Impact of a novel pre-hospital stroke notification programme on acute stroke care key performance indicators in Hong Kong: a multicentre prospective cohort study with historical controls.

INTRODUCTION: Early identification and initiation of reperfusion therapy is essential for suspected acute ischaemic stroke. A pre-hospital stroke notification (PSN) protocol using FASE (facial drooping, arm weakness, speech difficulties, and eye palsy) was implemented to improve key performance indicators (KPIs) in acute stroke care delivery. We assessed KPIs and clinical outcomes before and after PSN implementation in Hong Kong. METHODS: This prospective cohort study with historical controls was conducted in the Accident and Emergency Departments of four public hospitals in Hong Kong. Patients were screened using the PSN protocol between August 2021 and February 2022. Suspected stroke patients between August 2020 and February 2021 were included as historical controls. Door-to-needle (DTN) and door-to-computed tomography (DTC) times before and after PSN implementation were compared. Clinical outcomes including National Institutes of Health Stroke Scale score at 24 hours and modified Rankin Scale score at 3 months after intravenous recombinant tissue-type plasminogen activator (IV-rtPA) were also assessed. RESULTS: Among the 715 patients (266 PSN and 449 non-PSN) included, 50.8% of PSN patients and 37.7% of non-PSN patients had a DTC time within 25 minutes (P<0.001). For the 58 PSN and 134 non-PSN patients given IV-rtPA, median DTN times were 67 and 75.5 minutes, respectively (P=0.007). The percentage of patients with a DTN time within 60 minutes was higher in the PSN group than in the non-PSN group (37.9% vs 21.6%; P=0.019). No statistically significant differences in clinical outcomes were observed. CONCLUSION: Although the PSN protocol shortened DTC and DTN times, clinical outcomes did not significantly differ.

The health of parents with and without intellectual impairment in the UK.

BACKGROUND: Little is known about the health and well-being of the 'hidden majority' of parents with mild intellectual disability (ID), who are less likely to be in contact with disability services. METHOD: We sought to add to knowledge in this area by examining the health and living conditions of parents with and without intellectual impairment in a large contemporary nationally representative sample of UK parents aged between 16 and 49 years old (n = 14 371). RESULTS: Our results indicated that, as expected, parents with intellectual impairment were at significantly greater risk than other parents of having poorer self-reported general, mental and physical health. They were also at significantly greater risk of experiencing higher rates of household socio-economic disadvantage and environmental adversities and lower rates of neighbourhood social capital and intergenerational support. Adjusting risk estimates to take account of between group differences in household socio-economic disadvantage eliminated statistically significant differences in health status between parents with and without intellectual impairment on all but one indicator (obesity). Further adjusting risk estimates to take account of between group differences in neighbourhood adversity, neighbourhood social capital and intergenerational support had minimal impact on the results. CONCLUSIONS: That controlling for between-group differences in exposure to socio-economic disadvantage largely eliminated evidence of poorer health among parents with intellectual impairment is consistent with the view that a significant proportion of the poorer health of people with IDs may be attributable to their poorer living conditions rather than biological factors associated with ID per se.

p53 deficiency enhances mitotic arrest and slippage induced by pharmacological inhibition of Aurora kinases.

A number of small-molecule inhibitors of Aurora kinases have been developed and are undergoing clinical trials for anti-cancer therapies. Different Aurora kinases, however, behave as very different targets: while inhibition of Aurora A (AURKA) induces a delay in mitotic exit, inhibition of Aurora B (AURKB) triggers mitotic slippage. Furthermore, while it is evident that p53 is regulated by Aurora kinase-dependent phosphorylation, how p53 may in turn regulate Aurora kinases remains mysterious. To address these issues, isogenic p53-containing and -negative cells were exposed to classic inhibitors that target both AURKA and AURKB (Alisertib and ZM447439), as well as to new generation of inhibitors that target AURKA (MK-5108), AURKB (Barasertib) individually. The fate of individual cells was then tracked with time-lapse microscopy. Remarkably, loss of p53, either by gene disruption or small interfering RNA-mediated depletion, sensitized cells to inhibition of both AURKA and AURKB, promoting mitotic arrest and slippage respectively. As the p53-dependent post-mitotic checkpoint is also important for preventing genome reduplication after mitotic slippage, these studies indicate that the loss of p53 in cancer cells represents a major opportunity for anti-cancer drugs targeting the Aurora kinases.

Cholera risk factors, Papua New Guinea, 2010.

BACKGROUND: Cholera is newly emergent in Papua New Guinea but may soon become endemic. Identifying the risk factors for cholera provides evidence for targeted prevention and control measures. METHODS: We conducted a hospital-based case-control study to identify cholera risk factors. Using stool culture as the standard, we evaluated a cholera point of care test in the field. RESULTS: 176 participants were recruited: 54 cases and 122 controls. Independent risk factors for cholera were: being over 20 years of age (aOR 2.5; 95%CI 1.1, 5.4), defecating in the open air (or river) (aOR 4.5; 95% CI 1.4, 14.4) and knowing someone who travelled to a cholera affected area (aOR 4.1; 95%CI 1.6, 10.7); while the availability of soap for handwashing at home was protective (aOR 0.41; 95%CI 0.19, 0.87). Those reporting access to a piped water distribution system in the home were twice as likely to report the availability of soap for handwashing. The sensitivity and specificity of the rapid test were 72% (95% CI 47-90) and 71% (95%CI 44-90%). CONCLUSIONS: Improving population access to the piped water distribution system and sanitation will likely reduce transmission by enabling enhanced hygiene and limiting the contamination of water sources. The One step V. cholerae O1/O139 Antigen Test is of limited utility for clinical decision making in a hospital setting with access to traditional laboratory methods. Settlement dwellers and mobile populations of all age groups should be targeted for interventions in Papua New Guinea.

Moresby food isn't good: food security, nutritional information and adherence to antiretroviral therapy in Papua New Guinea.

The relationship between HIV (human immunodeficiency virus), food security and nutrition has become increasingly important to practitioners, policy makers and people living with HIV. In this paper we describe for the first time the connection between HIV and antiretroviral therapies, the extent of nutritional counselling for HIV-positive people and food security in Papua New Guinea (PNG). A total of 374 HIV-positive people who were over the age of 16 and who had been on antiretroviral therapy (ART) for more than two weeks were recruited from six provinces, using a non-probability, convenience sampling methodology. A subsample of 36 participants also completed an in-depth qualitative interview. Participants received nutritional advice when beginning ART which focused on three main domains, of which the first two were the most frequently mentioned: what foods to avoid; what foods to eat; and how frequently to eat. 72% of the sample reported that they had experienced an increase in their appetite. Of those who reported that their appetite had increased on ART 33% reported that they did not have enough food to satisfy hunger. People who lived in the capital city, Port Moresby, within the Southern Region of PNG, had significantly more difficulty with food security than those who lived in other regions of the country. Not having enough food was the third most commonly recorded reason for non-adherence to ART. Responses to the HIV epidemic in Papua New Guinea must also begin to address the phenomenon of food insecurity for people with HIV, in particular those who are receiving antiretroviral therapies and who live in the urban areas.

Who tells and what happens: disclosure and health service responses to screening for intimate partner violence.

Routine screening of women for intimate partner violence (IPV) has been introduced in many health settings to improve identification and responsiveness to hidden abuse. This cross-sectional study aimed to understand more about how women use screening programmes to disclose and access information and services. It follows women screened in ten Australian health care settings, covering antenatal, drug and alcohol and mental health services. Two samples of women were surveyed between March 2007 and July 2008; those who reported abuse during screening 6 months previously (122) and those who did not report abuse at that time (241). Twenty-three per cent (27/120) of women who reported abuse on screening were revealing this for the first time to any other person. Of those who screened negative, 14% (34/240) had experienced recent or current abuse, but chose not to disclose this when screened. The main reasons for not telling were: not considering the abuse serious enough, fear of the offender finding out and not feeling comfortable with the health worker. Just over half of both the positive and negative screened groups received written information about IPV and 35% of the positive group accessed further services. The findings highlight the fact that much abuse remains hidden and that active efforts are required to make it possible for women to talk about their experiences and seek help. Screening programmes, particularly those with established protocols for asking and referral, offer opportunities for women to disclose abuse and receive further intervention.

Six months after routine screening for intimate partner violence: attitude change, useful and adverse effects.

This evaluative study measured self-reported changes in abuse-related measures six months after routine screening for intimate partner violence. Participants were 122 women who disclosed abuse and 241 who did not report abuse, screened in antenatal, substance abuse, and mental health services according to an existing standardized protocol used in New South Wales, Australia. Six months after initial screening, abused women were more likely to report increased agreement with a number of attitudes relating to abuse, in particular that being hurt by a partner affects a woman's health and that health services should ask about abuse. The proportion reporting current abuse was significantly lower after six months. While 6% (7/119) reported negative emotional reactions, 34% (41/120) reported useful effects-most frequently re-evaluating their situation and reducing isolation. Women who had experienced abuse, but elected not to disclose it reported similar effects. The results of this study lend support to the use of protocols for asking about abuse and responding to disclosures of abuse.

Epidermal permeability barrier recovery is delayed in vitiligo-involved sites.

BACKGROUND/OBJECTIVES: Prior studies have demonstrated that both the skin surface pH and epidermal permeability barrier function vary with skin pigmentation types. Although melanin deficiency is the main feature of vitiligo, alterations in cutaneous biophysical properties in vitiligo have not yet been well defined. In the present study, stratum corneum (SC) hydration, the skin surface pH and epidermal permeability barrier function in vitiligo were evaluated. METHODS: A total of 30 volunteers with vitiligo comprising 19 males and 11 females aged 13-51 years (mean age: 27.91 +/- 2.06 years) were enrolled in this study. The skin surface pH, SC hydration, melanin/erythema index and transepidermal water loss (TEWL) were measured by respective probes connected to a Courage-Khazaka MPA5. SC integrity was determined by measuring the TEWL following each D-Squame application. The barrier recovery rate was assessed at 5 h following barrier disruption by repeated tape stripping. RESULTS: In addition to SC hydration, both melanin and erythema index were significantly lower in vitiligo lesions than in contralateral, nonlesional sites, while no difference in skin surface pH between vitiligo-involved and uninvolved areas was observed. In addition, neither the basal TEWL nor SC integrity in the involved areas differed significantly from that in the uninvolved areas. However, barrier recovery in vitiligo-involved sites was significantly delayed in comparison with uninvolved sites (40.83 +/- 5.39% vs. 58.30 +/- 4.71%; t = 2.441; p < 0.02). CONCLUSION: Barrier recovery following tape stripping of the SC is delayed in vitiligo. Therefore, improvement in epidermal permeability barrier function may be an important unrecognized factor to be considered in treating patients with vitiligo.

Evaluating different PrP genotype selection strategies for expected severity of scrapie outbreaks and genetic progress in performance in commercial sheep.

Stochastic computer simulations were used for quantifying the effect of selecting on prion protein (PrP) genotype on the risk of major outbreaks of classical scrapie and the rate of genetic progress in performance in commercial sheep populations already undergoing selection on performance. The risk of a major outbreak on a flock was measured by the basic reproduction ratio (R(0)). The effectiveness of different PrP selection strategies for reducing the population risk was assessed by the percentage of flocks with R(0)<1. When compared with the scenario where there was no selection on PrP genotype, selection against the VRQ allele had a minimal impact on genetic progress for performance traits. However, this strategy was not sufficient to eliminate the population risk after 15 years of selection when the initial frequency of the ARR allele was relatively low. More extreme PrP selection strategies aimed at increasing the frequency of the ARR allele and decreasing the frequency of the VRQ allele led to decreases in the rate of genetic progress for performance but reduced the population risk to very low values. The reduction in genetic progress was only large when the initial ARR frequency was low and, in general, the risk of major epidemics was very small when the frequency of this allele reached 0.7.

Associations of polymorphisms of the ovine prion protein gene with growth, carcass, and computerized tomography traits in Scottish Blackface lambs.

The objective of this study was to investigate and estimate the associations of the ovine prion protein (PrP) genotypes with a wide range of performance traits in Scottish Blackface lambs. Performance records of up to 7,138 sheep of known PrP genotypes born from 1999 to 2004 in 2 experimental farms were utilized. Performance traits studied were BW at birth, marking (when the sheep were identified with permanent ear tags at an average age of 52 d), and weaning (average age of 107 d); slaughter traits (BW at slaughter, slaughter age, carcass weight, and carcass conformation); ultrasonic muscle and fat depths; and computerized tomography-predicted carcass composition and carcass yield at weaning. Different linear mixed models, including random, direct animal effect, and up to 3 maternal effects (genetic, permanent, and temporary environmental) were used for the different traits. The PrP genotype was included in the model as a fixed effect, along with other fixed factors with significant effects (P < 0.05). Five separate analyses were carried out for each trait, differing in the method of PrP genotypic classification. The first analysis was based on classifying the sheep into categories according to all 9 available PrP genotypes. In the other 4 analyses, sheep were categorized according to the number of each PrP allele carried. Results showed that there were no significant differences between PrP genotypes for any of the performance traits studied when all 9 genotypes were compared (first analysis). Similarly, performance of the lambs did not significantly differ between genotypes with different numbers of ARR copies. However, there were significant variations in a few traits with respect to the number of ARQ, AHQ, and VRQ alleles carried. Heterozygous lambs for the AHQ or the ARQ allele were significantly heavier at some ages than lambs of the other genotypes. Lambs carrying the VRQ allele required approximately 10 d longer finishing time (P = 0.01) and yielded carcasses approximately 0.5 kg heavier (P = 0.03) compared with noncarriers. The few significant associations found do not have a negative influence on performance when selecting against the most susceptible PrP allele (VRQ) or in favor of the most resistant one (ARR). Overall, there were no major associations of PrP genotypes with most lamb performance traits in Scottish Blackface sheep.

A pedigree-analysis approach to the descriptive epidemiology of autosomal-recessive disorders.

We describe a pedigree-analysis approach to estimating descriptive epidemiological parameters for autosomal-recessive disorders when the ancestral source of the disorder is known. We show that the expected frequency of carriers in a cohort equals the gene contribution of the ancestral source to that cohort, which is equivalent to the direct (additive) genetic relationship of that ancestor to the cohort. Also, the expected incidence of affected foetuses ranges from (1/2)F* to F*, where F* is the mean partial inbreeding coefficient (due to the ancestor) of the cohort. We applied this approach to complex vertebral malformation (CVM) in Holstein-Friesians in Australia, for which the ancestral source is a USA-born bull, Carlin-M Ivanhoe Bell. The estimated frequency of carriers was 2.47% for the 1992-born and 4.44% for the 1997-born cohort of Holstein-Friesian cows in Australia. The estimated incidence of affected foetuses/calves was considerably less than one per thousand, ranging from 0.0024 to 0.0048% for the 1992-born cohort, and from 0.0288 to 0.0576% for the 1997-born cohort. These incidences correspond to expected numbers of affected female foetuses/calves ranging from 2 to 4 for the 1992-born cohort and from 28 to 56 for the 1997-born cohort. This approach is easy to implement using software that is readily available.