement effective policy. This has prompted an interest in incorporating spatial context into the analysis and modeling of obesity determinants, especially through the use of geographically weighted regression (GWR). Method This paper provides a critical review of previous GWR models of obesogenic processes and then presents a novel application of multiscale (M)GWR using the Phoenix metropolitan area as a case study. Results Though the MGWR model consumes more degrees of freedom than OLS, it consumes far fewer degrees of freedom than GWR, ultimately resulting in a more nuanced analysis that can incorporate spatial context but does not force every relationship to become local a priori . In addition, MGWR yields a lower AIC and AICc value than GWR and is also less prone to issues of multicollinearity. Consequently, MGWR is able to improve our understanding of the factors that influence obesity rates by providing determinant-specific spatial contexts. Conclusion The results show that a mix of global and local processes are able to best model obesity rates and that MGWR provides a richer yet more parsimonious quantitative representation of obesity rate determinants compared to both GWR and ordinary least squares.

Low maximally attained lung function increases the risk of chronic obstructive pulmonary disease irrespective of the subsequent rate of lung function decline. We aimed to determine if there were individuals with a distinct, persistently low lung function trajectory in the CRS (Tucson Children's Respiratory Study). The CRS, an ongoing birth cohort study, enrolled 1,246 participants between 1980 and 1984. Latent class linear mixed effects modeling of the ratio of FEV1 to FVC was used to identify distinct lung function trajectories among participants with two or more spirometry measurements between ages 11 and 32 years. Among 599 participants with 2,142 observations, a model with two distinct trajectories (a low trajectory [n = 56; 9.3%] and a normal trajectory) fit the data significantly better than a model with only one trajectory (P = 0.0007). As compared with those with a normal trajectory, participants with a persistently low trajectory were more likely to have a history of maternal asthma (20.0% vs. 9.9%; P = 0.02); early life lower respiratory illness caused by respiratory syncytial virus (41.2% vs. 21.4%; P = 0.001); and physician-diagnosed active asthma at age 32 years (43.9% vs. 16.2%; P < 0.001). Individuals with a persistently low trajectory also demonstrated lower lung function as measured by average maximal expiratory flow at functional residual capacity during infancy and at age 6 years. A distinct group of individuals in a nonselected population demonstrates a persistently low lung function trajectory that may be partly established at birth and predisposes them to chronic obstructive pulmonary disease later in life.

To estimate incidence rates of diabetes and associated risk factors among participants of the Strong Heart Study. Of the 4,549 Strong Heart Study participants examined at baseline, 3,638 returned for a similar examination after an average of 4 years. The 1985 World Health Organization criteria for diabetes were used to identify new diabetes cases. Rates of diabetes among participants who did not have diabetes at baseline examination were determined. The relationships between the incidence rates of diabetes and a number of risk factors measured at baseline examination were studied. Significant variables associated with the development of diabetes included triglycerides, obesity, fasting plasma glucose, insulin, and degree of American Indian blood among participants with NGT at baseline. For those with IGT at baseline, significant predictors included fasting plasma glucose, 2-h glucose, BMI, degree of American Indian blood, and albuminuria. The high incidence rates found in this study were alarming. To slow down the rapid increase of this disease in the American Indian population, preventive programs must be designed and implemented. Patients with IGT should be treated with diabetes medication or put on a rigid weight-reduction program to reduce the risk of progression to diabetes.

Background: Cadmium is a widespread toxic metal with potential cardiovascular effects, but no studies have evaluated cadmium and incident cardiovascular disease. We evaluated the association of urine cadmium concentration with cardiovascular disease incidence and mortality in a large population-based cohort. Methods: We conducted a prospective cohort study of 3348 American Indian adults 45—74 years of age from Arizona, Oklahoma, and North and South Dakota, who participated in the Strong Heart Study in 1989—1991. Urine cadmium was measured using inductively coupled plasma mass spectrometry. Follow-up extended through 31 December 2008. Results: The geometric mean cadmium level in the study population was 0.94 μg/g (95% confidence interval [CI] = 0.92—0.96). We identified 1084 cardiovascular events, including 400 deaths. After adjustment for sociodemographic and cardiovascular risk factors, the hazard ratios (HRs) (comparing the 80th to the 20th percentile of urine cadmium concentrations) was 1.43 for cardiovascular mortality (95% CI = 1.21—1.70) and 1.34 for coronary heart disease mortality (1.10—1.63). The corresponding HRs for incident cardiovascular disease, coronary heart disease, stroke, and heart failure were 1.24 (1.11—1.38), 1.22 (1.08—1.38), 1.75 (1.17—2.59), and 1.39 (1.01—1.94), respectively. The associations were similar in most study subgroups, including never-smokers. Conclusions: Urine cadmium, a biomarker of long-term exposure, was associated with increased cardiovascular mortality and increased incidence of cardiovascular disease. These findings support that cadmium exposure is a cardiovascular risk factor.

We conducted surveillance of respiratory syncytial virus (RSV) genomic sequences for 100 RSV-A and 27 RSV-B specimens collected during November 2022-April 2023 in Arizona, USA. We identified mutations within prefusion F-protein antigenic sites in both subtypes. Continued genomic surveillance will be critical to ensure RSV vaccine effectiveness.