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Adolescents have been largely neglected from tuberculosis control efforts. In low- to medium burden settings much of the tuberculosis burden in this age group occurs from school outbreaks. We report on a large tuberculosis outbreak in adolescents from a boarding high school in Jiangsu Province, China. From March to June 2018, a tuberculosis outbreak occurred in a boarding high school. We conducted an outbreak investigation involving clinical diagnostic tests and molecular analysis to determine the outbreak origin. Cases were detected through symptom screening, tuberculin skin testing (TST), chest radiography, sputum smear, solid sputum culture and GeneXpert MTB/RIF. Mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) genotyping and spoligotyping methods were performed on Mycobacterium tuberculosis (M. tuberculosis) isolates to identify the outbreak origin. A total of 845 students and 131 teachers/staff attended a TST screening for tuberculosis infection. The prevalence of elevated tuberculin reactions at ≥5, ≥10 and ≥15 mm was 12.19% (119/976), 6.35% (62/976) and 3.28% (32/976), respectively. Radiographic abnormalities were present in 5.73% (56 of 976) individuals, 40 students and 16 teachers/staff. Of these, 12 students were diagnosed with confirmed tuberculosis. In total, 14 students (two index cases and 12 confirmed cases) were diagnosed and reported in the tuberculosis outbreak, an attack rate of 1.7% (14/847) among students (two index cases and 845 screened students). Results from MIRU-VNTR typing and spoligotyping analyses demonstrated that three M. tuberculosis strains belong to the Beijing family with corresponding MIRU-VNTR alleles. This school-based tuberculosis outbreak among adolescents demonstrates that transmission among individuals in this age group is common and must be prioritised. It suggests that identifying and timely diagnosis of smear-positive cases, especially in the early phase of outbreaks, is the key to preventing further spread among close contacts.
Resource allocation planning for emergency medical services (EMS) systems determines appropriate resources including what paramedic qualification and how rapidly to respond to patients for optimal outcomes. The British Columbia Emergency Health Services implemented a revised response plan in 2013.
A pre- and post-methodology was used to evaluate the effect of the resource allocation plan revision on 24-hour mortality. All adult cases with evaluable outcome data (obtained through linked provincial health administrative data) were analyzed. Multivariable logistic regression was used to adjust for variations in other significant associated factors. Interrupted time series analysis was used to estimate immediate changes in level or trend of outcome after the start of the revised resource allocation plan implementation, while simultaneously controlling for pre-existing trends.
The derived cohort comprised 562,546 cases (April 2012–March 2015). When adjusted for age, sex, urban/metro region, season, day, hour, and dispatch determinant, the probability of dying within 24 hours of an EMS call was 7% lower in the post-resource allocation plan-revision cohort (OR = 0.936; 95% CI: 0.886–0.989; p = 0.018). A subgroup analysis of immediately life-threatening cases demonstrated similar effect (OR = 0.890; 95% CI: 0.808–0.981; p = 0.019). Using time series analysis, the descending changes in overall 24-hour mortality trend and the 24-hour mortality trend in immediately life-threatening cases, were both statistically significant (p < 0.001).
Comprehensive, evidence-informed reconstruction of a provincial EMS resource allocation plan is feasible. Despite change in crew level response and resource allocation, there was significant decrease in 24-hour mortality in this pan-provincial population-based cohort.
Background: To evaluate efficacy, safety, and tolerability of ubrogepant for acute treatment of migraine attacks. Methods: Multicenter, double-blind, phase 3 study (NCT02867709). Randomized patients (1:1:1, placebo or ubrogepant 25mg or 50mg) had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints (2 hours post initial dose): headache pain freedom and absence of most bothersome migraine-associated symptom (MBS). Secondary endpoints: pain relief, sustained pain relief, sustained pain freedom, and absence of migraine-associated symptoms. Results: 1686 patients were randomized (safety population: n=1465; mITT population: n=1355). Mean age: 41 years; white: 81%; female: 89%. Significantly greater proportions of ubrogepant- than placebo-treated patients achieved 2-hour pain freedom (placebo: 14.3%; 25mg: 20.7%, adjusted P=0.0285; 50mg: 21.8%, adjusted P=0.0129) and absence of MBS for 50mg (placebo: 27.4%; 50mg: 38.9%, adjusted P=0.0129). Secondary endpoints (except absence of nausea at 2h) met statistical significance versus placebo for ubrogepant 50mg. Absence of MBS and secondary outcomes were not significant for 25mg after multiplicity adjustment. Ubrogepant’s and placebo’s AE profiles were similar. Conclusions: Co-primary endpoints were met for ubrogepant 50mg. Ubrogepant 25mg was significantly superior to placebo for 2h pain freedom. Ubrogepant was well tolerated. Results support the efficacy, tolerability, and safety of ubrogepant for acute treatment of migraine attacks.
Background: To evaluate efficacy, safety, and tolerability of ubrogepant, an oral CGRP receptor antagonist, for acute treatment of a single migraine attack. Methods: Multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack, phase 3 study (NCT02828020). Patients randomized 1:1:1 to placebo, ubrogepant 50mg, or ubrogepant 100mg had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints: pain freedom 2 hours post initial dose and absence of most bothersome migraine-associated symptom (MBS). Results: 1672 patients were randomized (safety population: n=1436; mITT population: n=1327). Mean age: 40.7 years; white (82.4%); female (87.5%). A significantly greater percentage of ubrogepant- than placebo-treated patients achieved pain freedom 2 hours post initial dose (50mg: 19.2%, adjusted P=0.0023; 100mg: 21.2%, adjusted P=0.0003; placebo: 11.8%). A significantly greater percentage of ubrogepant patients achieved absence of MBS (50mg: 38.6%, adjusted P=0.0023, 100mg: 37.7%, adjusted P=0.0023; placebo: 27.8%). The adverse event (AE) profile of ubrogepant was similar to placebo. The most common AEs (incidence ≥2% in any treatment group) within 48 hours of initial or optional second dose were nausea, somnolence, and dry mouth (all with incidence <5%). Conclusions: Both co-primary endpoints were met, with clinically meaningful effects on migraine headache pain and MBS. Ubrogepant was well tolerated, with no identified safety concerns.
This study aimed to investigate endoscopic revision septoplasty with semi-penetrating straight and circular incisions in patients for whom septoplasty was unsuccessful.
Patients in this study (n = 14) had a deviation of the nasal septum after septoplasty. Pre-operative and post-operative assessments were performed using a visual analogue scale and nasal endoscope. Semi-penetrating straight and circular incisions in front of the caudal septum and at the margin of the nasal septal cartilage–bone defect, respectively, were made. The mucoperichondrium and mucoperiosteum were bilaterally dissected until interlinkage with the cartilage–bone defect was achieved. Mucous membranes within the circular incision as well as the right mucoperichondrium and mucoperiosteal flaps were protected by pushing them to the right. This exposed the osteocartilaginous framework and allowed correction of the residual deviation. The patients were followed up for 30–71 months.
For nasal obstruction and headaches, a significant improvement was noted in post-operative compared to pre-operative visual analogue scale scores. No patients had septal deviations, saddle nose, false hump nose or contracture of the nasal columella.
The technique allowed exposure of the septal osteocartilaginous framework and a broad operational vision, which enabled successful correction of various deformities of the nasal septum.
To compare the epidemiologic features (e.g. settings and transmission mode) and patient clinical characteristics associated with outbreaks of different norovirus (Nov) strains, we retrospectively analysed data of Nov outbreaks occurring in Guangzhou, China from 2012 to 2018. The results suggested that outbreaks of Nov GII.2, GII.17 and GII.4 Sydney exhibited different outbreak settings, transmission modes and symptoms. GII.2 outbreaks mainly occurred in kindergartens, elementary and high schools and were transmitted mainly through person-to-person contact. By contrast, GII.4 Sydney outbreaks frequently occurred in colleges and were primarily associated with foodborne transmission. Cases from GII.2 and GII.17 outbreaks reported vomiting more frequently than those from outbreaks associated with GII.4 Sydney.
Associations have been shown between father’s absence and menarcheal age, but most studies have focused on absence resulting from divorce, abandonment or death. Little research has been conducted to evaluate the effect on menarcheal age of paternal absence through migrant work. In a sample of 400 middle school students, this study examined the association between paternal migrant work and menarcheal age against a backdrop of extensive rural-to-urban migration in China. Data were collected through a self-reported questionnaire, including social-demographic characteristics, aspects of family relationships, information about father’s migrant work and age at menarche. After adjusting for BMI, parent marital status and perceived relationship with mother, lower self-perceived quality of father–daughter relationship (both ‘father present, relationship poor’ and ‘father absent, relationship poor’) and lower frequency of contact with the father were associated with higher odds for early menarche. These findings suggest that the assumption that father’s absence for work influences the timing of menarche needs to be examined in the context of the quality of the father–daughter relationship and paternal care, which appear to play a critical role in the timing of menarche. These findings also emphasize the importance of enhancing paternal involvement and improving father–daughter relationships in the development of appropriate reproductive strategy in daughters.
Favourable body composition has been associated with higher dietary protein intake. However, little is known regarding this relationship in a population of Chinese Americans (CHA), who have lower BMI compared with other populations. The aim of the present study was to assess the relationship between dietary protein intake, fat mass (FM) and fat-free mass (FFM) in CHA. Data were from the Chinese American Cardiovascular Health Assessment (CHA CHA) 2010–2011 (n 1707); dietary intake was assessed using an adapted and validated FFQ. Body composition was assessed using bioelectrical impedance analysis. The associations between protein intake (% energy intake) and BMI, percentage FM (FM%), percentage FFM (FFM%), FM index (FMI) and FFM index (FFMI) were examined using multiple linear regression adjusted for age, sex, physical activity, acculturation, total energy intake, sedentary time, smoking status, education, employment and income. There was a significant positive association between dietary protein and BMI (B = 0·056, 95 % CI 0·017, 0·104; P = 0·005), FM (B = 0·106, 95 % CI 0·029, 0·184; P = 0·007), FM% (B = 0·112, 95 % CI 0·031, 0·194; P = 0·007) and FMI (B = 0·045, 95 % CI 0·016, 0·073; P = 0·002). There was a significant negative association between dietary protein and FFM% (B = −0·116, 95 % CI −0·196, −0·036; P = 0·004). In conclusion, higher dietary protein intake was associated with higher adiposity; however, absolute FFM and FFMI were not associated with dietary protein intake. Future work examining the relationship between protein source (i.e. animal) and body composition is warranted in this population of CHA.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
This study examined whether L1-Mandarin learners of L2-English use verb bias and complementizer cues to process temporarily ambiguous English sentences the same way native speakers do. SVO word order places verbs early in sentences in both languages, allowing the use of verb-based knowledge to anticipate what could follow. The two languages differ, however, in whether an optional complementizer signals embedded clauses. In a self-paced reading experiment, native English speakers and L1-Mandarin learners of L2-English read sentences containing temporary ambiguity about whether a noun was the direct object of the verb preceding it or the subject of an embedded clause. Native speakers replicated previous work showing an optimally efficient interactive pattern of cue use, while non-native learners showed additive effects of the two cues, consistent with predictions of the Competition Model about learning how to use multiple cues in a second language that sometimes agree and sometimes do not.
We examine whether industry product market conditions are important in assessing the benefits and costs of chief executive officer (CEO) power. We find that firms are more likely to have powerful CEOs in high demand product markets where firms are facing entry threats. In these markets, investors react favorably to announcements granting more power to CEOs, and CEO power is associated with higher market value, sales growth, investment, advertising, and the introduction of more new products. Our results remain significant when addressing the endogeneity of CEO power by instrumenting CEO power with past non-CEO executive and director sudden deaths.
To search the international literature (any language) for publications reporting outcomes of tracheostomy performed to treat obstructive sleep apnoea in children.
Data sources included: Google Scholar, Cumulative Index to Nursing and Allied Health Literature, Embase, Scopus, and PubMed/Medline. Four authors searched systematically through to 20 January 2018.
A total of 597 studies were screened; 64 were downloaded and 11 met criteria. A total of 196 patients underwent tracheostomy (mean age, 4.2 years; range, newborn to 18 years); 40 had detailed qualitative data and 6 had detailed quantitative data. Apnoea/hypopnoea index showed a 97 per cent reduction (n = 2) and apnoea index showed a 98 per cent reduction (n = 3). Lowest oxygen saturation showed a 34 oxygen saturation point improvement (n = 3). Several patients demonstrated significant improvement in breathing. All identified patients were syndromic, had significant co-morbidities or had severe obstructive sleep apnoea.
Based on reports of children who have undergone a tracheostomy, for whom there are pre- and post-operative data, tracheostomy appears to be a successful treatment for obstructive sleep apnoea. However, additional research is recommended given the small number of patients in the literature.
Dengue is the fastest spreading mosquito-transmitted disease in the world. In China, Guangzhou City is believed to be the most important epicenter of dengue outbreaks although the transmission patterns are still poorly understood. We developed an autoregressive integrated moving average model incorporating external regressors to examine the association between the monthly number of locally acquired dengue infections and imported cases, mosquito densities, temperature and precipitation in Guangzhou. In multivariate analysis, imported cases and minimum temperature (both at lag 0) were both associated with the number of locally acquired infections (P < 0.05). This multivariate model performed best, featuring the lowest fitting root mean squared error (RMSE) (0.7520), AIC (393.7854) and test RMSE (0.6445), as well as the best effect in model validation for testing outbreak with a sensitivity of 1.0000, a specificity of 0.7368 and a consistency rate of 0.7917. Our findings suggest that imported cases and minimum temperature are two key determinants of dengue local transmission in Guangzhou. The modelling method can be used to predict dengue transmission in non-endemic countries and to inform dengue prevention and control strategies.
Heat shock proteins (HSPs) participate in diverse physiological processes in insects, and HSP70 is one of the most highly conserved proteins in the HSP family. In this study, full-length cDNAs of three HSP70 genes (Lthsc70, Lthsp701, and Lthsp702) were cloned and characterized from Liriomyza trifolii, an important invasive pest of vegetable crops and horticultural crops worldwide. These three HSP70s exhibited signature sequences and motifs that are typical of the HSP70 family. The expression patterns of the three Lthsp70s during temperature stress and in different insect development stages were studied by real-time quantitative PCR. Lthsp701 was strongly induced by high- and low-temperature stress, but Lthsc70 and Lthsp702 were not very sensitive to temperature changes. All three Lthsp70s were expressed during insect development stages, but the expression patterns were quite different. The expression of Lthsc70 and Lthsp702 showed significant differences in expression during leafminer development; Lthsc70 was most highly expressed in female adults, whereas Lthsp702 was abundantly expressed in larvae and prepupae. Lthsp701 expression was not significantly different among leafminer stages. These results suggest that functional differentiation within the LtHSP70 subfamily has occurred in response to thermal stress and insect development.
Litter size has a great impact on the profit of swine producers. Uterine development is an important determinant of reproduction efficiency and could hence affect litter size. Chinese Erhualian pig is one of the most prolific breeds in the world, even though large phenotypic variation in litter size was observed within Erhualian sows. To dissect the genetic basis of the phenotypic variation, we herein conducted genome-wide association studies for total number born and number born alive (NBA) of Erhualian sows. In total, one significant single nucleotide polymorphism (SNP) (P<1.78e−06) and 11 suggestive SNPs (P<3.57e−05) were identified on 10 chromosomes, confirming seven previously reported quantitative trait loci (QTL) and uncovering six QTL for litter size or uterus length. One locus on Sus scrofa chromosome (SSC) 13 (79.28 to 90.43 Mb) harbored a cluster of suggestive SNPs associated with multiparous NBA. The SNP (rs81447100) within this region was confirmed to be significantly (P<0.05) associated with litter size in Erhualian (n=313), Sutai (n=173) and Yorkshire (n=488) populations. Retinol binding protein 2 and retinol binding protein 1 functionally related to the development of uterus were located in a region of 2 Mb around rs81447100. Moreover, four genes related to embryo implantation and development were also detected around other significant SNPs. Taken together, our findings provide a potential marker (rs81447100) for the genetic improvement of litter size not only in Chinese Erhualian pigs but also in European commercial pig breeds like Yorkshire, and would facilitate the final identification of causative variant(s) underlying the effect of SSC13 QTL on litter size.
Multiple human immunodeficiency virus (HIV)-1 genotypes in China were first discovered in Yunnan Province before disseminating throughout the country. As the HIV-1 epidemic continues to expand in Yunnan, genetic characteristics and transmitted drug resistance (TDR) should be further investigated among the recently infected population. Among 2828 HIV-positive samples newly reported in the first quarter of 2014, 347 were identified as recent infections with BED-captured enzyme immunoassay (CEIA). Of them, 291 were successfully genotyped and identified as circulating recombinant form (CRF)08_BC (47.4%), unique recombinant forms (URFs) (18.2%), CRF01_AE (15.8%), CRF07_BC (14.4%), subtype C (2.7%), CRF55_01B (0.7%), subtype B (0.3%) and CRF64_BC (0.3%). CRF08_BC and CRF01_AE were the predominant genotypes among heterosexual and homosexual infections, respectively. CRF08_BC, URFs, CRF01_AE and CRF07_BC expanded with higher prevalence in central and eastern Yunnan. The recent common ancestor of CRF01_AE, CRF07_BC and CRF08_BC dated back to 1983.1, 1992.1 and 1989.5, respectively. The effective population sizes (EPS) for CRF01_AE and CRF07_BC increased exponentially during 1991–1999 and 1994–1999, respectively. The EPS for CRF08_BC underwent two exponential growth phases in 1994–1998 and 2001–2002. Lastly, TDR-associated mutations were identified in 1.8% of individuals. These findings not only enhance our understanding of HIV-1 evolution in Yunnan but also have implications for vaccine design and patient management strategies.