Clinical specimens from 9 states during 2008-2010 were tested by PCR for Bordetella pertussis and Bordetella parapertussis. Of the positive samples, 13.99% were identified as B. parapertussis. It was ...concluded that B. parapertussis infections are more common than previously realized and contribute to cases thought to be vaccine failures.
Delivering linguistically competent care is critical to serving patients who have limited English proficiency (LEP) and represents a key national strategy to help reduce health disparities. Current ...acceptable standards of communication with patients who have LEP include providers communicating through professional interpretive services or bilingual providers speaking the patients' preferred language directly. This randomized clinical trial tests the effect of patient-provider language concordance on patient satisfaction.
Eighty-three adult Spanish-speaking patients with cancer were randomly assigned to receive care from either (1) 1 of 2 bilingual physicians speaking to the patient directly in Spanish or (2) the same physicians speaking English and using a professional interpreter service. Validated questionnaires were administered to assess patient-reported satisfaction with both provider communication and overall care. Transcripts of initial consultations were analyzed for content variations.
Compared with patients receiving care through professional interpretive services, patients cared for in direct Spanish reported significantly improved general satisfaction, technical quality of care (mean composite score MCS, 4.41 vs 4.06; P = .005), care team interpersonal manner (MCS, 4.37 vs 3.88; P = .004), communication (MCS, 4.50 vs 4.25; P = .018), and time spent with patient,(MCS, 4.30 vs 3.92; P = .028). Specific to physician communication, patients rated direct-Spanish care more highly in perceived opportunity to disclose concerns (MCS 4.91 vs 4.62; P = .001), physician empathy (MCS, 4.94 vs 4.59; P <.001), confidence in physician abilities (MCS, 4.84 vs 4.51; P = .001), and general satisfaction with their physician (MCS, 4.88 vs 4.59; P <.001). Analyzing the content of consultation encounters revealed differences between study arms, with the direct-Spanish arm having more physician speech related to patient history verification (mean number of utterances, 13 vs 9; P = .01) and partnering activities (mean utterances, 16 vs 5; P <.001). Additionally, patients in the direct-Spanish arm were more likely to initiate unprompted speech (mean utterances, 11 vs 3; P <.001) and asked their providers more questions (mean utterances, 11 vs 4; P = .007).
This study shows improved patient-reported satisfaction among patients with cancer who had LEP and were cared for in direct Spanish compared with interpreter-based communication. Further research into interventions to mitigate the patient-provider language barrier is necessary to optimize care for this population.
Existing clinical case definitions of pertussis are decades old and based largely on clinical presentation in infants and children, yet an increasing burden is borne by adolescents and adults who may ...manifest distinct signs/symptoms. Therefore, a "one-size-fits-all" clinical case definition is no longer appropriate. Seeking to improve pertussis diagnosis, the Global Pertussis Initiative (GPI) developed an algorithm that delineates the signs/symptoms of pertussis most common to 3 age groups: 0-3 months, 4 months to 9 years, and ≥10 years. These case definitions are based on clinical presentation alone, but do include recommendations on laboratory diagnostics. Until pertussis can be accurately diagnosed, its burden will remain underestimated, making the introduction of epidemiologically appropriate preventive strategies difficult. The proposed definitions are intended to be widely applicable and to encourage the expanded use of laboratory diagnostics. Determination of their utility and their sensitivity and/or specificity versus existing case definitions is required.
The SARS-CoV-2 Omicron BA.1 variant emerged in 2021
and has multiple mutations in its spike protein
. Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with ...Delta, and a marked change in its antigenicity increases Omicron's evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2, and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways
demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.
Costa Rica is an upper middle-income country in Central America with a vigorous public health system. We have studied the number of cases, hospitalizations, and deaths due to pertussis from 1961 to ...2018, in relation to vaccine coverage. Following the introduction of the fourth and fifth doses of DTP (booster doses) in 1973 there was a marked reduction of reported pertussis. In 2002 pertussis surveillance and laboratory diagnosis were improved. In 2007, Tdap post-partum immunization was introduced and then switched to intrapartum Tdap immunization in 2011. Of these two strategies post-partum vaccination seemed to have a greater effect in decreasing hospitalizations and deaths, nevertheless, since 2011 there has been only 4 infant deaths due to pertussis.
Treatment with nivolumab-ipilimumab combination therapy was found to improve overall survival compared with chemotherapy among patients with advanced non-small cell lung cancer (NSCLC) in the ...CheckMate 227 clinical trial. However, these drugs are substantially more expensive than chemotherapy and, given the high incidence of advanced NSCLC, the incorporation of dual immune checkpoint inhibitors into the standard of care could have substantial economic consequences.
To assess whether nivolumab-ipilimumab combination therapy is a cost-effective first-line treatment for patients with advanced NSCLC.
This economic evaluation designed a Markov model to compare the cost-effectiveness of nivolumab-ipilimumab combination therapy with platinum-doublet chemotherapy as first-line treatment for patients with advanced NSCLC. The Markov model was created to simulate patients with advanced NSCLC who were receiving either nivolumab-ipilimumab combination therapy or platinum-doublet chemotherapy. Transition probabilities, including disease progression, survival, and treatment toxic effects, were derived using data from the CheckMate 227 clinical trial. Costs and health utilities were obtained from published literature. Data analyses were conducted from November 2019 to September 2020.
Nivolumab-ipilimumab combination therapy.
The primary study outcomes were quality-adjusted life-years (QALYs) and cost in 2020 US dollars. Cost-effectiveness was measured using an incremental cost-effectiveness ratio (ICER), with an ICER less than $100 000 per QALY considered cost-effective. Model uncertainty was assessed with 1-way and probabilistic sensitivity analyses.
Treatment with nivolumab-ipilimumab combination therapy was associated with an increase in overall cost of $201 900 and improved effectiveness of 0.50 QALYs compared with chemotherapy, yielding an ICER of $401 700 per QALY. The study model was sensitive to the cost and duration of immunotherapy. Treatment with nivolumab-ipilimumab combination therapy became cost-effective when monthly treatment costs were reduced from $26 425 to $5058 (80.9% reduction) or when the maximum duration of immunotherapy was reduced from 24.0 months to 1.4 months. The model was not sensitive to assumptions about survival or programmed cell death 1 ligand 1 status. A probabilistic sensitivity analysis indicated that, at a willingness-to-pay threshold of $100 000 per QALY, nivolumab-ipilimumab combination therapy was less cost-effective than chemotherapy 99.9% of the time.
In this study, first-line treatment with nivolumab-ipilimumab combination therapy was not found to be cost-effective at current prices despite clinical trial data indicating that this regimen increases overall survival among patients with advanced NSCLC.
In the past decade, numerous sources have noted an increase in reported pertussis in highly immunized populations. This has been accompanied by a perceived change in disease epidemiology, ...characterized by a significant increase in reported pertussis incidence among adolescents and adults. In populations where children are routinely immunized, adolescents and adults now constitute the main source of infection in infants. However, a range of factors makes delineation of these epidemiologic trends difficult. Reported cases of pertussis represent only a fraction of the actual number of Bordetella pertussis symptomatic infections, because underconsulting, underrecognition and underdiagnosis are widespread and are a particular problem in adolescents and adults. Possible explanations for failure to diagnose pertussis include the heterogeneity in pertussis disease expression and low physician awareness and index of suspicion. Consequently defining pertussis from a clinical perspective is difficult, and this is reflected by a lack of consistency between case definitions. Although case definitions for specific circumstances have been established by the World Health Organization and the United States Centers for Disease Control, these are not universally useful, making intercountry comparisons and global evaluation difficult. Less-than-optimal and poorly performed laboratory tests, or their lack of availability, also make confirmation of B. pertussis infection difficult. To overcome these problems, clinical case definitions should be standardized for outbreak and endemic situations. Rapid, easy-to-use and inexpensive laboratory diagnostic techniques also must be made available and be widely implemented. In particular, polymerase chain reaction and single serum serology are 2 techniques that should be more widely adopted.
Abstract
Background
Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly ...their growth trajectories. They are at high risk of adverse outcomes in the first year of life.
Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional PM or disproportional DM) or SGA at birth were evaluated with anthropometric measurements and health outcomes.
Methods
Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed.
Results
Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio OR, 3.4 (95% confidence interval CI, 1.1–10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2–12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life.
Conclusions
ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.
Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.
PDF
