Surveillance for Guillain-Barré syndrome after influenza vaccination among U.S. Medicare beneficiaries during the 2017–2018 season

BackgroundThe U.S. Food and Drug Administration and the Centers for Medicare & Medicaid Services have been actively monitoring the risk of Guillain-Barré syndrome (GBS) following influenza vaccination among Fee-for-Service (FFS) Medicare beneficiaries every season since 2008. We present our evaluation of the GBS risk following influenza vaccinations during the 2017–2018 season.MethodsWe implemented a multilayered approach to active safety surveillance that included near real-time surveillance early in the season, comparing GBS rates post-vaccination during the 2017–2018 season with rates from five prior seasons using the Updating Sequential Probability Ratio Test (USPRT), and end-of-season self-controlled risk interval (SCRI) analyses.ResultsWe identified approximately 16 million influenza vaccinations. The near real-time surveillance did not signal for a potential 2.5-fold increased GBS risk either in days 8–21 or 1–42 post-influenza vaccination. In the SCRI analyses, we did not detect statistically significant increased GBS risks among influenza-vaccinated Medicare beneficiaries ≥65 years for either the 8–21 or 1–42-day risk windows for all seasonal vaccines combined, high-dose vaccine, or standard-dose vaccines; we did detect an increased GBS risk in days 8–21 post-vaccination for individuals vaccinated with the adjuvanted vaccine (OR: 3.75; 95% CI: 1.01, 13.96), although this finding was not statistically significant after multiplicity adjustment (p = 0.146).ConclusionsOur multilayered surveillance approach—which allows for early detection of elevated GBS risk and provides reliable end-of-season SCRI estimates of effect size—did not identify an increased GBS risk following 2017–2018 influenza vaccinations. The slightly increased GBS risk with the adjuvanted vaccine, which was not statistically significant following multiplicity adjustment, is consistent with the package inserts of all U.S.-licensed influenza vaccines, which warn of a potential low increased GBS risk. The benefits of influenza vaccines in preventing morbidity and mortality heavily outweigh this potential risk.     

Micro-geographic targeting for precision public policy: Analysis of child sex ratio across 587,043 census villages in India, 2011

Child sex ratio (CSR) is a marker of disproportionate sex ratio at birth and discriminatory practices that lead to differential survival in early childhood by sex. We used the 2011 Census on rural India to present the first local analysis of CSR across 587,043 villages. In our multilevel analysis considering villages, tehsils, districts, and states/union territories, we found 96% of the total variation in CSR to be attributed to villages. About 39% of the villages were ‘boy’ areas (CSR≤88 girls per 100 boys) and another 12% had deficits in girls (88 < CSR≤93), while 11% fell in the normal range of CSR (93<CSR≤98), another 10% had 98 < CSR≤103, and the remaining 28% were ‘girl’ villages (CSR>103). The magnitude of local variation in CSR was heterogeneous across states/union territories and districts. Our findings provide timely evidence to inform localized programmes like Beti Bachao, Beti Padhao to be implemented with greater precision.     

Clinical Features of Spontaneous Remission in the Classic Fever of Unknown Origin: A Retrospective Study

ObjectiveTo summarize the clinical features of spontaneous remission in classic fever of unknown origin (FUO).MethodsMedical records of 121 patients diagnosed with FUO at admission in Peking Union Medical College Hospital between January 2018 and June 2018 were reviewed retrospectively. Patients who were discharged without etiological diagnoses were followed for 2 years. The clinical features and outcomes of these patients were summarized. Multivariate logistic regression was used to analyze related factors of spontaneous remission of FUO.ResultsAfter excluding 2 patients who lost to follow-up, the etiology of 119 FUO patients were as follows: infectious diseases in 30 (25.2%) cases, connective tissue diseases in 28 (23.5%) cases, tumor diseases in 8 (6.7%) cases, other diseases in 6 (5.0%) cases, and unknown diagnoses in 47 (39.5%) cases. Totally, 41 patients experienced spontaneous remission of fever (the median time from onset to remission was 9 weeks, ranging from 4 to 39 weeks). In patients with spontaneous remission in FUO, lymphadenopathy was less common clinical manifestation, the levels of inflammatory markers including leukocyte count, neutrophil count, neutrophil ratio, C-reactive protein, and ferritin were lower, and the proportion of CD8 positive T lymphocytes expressing CD38 was lower. Multivariate logistic regression analysis of factors with a P-value < 0.05 in univariate analysis shown that white blood cell count (OR: 0.545, 95%CI: 0.306-0.971, P = 0.039), neutrophil count (OR: 2.074, 95%CI: 1.004-4.284, P = 0.049), and proportion of neutrophils (OR: 0.928, 95%CI: 0.871-0.990, P = 0.022) were independent significant factors associated with spontaneous remission in FUO.ConclusionsThis study suggested that most patients discharged with undiagnosed classic FUO would remit spontaneously. Thus, for patients with stable clinical conditions, follow-up and observation could be the best choice. Patients with lower level of some inflammatory factors may have a high likelihood of spontaneous remission in classic FUO.     

Networking in rare cancers: What was done,what's next

Rare cancers represent approximately one fourth of all cancers. Despite being a heterogeneous group of diseases, they share similar problems including lack of expertise, issues in quality of care, discrepancies in outcome and limitations in research. Traditionally, centralization of rare cancer patients to dedicated reference centres has been recommended to ensure expertise, multidisciplinarity and access to innovation. However, centralization entails health migration, rationing of resources and a potential failure in routine care. By ensuring appropriate care to all patients regardless the point of access, networking seems the most appropriate answer to the problem of rare cancers. The launch of the Joint Action on Rare Cancers as well as the recent establishment of the European Reference Networks represent for the first time a concrete opportunity to make networking a reality and ultimately reduce disparities and improve outcome in these diseases.     

Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

IntroductionNo previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values).MethodsEmbase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis.ResultsOf 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria.Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4–94; specificity 98.5–99; accuracy 97.2–97.7; PPV 88.9–99.1; NPV 95.8–98.9).ConclusionsXpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance.Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB.     

“Please Keep Mom Alive One More Day”—Clashing Directives of a Dying Patient and Her Surrogate

All medical care providers are legally and ethically bound to respect their patients' wishes. However, as patients lose decision-making capacity and approach end of life, their families or surrogates, who are confronted with grief, fear, self-doubt, and/or uncertainty, may ask physicians to provide treatment that contradicts the patients' previously stated wishes. Our work discusses the legal and ethical issues surrounding such requests and provides guidance for clinicians to ethically and compassionately respond—without compromising their professional and moral obligations to their patients.     

Structural changes in collagen fibrils across a mineralized interface revealed by cryo-TEM

The structure of the mineralized collagen fibril, which is the basic building block of mineralized connective tissues, is critical to its function. We use cryo-TEM to study collagen structure at a well-defined hard–soft tissue interface, across which collagen fibrils are continuous, in order to evaluate changes to collagen upon mineralization. To establish a basis for the analysis of collagen banding, we compared cryo-TEM images of rat-tail tendon collagen to a model based on the X-ray structure. While there is close correspondence of periodicity, differences in band intensity indicate fibril regions with high density but lacking order, providing new insight into collagen fibrillar structure. Across a mineralized interface, we show that mineralization results in an axial contraction of the fibril, concomitant with lateral expansion, and that this contraction occurs only in the more flexible gap region of the fibril. Nevertheless, the major features of the banding pattern are not significantly changed, indicating that the axial arrangement of molecules remains largely intact. These results suggest a mechanism by which collagen fibrils are able to accommodate large amounts of mineral without significant disruption of their molecular packing, leading to synergy of mechanical properties.     

The role of treatment delivery factors in exposure-based cognitive behavioral therapy for panic disorder with agoraphobia

Treatment delivery factors (i.e., therapist adherence, therapist competence, and therapeutic alliance) are considered to be important for cognitive behavioral therapy (CBT) for panic disorder and agoraphobia (PD/AG). In the current study, four independent raters conducted process evaluations based on 168 two-hour videotapes of 84 patients with PD/AG treated with exposure-based CBT. Two raters evaluated patients’ interpersonal behavior in Session 1. Two raters evaluated treatment delivery factors in Session 6, in which therapists provided the rationale for conducting exposure exercises. At the 6-month follow-up, therapists’ adherence (r = 0.54) and therapeutic alliance (r = 0.31) were significant predictors of changes in agoraphobic avoidance behavior; therapist competence was not associated with treatment outcomes. Patients’ interpersonal behavior in Session 1 was a significant predictor of the therapeutic alliance in Session 6 (r = 0.17). The findings demonstrate that treatment delivery factors, particularly therapist adherence, are relevant to the long-term success of CBT for PD/AG.