Temporal trends and predictors of phthalate, phthalate replacement, and phenol biomarkers in the LIFECODES Fetal Growth Study.

BACKGROUND: Exposure to many phthalates and phenols is declining as replacements are introduced. There is little information on temporal trends or predictors of exposure to these newer compounds, such as phthalate replacements, especially among pregnant populations. OBJECTIVE: Examine temporal trends and predictors of exposure to phthalates, phthalate replacements, and phenols using single- and multi-pollutant approaches. METHODS: We analyzed data from 900 singleton pregnancies in the LIFECODES Fetal Growth Study, a nested case-cohort with recruitment from 2007 to 2018. We measured and averaged concentrations of 12 phthalate metabolites, four phthalate replacement metabolites, and 12 phenols in urine at three timepoints during pregnancy. We visualized and analyzed temporal trends and predictors of biomarker concentrations. To examine chemical mixtures, we derived clusters of individuals with shared exposure profiles using a finite mixture model and examined temporal trends and predictors of cluster assignment. RESULTS: Exposure to phthalates and most phenols declined across the study period, while exposure to phthalate replacements (i.e., di(isononyl) cyclohexane-1,2-dicarboxylic acid, diisononyl ester [DINCH] and di-2-ethylhexyl terephthalate [DEHTP]) and bisphenol S (BPS) increased. For example, the sum of DEHTP biomarkers increased multiple orders of magnitude, with an average concentration of 0.92 ng/mL from 2007 to 2008 and 61.9 ng/mL in 2017-2018. Biomarkers of most chemical exposures varied across sociodemographic characteristics, with the highest concentrations observed in non-Hispanic Black or Hispanic participants relative to non-Hispanic White participants. We identified five clusters with shared exposure profiles and observed temporal trends in cluster membership. For example, at the end of the study period, a cluster characterized by high exposure to phthalate replacements was the most prevalent. SIGNIFICANCE: In a large and well-characterized pregnancy cohort, we observed exposure to phthalate replacements and BPS increased over time while exposure to phthalates and other phenols decreased. Our results highlight the changing nature of exposure to consumer product chemical mixtures.

A scoping review of risk-stratified bowel screening: current evidence, future directions.

PURPOSE: In this scoping review, we examined the international literature on risk-stratified bowel screening to develop recommendations for future research, practice and policy. METHODS: Six electronic databases were searched from inception to 18 October 2021: Medline, Embase, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials. Forward and backwards citation searches were also undertaken. All relevant literature were included. RESULTS: After de-deduplication, 3,629 records remained. 3,416 were excluded at the title/abstract screening stage. A further 111 were excluded at full-text screening stage. In total, 102 unique studies were included. Results showed that risk-stratified bowel screening programmes can potentially improve diagnostic performance, but there is a lack of information on longer-term outcomes. Risk models do appear to show promise in refining existing risk stratification guidelines but most were not externally validated and less than half achieved good discriminatory power. Risk assessment tools in primary care have the potential for high levels of acceptability and uptake, and therefore, could form an important component of future risk-stratified bowel screening programmes, but sometimes the screening recommendations were not adhered to by the patient or healthcare provider. The review identified important knowledge gaps, most notably in the area of organisation of screening services due to few pilots, and what risk stratification might mean for inequalities. CONCLUSION: We recommend that future research focuses on what organisational challenges risk-stratified bowel screening may face and a consideration of inequalities in any changes to organised bowel screening programmes.

The burden of COVID-19 infection in a rural Tamil Nadu community.

BACKGROUND: There have been over 30 million cases of COVID-19 in India and over 430,000 deaths. Transmission rates vary from region to region, and are influenced by many factors including population susceptibility, travel and uptake of preventive measures. To date there have been relatively few studies examining the impact of the pandemic in lower income, rural regions of India. We report on a study examining COVID-19 burden in a rural community in Tamil Nadu. METHODS: The study was undertaken in a population of approximately 130,000 people, served by the Rural Unit of Health and Social Affairs (RUHSA), a community health center of CMC, Vellore. We established and evaluated a COVID-19 PCR-testing programme for symptomatic patients-testing was offered to 350 individuals, and household members of test-positive cases were offered antibody testing. We also undertook two COVID-19 seroprevalence surveys in the same community, amongst 701 randomly-selected individuals. RESULTS: There were 182 positive tests in the symptomatic population (52.0%). Factors associated with test-positivity were older age, male gender, higher socioeconomic status (SES, as determined by occupation, education and housing), a history of diabetes, contact with a confirmed/suspected case and attending a gathering (such as a religious ceremony, festival or extended family gathering). Amongst test-positive cases, 3 (1.6%) died and 16 (8.8%) suffered a severe illness. Amongst 129 household contacts 40 (31.0%) tested positive. The two seroprevalence surveys showed positivity rates of 2.2% (July/Aug 2020) and 22.0% (Nov 2020). 40 tested positive (31.0%, 95% CI: 23.02 - 38.98). Our estimated infection-to-case ratio was 31.7. CONCLUSIONS: A simple approach using community health workers and a community-based testing clinic can readily identify significant numbers of COVID-19 infections in Indian rural population. There appear, however, to be low rates of death and severe illness, although vulnerable groups may be under-represented in our sample. It's vital these lower income, rural populations aren't overlooked in ongoing pandemic monitoring and vaccine roll-out in India.

Risk of missing colorectal cancer with a COVID-adapted diagnostic pathway using quantitative faecal immunochemical testing.

BACKGROUND: COVID-19 has brought an unprecedented challenge to healthcare services. The authors' COVID-adapted pathway for suspected bowel cancer combines two quantitative faecal immunochemical tests (qFITs) with a standard CT scan with oral preparation (CT mini-prep). The aim of this study was to estimate the degree of risk mitigation and residual risk of undiagnosed colorectal cancer. METHOD: Decision-tree models were developed using a combination of data from the COVID-adapted pathway (April-May 2020), a local audit of qFIT for symptomatic patients performed since 2018, relevant data (prevalence of colorectal cancer and sensitivity and specificity of diagnostic tools) obtained from literature and a local cancer data set, and expert opinion for any missing data. The considered diagnostic scenarios included: single qFIT; two qFITs; single qFIT and CT mini-prep; two qFITs and CT mini-prep (enriched pathway). These were compared to the standard diagnostic pathway (colonoscopy or CT virtual colonoscopy (CTVC)). RESULTS: The COVID-adapted pathway included 422 patients, whereas the audit of qFIT included more than 5000 patients. The risk of missing a colorectal cancer, if present, was estimated as high as 20.2 per cent with use of a single qFIT as a triage test. Using both a second qFIT and a CT mini-prep as add-on tests reduced the risk of missed cancer to 6.49 per cent. The trade-off was an increased rate of colonoscopy or CTVC, from 287 for a single qFIT to 418 for the double qFIT and CT mini-prep combination, per 1000 patients. CONCLUSION: Triage using qFIT alone could lead to a high rate of missed cancers. This may be reduced using CT mini-prep as an add-on test for triage to colonoscopy or CTVC.

Attitudes of Dutch intensive care unit clinicians towards oxygen therapy.

BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly.

Fampridine-induced changes in walking kinetics are associated with clinical improvements in patients with multiple sclerosis.

Gait dysfunction is common in patients with multiple sclerosis (PwMS). Treatment with prolonged-release fampridine (PR-fampridine) improves walking ability in some PwMS. Associated fampridine-induced changes in the walking pattern are still poorly understood but may provide a better understanding of the mechanisms underlying the beneficial drug effects. 61 PwMS were treated with PR-fampridine in a randomized, monocentric, double-blind and placebo-controlled clinical trial with crossover design (FAMPKIN). Drug-induced improvements in walking speed (Timed-25-Foot Walk; T25FW) and endurance (6-Minute Walk Test; 6MWT) were quantified. In this sub-study of the FAMPKIN trial, fampridine-induced changes in kinetic gait patterns were analyzed by pressure-based foot print analysis during treadmill walking. Vertical ground reaction forces were analyzed during different gait phases. Kinetic data of 44 PwMS was eligible for analysis. During double-blind treatment with PR-fampridine, patients performed significantly better in the T25FW and 6MWT than during placebo treatment (p < 0.0001 for both). At the group level (n = 44), there were no significant changes of gait kinetics under PR-fampridine vs. placebo. However, we found relevant changes of walking kinetics regarding forces during loading, single limb and pre-swing phase in a patient sub-group (n = 8). Interestingly, this sub-group demonstrated superior responsiveness to PR-fampridine in the clinical walking tests compared to those patients without any fampridine-induced changes in kinetics (n = 36). Our results demonstrate fampridine-induced changes in gait kinetics in a sub-group of PwMS. These gait pattern changes were accompanied by improved clinical walking performance under PR-fampridine. These results shed some light on the biomechanical changes in walking patterns underlying enhanced fampridine-induced gait performance.

Direct access CT for suspicion of brain tumour: an analysis of referral pathways in a population-based patient group.

BACKGROUND: Brain tumour patients see their primary care doctor on average three or more times before diagnosis, so there may be an opportunity to identify 'at risk' patients earlier. Suspecting a brain tumour diagnosis is difficult because brain tumour-related symptoms are typically non-specific. METHODS: We explored the predictive value of referral guidelines (Kernick and NICE 2005) for brain imaging where a tumour is suspected, in a population-based patient group referred for direct access CT of the head. A consensus panel reviewed whether non-tumour findings were clinically important or whether further investigation was necessary. RESULTS: Over a 5-year period, 3257 head scans were performed; 318 scans were excluded according to pre-specified criteria. 53 patients (1.8%) were reported to have intracranial tumours, of which 42 were significant (diagnostic yield of 1.43%). There were no false negative CT scans for tumour. With symptom-based referral guidelines primary care doctors can identify patients with a 3% positive predictive value (PPV). 559 patients had non-tumour findings, 31% of which were deemed clinically significant. In 34% of these 559 patients, referral for further imaging and/or specialist assessment from primary care was still thought warranted. CONCLUSION: Existing referral guidelines are insufficient to stratify patients adequately based on their symptoms, according to the likelihood that a tumour will be found on brain imaging. Identification of non-tumour findings may be significant for patients and earlier specialist input into interpretation of these images may be beneficial. Improving guidelines to better identify patients at risk of a brain tumour should be a priority, to improve speed of diagnosis, and reduce unnecessary imaging and costs. Future guidelines may incorporate groups of symptoms, clinical signs and tests to improve the predictive value.

Placental levels of metals and associated factors in urban and sub-urban areas of Seville (Spain).

Environmental exposure to metals among women, revealed their adverse effects on pregnancy. The fetus is exposed to these toxic elements only via the placenta which are able to accumulate there or cross it, compromising the protective functions of this organ. Numerous studies have shown associations between the prenatal exposition to some metals and an impact on cognitive, motor and intellectual development of the child. Sixty two placental samples were taken at delivery to determine the mineral content (Al, B, Ba, Ca, Cd, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, Pb, Sr, V, Zn) by ICP-OES. Among these metals, essential ones (B, Ca, Cu, Fe, Mg, Mn, Mo, Na, Zn) can have health beneficial effects at low levels however, in high concentration are potentially toxic. On the other hand, elements such as Al, Cd, Pb, are classified as toxic metals, no matter what its concentration is. The aim of this study is to find the potential relationships between these metals levels, newborn's parameters, pregnancy details and the epidemiologic information obtained using a questionnaire data from the participant pregnant women from Seville (Spain). The main maternal determinant of detectable placenta Cd levels was smoking during pregnancy. Other maternal factors that may affect placenta metal levels were gestational age (Al, B, Ba, and Pb) or dietary supplement (Fe). It has to be stressed that our results have to be interpreted with caution, because of the small study group and the low exposure levels, along with the lack of information on potential sources of exposure to these metals. The use of placenta samples obtained at delivery can be considered strength of this study since the concentration of some metals in placenta can indicate the extent of maternal exposure during gestation.

Presentation of lung cancer in primary care.

Survival from lung cancer has seen only modest improvements in recent decades. Poor outcomes are linked to late presentation, yet early diagnosis can be challenging as lung cancer symptoms are common and non-specific. In this paper, we examine how lung cancer presents in primary care and review roles for primary care in reducing the burden from this disease. Reducing rates of smoking remains, by far, the key strategy, but primary care practitioners (PCPs) should also be pro-active in raising awareness of symptoms, ensuring lung cancer risk data are collected accurately and encouraging reluctant patients to present. PCPs should engage in service re-design and identify more streamlined diagnostic pathways-and more readily incorporate decision support into their consulting, based on validated lung cancer risk models. Finally, PCPs should ensure they are central to recruitment in future lung cancer screening programmes-they are uniquely placed to ensure the right people are targeted for risk-based screening programmes. We are now in an era where treatments can make a real difference in early-stage lung tumours, and genuine progress is being made in this devastating illness-full engagement of primary care is vital in effecting these improvements in outcomes.

Metal Concentrations in Wild-Harvested Phaeophyta Seaweed from the Atlantic Ocean (Canary Islands, Spain).

Seaweeds are being consumed more often worldwide and are a source of essential minerals, fiber, vitamins, amino acids, and various bioactive compounds that have many beneficial effects on human health. However, marine pollution and the high capacity of seaweed to absorb metals may mean this food can also be dangerous to human health. The concentrations of some trace elements (B, Ba, Fe, Ni, Li, and V) and toxic metals (Al, Cd, and Pb) were determined in various species of wild seaweeds in the Phaeophyta group of brown algae from the Atlantic Ocean. Inductively coupled plasma atomic emission spectrometry revealed high concentrations of Al (256 mg/kg dry weight), Pb (3.92 mg/kg dry weight), and Cd (0.20 mg/kg dry weight) in Padina pavonica. Pb contributed the most to the tolerable daily intake (TDI) of toxic metals in these samples; 57.2 and 45.3% of the TDI for Pb was found in 5 g of dehydrated P. pavonica and Halopteris scoparia, respectively. This percent contribution is half of the recommended TDI for this metal, which is 34.24 µg/day; therefore, high consumption of these species is discouraged. The maximum TDIs established by various institutions for the other metals were not exceeded from the daily consumption of 5 g of the other dehydrated seaweeds evaluated in this study.

Metal Concentrations in Samples of Frozen Cephalopods (Cuttlefish, Octopus, Squid, and Shortfin Squid): An Evaluation of Dietary Intake.

Cephalopods are an important source of nutrients and some of the most widely consumed marine foods. However, because of contamination of the oceans and the bioaccumulative nature of toxic metals, these foods may pose a health risk. For this reason, the concentrations of some trace elements (chromium [Cr], lithium, strontium [Sr], copper [Cu], and nickel) and toxic metals (aluminum [Al], cadmium, and lead) were determined in 65 frozen samples of cuttlefish, octopus, common squid, and shortfin squid by inductively coupled plasma optical emission spectrometry to evaluate dietary intake and toxic risk. Sr was the major trace element (3.03 mg/kg) in cuttlefish; however, Cu (1.57 mg/kg) was found in the highest concentration in common squid. Among the toxic metals, Al had the highest concentration (3.09 mg/kg) in common squid. Al can pose an important health risk to individuals with kidney problems and to children because these groups are most vulnerable to the toxic effects. Significant differences among the four cephalopod types were found in the concentrations of most of the metals examined. Taking into account the average consumption of cephalopods, the contribution of toxic metals does not pose a risk to the health of adults.

Metals in edible seaweed.

The concentration levels of 20 metals were analyzed by ICP-OES in edible seaweed (Chondrus, Eisenia, Gelidium, Himanthalia, Laminaria, Palmaria, Porphyra, Undaria), from two origins (Asia vs EU) according to their cultivation practices (conventional vs organic). Red seaweed showed higher concentrations of trace and toxic elements. Porphyra may be used as a potential bioindicator for metals. Significant differences were found between the Asian vs European mean contents. The mean Cd level from the conventional cultivation (0.28 mg/kg) was two points higher than the organic cultivation (0.13 mg/kg). A daily consumption of seaweed (4 g/day) contributes to the dietary intake of metals, mainly Mg and Cr. The average intakes of Al, Cd and Pb were 0.064, 0.001 and 0.0003 mg/day, respectively. Based on obtained results, this study suggests that exposure to the toxic metals analyzed (Al, Cd and Pb) through seaweed consumption does not raise serious health concerns, but other toxic metals should be monitored.

Concerns, perceived need and competing priorities: a qualitative exploration of decision-making and non-participation in a population-based flexible sigmoidoscopy screening programme to prevent colorectal cancer.

OBJECTIVE: Optimising uptake of colorectal cancer (CRC) screening is important to achieve projected health outcomes. Population-based screening by flexible sigmoidoscopy (FS) was introduced in England in 2013 (NHS Bowel scope screening). Little is known about reactions to the invitation to participate in FS screening, as offered within the context of the Bowel scope programme. We aimed to investigate responses to the screening invitation to inform understanding of decision-making, particularly in relation to non-participation in screening. DESIGN: Qualitative analysis of semistructured in-depth interviews and written accounts. PARTICIPANTS AND SETTING: People from 31 general practices in the North East and East of England invited to attend FS screening as part of NHS Bowel scope screening programme were sent invitations to take part in the study. We purposively sampled interviewees to ensure a range of accounts in terms of beliefs, screening attendance, sex and geographical location. RESULTS: 20 screeners and 25 non-screeners were interviewed. Written responses describing reasons for, and circumstances surrounding, non-participation from a further 28 non-screeners were included in the analysis. Thematic analysis identified a range of reactions to the screening invitation, decision-making processes and barriers to participation. These include a perceived or actual lack of need; inability to attend; anxiety and fear about bowel preparation, procedures or hospital; inability or reluctance to self-administer an enema; beliefs about low susceptibility to bowel cancer or treatment and understanding of harm and benefits. The strength, rather than presence, of concerns about the test and perceived need for reassurance were important in the decision to participate for screeners and non-screeners. Decision-making occurs within the context of previous experiences and day-to-day life. CONCLUSIONS: Understanding the reasons for non-participation in FS screening can help inform strategies to improve uptake and may be transferable to other screening programmes.