The importance of falsification endpoints in observational studies of vaccination to prevent severe disease: A critique of a harm-benefit analysis of BNT162b2 vaccination of 5- to 11-year-olds.

We explore one systematic review and meta-analysis of both observational and randomized studies examining COVID-19 vaccines in 5- to 11-year-olds, which reported substantial benefits associated with vaccinating this age group. We discuss the limitations of the individual studies that were used to estimate vaccination benefits. The review included five observational studies that evaluated vaccine effectiveness (VE) against COVID-19 severe disease or hospitalization. All five studies failed to adequately assess differences in underlying health between vaccination groups. In terms of vaccination harms, looking only at the randomized studies, a significantly higher odds of adverse events was identified among the vaccinated compared with the unvaccinated. Observational studies are at risk of overestimating the effectiveness of vaccines against severe disease if healthy vaccinee bias is present. Falsification endpoints can provide valuable information about underlying healthy vaccinee bias. Studies that have not adequately ruled out bias due to better health among the vaccinated or more vaccinated should be viewed as unreliable for estimating the VE of COVID-19 vaccination against severe disease and mortality. Existing systematic reviews that include observational studies of the COVID-19 vaccine in children may have overstated or falsely inferred vaccine benefits due to unidentified or undisclosed healthy vaccinee bias.

Ultramarathon Plasma Metabolomics: Phosphatidylcholine Levels Associated with Running Performance.

The purpose of this study was to identify plasma metabolites associated with superior endurance running performance. In 2016, participants at the Western States Endurance Run (WSER), a 100-mile (161-km) foot race, underwent non-targeted metabolomic testing of their post-race plasma. Metabolites associated with faster finish times were identified. Based on these results, runners at the 2017 WSER underwent targeted metabolomics testing, including lipidomics and choline levels. The 2017 participants' plasma metabolites were correlated with finish times and compared with non-athletic controls. In 2016, 427 known molecules were detected using non-targeted metabolomics. Four compounds, all phosphatidylcholines (PCs) were associated with finish time (False Discovery Rate (FDR) < 0.05). All were higher in faster finishers. In 2017, using targeted PC analysis, multiple PCs, measured pre- and post-race, were higher in faster finishers (FDR < 0.05). The majority of PCs was noted to be higher in runners (both pre- and post-race) than in controls (FDR < 0.05). Runners had higher choline levels pre-race compared to controls (p < 0.0001), but choline level did not differ significantly from controls post-race (p = 0.129). Choline levels decreased between the start and the finish of the race (p < 0.0001). Faster finishers had lower choline levels than slower finishers at the race finish (p = 0.028).

Eye function and physiology following a 161-km foot race.

Significant visual impairment occurs in a small percentage of ultramarathon participants and is thought to be due to corneal edema. Yet, the usual effects of prolonged exercise on the eye have not been previously reported. Eight study volunteers who completed the 161-km Western States Endurance Run underwent pre-race and post-race binocular and monocular visual acuity, intraocular pressure, and corneal thickness measurements. None was symptomatic with visual impairment during the race and they demonstrated no changes from pre-race to post-race in visual acuity (p = 0.11-0.95 for right, left and combined), intraocular pressure (p = 0.11-0.43 for the both eyes) and corneal thickness (p = 0.30-0.99 for both eyes at three corneal areas). We conclude that there is no evidence that ultramarathon running has an acute effect on eye function or physiology when the runner has no symptoms or findings of visual impairment.

THE ASSOCIATION BETWEEN CUTICULAR DRUSEN AND KIDNEY FUNCTION: A Population-Based Case-Control Study.

PURPOSE: To determine the association between cuticular drusen (CD) and kidney function. DESIGN: observational case-control study. SETTING: Population-based. Patients or Study Population: 53 participants with (CD) and 53 age- and sex-matched controls, selected from the Danish Rural Eye Study. Cuticular drusen participants were diagnosed using fluorescein angiography and controls were excluded if the patients were suspected of having CD on fundus photography or did not have an available estimated glomerular filtration rate. MAIN OUTCOME MEASURES: creatinine and estimated glomerular filtration rate. RESULTS: The mean estimated glomerular filtration rate of those with CD was 73.3 mL·min·1.73 m (95% confidence interval [CI]: 70.0-76.6) and 73.4 mL·minute·1.73 m (95% CI: 69.5-77.3) in controls. The difference was not significant (P: 0.970). The mean creatinine among those with CD was 72.8 µmol/L (69.3-76.4) and 73.5 µmol/L (95% CI: 69.3-77.6) among controls. The difference was not significant (P = 0.820). CONCLUSION: The authors did not find an association between a (CD) diagnosis and decreased kidney function at a population level.

An evaluation of fundus photography and fundus autofluorescence in the diagnosis of cuticular drusen.

PURPOSE: To examine non-mydriatic fundus photography (FP) and fundus autofluorescence (FAF) as alternative non-invasive imaging modalities to fluorescein angiography (FA) in the detection of cuticular drusen (CD). METHODS: Among 2953 adults from the Danish Rural Eye Study (DRES) with gradable FP, three study groups were selected: (1) All those with suspected CD without age-related macular degeneration (AMD) on FP, (2) all those with suspected CD with AMD on FP and (3) a randomly selected group with early AMD. Groups 1, 2 and 3 underwent FA and FAF and group 4 underwent FAF only as part of DRES CD substudy. Main outcome measures included percentage of correct positive and correct negative diagnoses, Cohen's κ and prevalence-adjusted and bias-adjusted κ (PABAK) coefficients of test and grader reliability. RESULTS: CD was correctly identified on FP 88.9% of the time and correctly identified as not being present 83.3% of the time. CD was correctly identified on FAF 62.0% of the time and correctly identified as not being present 100.0% of the time. Compared with FA, FP has a PABAK of 0.75 (0.60 to 1.5) and FAF a PABAK of 0.44 (0.23 to 0.95). CONCLUSIONS: FP is a promising, non-invasive substitute for FA in the diagnosis of CD. FAF was less reliable than FP to detect CD.

An investigation of ultramarathon-associated visual impairment.

OBJECTIVE: The purpose of this study was to investigate the characteristics under which ultramarathon-associated visual impairment occurs and to seek to identify its physiological basis and risk factors. METHODS: Through an online questionnaire, distributed worldwide, we obtained information from 173 self-identified ultramarathon runners who had experienced visual impairment during an ultramarathon. We attempted to characterize this vision impairment-its symptoms, duration, and the conditions under which it occurs. Select characteristics were compared with a reference group of 412 registrants of the 161-km Western States Endurance Run. RESULTS: Ultramarathon-associated visual impairment was typically characterized as painless clouding of vision that resolved either during (13.5%) or after racing within a median of 3.5 hours (range 0 to 48 hours) upon cessation of running. The mean (±SD) distance at which vision impairment occurred was 73±40 km, and the 161-km distance was the most frequent race distance (46.8%) in which visual impairment occurred. Visual impairment was often recurrent, with respondents reporting having it develop during a median of 2 races. Respondents with a history of refractive surgery had more episodes than those without such history (median 3.5 vs 2 episodes, P=.010). Compared with the reference group, runners with visual impairment were nearly twice as likely (23.7% vs 12.1%, P<.001) to have had refractive surgery. CONCLUSIONS: Ultramarathon-associated visual impairment typically presents as a painless clouding of vision that is self-limited but tends to recur in certain runners. Risk appears higher among those with a history of refractive surgery, which is relevant for ultramarathon runners who are considering, or who have a history of, refractive surgery.

Danish Rural Eye Study: the association of preschool vision screening with the prevalence of amblyopia.

PURPOSE: To determine the prevalence of amblyopia in Denmark before and after the initiation of the Danish national preschool vision screening programme. METHODS: In a population-based cross-sectional study, 3826 participants of the Danish General Suburban Population Study (GESUS) aged 20 years and older from a Danish rural municipality received a complete general health examination and an ophthalmological interview and examination. This study included a comprehensive ophthalmologic interview, measurement of best corrected visual acuity (BCVA) in each eye, Hirschberg's test for strabismus and two 45-degree retinal fundus photographs of each eye. A complete ophthalmologic examination was performed when indicated. RESULTS: The prevalence of monocular visual impairment (MVI) was 4.26% (95% CI, 3.66-4.95, n = 163). Amblyopia was the most common cause, accounting for 33%. The prevalence of amblyopia was 1.44% (95% CI, 1.01-1.81, n = 55), being higher among non-preschool vision screened persons compared to those who were offered (estimated 95% attendance) preschool vision screening (1.78%, n = 41, 95% CI 1.24-2.33 versus 0.44%, n = 2, 95% CI, 0.12-1.60, p = 0.024). The leading cause of amblyopia was anisometropia (45.5%, 25/55). CONCLUSIONS: Amblyopia was the most common cause of MVI. Following the initiation of the Danish national preschool vision screening programme, which has an approximate attendance rate of 95%, the prevalence of amblyopia decreased by fourfold.

Evaluation of a tool to teach medical students direct ophthalmoscopy.

INTRODUCTION: With declining exposure to the ophthalmologic examination in medical school, medical students and their instructors need a simple, effective method for teaching direct ophthalmoscopy. OBJECTIVE: Evaluation of canisters as direct ophthalmoscopy teaching aids for medical students. METHODS: Two ounce plastic canisters were designed to simulate an eye with 35 mm fundus photographs placed at the base and an 8mm hole drilled in the center of the cap to simulate a dilated pupil. These tools were used as an optional supplement to the instruction of ophthalmoscopy. Participants included 102 second-year medical students from the Medical College of Wisconsin and 11 residents and instructors from The Eye Institute in Milwaukee, Wis. RESULTS: Effectiveness and ease of use of the canisters were assessed by analyzing questionnaires completed by the medical students and instructors. According to 76% of students and 93% of instructors, the canisters "supplemented their learning/teaching." Most students (90%) and instructors (88%) found them "easy to use." CONCLUSION: This device is a simple and effective tool for teaching direct ophthalmoscopy to medical students.