Identification of a novel pathogenic TBCK variant in a Chinese patient with infantile hypotonia with psychomotor retardation and characteristic facies type 3 (IHPRF3): a case report.

BACKGROUND: Infantile hypotonia with psychomotor retardation and characteristic facies type 3(IHPRF3) (OMIM #616,900) is an autosomal recessive disorder caused by biallelic pathogenic variants of the TBCK gene, and to date, this disease was reported rather limitedly in number and all described cases were Caucasians. CASE PRESENTATION: This paper reported the clinical and genetic features of a Chinese patient with IHPRF3. The patient was a 15-month-old male with global developmental delay, profound hypotonia, and typical facial dysmorphic features including mildly coarse facial appearance, hypertelorism, tented upper lip, exaggerated Cupid's bow, macroglossia and arched eyebrows. Magnetic Resonance Imaging (MRI) analysis of the brain revealed slightly widened bilateral ventricles and subarachnoid space. On genetic analysis, the patient was homozygous for a novel TBCK variant c.247C > T(p.Arg83Ter). The parents were both carriers without any positive symptoms or signs. With an extremely low frequency (0.0000082) in Exome Aggregation Consortium, the variant has not been reported in any other databases or official literatures, and was diagnosed to be pathogenic according to the American College of Medical Genetics and Genomics(ACMG) standards and guidelines. Neurorehabilitation training did not work well and the long-term prognosis remained to be observed. CONCLUSIONS: This study reported the clinical and molecular features of the first non-Caucasian patient with IHPRF3 arising from a novel homozygous TBCK mutation, which provided a novel molecular marker for the definite diagnosis of IHPRF3 patients and for its genetic counseling and prenatal diagnosis in the affected families.

Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review.

Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.

Influenza vaccine coverage and predictors of vaccination among aged care workers in Sydney Australia.

Aged care facilities (ACFs) are residential communities with a concentration of vulnerable individuals with increased risk of severe influenza infection and complications such as outbreaks, hospitalisations and deaths. Aged care workers (ACW) are potential sources of influenza introduction and transmission in ACFs. Little is known about vaccine uptake among ACW. This study aimed to measure the vaccine uptake rate among Australian ACW and evaluate the demographic determinants of uptake during the influenza season of 2018. 146 ACWs were recruited from 7 facilities of a multisite aged care provider in Sydney. ACWs completed a questionnaire regarding their demographic, occupational and vaccination status. Vaccine coverage was calculated and variables were examined against their 2018 influenza vaccination status in statistical analysis. ACWs in our study were predominantly from a non-health occupational background with a large proportion of migrant workers (56%, 75/134). Vaccine coverage in 2018 was 48% (65/135). The strongest determinants of vaccine uptake were previous year vaccination history (Odds Ratio [OR] 10.49, 95% CI 3.33-33.10), workplace immunisation programs for employees (OR 7.87, 95% CI 2.47-25.10), casual work as employment status (OR 0.14, 95% CI 0.02-0.77), and presence of comorbidities (OR 4.04, 95% CI 1.23-13.32). ACW are a unique and understudied group who are critical to infection control in ACFs. Few ACWs have formal health training, and many are migrants who may lack access to subsidised health care and face out of pocket costs for vaccination. Vaccine coverage among ACW were below recommended levels. Provision of influenza vaccine for staff in workplaces is highly effective in raising vaccine coverage amongst ACWs. More research on the aged care sector workforce is needed in order to evaluate the determinants of vaccine uptake among Australian ACWs.

Prevalence and predictors of influenza vaccination among residents of long-term care facilities.

Influenza is a respiratory illness which results in significant morbidity and mortality, especially in the older population. Older people living in Long-Term Care Facilities (LTCFs) have a significantly higher risk of infection and complications from influenza. Influenza vaccine is considered the best strategy to prevent infection in high-risk populations. In Australia, the Communicable Diseases Network Australia (CNDA) suggests a vaccination coverage rate of 95% in both staff and residents1. This study aims to measure the vaccination coverage rates for residents in LTCFs and identify predictors of vaccination uptake for these individuals. This study was conducted in nine LTCFs in four sites from March to September 2018. This was done via medical record reviews for residents over 65 years old in these LTCFs, collecting information such as vaccination status, age, gender, ethnicity and occupation. Simple and multivariable logistic regression was used to calculate the Odds Ratio (OR) to determine significant predictors of influenza vaccination uptake. The overall vaccination rate among LTCF residents was 83.6%. Significant predictors of vaccination were LTCF location, ethnicity and previous year vaccination status. Residents in LTCF Site D were less likely to be vaccinated compared to Site A (OR 0.11, 95% CI 0.02-0.61), non-Caucasians were less likely to get vaccinated (OR 0.09, 95% CI 0.01-0.67), and residents who refused the 2017 vaccine were less likely to be vaccinated (OR 0.04, 95% CI 0.01-0.15). Compared with previous Australian studies on LTCF vaccination rates, the overall vaccination rate was high in these LTCFs (83.6% versus 66-84%), but it varied across different sites. Reasons for varying vaccination rates should be explored further - for example, lower rates in non-Caucasians with diverse cultural backgrounds. Better understanding the causes of under-vaccination can help improve vaccination programs in LTCFs.