An outbreak of SARS-CoV-2 in a public-facing office in England.

BACKGROUND: An outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with an attack rate of 55% (22/40 workers) occurred at a public-facing office in England from August to September 2021. Published evidence regarding outbreaks in office workplaces remains limited. AIMS: To describe an investigation of workplace- and worker-related risk factors following an outbreak of SARS-CoV-2 in a public-facing office. METHODS: The COVID-19 (coronavirus disease 2019) Outbreak Investigation to Understand Transmission (COVID-OUT) study undertook an investigation of the outbreak. This included surface sampling, occupational environmental assessment, molecular and serological testing of workers, and detailed questionnaires. RESULTS: Despite existing COVID-19 control measures, surface sampling conducted during a self-imposed 2-week temporary office closure identified viral contamination (10/60 samples, 17% positive), particularly in a small, shared security office (6/9, 67% positive) and on a window handle in one open-plan office. Targeted enhanced cleaning was, therefore, undertaken before the office reopened. Repeat surface sampling after this identified only one positive (2%) sample. Ventilation was deemed adequate using carbon dioxide monitoring (typically ≤1000 ppm). Twelve workers (30%) responded to the COVID-OUT questionnaire, and all had been vaccinated with two doses. One-third of respondents (4/12) reported direct physical or close contact with members of the public; of these, 75% (3/4) reported a divider/screen between themselves and members of the public. CONCLUSIONS: The results highlight the potential utility of surface sampling to identify SARS-CoV-2 control deficiencies and the importance of evolving, site-specific risk assessments with layered COVID-19 mitigation strategies.

Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.

BACKGROUND: Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity. OBJECTIVES: To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables. METHODS: We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results. RESULTS: There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other. CONCLUSIONS: Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.

Venous drainage of the left liver: an evaluation of anatomical variants and their clinical relevance.

AIM: To evaluate the variations in venous drainage from the left liver. MATERIALS AND METHODS: A retrospective evaluation was performed of all consecutive abdominal computed tomography (CT) examinations at a tertiary referral facility between 1 January and 30 June 2018. Osirix (Pixmeo SARL, Bernex, Switzerland) was used to examine the major hepatic veins and their tributaries in each scan. The classification of variants as proposed by Nakamura and Tsuzuki was used to describe the findings. The following information was collected: ramification pattern, number, length and diameter of middle (MHV) and left (LHV) hepatic vein tributaries. Two researchers collected data independently, and the average measurements were used as the final dimensions. RESULTS: Of 102 examinations evaluated, only 27 demonstrated the conventional venous drainage patterns. The LHV and MHV combined to form a common trunk that emptied into the inferior vena cava (IVC) in 75 (73.5%) cases. The common trunk had a mean length of 8.89 mm and mean diameter of 20.18 mm. Other patterns included Nakamura and Tsuzuki type I (27.5%), type II (29.4%) and type III variants (16.7%). In addition, 4.9% of patients had absent superior middle veins and 80% had supernumerary short hepatic veins (4%). CONCLUSION: Only 26.5% of patients in this population had conventional venous drainage from the left liver. Surgeons and radiologists in hepatobiliary practice should be aware of these variants in order to minimise morbidity when performing invasive procedures.

Blood pressure and risk of dementia and its subtypes: a historical cohort study with long-term follow-up in 2.6 million people.

BACKGROUND AND PURPOSE: Elevated blood pressure (BP) is prevalent and modifiable and has been hypothesized to lead to increased risk of dementia. DATA: Data on 2 593 629 people from the UK Clinical Practice Research Database aged ≥40 years with a BP measurement between 1992 and 2011 and no prior record of dementia were collected. METHODS: Poisson regression models were used to study the association between BP and physician-diagnosed dementia. BP is believed to fall during the prodromal phase of dementia development, so associations were investigated by categories of time since BP measurement (<5, 5-10, >10 years) and by subtypes of dementia. RESULTS: During a median follow-up of 8.2 years, 65 618 cases of dementia were observed: 49 161 Alzheimer's, 13 816 vascular dementia and 2541 other subtypes. For each 10 mmHg higher systolic BP, the future dementia risk was 9.2% (95% confidence interval 8.4%-10.0%) lower, but this association varied markedly by time since BP measurement. Short-term associations with dementia were inverse with a 15.8% (15.5%-17.0%) lower risk 0-5 years after BP measurement and a 5.8% (7.7%-4.4%) lower risk 5-10 years after BP measurement. During the period >10 years after BP measurement, dementia risk was only 1.6% (0.1%-3.0%) lower, with a 4.3% (2.5%-6.0%) lower risk of Alzheimer's disease and a 7.0% (3.8%-10.2%) higher risk of vascular dementia. CONCLUSIONS: Elevated BP is associated with decreased risk of dementia in the short term, possibly due to reverse causation. Long-term associations of BP with dementia are less marked and differ by dementia subtype.

Proactive multi-modality treatment of Pancreatic Neuroendocrine Tumours (PNETs): Potential survival benefits.

BACKGROUND/OBJECTIVES: Primary and metastatic pancreatic neuroendocrine tumours (PNET) can be treated with combination of surgery, locoregional and systemic therapy. Survival benefits from individual treatments have been well reported, however, the combined outcome from multimodal treatments are not well described in the literature. We report outcomes in a cohort of PNET patients treated with proactive, multimodality therapy. METHODS: 106 patients were identified from a single tertiary referral centre prospective database. Outcomes of treatment were studied, with the primary end point being death from any cause. RESULTS: Median follow-up was 71 months and overall 5-year survival of 62%. In patients with stage I-III disease (51 patients) estimated 5-year survival was 90%. Median survival in patients with stage IV disease was 51 months with an estimated 5-year survival of 40% in this group. A total of 80 patients (75%) had surgery of which 16% suffered complications requiring intervention. There was no perioperative mortality. CONCLUSIONS: This study demonstrates that proactive multimodal treatment is safe and may confer a survival benefit to patients in this cohort compared to historical data.

Propensity score-based analysis of outcomes of laparoscopic versus open liver resection for colorectal metastases.

BACKGROUND: There is a need for high-level evidence regarding the added value of laparoscopic (LLR) compared with open (OLR) liver resection. The aim of this study was to compare the surgical and oncological outcomes of patients with colorectal liver metastases (CRLM) undergoing LLR and OLR using propensity score matching to minimize bias. METHODS: This was a single-centre retrospective study using a prospective database of patients undergoing liver resection for CRLM between August 2004 and April 2015. Co-variates selected for matching included: number and size of lesions, tumour location, extent and number of resections, phase of surgical experience, location and lymph node status of primary tumour, perioperative chemotherapy, unilobar or bilobar disease, synchronous or metachronous disease. Prematching and postmatching analyses were compared. Surgical and oncological outcomes were analysed. RESULTS: Some 176 patients undergoing LLR and 191 having OLR were enrolled. After matching, 133 patients from each group were compared. At prematching analysis, patients in the LLR group showed a longer overall survival (OS) and higher R0 rate than those in the OLR group (P = 0·047 and P = 0·030 respectively). Postmatching analyses failed to confirm these results, showing similar OS and R0 rate between the LLR and OLR group (median OS: 55·2 versus 65·3 months respectively, hazard ratio 0·70 (95 per cent c.i. 0·42 to 1·05; P = 0·082); R0 rate: 92·5 versus 86·5 per cent, P = 0·186). The 5-year OS rate was 62·5 (95 per cent c.i. 45·5 to 71·5) per cent) for OLR and 64·3 (48·2 to 69·5) per cent for LLR. Longer duration of surgery, lower blood loss and morbidity, and shorter postoperative stay were found for LLR on postmatching analysis. CONCLUSION: Propensity score matching showed that LLR for CRLM may provide R0 resection rates and long-term OS comparable to those for OLR, with lower blood loss and morbidity, and shorter postoperative hospital stay.

Changes in the prevalence of cigarette smoking and quitting smoking determinants in adult inhabitants of rural areas in Poland between 2003 and 2012.

OBJECTIVES: We investigate trends in the prevalence of cigarette smoking among adults at all ages in two time points 9 years apart in two neighbouring rural populations and examine social and respiratory health determinants of quitting smoking. STUDY DESIGN: Repeated cross-sectional study. METHODS: Two cross-sectional surveys were conducted in the same rural area of lower Silesia in Poland in 2003 and 2012. A total of 1328 (91% of adult eligible individuals) in 2003 and 1449 (92% of eligible) in 2012 adult inhabitants were surveyed, 908 people (560 villagers and 348 town inhabitants) participated in both surveys. Participants completed a questionnaire on smoking behaviour, education level and respiratory diseases. RESULTS: Current smoking was higher in the villages than the town, among men than women and those with a middle level of education. The prevalence of current smokers decreased over time, although this decline was much more pronounced in the town than in the villages (30.2% vs 23% and 35.5% vs 33.7%, respectively). Men were more likely to stop smoking than women both in villages and in town. The prevalence of current smokers among village women even increased between the two surveys from 27.6% to 29.3%. Respiratory diseases did not influence quitting smoking. CONCLUSIONS: The degree of decreasing trend in smoking prevalence varied considerably within neighbouring populations. It was mainly seen in the town and among younger people. Men and those better educated were more willing to quit smoking. The discrepancies between two close rural populations indicates the need for an individual approach when designing programs of tobacco control.

Are too many compression ultrasounds being performed for acute lower limb deep venous thrombosis in tertiary inpatients?

BACKGROUND: Venous thromboembolism (VTE) is a complex and serious condition, with high morbidity and mortality, especially in hospitalised patients. Yet its diagnosis remains challenging because of its unspecific clinical presentation. The objective of this study was to apply an algorithmic combination approach to diagnosing VTE by the addition of a D-dimer assay and Wells' criteria for our hospital's internal referral forms requesting compression ultrasound (CUS), to determine the effect on the number of referrals for CUS and the incidence of deep vein thrombosis (DVT) diagnoses. METHOD: Inpatients who had been referred to the hospital's vascular laboratory and who had undergone a CUS to exclude an acute lower limb DVT were retrospectively analysed between January 2009 and December 2013, and compared to prospectively collected data for the full year (2014) after the introduction of the new referral form. Comparisons included the mean annual number of referrals for CUS and the incidence of DVT diagnoses. RESULTS: The hospital incidence of diagnosed DVTs for 2009-2013 was 0.17%, compared to 0.16% for 2014 (ρ = 0.930). In contrast, the total number of referrals for CUS as a percentage of all hospital admissions dropped from 0.84% in 2009-2013 to 0.63% in 2014 (ρ = 0.009, odds ratio 0.76, 95% confidence interval: 0.62-0.93). CONCLUSION: The implementation of Wells' criteria and D-dimer to the new request form for CUS significantly decreased referrals to the hospital's vascular laboratory without impacting on the number of DVT cases diagnosed. This is a positive change which simplifies care and reduces the expense of ultrasonography investigations.

Siblings, asthma, rhinoconjunctivitis and eczema: a worldwide perspective from the International Study of Asthma and Allergies in Childhood.

BACKGROUND: Associations of larger families with lower prevalences of hay fever, eczema and objective markers of allergic sensitization have been found fairly consistently in affluent countries, but little is known about these relationships in less affluent countries. METHODS: Questionnaire data for 210,200 children aged 6-7 years from 31 countries, and 337,226 children aged 13-14 years from 52 countries, were collected by Phase Three of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations of disease symptoms and labels of asthma, rhinoconjunctivitis and eczema were analysed by numbers of total, older and younger siblings, using mixed (multi-level) logistic regression models to adjust for individual covariates and at the centre level for region, language and national affluence. RESULTS: In both age groups, inverse trends (P < 0.0001) were observed for reported 'hay fever ever' and 'eczema ever' with increasing numbers of total siblings, and more specifically older siblings. These inverse associations were significantly (P < 0.005) stronger in more affluent countries. In contrast, symptoms of severe asthma and severe eczema were positively associated (P < 0.0001) with total sibship size in both age groups. These associations with disease severity were largely independent of position within the sibship and national GNI per capita. CONCLUSIONS: These global findings on sibship size and childhood asthma, rhinoconjunctivitis and eczema suggest at least two distinct trends. Inverse associations with older siblings (observations which prompted the 'hygiene hypothesis' for allergic disease) are mainly a phenomenon of more affluent countries, whereas greater severity of symptoms in larger families is globally more widespread.

Changes in atopy prevalence and sibship effect in rural population at all ages.

BACKGROUND: We examined the associations of family size and birth order with atopy prevalence in rural Poland at two time periods. METHODS: Two cross-sectional surveys were conducted in the same villages and a small town of lower Silesia at an interval of 9 years. In 2003, 1700 (88% of eligible individuals), and in 2012, 1730 (86%) inhabitants aged 5 years or more completed a questionnaire and had a skin prick test for atopy. RESULTS: There was an inverse association between family size and atopy in the village population in 2003; the prevalence of atopy was the highest for those with no siblings (15.2%) and decreased to 5.4% for those with three and more siblings (OR = 0.22; 0.07-0.66). In contrast, there was little or no such protective effect in the town population where the prevalence of atopy was much higher (7.3% in the villages, 20.0% in the town). Nine years later, the prevalence of atopy had increased in the village to be similar to that in the town (19.6% and 19.9% respectively), and the protective effects of family size and birth order in the villages were much weaker (OR = 0.64; 95% CI 0.33-1.27 for three or more siblings). Both protective effects were strongest among children. CONCLUSIONS: The protective effects of family size and birth order on atopy were much stronger in children than in adults and among those living in a village. They largely disappeared with the steep increase in atopy prevalence at all ages; this followed environmental changes on the village farms.

Total laparoscopic management of lesions involving liver segment 7.

BACKGROUND: Until recently, laparoscopic resection of tumors involving segment 7 (s7) of the liver was seen as a relative contraindication. We analyzed our experiences with laparoscopic resection of tumors in s7. METHODS: Retrospective analysis of prospective database on operative and postoperative characteristics and surgical outcomes of patients in whom the intention was to remove tumors located in s7 of the liver laparoscopically. We defined two groups: those with laparoscopic metastasectomy of s7 (s7 group) and those undergoing laparoscopic right posterior sectionectomy (RPS group). RESULTS: Of 400 patients undergoing laparoscopic liver resection, 20 patients (5 %) underwent total laparoscopic resections of tumors in s7 (7 metastasectomy of s7 and 13 RPS). The type of resection was decided on the basis of tumor size and location. Median age was 70 years (range 46-82), and the indication for surgery was mainly CRLM (n = 13, 65 %) and HCC (n = 4, 20 %). There was 1 (5 %) conversion. Mean operative times were 252 min (±69) for s7 and 271 min (±102) for RPS. The mean intraoperative blood loss was 400 mL (±493) for s7 and 625 mL (±363) for RPS. A Pringle maneuver was used in 86 % of patients in s7 group and 75 % of patients in RPS group. Mean total hospital stay was 4.6 days (±2.5) in s7 and 6.9 days (±7.8) for RPS. The overall R0 resection rate was 95 % (s7 100 %, RPS 92 %). CONCLUSION: Although resection of lesions in s7 is technically demanding, a laparoscopic approach can be performed safely and effectively in experienced hands.

Outcomes of repeat laparoscopic liver resection compared to the primary resection.

BACKGROUND: Repeat laparoscopic liver resection (R-LLR) can be technically challenging. Data on this topic are scarce and many investigators would question its feasibility and outcomes. The aim of the present study was to evaluate the safety, feasibility, oncological efficiency and outcomes of R-LLR. METHODS: We reviewed a prospectively collected database of 403 patients undergoing 422 laparoscopic liver resections (LLRs) from August 2003 to August 2013. Data of 19 patients undergoing R-LLR were analyzed and compared to the primary resection (P-LLR) in these patients. Demographic and clinical data were studied. A subgroup analysis was done for minor resections. RESULTS: Twenty R-LLRs were performed in 19 patients (female 58 %; mean age: 57.5 years; age range: 23-79 years). Colorectal liver metastases (CRLM) were the commonest indication for R-LLR (60 %), followed by neuroendocrine tumor liver metastases (NETLM) (20 %) and hepatocellular carcinoma (HCC) (10 %). The majority (90 %) of resections were for malignant disease (18/20). There were three conversions (15 %), and two patients developed complications (10 %). The operative time (p = 0.005) and blood loss (p = 0.03) were both significantly greater in R-LLR compared to P-LLR, whereas length of stay (median 4 days; p = 0.30) and complications (p = 0.58) did not differ between the groups. R0 resection rates for P-LLR and R-LLR were 95 and 90 %, respectively (p = 0.73). CONCLUSIONS: Repeat LLR is safe, feasible, and can be performed with minimal morbidity. It appears to be technically more challenging than P-LLR, but without any increase in complications or length of hospital stay.

Consumption of unpasteurized milk and its effects on atopy and asthma in children and adult inhabitants in rural Poland.

BACKGROUND: Consumption of unpasteurized cow's milk has been identified as a possible protective factor for atopy and asthma. Most studies have been conducted among children and in farming populations. We investigated the effects of consumption of unpasteurized milk in early life on atopy, asthma, and rhinitis in village and town inhabitants in a region of Poland and assessed whether any protective effects of milk consumption differed according to place of residence and farming status. METHODS: We surveyed the inhabitants (aged >5 years) of a small town and seven nearby villages in southwest Poland (n = 1700, response rate 88%). Participants (or their parents for those <16 years of age) completed a questionnaire on farm exposures and symptoms of asthma and rhinitis. In particular, information was collected on unpasteurized milk consumption in early life. Atopy was assessed using skin prick tests. RESULTS: Consumption of unpasteurized milk in the first year of life was inversely associated with atopy and asthma both among town and village inhabitants - town: adjusted odds ratio (aOR) for atopy 0.46 [95% confidence interval (CI) 0.37-0.52] asthma 0.51 (0.32-0.74); villages: atopy 0.59 (0.44-0.70) and asthma 0.59 (0.42-0.74). For atopy, the protective effect was more clearly seen among nonfarmers (0.42; 0.34-0.46) than in farmers (0.82; 0.54-1.11). For doctor-diagnosed hay fever and current rhinitis symptoms, the protective effect was only observed among town inhabitants and/or nonfarmers. CONCLUSIONS: Early-life exposure to unpasteurized milk may protect against atopy, asthma, and related conditions, independently of place of residence and farming status, and in both children and adults.

Variants of hepatic arterial supply in a Caribbean population: a computed tomography based study.

AIM: To evaluate the spectrum of hepatic arterial variants in unselected patients undergoing computed tomography (CT) of the abdomen at the main regional referral centre in the northern Anglophone Caribbean. MATERIALS AND METHODS: Two radiologists independently reviewed 309 CT angiographic studies performed over 2 years between 1 July 2010 and 30 June 2012 at a regional hepatobiliary referral centre for the Northern Caribbean. The anatomical variations were described according to a conventional classification proposed by Michels et al. RESULTS: In this Caribbean population, the majority of patients had conventional Michels' type 1 vascular anatomy (63.4%). However, a statistically significantly greater incidence of Michels' type 2 variations (20.4%) were found than that reported in the international literature and a lower incidence of type 3 (5.2%), type 6 (0.6%), and type 9 (0) patterns than previously reported. One case with variations not previously described in this classification was also encountered. CONCLUSION: Although 63.4% of persons in a Caribbean population have conventional vascular anatomy, the distribution of anatomical variants is quite different to that seen in North American and European centres. Interventional radiologists and hepatobiliary surgeons practicing in the Caribbean must be cognizant of these differences in order to minimize morbidity and mortality during invasive procedures.

The prevalence and demographic distribution of treated epilepsy: a community-based study in Tasmania, Australia.

OBJECTIVES: To estimate the prevalence and demographic distribution of treated epilepsy in a community-based population. MATERIALS & METHODS: We surveyed all residents in Tasmania, Australia, who were supplied at least one antiepileptic drug prescription between July 1, 2001 and June 30, 2002, recorded on the national prescription database. We adjusted for the effect of disease-related non-response bias by imputation methods. RESULTS: After three mail contacts, 54.0% (4072/7541) responded, with 1774 (43.6%) indicating treatment for epilepsy, representing 86.0% of the estimated total possible cases in Tasmania. The adjusted treated epilepsy prevalence was 4.36 per 1000 (95% CI 4.34, 4.39); lower in women (prevalence ratio 0.92 (95% CI 0.84, 1.00)); greater with increasing age (P < 0.001); similar in the three main geographic regions; and similar with socioeconomic status of postcode of residence. CONCLUSIONS: Although our estimates are likely to be affected by access to health services, overall treated epilepsy prevalence of 4.4 per 1000 is similar to previous studies. Our finding of high elderly prevalence has been reported in a few recent studies in developed countries and has important clinical and public health implications in populations with similar aging demographics.

Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action.

The cellular basis of the specific unresponsiveness that develops in DA rats treated with cyclosporine (CSA) for 10 d after grafting a PVG heart was examined using an adoptive transfer assay. CD4+ cells from rats with long survival grafts specifically lack the capacity to restore PVG heart graft rejection, and can also inhibit the capacity of naive T cells to restore rejection, while in the first few weeks post-transplant, both CD4+ and CD8+ T cells from CSA-treated hosts have the capacity to effect PVG graft rejection. In this study, we demonstrated the CD4+ suppressor cells also had the capacity to inhibit restoration of rejection by CD4+ cells from CSA-treated DA rats recently transplanted with PVG hearts, and from rats sensitized to third party, but not from those specifically sensitized to PVG. They also inhibited the capacity of both naive CD8+ and sensitized CD8+ cells to effect rejection. These results showed that the CD4+ suppressor cell was capable of overriding the capacity to effect rejection of the CD4+ cell and activated CD8+ cells that were present in the CSA-treated host shortly after transplantation. The failure of naive CD8+ cells to augment suppression and the capacity of CD4+ suppressor cells to transfer unresponsiveness to irradiated hosts in which regeneration of CD8+ cells was abolished by thymectomy suggested that it was the CD4+ cell alone that mediated suppression. However, the failure of CD4+ suppressor cells to reinduce unresponsiveness in irradiated hosts whose CD8+ cells had been depleted by therapy with the mAb MRC Ox8 showed that a radioresistant CD8+ cell was required to reestablish the state of specific unresponsiveness. The induction of CD4+ suppressor cells in thymectomized hosts suggested that these cells were derived from long-lived CD4+ lymphocytes. However, their sensitivity to cyclophosphamide and their loss of suppressor function both after removal of the graft and after 3 d in culture demonstrated that the suppressor cell itself had a short lifespan. The CD4+ suppressor was shown to be MRC Ox22+ (CD45R+), MRC Ox17+ (MHC class II), and MRC Ox39+ (CD25, IL-2-R). These studies demonstrated the CD4+ suppressive cell identified in rats with specific unresponsiveness induced by CSA therapy had many features of the suppressor inducer cell identified in in vitro studies of the alloimmune response.(ABSTRACT TRUNCATED AT 400 WORDS)

Short- and medium-term results of totally laparoscopic resection for colorectal liver metastases.

BACKGROUND: Laparoscopic surgery for primary colorectal cancer is now commonplace but the uptake of laparoscopic surgery for colorectal liver metastasis (CRLM) has been slow, mainly owing to doubts regarding safety, feasibility and oncological efficiency. METHODS: Prospectively collected data of all patients treated for CRLM between 2004 and 2009 were reviewed retrospectively. The database was analysed for operative details, hospital stay, postoperative results and medium-term survival. RESULTS: Over 5 years, 135 patients underwent liver surgery for CRLM. For laparoscopic procedures, the median duration of operation was 220 min and median blood loss was 363 ml; a mean tumour-free resection margin of 17.0 mm was achieved (more than 1 cm in 76 per cent), and no port-site metastasis or surgical-site recurrence was observed. The procedure was converted to open surgery in six patients (two for bleeding). Overall survival for the laparoscopic group approached 90 per cent with median follow-up of 22 months. CONCLUSION: In this series totally laparoscopic CRLM resection had good short- and medium-term results in terms of mortality, morbidity, resection margins, local recurrence or port-site metastasis, and survival. Compared with contemporaneous open experience, the laparoscopic approach was safe and effective in a highly selected consecutive series.

Risk of Bias Assessments and Evidence Syntheses for Observational Epidemiologic Studies of Environmental and Occupational Exposures: Strengths and Limitations.

BACKGROUND: Increasingly, risk of bias tools are used to evaluate epidemiologic studies as part of evidence synthesis (evidence integration), often involving meta-analyses. Some of these tools consider hypothetical randomized controlled trials (RCTs) as gold standards. METHODS: We review the strengths and limitations of risk of bias assessments, in particular, for reviews of observational studies of environmental exposures, and we also comment more generally on methods of evidence synthesis. RESULTS: Although RCTs may provide a useful starting point to think about bias, they do not provide a gold standard for environmental studies. Observational studies should not be considered inherently biased vs. a hypothetical RCT. Rather than a checklist approach when evaluating individual studies using risk of bias tools, we call for identifying and quantifying possible biases, their direction, and their impacts on parameter estimates. As is recognized in many guidelines, evidence synthesis requires a broader approach than simply evaluating risk of bias in individual studies followed by synthesis of studies judged unbiased, or with studies given more weight if judged less biased. It should include the use of classical considerations for judging causality in human studies, as well as triangulation and integration of animal and mechanistic data. CONCLUSIONS: Bias assessments are important in evidence synthesis, but we argue they can and should be improved to address the concerns we raise here. Simplistic, mechanical approaches to risk of bias assessments, which may particularly occur when these tools are used by nonexperts, can result in erroneous conclusions and sometimes may be used to dismiss important evidence. Evidence synthesis requires a broad approach that goes beyond assessing bias in individual human studies and then including a narrow range of human studies judged to be unbiased in evidence synthesis. https://doi.org/10.1289/EHP6980.

Global map of the prevalence of symptoms of rhinoconjunctivitis in children: The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three.

BACKGROUND: Phase One of the International Study of Asthma and Allergies in Childhood (ISAAC) measured the global patterns of prevalence and severity of symptoms of rhinoconjunctivitis in children in 1993-1997. METHODS: International Study of Asthma and Allergies in Childhood Phase Three was a cross-sectional survey performed 5-10 years after Phase One using the same methodology. Phase Three covered all of the major regions of the world and involved 1 059 053 children of 2 age groups from 236 centres in 98 countries. RESULTS: The average overall prevalence of current rhinoconjunctivitis symptoms was 14.6% for the 13- to 14-year old children (range 1.0-45%). Variation in the prevalence of severe rhinoconjunctivitis symptoms was observed between centres (range 0.0-5.1%) and regions (range 0.4% in western Europe to 2.3% in Africa), with the highest prevalence being observed mainly in the centres from middle and low income countries, particularly in Africa and Latin America. Co-morbidity with asthma and eczema varied from 1.6% in the Indian sub-continent to 4.7% in North America. For 6- to 7-year old children, the average prevalence of rhinoconjunctivitis symptoms was 8.5%, and large variations in symptom prevalence were also observed between regions, countries and centres. DISCUSSION: Wide global variations exist in the prevalence of current rhinoconjunctivitis symptoms, being higher in high vs low income countries, but the prevalence of severe symptoms was greater in less affluent countries. Co-morbidity with asthma is high particularly in Africa, North America and Oceania. This global map of symptom prevalence is of clinical importance for health professionals.