Response to the 2004-2005 influenza vaccine shortage in veterans with spinal cord injuries and disorders and their providers

BACKGROUND/OBJECTIVES: To assess patient and provider behaviors regarding influenza vaccination, diagnosis, and testing strategies and the availability of influenza vaccine during the 2004-2005 nationwide influenza vaccine shortage. DESIGN/METHODS: Multisite, anonymous, cross-sectional surveys of patients and providers and qualitative interviews after the 2004-2005 influenza season. SETTING: Department of Veterans Affairs (VA) health care facilities with spinal cord injury centers or clinics. PARTICIPANTS: Stratified random sample of 3,958 veterans with spinal cord injuries and disorders (SCI & D; 31% response rate), 177 providers who treat persons with SCI&D, and 17 key informants. RESULTS: Most patient respondents (96.1%) reported awareness of a vaccine shortage (n = 938). When asked whether the shortage affected their ability to get the vaccine, 64.8% said they had no problem, whereas 12.1% reported an inability to get the vaccine. The vaccination rate was 71.8%; most veterans received the vaccine early (October-November) at the VA, and vaccination rates increased with age (P < 0.0001). Although vaccine shortages were reported by 47.5% of provider survey respondents (n = 177), most reported that the vaccine shortage did not affect availability of vaccine for patients with SCI&D. Few clinicians conducted diagnostic tests for influenza more often than in past years (4.9%). Although providers reported shortages at 12 centers (n = 23), patients with SCI&D had priority at 11 of 12 centers. CONCLUSIONS: Most patients were aware of the vaccine shortage, and the vaccination rate remained high and comparable with previous years. VA providers and facilities targeted SCI&D as a high-risk group and prioritized use of the limited vaccine supply for them.     

Emergency Department Presentation of Superior Mesenteric Artery Syndrome: Two Cases in Marine Corps Recruits

Background: Superior mesenteric artery (SMA) syndrome is a relatively rare etiology of proximal intestinal obstruction. Obstruction results from marked narrowing of the angle between the SMA and aorta, causing compression of the third portion of the duodenum, most commonly as a result of precipitous weight loss. Intermittent non-specific symptoms at presentation often result in a delayed diagnosis, thus the importance of being aware of this condition. Objective: To familiarize emergency physicians with the presentation of SMA syndrome and discuss its diagnosis and management in the emergency department (ED). Case Report: We present two cases of SMA syndrome identified in Marine Corps recruits presenting to our ED. Conclusion: Emergency physicians should include SMA syndrome in the differential diagnosis of abdominal pain and vomiting in individuals with predisposing factors.     

Ontogeny of Vestibular Compound Action Potentials in the Domestic Chicken

Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of –0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately –25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6–P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 μV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.     

Further evidence for association of GRK3 to bipolar disorder suggests a second disease mutation

OBJECTIVES: Two genome-wide linkage surveys suggest chromosome 22q12 may contain a susceptibility locus for bipolar disorder (BPD) in the immediate region of the gene G protein receptor kinase-3 (GRK3). We previously published evidence that a single nucleotide polymorphism (SNP) in the promoter region of GRK3, designated P5, was associated with BPD. This SNP, however, was too rare (allele frequency 0.007) to explain the evidence for linkage. METHODS: To identify other SNPs or haplotypes associated with illness, we have now sequenced an additional 28-kb genomic segment of GRK3 and tested an additional 35 SNPs for association with BPD in 181 Caucasian nuclear families. RESULTS: Transmission disequilibrium test analyses identified two closely related disease-associated haplotypes defined by four SNPs located upstream of the promoter region: transmission to nontransmission ratios=54:22 and 20:9, odds ratios=2.50 and 2.36, and P values=0.0009 and 0.05. The best P value remained significant after correction for multiple testing. These two haplotypes were found on an entirely different set of chromosomes from the previously identified SNP P5. They had a combined frequency of approximately 0.10 and, therefore, a much greater population attributable risk for disease than the previously identified P5 haplotype. CONCLUSIONS: These data provide evidence that at least two distinct haplotypes, and possibly two or more different underlying mutations, in GRK3 might be associated with BPD. These new findings add support for the hypothesis that a dysregulation in GRK3 expression alters signaling desensitization and thereby predisposes to the development of BPD.     

Disparities Rank High in Prioritized Research,Systems and Service Delivery Needs in Missouri

Objectives: An essential function of public health is to conduct research and in Missouri, a research agenda was initiated to promote the health and well being of women and children. In 2005, a survey was emailed to 180 maternal and child health (MCH) researchers throughout the state, with 130 responding for a 72.2% response rate. These individuals were asked to select research priorities out of a list of 130 research agenda items, identify personal areas of expertise, and to recommend new research topics. Results: Results focused on identifying research priorities and research experts. The first, of the five leading research priorities, was researching disparities in terms of age, race, ethnicity, and gender, regarding sexually transmitted diseases, chronic disease, birth outcomes, prenatal care, access to care, childhood exposure to lead, immunizations and vaccinations, mental health, substance abuse, and oral health. The four remaining, of the top five specific research priorities, in order of priority, included (2) reducing barriers to health care access, (3) constructing research ecologically, (4) increasing access to oral health care for children, and (5) reducing the prevalence of children who are at-risk for being overweight. Of the 130 respondents, 83.1% reported at least one area of expertise, with a mean of 7.4 areas of expertise per respondent (range 0–41). Forty percent of the respondents reported health care access as an area of expertise, followed by school health, community development, family support, and pre/post natal care (38.5%, 36.2%, 30.0%, 28.5%, and 26.9%) respectively. Interestingly, only 17.7% of the respondents reported disparities as their area of expertise. Conclusions: The goal of moving innovations towards changes in practice can only happen when resources are available to assess innovations and communities are ready to implement those innovations. The prioritization of this MCH research agenda, prioritized by a community of MCH researchers with expertise in conducting MCH related research, is the first step towards changes in practice, ultimately leading to improvements in the health of women and children in Missouri.     

Cyclin Pathway Genomic Alterations Across 190,247 Solid Tumors: Leveraging Large‐Scale Data to Inform Therapeutic Directions

BackgroundWe describe the landscape of cyclin and interactive gene pathway alterations in 190,247 solid tumors.MethodsUsing comprehensive genomic profiling (315 genes, >500× coverage), samples were analyzed for alterations in activating/sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), hormone genes (estrogen receptor 1 [ESR1], androgen receptor [AR]), and co‐alterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1).ResultsAlterations in at least one cyclin activating/sensitizing gene occurred in 24% of malignancies. Tumors that frequently harbored at least one cyclin alteration were brain gliomas (47.1%), esophageal (40.3%) and bladder cancer (37.9%), and mesotheliomas (37.9%). The most frequent alterations included CDKN2A (13.9%) and CDKN2B loss (12.5%). Examples of unique patterns of alterations included CCND1 amplification in breast cancer (17.3%); CDK4 alterations in sarcomas (12%); CCND2 in testicular cancer (23.4%), and SMARCB1 mutations in kidney cancer (3% overall, 90% in malignant rhabdoid tumors). Alterations in resistance genes RB1 and CCNE1 affected 7.2% and 3.6% of samples. Co‐occurrence analysis demonstrated a lower likelihood of concomitant versus isolated alterations in cyclin activating/sensitizing and resistance genes (odds ratio [OR], 0.35; p < .001), except in colorectal, cervical, and small intestine cancers. AR and cyclin activating/sensitizing alterations in prostate cancer co‐occurred more frequently (vs. AR alterations and wild‐type cyclin activating/sensitizing alterations) (OR, 1.79; p < .001) as did ESR1 and cyclin activating/sensitizing alterations in breast (OR, 1.62; p < .001) and cervical cancer (OR, 4.08; p = .04) (vs. ESR1 and cyclin wild‐type activating/sensitizing alterations).ConclusionCyclin pathway alterations vary according to tumor type/histology, informing opportunities for targeted therapy, including for rare cancers.Implications for PracticeCyclin pathway genomic abnormalities are frequent in human solid tumors, with substantial variation according to tumor site and histology. Opportunities for targeted therapy emerge with comprehensive profiling of this pathway.