HLA-A*31:01 was reported to be associated with carbamazepine (CBZ)-induced severe cutaneous adverse reactions (SCAR), including drug reaction with eosinophilia and systemic symptoms (DRESS), ...Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We conducted an international study using consensus diagnosis criteria to enroll a total of 93 patients with CBZ-SCAR from Europe or Asia. We found that HLA-A*31:01 showed a significant association with CBZ-DRESS in Europeans (P<0.001; odds ratio (OR) (95% confidence interval (CI))=57.6 (11.0-340)), and the strong association was also found in Chinese (P<0.001; OR (95% CI)=23.0 (4.2-125)). However, HLA-A*31:01 had no association with CBZ-SJS/TEN in neither Chinese nor Europeans. By comparison, HLA-B*15:02 showed a strong association with CBZ-SJS/TEN in Chinese (P<0.001, OR (95% CI)=58.1 (17.6-192)). A meta-analysis of this and other published studies confirmed that in all populations, HLA-A*31:01 had an extremely strong association with CBZ-DRESS (P<0.001, a pooled OR (95% CI)=13.2 (8.4-20.8)), but a much weaker association with CBZ-SJS/TEN (P=0.01, OR (95% CI)=3.94 (1.4-11.5)). Our data revealed that HLA-A*31:01 is a specific predictor for CBZ-DRESS but not for CBZ-SJS/TEN. More studies are needed to investigate the genetic determinant of CBZ-SJS/TEN in Europeans. Considering the potential clinical utility, the cost-effectiveness of the combined HLA-A*31:01 and HLA-B*15:02 genetic test to prevent CBZ-SCAR in Chinese needs further investigation.
RNA interference (RNAi) is a powerful gene-silencing process that holds great promise in the field of cancer therapy. The discovery of RNAi has generated enthusiasm within the scientific community, ...not only because it has been used to rapidly identify key molecules involved in many disease processes including cancer, but also because RNAi has the potential to be translated into a technology with major therapeutic applications. Our evolving understanding of the molecular pathways important for carcinogenesis has created opportunities for cancer therapy employing RNAi technology to target the key molecules within these pathways. Many gene products involved in carcinogenesis have already been explored as targets for RNAi intervention, and RNAi targeting of molecules crucial for tumor-host interactions and tumor resistance to chemo- or radiotherapy has also been investigated. In most of these studies, the silencing of critical gene products by RNAi technology has generated significant antiproliferative and/or proapoptotic effects in cell-culture systems or in preclinical animal models. Nevertheless, significant obstacles, such as in vivo delivery, incomplete suppression of target genes, nonspecific immune responses and the so-called off-target effects, need to be overcome before this technology can be successfully translated into the clinical arena. Significant progress has already been made in addressing some of these issues, and it is foreseen that early phase clinical trials will be initiated in the very near future.
Cutaneous idiosyncratic drug reactions (CIDRs) are usually unpredictable, ranging from mild maculopapular exanthema (MPE) to severe cutaneous adverse drug reactions (SCARs) such as drug reaction with ...eosinophilia and systemic symptoms (DRESS), Stevens‐Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Increasing evidence suggests that HLA alleles are strongly associated with drug‐induced‐CIDRs. The pathomechanisms for CIDRs include genetic polymorphisms affecting complex immune‐specific HLA/drug antigen/T‐cell receptor interactions and drug metabolism. Pharmacogenomic tests to prevent CIDRs have been widely implemented in clinical practice in recent years.
: Objective
To review the evidence regarding the mechanisms of silver diamine fluoride (SDF) for arresting caries.
Methods
A literature search was conducted using the keywords silver diamine ...fluoride, and its alternative names, in seven databases: PubMed, Embase and Scopus (English); China National Knowledge Infrastructure (Chinese); Bilioteca Virtual em Saude (Portuguese); Biblioteca Virtual en Salud Espana (Spanish); and Ichushi‐Web (Japanese). The titles and s were screened. Full texts were retrieved for publications that studied mechanisms of actions of SDF, including its effects on remineralisation of carious lesions and on cariogenic bacteria.
Results
A total of 1,123 publications were identified. Twenty‐nine articles were included and they investigated the effect of SDF on cariogenic bacteria and dental hard tissues. Eleven studies investigated the antibacterial properties of SDF. They found that SDF was bactericidal to cariogenic bacteria, mainly Streptococcus mutans. It inhibited the growth of cariogenic biofilms on teeth. Twenty studies reported the remineralisation of demineralised enamel or dentine by SDF. They found that mineral loss of demineralised enamel and dentine was reduced after SDF treatment. A highly mineralised surface rich in calcium and phosphate was formed on arrested carious lesions. Four studies examined the effect of SDF on dentine collagen. They found that SDF inhibited collagenases (matrix metalloproteinases and cysteine cathepsins) and protected dentine collagen from destruction.
Conclusion
SDF is a bactericidal agent and reduces the growth of cariogenic bacteria. It inhibits demineralisation and promotes the remineralisation of demineralised enamel and dentine. It also hampers degradation of the dentine collagen.
Summary After the outbreak of severe acute respiratory syndrome in Hong Kong, the importance of preventing nosocomial transmission of respiratory viruses has become a top priority in infection ...control. During the containment and early mitigation phases of the swine-origin influenza virus (S-OIV) A H1N1 pandemic, an infection control bundle consisting of multiple coherent measures was organised by our infection control team to minimise nosocomial transmission. This included repeated open staff forum achieving high attendance; early recognition of index cases among inpatients by liberal testing; early relief of sick staff from work; directly observed hand hygiene practice during outbreaks; and monitoring of compliance with infection control practice. During the first 100 days (from 1 May to 8 August 2009) when the first 100 laboratory-confirmed patients with S-OIV and 12 infected healthcare workers (HCWs) were identified, a total of 836 asymptomatic exposed persons (184 patients and 652 HCWs) were required to undergo a seven-day medical surveillance. The infection control nurses monitored them for the onset of symptoms. Four (0.48%) exposed persons (one house officer, two non-clinical staff, and one patient) were virologically confirmed with S-OIV. Not wearing a surgical mask either by the exposed persons during contact with the index cases (4/4 vs 264/832, P = 0.010) or vice versa (4/4 vs 300/832, P = 0.017, Fisher's exact test) were found to be significant risk factors for nosocomial acquisition of S-OIV.
Background The usefulness of the drug patch testing for Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) is still controversial. Recent studies have shown that HLA‐B*1502 is ...strongly associated with CBZ‐SJS/TEN in Chinese and Southeast Asian populations.
Objective To evaluate the usefulness of patch tests for patients with carbamazepine (CBZ)‐induced SJS, TEN and drug reaction with eosinophilia and systemic symptoms (DRESS) and the cross‐reactivity in patch tests among the aromatic antiepileptic drugs.
Methods We measure the frequency of positive patch test reactions and cross‐sensitivity to structure‐related aromatic anti‐epileptic drugs (AEDs) for patients after SJS/TEN or DRESS episodes caused by CBZ. CBZ and other structure‐related AEDs used for patch testing were prepared in 10% and 30% petrolatum. Secondary measures included the association of HLA‐B*1502 genotype and frequency of possible side effects from the patch tests.
Results Positive patch test reactions to 30% CBZ in the CBZ‐SJS/TEN were 62.5% (10/16), and 70% (7/10) in the CBZ‐DRESS. None of the 10 healthy controls displayed a positive reaction to tested agents. Cross‐sensitivity to other aromatic AEDs was observed in both the CBZ‐SJS/TEN and the CBZ‐DRESS. Only the HLA‐B*1502 genotype was present and strongly associated with the CBZ‐SJS/TEN, but not with the CBZ‐DRESS.
Conclusion Drug patch testing is a safe and useful method for the identification of CBZ as the culprit drug of SJS/TEN as well as DRESS. Testing of chemically or pharmacologically related AEDs may provide information on cross‐reactivity for these patients.
With the increasing threat of hazardous events at local, national, and global levels, an effective workforce for health emergency and disaster risk management (Health EDRM) in local, national, and ...international communities is urgently needed. However, there are no universally accepted competencies and curricula for Health EDRM. This study aimed to identify Health EDRM competencies and curricula worldwide using literature reviews and a cross-sectional survey.
Literature reviews in English and Japanese languages were performed. We searched MEDLINE, EMBASE, CINAHL (English), and the ICHUSHI (Japanese) databases for journal articles published between 1990 and 2020. Subsequently, a cross-sectional survey was sent to WHO Health EDRM Research Network members and other recommended experts in October 2021 to identify competency models and curricula not specified in the literature search.
Nineteen studies from the searches were found to be relevant to Health EDRM competencies and curricula. Most of the competency models and curricula were from the US. The domains included knowledge and skills, emergency response systems (including incident management principles), communications, critical thinking, ethical and legal aspects, and managerial and leadership skills. The cross-sectional survey received 65 responses with an estimated response rate of 25%. Twenty-one competency models and 20 curricula for managers and frontline personnel were analyzed; managers' decision-making and leadership skills were considered essential.
An increased focus on decision-making and leadership skills should be included in Health EDRM competencies and curricula to strengthen the health workforce.
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