Development and Implementation of an Influenza Point-of-Care Testing Service in a Chain Community Pharmacy Setting

Point-of-care testing is becoming increasingly commonplace in community pharmacy settings. These tests are often used in the management of chronic disease, such as blood sugar, hemoglobin A1c and lipid levels, but can also be used for acute conditions such as influenza infection and group A streptococcus pharyngitis. When used for these acute infections, point-of-care tests can allow for pharmacist-initiated treatment. In this study, an influenza point-of-care testing service was developed and implemented in a chain community pharmacy setting and a retrospective review was conducted to assess the service. Of patients tested, 29% tested positive for influenza A and/or B; 92% of patients testing positive received a prescription as a result. While health insurance cannot be billed for the service due to current pharmacy reimbursement practices, this did not appear to negatively affect patient willingness to participate. As point-of-care testing services become more commonplace in community pharmacy settings, patient awareness will similarly increase and allow for more widespread access to acute outpatient care

Driving Simulator Performance Across the Lifespan: A Preliminary Study

OBJECTIVES Normal aging is associated with decline in abilities that may put an individual at increased riskfor a crash. Older individuals may have slowed processing speed and motor responses, a reduceduseful field of view (Ball et al., 1988), and greater difficulty with mental rotation (Armstrong etal., 1998). Although collision rates increase with age (Transportation Research Board, 1988), ithas been argued that specific age-related functional impairments, and not age itself, put one atrisk (Ball & Owsley, 2003). The goal of this study was to examine the relationship betweenaging and performance on driving simulations assessing specific components of driving—accident avoidance, divided attention, and navigation—and the degree to which they predict onroaddriving performance.METHODSForty control drivers (age 22 to 84; \u3c 50 yo, n = 14; 50-70 yo, n = 13; and \u3e 70 yo, n = 13)completed 3 simulations and an on-road driving evaluation. Exclusion criteria includedneurologic confounds, substance use and psychiatric disorders, as well as abnormalneuropsychological performance (based upon demographically-corrected norms). Thesimulations were presented on a Pentium III PC computer using a 17” monitor at 1280 x 1024resolution, and running STISIM Drive version 2.0 software (Systems Technology, Inc.;Hawthorne, CA). Hardware included a steering wheel, turn signal, and brake/accelerator pedals.The simulations consisted of 1) Advanced Routine and Emergency Driving (ARED), a 15-minute route simulating city/country driving, in which drivers must obey traffic signs, pass cars,and respond to high-risk crash scenarios; 2) Virtual City (VC), in which drivers must navigate toand from a location in a 5 x 5 block simulated city, and 3) Divided Attention, in which driversare to maintain a constant speed and lane position while responding to divided attention tasks inthe corner of the monitor. Participants also completed a 35-minute on-road assessment. Lastly,participants were assessed on a battery of neuropsychological tests. Earlier versions of thesimulations were predictive of on-road driving performance in an HIV-infected cohort (Marcotteet al., 2004). RESULTSThe three groups performed similarly on ARED (crashes, speeding tickets), as well as on the VCtask when the map was oriented to the same direction as the participant. On the other hand, olderparticipants had significantly more difficulty navigating when their orientation on the map wasreversed (e.g., the \u3c 50 group took 1.2 blocks beyond optimum to return from the destination; the50-70 and \u3e 70 years old groups took approximately 7.5 blocks). The three groups performedsimilarly with respect to lane deviation on the Divided Attention task, but the older groups hadincreased variability in speed maintenance, and the oldest group failed to respond to a greaternumber of divided attention stimuli (\u3c 50 yo = .3 (.83), 50-70 yo = 1.0 (1.3), \u3e 70 yo = 3.6 (2.7)).Although only one participant failed the on-road drive (50-70 yo), the percent of driversconsidered marginal or worse increased with age (7% vs. 25% vs. 55%). In a logistic regression,the simulator variables that best discriminated safe vs. marginal on-road came from the DividedAttention task: the number of missed stimuli and speed deviation, both of which require an intactuseful field of view and the shifting of gaze away from the roadway. Age did not enter into amodel that included these variables.CONCLUSIONSIn this study of normal, healthy controls, older participants drove similarly to young-to-middleaged participants on a simulation that most closely approximated real driving. Consistent withcognitive declines seen in normal aging, older participants had greater difficulty on a taskrequiring navigating when map orientation was reversed (perhaps indicative of impairedegocentric spatial abilities), as well as on a measure of driving-related divided attention, witholder participants appearing to allocate more attention to the roadway at the cost of attending andresponding to peripheral cues. Although older drivers had more difficulty during the on-road test,these difficulties were a function of deficits in the ability to divide attention efficiently, ratherthan aging per se.REFERENCESArmstrong, C.L., & Cloud, B. (1998). The emergence of spatial rotation deficits in dementia andnormal aging. Neuropsychology, 12(2), 208-217.Ball, K.K., Beard, B.L., Roenker, D.L., Miller, R.L., & Griggs, D.S. (1988). Age and visualsearch: Expanding the useful field of view. J Opt Soc Am A, 5(12), 2210-2219.Ball, K., & Owsley, C. (2003). Driving competence: It\u27s not a matter of age. J Am Geriatr Soc,51(10), 1499-1501.Marcotte, T.D., Wolfson, T., Rosenthal, T.J., Heaton, R.K., Gonzalez, R., Ellis, R.J., et al.(2004). A multimodal assessment of driving performance in HIV infection. Neurology, 63(8),1417-1422.Transportation Research Board. (1988). Transportation in an Aging Society, Vol 1. Washington,D.C.: National Research Council

Autoimmune hyperphosphatemic tumoral calcinosis in a patient with FGF23 autoantibodies

Hyperphosphatemic familial tumoral calcinosis (HFTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is an autosomal recessive disorder of ectopic calcification due to deficiency of or resistance to intact fibroblast growth factor 23 (iFGF23). Inactivating mutations in FGF23, N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO (KL) have been reported as causing HFTC/HHS. We present what we believe is the first identified case of autoimmune hyperphosphatemic tumoral calcinosis in an 8-year-old boy. In addition to the classical clinical and biochemical features of hyperphosphatemic tumoral calcinosis, the patient exhibited markedly elevated intact and C-terminal FGF23 levels, suggestive of FGF23 resistance. However, no mutations in FGF23, KL, or FGF receptor 1 (FGFR1) were identified. He subsequently developed type 1 diabetes mellitus, which raised the possibility of an autoimmune cause for hyperphosphatemic tumoral calcinosis. Luciferase immunoprecipitation systems revealed markedly elevated FGF23 autoantibodies without detectable FGFR1 or Klotho autoantibodies. Using an in vitro FGF23 functional assay, we found that the FGF23 autoantibodies in the patient's plasma blocked downstream signaling via the MAPK/ERK signaling pathway in a dose-dependent manner. Thus, this report describes the first case, to our knowledge, of autoimmune hyperphosphatemic tumoral calcinosis with pathogenic autoantibodies targeting FGF23. Identification of this pathophysiology extends the etiologic spectrum of hyperphosphatemic tumoral calcinosis and suggests that immunomodulatory therapy may be an effective treatment

Dietary Intake and Nitrogen Balance in British Army Infantry Recruits Undergoing Basic Training

We assessed dietary intake and nitrogen balance during 14 weeks of Basic Training (BT) in British Army Infantry recruits. Nineteen men (mean ± SD: age 19.9 ± 2.6 years, height: 175.7 ± 6.5 cm, body mass 80.3 ± 10.1 kg) at the Infantry Training Centre, Catterick (ITC(C)) volunteered. Nutrient intakes and 24-h urinary nitrogen balance were assessed in weeks 2, 6 and 11 of BT. Nutrient intake was assessed using researcher-led weighed food records and food diaries, and Nutritics professional dietary software. Data were compared between weeks using a repeated-measures analysis of variance (ANOVA) with statistical significance set at p ≤ 0.05. There was a significant difference in protein intake (g) between weeks 2 and 11 of BT (115 ± 18 vs. 91 ± 20 g, p = 0.02, ES = 1.26). There was no significant difference in mean absolute daily energy (p = 0.44), fat (p = 0.79) or carbohydrate (CHO) intake (p = 0.06) between weeks. Nitrogen balance was maintained in weeks 2, 6 and 11, but declined throughout BT (2: 4.6 ± 4.1 g, 6: 1.6 ± 4.5 g, 11: −0.2 ± 5.5 g, p = 0.07). A protein intake of 1.5 g·kg−1·d−1 may be sufficient in the early stages of BT, but higher intakes may be individually needed later on in BT

An evidence-based definition of anemia for singleton, uncomplicated pregnancies

BACKGROUND: The definition for anemia in pregnancy is outdated, derived from Scandinavian studies in the 1970\u27s to 1980\u27s. To identity women at risk of blood transfusion, a common cause of Severe Maternal Morbidity, a standard definition of anemia in pregnancy in a modern, healthy United States cohort is needed. OBJECTIVE: To define anemia in pregnancy in a United States population including a large county vs. private hospital population using uncomplicated patients. MATERIALS AND METHODS: Inclusion criteria were healthy women with the first prenatal visit before 20 weeks. Exclusion criteria included preterm birth, preeclampsia, hypertension, diabetes, short interval pregnancy (\u3c18 months), multiple gestation, abruption, and fetal demise. All women had iron fortification (Ferrous sulfate 325 mg daily) recommended. The presentation to care and pre-delivery hematocrits were obtained, and the percentiles determined. A total of 2000 patients were included, 1000 from the public county hospital and 1000 from the private hospital. Each cohort had 250 patients in each 2011, 2013, 2015, and 2018. The cohorts were compared for differences in the fifth percentile for each antepartum epoch. Student\u27s t-test and chi-squared statistical tests were used for analysis, p-value of ≤0.05 was considered significant. RESULTS: In the public and private populations, 777 and 785 women presented in the first trimester while 223 and 215 presented in the second. The women at the private hospital were more likely to be older, Caucasian race, nulliparous, and present earlier to care. The fifth percentile was compared between the women in the private and public hospitals and were clinically indistinguishable. When combining the cohorts, the fifth percentile for hemoglobin/hematocrit was 11 g/dL/32.8% in the first trimester, 10.3 g/dL/30.6% in the second trimester, and 10.0 g/dL/30.2% pre-delivery. CONCLUSIONS: Fifth percentile determinations were made from a combined cohort of normal, uncomplicated pregnancies to define anemia in pregnancy. Comparison of two different cohorts confirms that the same definition for anemia is appropriate regardless of demographics or patient mix

Does Protein Supplementation Support Adaptations to Arduous Concurrent Exercise Training? A Systematic Review and Meta-Analysis with Military Based Applications

We evaluated the impact of protein supplementation on adaptations to arduous concurrent training in healthy adults with potential applications to individuals undergoing military training. Peer-reviewed papers published in English meeting the population, intervention, comparison and outcome criteria were included. Database searches were completed in PubMed, Web of science and SPORTDiscus. Study quality was evaluated using the COnsensus based standards for the selection of health status measurement instruments checklist. Of 11 studies included, nine focused on performance, six on body composition and four on muscle recovery. Cohen’s d effect sizes showed that protein supplementation improved performance outcomes in response to concurrent training (ES = 0.89, 95% CI = 0.08–1.70). When analysed separately, improvements in muscle strength (SMD = +4.92 kg, 95% CI = −2.70–12.54 kg) were found, but not in aerobic endurance. Gains in fat-free mass (SMD = +0.75 kg, 95% CI = 0.44–1.06 kg) and reductions in fat-mass (SMD = −0.99, 95% CI = −1.43–0.23 kg) were greater with protein supplementation. Most studies did not report protein turnover, nitrogen balance and/or total daily protein intake. Therefore, further research is warranted. However, our findings infer that protein supplementation may support lean-mass accretion and strength gains during arduous concurrent training in physical active populations, including military recruits

Profiling microRNAs through development of the parasitic nematode Haemonchus identifies nematode-specific miRNAs that suppress larval development

Parasitic nematodes transition between dramatically different free-living and parasitic stages, with correctly timed development and migration crucial to successful completion of their lifecycle. However little is known of the mechanisms controlling these transitions. microRNAs (miRNAs) negatively regulate gene expression post-transcriptionally and regulate development of diverse organisms. Here we used microarrays to determine the expression profile of miRNAs through development and in gut tissue of the pathogenic nematode Haemonchus contortus. Two miRNAs, mir-228 and mir-235, were enriched in infective L3 larvae, an arrested stage analogous to Caenorhabditis elegans dauer larvae. We hypothesized that these miRNAs may suppress development and maintain arrest. Consistent with this, inhibitors of these miRNAs promoted H. contortus development from L3 to L4 stage, while genetic deletion of C. elegans homologous miRNAs reduced dauer arrest. Epistasis studies with C. elegans daf-2 mutants showed that mir-228 and mir-235 synergise with FOXO transcription factor DAF-16 in the insulin signaling pathway. Target prediction suggests that these miRNAs suppress metabolic and transcription factor activity required for development. Our results provide novel insight into the expression and functions of specific miRNAs in regulating nematode development and identify miRNAs and their target genes as potential therapeutic targets to limit parasite survival within the host

Delivering clinical studies of exercise in the COVID-19 pandemic: challenges and adaptations using a feasibility trial of isometric exercise to treat hypertension as an exemplar.

The COVID-19 pandemic has significantly impacted on the delivery of clinical trials in the UK, posing complicated organisational challenges and requiring adaptations, especially to exercise intervention studies based in the community. We aim to identify the challenges of public involvement, recruitment, consent, follow-up, intervention and the healthcare professional delivery aspects of a feasibility study of exercise in hypertensive primary care patients during the COVID-19 pandemic. While these challenges elicited many reactive changes which were specific to, and only relevant in the context of 'lockdown' requirements, some of the protocol developments that came about during this unprecedented period have great potential to inform more permanent practices for carrying out this type of research. To this end, we detail the necessary adaptations to many elements of the feasibility study and critically reflect on our approach to redesigning and amending this ongoing project in order to maintain its viability to date. Some of the more major protocol adaptations, such as moving the study to remote means wherever possible, had further unforeseen and undesirable outcomes (eg, additional appointments) with regards to extra resources required to deliver the study. However, other changes improved the efficiency of the study, such as the remote informed consent and the direct advertising with prescreening survey. The adaptations to the study have clear links to the UK Plan for the future of research delivery. It is intended that this specific documentation and critical evaluation will help those planning or delivering similar studies to do so in a more resource efficient and effective way. In conclusion, it is essential to reflect and respond with protocol changes in the current climate in order to deliver clinical research successfully, as in the case of this particular study. [Abstract copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.

Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections

The specificity of CD8+ T cell responses can vary dramatically between primary and secondary infections. For example, NP366–374/Db- and PA224–233/Db-specific CD8+ T cells respond in approximately equal numbers to a primary influenza virus infection in C57BL/6 mice, whereas NP366–374/Db-specific CD8+ T cells dominate the secondary response. To investigate the mechanisms underlying this changing pattern of immunodominance, we analyzed the role of antigen presentation in regulating the specificity of the T cell response. The data show that both dendritic and nondendritic cells are able to present the NP366–374/Db epitope, whereas only dendritic cells effectively present the PA224–233/Db epitope after influenza virus infection, both in vitro and in vivo. This difference in epitope expression favored the activation and expansion of NP366–374/Db-specific CD8+ memory T cells during secondary infection. The data also show that the immune response to influenza virus infection may involve T cells specific for epitopes, such as PA224–233/Db, that are poorly expressed at the site of infection. In this regard, vaccination with the PA224–233 peptide actually had a detrimental effect on the clearance of a subsequent influenza virus infection. Thus, differential antigen presentation impacts both the specificity of the T cell response and the efficacy of peptide-based vaccination strategies