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An observational, cohort, multi-centre, open label phase IV extension study comparing preschool DTAP-IPV booster vaccine responses in children whose mothers were randomised to one of two pertussis-containing vaccines or received no pertussis-containing vaccine in pregnancy in England

Vaccine. 2022 Oct 19:S0264-410X(22)01243-9. doi: 10.1016/j.vaccine.2022.10.005. Online ahead of print.

ABSTRACT

An antenatal pertussis vaccination programme was introduced in 2012 in the UK in the context of a national outbreak of pertussis. It has been shown that a lower antibody response to primary immunisation can be seen for certain pertussis antigens in infants born to women who received pertussis-containing antenatal vaccines, a phenomenon known as blunting. The longer-term impact of this has not been documented previously, and accordingly was evaluated in this study. Children were predominantly recruited from a previous study in which their mothers had received acellular pertussis-containing antenatal vaccines (dTaP3-IPV [diphtheria toxoid, tetanus toxoid, three antigen acellular pertussis and inactivated polio] or dTaP5-IPV [diphtheria toxoid, tetanus toxoid, five antigen acellular pertussis and inactivated polio]), or no pertussis-containing vaccine. Blood samples were obtained prior to and one month after the acellular pertussis-containing preschool booster (dTaP5-IPV) was given at around age 3 years 4 months. Pre- and post-booster immunoglobulin G (IgG) geometric mean concentrations (GMCs) against pertussis toxin, filamentous haemagglutinin, fimbriae 2 & 3, and pertactin, were compared. Prior to the receipt of the preschool booster, there was no difference in the IgG GMCs against pertussis-specific antigens between children born to women vaccinated with dTaP3-IPV and dTaP5-IPV; however, IgG GMCs against pertussis toxin were significantly lower in children born to women vaccinated with dTaP3-IPV compared with children born to unvaccinated women (geometric mean ratio 0.42 [95 % CI 0.22-0.78], p = 0.03). One month after the receipt of the preschool booster there was no differences between the groups. The blunting effect of antenatal pertussis vaccine on pertussis responses in children can persist until preschool age, although it is overcome by the administration of a booster dose. ClinicalTrials.gov registration number: NCT03578120.

PMID:36272877 | DOI:10.1016/j.vaccine.2022.10.005

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Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: a psychophysical case-control study

Rhinology. 2022 Oct 22. doi: 10.4193/Rhin22.294. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study was to compare the prevalence of olfactory dysfunction (OD) at different stages of the COVID-19 pandemic by evaluating subjects diagnosed with SARS-CoV-2 infection during the Omicron wave with psychophysical tests and comparing the results with those obtained from patients infected during the D614G, Alpha and Delta waves and with those of a control group.

METHODOLOGY: The study included adult patients diagnosed with SARS-CoV-2 infection. Depending on the time of diagnosis, the subjects were divided into four study groups: D614G; Alpha, Delta and Omicron variant groups. A group of uninfected individuals was used as control. All subjects underwent psychophysical evaluation of the olfactory function with the Connecticut Chemosensory Clinical Research Center olfactory test (D614G and Alpha groups) or the extended version of the Sniffin’Sticks test (Delta, Omicron and control groups).

RESULTS: 372 cases (134 D614G group, 118 Alpha group, 32 in Delta group and 88 Omicron group) were recruited and evaluated within 10 days of infection, alongside 80 controls. Patients self-reported olfactory loss in 72.4% of cases in the D614G group, in 75.4% of cases in the Alpha group, in 65.6% of cases in the Delta group and in 18.1% in the Omicron group. Psychophysical evaluation revealed a prevalence of OD: 80.6%, 83.0%, 65.6% and 36.3% in the D614G, Alpha, Delta and Omicron group respectively. The differences between the D614G, Alpha and Delta groups were not statistically significant. The Omicron group demonstrated a significantly lower prevalence of OD than the other variants but still significantly higher than the controls.

CONCLUSIONS: During the Omicron wave OD was less prevalent than during the D614G, Alpha and Delta periods. One-third of patients have reduced olfactory function on psychophysical evaluation during the Omicron wave. Our results should be considered with caution as the VOC has not been determined with certainty.

PMID:36272169 | DOI:10.4193/Rhin22.294

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Follow-up evaluation for norovirus asymptomatic infection among healthy adults: a prospective matched cohort study

Infect Dis (Lond). 2022 Oct 22:1-8. doi: 10.1080/23744235.2022.2134447. Online ahead of print.

ABSTRACT

OBJECTIVES: No study has evaluated the follow-up of asymptomatic norovirus infection among healthy adults. This study compared norovirus detection rates between previously known norovirus-positive and norovirus-negative adults without diarrheal symptoms, and evaluated reinfection risk among the previously-norovirus-positive group, and new asymptomatic norovirus infection risk among the previously-norovirus-negative group after 600 days.

METHODS: This prospective age- and sex-matched cohort study, conducted in 2019 at a Japan teaching hospital, included apparently healthy asymptomatic adults with a positive norovirus result and those with a negative result (ratio 1:3) during the 2016-2017 screening. The primary outcome was real-time reverse-transcription polymerase chain reaction-confirmed norovirus in stool specimens. We evaluated descriptive statistics and associated factors, including demographics, social habits, and clinical parameters.

RESULTS: Of 288 participants [mean age, 59.9 (standard deviation: 12.6) years; male, 143 (49.7%)], 73 [genogroup (G) I 35; GII 37; both included 1 each] were positive for norovirus previously, while 215 were negative. After a median of 599 (interquartile range 515-799) days between baseline screening and follow-up, 14 (4.9%; GI 0; GII 14) tested positive for norovirus (2.7% and 5.6% among positive- and negative-norovirus groups at baseline, respectively). Among previously norovirus-negative participants, being older, having elevated blood pressure and haemoglobin A1c level, and drinking Japanese sake at baseline were associated with positive results at follow-up.

CONCLUSIONS: Genogroup homotypic protective effect may exist for subsequent asymptomatic infection. There may be higher risks of future asymptomatic norovirus infection in previously no-norovirus asymptomatic infection people with specific lifestyles or medical histories. SUMMARYThe detection follow-up rates of norovirus were 2.7% and 5.6% among asymptomatic adults with positive- and negative-norovirus status at baseline, respectively. Specific lifestyles or medical histories may confer higher risk of norovirus detection.

PMID:36272144 | DOI:10.1080/23744235.2022.2134447

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Diagnosis of abdominal tuberculosis by multi-targeted (mpt64 and IS6110) loop-mediated isothermal amplification assay

J Gastroenterol Hepatol. 2022 Oct 22. doi: 10.1111/jgh.16036. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Diagnosis of abdominal TB is an exigent task due to variable anatomical sites and non-specific clinical manifestations that closely resemble other diseases. Most of the available diagnostic modalities yield low sensitivities and need expertise to handle the specialized equipments. Hence, there is an urgent need to develop a rapid and reliable diagnostic test, so as to reduce the unnecessary morbidity. Therefore, we designed a multi-targeted loop-mediated isothermal amplification (MT-LAMP) for diagnosing abdominal TB.

METHODS: We evaluated an MT-LAMP (using mpt64 and IS6110) to diagnose abdominal TB within ascitic fluids and intestinal/peritoneal biopsies, and compared these results with multiplex-PCR (M-PCR) using the same targets. MT-LAMP products were analyzed by gel electrophoresis and visual detection methods, i.e. hydroxy naphthol blue and SYBR Green I reaction.

RESULTS: Sensitivities of 80.9% and 84.6% were obtained in suspected (n=42) and total abdominal TB (n=52) cases, respectively by gel-based MT-LAMP, with 97.3% (n=37) specificity in non-TB controls. Notably, sensitivities attained by gel-based/SYBR Green I MT-LAMP in both clinically suspected and total abdominal TB cases were significantly higher (p<0.05) than M-PCR. Furthermore, sensitivity obtained with SYBR Green I was equivalent to that of gel-based MT-LAMP, while somewhat lesser specificity (94.6%) was attained with SYBR Green I, compared with gel-based MT-LAMP.

CONCLUSION: Both gel-based and SYBR Green MT-LAMP exhibited equivalent sensitivities to diagnose abdominal TB. Since SYBR Green LAMP is easier to perform than a gel-based assay, we are currently focused on improving the specificity of this assay so as to develop a diagnostic kit.

PMID:36272130 | DOI:10.1111/jgh.16036

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Spinal injuries after ejection seat evacuation in fighter aircraft of the German Armed Forces between 1975 and 2021

J Neurosurg Spine. 2022 Oct 21:1-8. doi: 10.3171/2022.8.SPINE22644. Online ahead of print.

ABSTRACT

OBJECTIVE: The ejection seat is one of the most important rescue tools for military aircrews. However, the high ejection speeds place high loads on the pilots, which is mainly absorbed by the pilot’s spine. The differentiated evaluation of spinal injuries is of particular importance because this has a decisive influence on the further personal life and career of the affected aircrew members. Factors influencing the occurrence of a fracture as well as the impact of a spinal injury on military flight certification have not been addressed sufficiently to date.

METHODS: The authors conducted a retrospective evaluation of ejection seat evacuations in German Armed Forces combat aircraft accidents between 1975 and 2021. The total number of aviation accidents with ejection seat initiations and the survived ejections were collected. Accident-specific data and pilot-specific data were collected. In addition, it was evaluated whether aircrew members were recertified for military flight after the accident. The type of spinal injury and the location of the injury were evaluated. In addition to the descriptive statistics, two logistic regression models were developed to assess prediction values of accident- and pilot-specific factors for spine injuries.

RESULTS: A total of 103 aircrew members were included in this retrospective analysis. The overall prevalence of spine injuries was 56.3%, and the overall prevalence of spine fractures was 33.0%. In the first regression model analysis, there was no association with pilot flight experience, age, height, weight, BMI, and being diagnosed with a spine fracture. Similarly, aircraft type, altitude, and airspeed were not associated with the occurrence of spine fractures. In the regression model analysis for predictors of rejection in military flight recertification after ejection seat evacuation, lumbar spine fractures were associated with higher odds of being rejected for recertification.

CONCLUSIONS: Military aircraft crew members have a high risk of suffering from a spine injury after emergency evacuation using an ejection seat. In the subsequent medical workup, special attention should be paid to the spine, and ideally a consultation with a spine surgeon should be performed. Lumbar spine fractures may have major consequences for military flight certification, and therefore special attention should be paid to successful rehabilitation.

PMID:36272126 | DOI:10.3171/2022.8.SPINE22644

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Phase II trial of icotinib in adult patients with neurofibromatosis type 2 and progressive vestibular schwannoma

J Neurosurg. 2022 Oct 21:1-8. doi: 10.3171/2022.9.JNS22699. Online ahead of print.

ABSTRACT

OBJECTIVE: Neurofibromatosis type 2 (NF2) is a rare autosomal dominant syndrome associated primarily with bilateral vestibular schwannomas (VSs). Conventional surgical or radiosurgical treatments for VS in NF2 usually result in high risks of hearing loss and facial nerve impairment, while there is no validated medical option to date. This single-institution phase II study evaluated the efficacy and safety of icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with NF2 and progressive VS.

METHODS: Icotinib was administered daily at 375 mg orally in a continuous 28-day course for up to 12 courses. The primary endpoint of the study was radiographic response assessed by brain MRI using 3D volumetric tumor analysis and defined as a ≥ 20% decrease in VS volume. Hearing function was evaluated as a secondary endpoint, with response defined as a statistically significant increase in word recognition scores.

RESULTS: Ten eligible patients with a mean age of 23.8 years were enrolled. One patient (10%) with bilateral tumors experienced an objective radiographic response (-23.58% and -22.01%). Three (43%) of 7 patients met the hearing response criteria. At 12 months, the estimated progression-free survival was 82.0% (95% CI 42.3%-95.5%) for volumetric progression and 69.2% (95% CI 37.3%-87.2%) for hearing progression. Common mild to moderate adverse events included rash (90%), diarrhea (50%), myalgia (20%), and nausea/gastrointestinal pain (20%).

CONCLUSIONS: Icotinib carries minor toxicity and is associated with radiographic and hearing responses in patients with NF2 and progressive VS.

PMID:36272122 | DOI:10.3171/2022.9.JNS22699

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Neurodevelopment in unilateral coronal craniosynostosis: a systematic review and meta-analysis

J Neurosurg Pediatr. 2022 Oct 21:1-8. doi: 10.3171/2022.9.PEDS22283. Online ahead of print.

ABSTRACT

OBJECTIVE: The current literature on unilateral coronal craniosynostosis is replete with repair techniques and surgical outcomes; however, information regarding neurodevelopment remains unclear. Therefore, the aim of this systematic review and meta-analysis was to comprehensively assess the neurodevelopmental outcomes of patients with unicoronal craniosynostosis compared with their healthy peers or normative data.

METHODS: A systematic review of the Ovid MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases from database inception to January 19, 2022, was performed. Included studies assessed neurodevelopment of patients with unicoronal craniosynostosis. Two independent reviewers selected studies and extracted data based on a priori inclusion and exclusion criteria. Results of developmental tests were compared with normative data or controls to generate Hedges’ g statistics for meta-analysis. The quality of included studies was evaluated using the National Institutes of Health Assessment Tool.

RESULTS: A total of 19 studies were included and analyzed, with an overall fair reporting quality. A meta-analysis of 325 postoperative patients demonstrated that scores of general neurodevelopment were below average but within one standard deviation of the norm (Hedges’ g = -0.68 [95% CI -0.90 to -0.45], p < 0.001). Similarly, postoperative patients exhibited lower scores in verbal, psychomotor, and mathematic outcome assessments.

CONCLUSIONS: This systematic review and meta-analysis found that patients with unicoronal craniosynostosis had poorer neurodevelopment, although scores generally remained within the normal range. These data may guide implementation of regular neurocognitive assessments and early learning support of patients with unicoronal craniosynostosis.

PMID:36272117 | DOI:10.3171/2022.9.PEDS22283

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Effect Modification of Selenium Supplementation by Intake and Serum Concentrations of Antioxidants on the Development of Metachronous Colorectal Adenoma

Nutr Cancer. 2022 Oct 22:1-10. doi: 10.1080/01635581.2022.2135745. Online ahead of print.

ABSTRACT

BACKGROUND: Selenium (Se) is a trace element that has been investigated as a potential chemopreventive agent for colorectal cancer. Dietary intake of other antioxidant nutrients may modify the effect of Se.

OBJECTIVE: We examined the association between intake and serum concentrations of retinol, β-carotene, β-cryptoxanthin, lycopene, lutein/zeaxanthin, and α- and γ-tocopherol and the development of metachronous colorectal adenoma, and if these nutrients modified the effect of Se.

METHODS: We conducted a prospective study of 1874 participants from the Se Trial with data for antioxidant intake, as well as a subcohort of 508 participants with serum biomarker concentrations.

RESULTS: Statistically significantly lower odds for the development of metachronous adenoma were observed for those participants in the highest tertile of intake for lutein/zeaxanthin compared to the lowest, with an OR (95% CI) of 0.72 (0.56-0.94). No effect modification for intake of any nutrient was observed. However, circulating concentrations of lycopene exhibited statistically significant effect modification of selenium supplementation (p < 0.06).

CONCLUSION: These findings show that intake and circulating concentrations of antioxidant nutrients were not consistently associated with reduced odds for the development of metachronous lesions, although blood concentrations of lycopene may modify the effect of selenium supplementation.

PMID:36272100 | DOI:10.1080/01635581.2022.2135745

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Correction to: Training During the COVID-19 Lockdown: Knowledge, Beliefs, and Practices of 12,526 Athletes from 142 Countries and Six Continents

Sports Med. 2022 Oct 22. doi: 10.1007/s40279-022-01776-y. Online ahead of print.

NO ABSTRACT

PMID:36272061 | DOI:10.1007/s40279-022-01776-y

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Health-related quality of life amongst children with chronic kidney disease in Malaysia: performance of the Bahasa Melayu version of the PedsQL 3.0 ESRD Module : (PedsQL 3.0 VerBATIM: version in Bahasa Melayu. Translated for use in Malaysia)

Pediatr Nephrol. 2022 Oct 22. doi: 10.1007/s00467-022-05774-0. Online ahead of print.

ABSTRACT

BACKGROUND: The PedsQL 3.0 End Stage Renal Disease (ESRD) Module is a well-accepted instrument internationally but it is not available in the local language. We aimed to validate the Bahasa Melayu (Malay language) version and determine the health-related quality of life (HRQoL) scores amongst children with CKD in Malaysia.

METHODS: The source questionnaire in English was translated into Bahasa Melayu. Linguistic validation guidelines by the MAPI Research Institute were followed. The already validated Bahasa Melayu PedsQL 4.0 Generic Core Scales was used for comparison. Sociodemographic data were collected during the interview. Statistical analyses were performed using SPSS version 25.0.

RESULTS: Sixty-nine children aged 8 to 18 with CKD stages 4 and 5, with or without dialysis, and their caregivers were recruited. Mean age was 12.62 ± 2.77 (SD). Evaluation of the PedsQL 3.0 ESRD Module Bahasa Melayu version demonstrated good internal consistency (Cronbach alpha 0.82). There was good agreement between child self-report and parent proxy report in all domains; average intraclass correlation coefficients (ICC) were 0.78, 95% CI (0.71, 0.84). Scores obtained from Generic 4.0 scales correlated with the disease-specific ESRD 3.0 scale, Spearman’s rho = 0.32, p = 0.007. The Kruskal-Wallis H test indicated that there were no significant differences between stages of CKD and their respective mean HRQoL score, χ2(2) = 2.88, p = 0.236.

CONCLUSIONS: The PedsQL 3.0 ESRD Module Bahasa Melayu version is a reliable and feasible tool for cross-cultural adaptation. A longer prospective study may help better illustrate the quality of life in this group of children.

PMID:36272027 | DOI:10.1007/s00467-022-05774-0