Effect of the COVID-19 pandemic on incidence of long-term conditions in Welsh residents: a population linkage study.

BACKGROUND: The COVID-19 pandemic had direct and indirect effects on health. Indirect effects on long term medical conditions (LTCs) are unclear. We examined trends in recorded incidences of LTCs and quantified differences between expected rates and observed rates from 2020 onwards. METHODS: This is a population data linkage study using primary and secondary care data within the Secure Anonymised Information Linkage Databank. We included data of Welsh residents diagnosed with any of 17 identified LTCs for the first time between Jan 1, 2000, and Dec 31, 2021. LTC's include mental health conditions, respiratory diseases, and heart conditions among others, generally chosen in line with the Quality and Outcomes Framework. The primary outcome was incidence rates (monthly number of new cases per 100 000 population). For each LTC, we did interrupted time series analysis of incidence rates from 2015 to 2021. Expected rates from between Jan 1, 2020, to Dec 31, 2021, were predicted using overall trends and seasonal patterns from the preceding 5 years and compared with observed rates. FINDINGS: We included 5 476 012 diagnoses from 2 257 992 individuals diagnosed with at least one LTC between Jan 1, 2000, to Dec 31, 2021. Across multiple long-term conditions, there was an abrupt reduction in observed incidence of new diagnoses from March to April 2020, followed by a general increase in incidence towards prepandemic rates. The conditions with the largest percentage difference between the observed and expected incidence rates in 2020 and 2021 were chronic obstructive pulmonary disease (38·4% lower than expected), depression (28·3% lower), hypertension (25·5% lower), and anxiety disorders (24·9% lower). The condition with the largest absolute difference between observed and expected incidence rates was anxiety disorders, with 830 per 100 000 less in 2020 and 2021 compared with observed rates. INTERPRETATION: The reduction in incidence rates of LTCs suggests an underreporting of LTCs, especially during 2020 and early 2021. The emergence of these yet undiagnosed cases could result in a surge of new patients in the near future. FUNDING: This work was supported by the Wales COVID-19 Evidence Centre, funded by Health and Care Research Wales.

Exploring the perceived influence of social media use on disordered eating in nutrition and dietetics students.

BACKGROUND: Social media use (SMU) is increasingly widespread. More recently, SMU has been associated with increases in disordered eating; however, few qualitative studies have explored this issue in nutrition and dietetics students specifically, where susceptibility to disordered eating may be particularly high. The present study therefore aimed to investigate the perceived impact of SMU on disordered eating in nutrition and dietetics students. METHODS: One-to-one, in-depth, semi-structured interviews were conducted with nutrition and dietetics students from universities across the UK. Interviews explored students' views on the potential influence of SMU on their eating-related thoughts, feelings and behaviours. Data were thematically analysed to identify key themes. RESULTS: The findings suggested that SMU may provide students with a useful tool for the exploration of new recipes, ingredients and health-related information, thus enabling them to improve their eating behaviour and diet quality. However, students also showed high levels of objective awareness regarding the problems associated with SMU, including the presence of misinformation, body image dissatisfaction, social pressures and disordered eating. Interestingly, despite enabling them to detect sources of misinformation, students also discussed the negative impact that their course had on their eating habits, suggesting course content may be an additional risk factor for the development of disordered eating for this particular group. CONCLUSIONS: Future research should investigate ways to mitigate the negative impact of SMU and course content on disordered eating in nutrition and dietetics students.

Diagnostic routes and time intervals for ovarian cancer in nine international jurisdictions; findings from the International Cancer Benchmarking Partnership (ICBP).

BACKGROUND: International Cancer Benchmarking Partnership Module 4 reports the first international comparison of ovarian cancer (OC) diagnosis routes and intervals (symptom onset to treatment start), which may inform previously reported variations in survival and stage. METHODS: Data were collated from 1110 newly diagnosed OC patients aged >40 surveyed between 2013 and 2015 across five countries (51-272 per jurisdiction), their primary-care physicians (PCPs) and cancer treatment specialists, supplement by treatment records or clinical databases. Diagnosis routes and time interval differences using quantile regression with reference to Denmark (largest survey response) were calculated. RESULTS: There were no significant jurisdictional differences in the proportion diagnosed with symptoms on the Goff Symptom Index (53%; P = 0.179) or National Institute for Health and Care Excellence NG12 guidelines (62%; P = 0.946). Though the main diagnosis route consistently involved primary-care presentation (63-86%; P = 0.068), onward urgent referral rates varied significantly (29-79%; P < 0.001). In most jurisdictions, diagnostic intervals were generally shorter and other intervals, in particular, treatment longer compared to Denmark. CONCLUSION: This study highlights key intervals in the diagnostic pathway where improvements could be made. It provides the opportunity to consider the systems and approaches across different jurisdictions that might allow for more timely ovarian cancer diagnosis and treatment.

Pharmacogenomics of Clozapine-induced agranulocytosis: a systematic review and meta-analysis.

Although clozapine is the most effective pharmacotherapy for treatment-resistant schizophrenia, it is under-utilized, and initiation is often delayed. One reason is the occurrence of a potentially fatal adverse reaction, clozapine-induced agranulocytosis (CIA). Identifying genetic variations contributing to CIA would help predict patient risk of developing CIA and personalize treatment. Here, we (1) review existing pharmacogenomic studies of CIA, and (2) conduct meta-analyses to identify targets for clinical implementation. A systematic literature search identified studies that included individuals receiving clozapine who developed CIA and controls who did not. Results showed that individuals carrying the HLA-DRB1*04:02 allele had nearly sixfold (95% CI 2.20-15.80, pcorrected = 0.03) higher odds of CIA with a negative predictive value of 99.3%. Previously unreplicated alleles, TNFb5, HLA-B*59:01, TNFb4, and TNFd3 showed significant associations with CIA after multiple-testing corrections. Our findings suggest that a predictive HLA-DRB1*04:02-based pharmacogenomic test may be promising for clinical implementation but requires further investigation.

Characterisation of seven medications approved for attention-deficit/hyperactivity disorder using in vitro models of hepatic metabolism.

The metabolism of most medications approved for the treatment of attention deficit/hyperactivity disorder (ADHD) is not fully understood.In vitro studies using cryopreserved, plated human hepatocytes (cPHHs) and pooled human liver microsomes (HLMs) were performed to more thoroughly characterise the metabolism of several ADHD medications.The use of enzyme-specific chemical inhibitors indicated a role for CYP2D6 in atomoxetine (ATX) metabolism, and roles for CYP3A4/5 in guanfacine (GUA) metabolism.The 4-hydroxy-atomoxetine and N-desmethyl-atomoxetine pathways represented 98.4% and 1.5% of ATX metabolism in cPHHs, respectively. The 3-OH-guanfacine pathway represented at least 2.6% of GUA metabolism in cPHHs, and 71% in HLMs.The major metabolising enzyme for methylphenidate (MPH) and dexmethylphenidate (dMPH) could not be identified using these methods because these compounds were too unstable. Hydrolysis of these medications was spontaneous and did not require the presence of protein to occur.Clonidine (CLD), amphetamine (AMPH), and dextroamphetamine (dAMPH) did not deplete substantially in cPHHs nor HLMs, suggesting that these compounds may not undergo considerable hepatic metabolism. The major circulating metabolites of AMPH and dAMPH (benzoic acid and hippuric acid) were not observed in either system, and therefore could not be characterised. Additionally, inhibition experiments suggested a very minimal role for CYP2D6 in CLD and AMPH metabolism.

Dose response effect of chemical surface concentration on percutaneous penetration in human: In vivo + in vitro.

The concentration of a formulation, defined as the mass of applied chemical per unit of skin surface area, is a key variable of skin absorption. Often only one concentration is available in the literature, hence a general evidence-based theory could allow prediction of how altering the concentration would produce a linear, increased, or decreased relative permeation. Here, we group topical chemicals into groups of how they permeate the skin when we increase or decrease their concentrations per unit area and discuss why we would like to predict their permeability in ranges of studied concentrations. PURPOSE: Our research question is: How, if at all, do changes in surface chemical concentration affect percutaneous penetration/absorption in man? Specifically, as the drug concentration is relatively increased, is the rate or extent of absorption proportionally affected? And if so, how? METHODS: We searched PubMed, Google Scholar, the United States Food and Drug Administration, Scientific Committee on Consumer Safety, and the European Food Safety Authority for approved transdermal delivery systems from January 1965 to October 2020. Search terms included combinations of the following words: topical + [absorption/penetration] + cm + [human/man]. RESULTS: Of the nineteen chemicals identified, five (testosterone, hydrocortisone, benzoic acid, fluazifop-butyl and lindane) showed decreased percent absorbed with increased dose, one (2-butoxyethanol) showed decreased flux with increased concentration, and thirteen (Basic Brown 17, benzene in gasoline, benzophenone-3, benzoyl peroxide, boric acid, caffeine, climbazole, diclofenac, ethanolamines, ibuprofen, N-octylamine, 2-phenoxyethanol, 2-pyrrolidone) showed increased flux with increasing concentrations. CONCLUSION: Dermal absorption depends on the interaction between the characteristics of the substance, the vehicle, and the skin. Without experiments investigating these characteristics, we cannot accurately predict the percent absorbed or flux of a formulation without in vitro or in vivo data. More experimental data, especially in vivo, is mandated before a highly efficient prediction model will be reached for validation.

Efficacy of water skin decontamination in vivo in humans: A systematic review.

With the constant possibility of occupational exposures, chemical warfare, and targeted attacks, increased attention has been given to determining effective and timely dermal decontamination strategies. This systematic review summarises experimental studies reporting decontamination with water-based solutions of dermal chemical contaminants with in vivo human data. Embase, MEDLINE, PubMed, Web of Science, and Google Scholar databases were comprehensively searched using search terms ("cutaneous" or "skin" or "dermal" or "percutaneous") and ("decontamination" or "decontaminant" or "skin decontamination") to include 10 studies, representing 18 chemical contaminants, 199 participants, and 351 decontamination outcomes. Three studies included data from decontamination with water (10.8%, n = 38/351 decontamination outcomes), seven with soap and water (68.4%, n = 240/351 decontamination outcomes), and two with 10% isopropanol distilled water (20.8%, n = 73/351 decontamination outcomes). Results of dermal decontamination using water showed complete decontamination (CD) outcomes in 52.6% (n = 20/38) and partial decontamination (PD) in 47.4% (n = 18/38); using soap and water showed PD outcomes in 92.9% (n = 223/240) and minimal to no effect in 7.1% (n = 17/240); and using 10% isopropanol distilled water achieved PD outcomes in 100.0% (n = 73/73). Available data show that decontamination with water, soap and water, and 10% isopropanol distilled water is incomplete. Much remains to be learned about decontamination of the large variety of chemical contaminants including a range of molecular weights, lipid and water solubilities, melting points, volatility, and hydrogen bonds, as well as clinically relevant anatomic sites. A major void exists in data confirming or denying the completeness of decontamination by measuring absorption and excretion. The development of effective decontamination solutions is of high priority.

Efficacy of water-only or soap and water skin decontamination of chemical warfare agents or simulants using in vitro human models: A systematic review.

Water-only or water and soap are widely recommended as preferred solutions for dermal decontamination. However, limited efficacy data exist. We summarized experimental studies evaluating in vitro efficacy of water-only or soap and water in decontaminating chemical warfare agents (CWA) or their simulants from human skin models. Embase, Covidence®, MEDLINE, PubMed, Web of Science, and Google Scholar were searched for articles using water-only or soap and water decontamination methods for removal of CWA/CWA simulants in in vitro human skin models. Data extraction was completed from seven studies, yielding seven contaminants. Water-only decontamination led to partial decontamination in all skin samples (100%, n = 81/81). Soap and water decontamination led to partial decontamination in all skin samples (100%, n = 143/143). Four studies found decontamination to either paradoxically enhance absorption of contaminants or their penetration rates, known as the "wash-in" effect. Despite recommendations, water-only or water and soap decontamination were found to yield partial decontamination of CWA or their simulants in all human in vitro studies. Thus, more effective decontaminating agents are needed. Some studies demonstrated increased or faster penetration of chemicals following decontamination, which could prove deadly for agents such as VX, although these findings require in vivo validation. Heterogeneity in experimental setups limits interstudy comparison, and it remains unclear when water-only or water and soap are ideal decontaminants, which requires more studies. Pending manuscripts will summarize in vivo human and animal efficacy data. International harmonized efficacy protocol should enable more efficient public health decisions for evidence-based public health decisions.

Efficacy of soap and water based skin decontamination using in vivo animal models: a systematic review.

Water-only or soap and water solutions are considered a gold standard for skin decontamination. However, there is lack of conclusive data regarding their efficacy. The aim of this study was to summarize in vivo animal model data on skin decontamination using water-only, and/or soap and water. Covidence, Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched to identify relevant articles using water-only or soap and water decontamination methods in in vivo animals. Data extraction was completed from studies, representing three animal models, and 11 contaminants. Results demonstrated water-only decontamination solutions led to complete decontamination in 3.1% (n = 16/524) protocols, incomplete decontamination in 90.6% (n = 475/524) of protocols, and mortality in 6.3% (n = 33/524) of protocols. Soap and water decontamination solutions resulted in complete decontamination in 6.9% (n = 8/116) protocols, incomplete decontamination in 92.2% (n = 107/116) of protocols, and mortality in 6.9% (n = 8/116) of protocols. Although water only, or soap and water is considered a gold standard for skin decontamination, most papers investigated found that water only, and soap and water provided incomplete decontamination. Due to the insufficient data, and limitations that hinder the applicability of available data, evidence indicates that more contemporary studies investigating skin decontamination are needed, and compared to other model species, including humans, when practical.

Efficacy of water-based skin decontamination of occupational chemicals using in vitro human skin models: a systematic review.

Percutaneous absorption of chemicals is a potential route of topical and systemic toxicity. Skin decontamination interrupts this process by removing contaminants from the skin surface. Decontamination using water-only or soap and water solutions is the current gold standard despite limited efficacy data. A summary of studies evaluating their efficacy in decontaminating occupational contaminants from in vitro human skin models is presented. Embase, MEDLINE, PubMed, Web of Science, and Google Scholar were searched for relevant articles and data extracted from 15 investigations that reported on 21 occupational contaminants, which were further classified as industrial chemicals, drugs, or pesticides. Water-only decontamination yielded no response in 4.3% (n = 6/140) and partial decontamination in 95.7% (n = 134/140) of skin samples. Soap and water decontamination yielded complete decontamination in 4.9% (n = 13/264) and partial decontamination in 95.1% (n = 251/264) of skin samples. Four studies (26.7%, n = 4/15) reported increased penetration rates or skin concentration of contaminants following decontamination, demonstrating a "wash-in" effect. Varying study methodologies hinder our ability to compare data and determine when water alone or soap and water are best used. International harmonized efficacy protocol might enhance our decontamination understanding and enable a more customized approach to decontamination clinical practice and research.

Ability of mathematical models to predict human in vivo percutaneous penetration of steroids.

Human skin is a common route for topical steroids to enter the body. To aid with risk management of therapeutic steroid usage, the US Environmental Protection Agency estimates percutaneous penetration using mathematical models. However, it is unclear how accurate are mathematical models in estimating percutaneous penetration/absorption of steroids. In this study, accuracy of predicted flux (penetration/absorption) by the main mathematical model used by the EPA, the Potts and Guy model based on in vitro data is compared to actual human in vivo data from our laboratory of percutaneous absorption of topical steroids. We focused on steroids due to the availability of steroid in vivo human data in our laboratory. For most steroids the flux was underestimated by a factor 10-60. However, within the group itself, there was an association between the Potts and Guy model and experimental human in vivo data (Pearson Correlation = 0.8925, p = 0.000041). Additionally, some physiochemical parameters used in the Potts and Guy equation, namely log Kp (Pearson Correlation = 0.7307, p = 0.0046) and molecular weight (Pearson correlation = -0.6807, p = 0.0105) correlated significantly with in vivo flux. Current mathematical models used in estimating percutaneous penetration/absorption did not accurately predict in vivo flux of steroids. Why? Proposed limitations to mathematical models currently used include: not accounting for volatility, lipid solubility, hydrogen bond effects, drug metabolism, as well as protein binding. Further research is needed in order to increase the predictive nature of such models for in vivo flux.

Organic compounds percutaneous penetration in vivo in man: Relationship to mathematical predictive model.

Human skin is a common pathway through which chemicals in our environment enter the body. To aid with risk management of environmental chemicals, the US EPA utilizes mathematical models to estimate percutaneous penetration when experimental data is not available. Here, the accuracy of predicted flux by the Potts and Guy model based on in vitro penetration is compared to human in vivo data of percutaneous absorption of various organic compounds. For most chemicals, the flux was over- or underestimated by a factor 10-100. In vitro flux was significantly correlated to experimental human in vivo flux; however, the physiochemical parameters used in the Potts and Guy equation, Kp, Koctanol, and molecular weight, did not correlate significantly with in vivo flux. We discuss possible explanations for why the computer model did not accurately predict in vivo flux. Further research is needed with different types of chemicals encountered in the environment, and/or as used in clinical practice. This manuscript discusses limitations to the mathematical models currently used, and why the models should be further refined for use.

The time course and mechanisms of change in biomarkers of joint metabolism in response to acute exercise and chronic training in physiologic and pathological conditions.

PURPOSE: The benefits of exercise across the lifespan and for a wide spectrum of health and diseases are well known. However, there remains less clarity as to the effects of both acute and chronic exercise on joint health. Serum biomarkers of joint metabolism are sensitive to change and have the potential to differentiate between normal and adverse adaptations to acute and chronic load. Therefore, the primary objective of this review is to evaluate how serum biomarkers can inform our understanding of how exercise affects joint metabolism. METHODS: A comprehensive literature search was completed to identify joint biomarkers previously used to investigate acute and chronic exercise training. RESULTS: Identified biomarkers included those related to joint cartilage, bone, synovium, synovial fluid, and inflammation. However, current research has largely focused on the response of serum cartilage oligomeric matrix protein (COMP) to acute loading in healthy young individuals. Studies demonstrate how acute loading transiently increases serum COMP (i.e., cartilage metabolism), which is mostly dependent on the duration of exercise. This response does not appear to be associated with any lasting deleterious changes, cartilage degradation, or osteoarthritis. CONCLUSION: Several promising biomarkers for assessing joint metabolism exist and may in future enhance our understanding of the physiological response to acute and chronic exercise. Defining 'normal' and 'abnormal' biomarker responses to exercise and methodological standardisation would greatly improve the potential of research in this area to understand mechanisms and inform practice.

Informing evidence-based policy during the COVID-19 pandemic and recovery period: learning from a national evidence centre.

BACKGROUND: The COVID-19 pandemic demonstrated the vital need for research to inform policy decision-making and save lives. The Wales COVID-19 Evidence Centre (WCEC) was established in March 2021 and funded for two years, to make evidence about the impact of the pandemic and ongoing research priorities for Wales available and actionable to policy decision-makers, service leads and the public. OBJECTIVES: We describe the approaches we developed and our experiences, challenges and future vision. PROGRAM IMPLEMENTATION: The centre operated with a core team, including a public partnership group, and six experienced research groups as collaborating partners. Our rapid evidence delivery process had five stages: 1. Stakeholder engagement (continued throughout all stages); 2. Research question prioritisation; 3. Bespoke rapid evidence review methodology in a phased approach; 4. Rapid primary research; and 5. Knowledge Mobilisation to ensure the evidence was available for decision-makers. MAIN ACHIEVEMENTS: Between March 2021-23 we engaged with 44 stakeholder groups, completed 35 Rapid Evidence Reviews, six Rapid Evidence Maps and 10 Rapid Evidence Summaries. We completed four primary research studies, with three published in peer reviewed journals, and seven ongoing. Our evidence informed policy decision-making and was cited in 19 Welsh Government papers. These included pandemic infection control measures, the Action Plan to tackle gender inequalities, and Education Renew and Reform policy. We conducted 24 Welsh Government evidence briefings and three public facing symposia. POLICY IMPLICATIONS: Strong engagement with stakeholder groups, a phased rapid evidence review approach, and primary research to address key gaps in current knowledge enabled high-quality efficient, evidence outputs to be delivered to help inform Welsh policy decision-making during the pandemic. We learn from these processes to continue to deliver evidence from March 2023 as the Health and Care Research Wales Evidence Centre, with a broader remit of health and social care, to help inform policy and practice decisions during the recovery phase and beyond.

Transdermal Blood Sampling for C-Peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes.

OBJECTIVE: C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative. RESEARCH DESIGN AND METHODS: Ninety-one individuals (71 with type 1 diabetes, 20 control; individuals with type 1 diabetes: aged median 14.8 years [interquartile range (IQR) 9.1-17.1], diabetes duration 4.0 years [1.5-7.7]; control individuals: 42.2 years [38.0-52.1]) underwent contemporaneous venous and TCB sampling for measurement of plasma C-peptide. Participants with type 1 diabetes also provided venous serum and plasma, and TCB plasma for measurement of autoantibodies to glutamate decarboxylase, islet antigen-2, and zinc transporter 8. The ability of TCB plasma to detect significant endogenous insulin secretion (venous C-peptide ≥200 pmol/L) was compared along with agreement in levels, using Bland-Altman. Venous serum was compared with venous and TCB plasma for detection of autoantibodies, using established thresholds. Acceptability was assessed by age-appropriate questionnaire. RESULTS: Transdermal sampling took a mean of 2.35 min (SD 1.49). Median sample volume was 50 µL (IQR 40-50) with 3 of 91 (3.3%) failures, and 13 of 88 (14.7%) <35 µL. TCB C-peptide showed good agreement with venous plasma (mean venous ln[C-peptide] - TCB ln[C-peptide] = 0.008, 95% CI [-0.23, 0.29], with 100% [36 of 36] sensitivity/100% [50 of 50] specificity to detect venous C-peptide ≥200 pmol/L). Where venous serum in multiple autoantibody positive TCB plasma agreed in 22 of 32 (sensitivity 69%), comparative specificity was 35 of 36 (97%). TCB was preferred to venous sampling (type 1 diabetes: 63% vs. 7%; 30% undecided). CONCLUSIONS: Transdermal capillary testing for C-peptide is a sensitive, specific, and acceptable alternative to venous sampling; TCB sampling for islet autoantibodies needs further assessment.

Tensions in primary care cancer detection: An embedded qualitative intervention development study.

BACKGROUND: UK cancer mortality is worse than many other high-income countries, partly due to diagnostic delays in primary care. AIM: To understand beliefs and behaviour of GPs, and systems of general practice teams, to inform the Think Cancer! intervention development. DESIGN AND SETTING: An embedded qualitative study guided by behaviour change models (COM-B and TDF) in primary care in Wales, UK. METHOD: Twenty qualitative, semi-structured telephone interviews with GPs and four face-to-face focus groups with practice teams. Analysis used Framework, results were mapped to multiple, overlapping components of COM-B and TDF. RESULTS: Three themes illustrate (1) complex, multi-level referral considerations facing GPs and practice teams, (2) external influences and constraints, (3) the role of practice systems and culture. Tensions emerged between individual considerations of GPs (Capability, Motivation) and context-dependent external pressures (Opportunity). Detecting cancer was guided not only by external requirements, but also by motivational factors GPs described as part of their cancer diagnostics process. External influences on the diagnosis process often resulted from the primary-secondary care interface and social pressures. GPs adapted their behaviour to deal with this disconnect. Positive practice culture and supportive practice-based systems ameliorated these tensions and complexity. CONCLUSION: By exploring individual GP behaviours together with practice systems and culture we contribute new understandings on how cancer diagnosis operates in primary care and how delays can be improved. We highlight commonly overlooked dynamics and tensions, experienced by GPs as a tension between individual decision-making (Capability, Motivation) and external considerations such as pressures in secondary care (Opportunity).

Use of natural health products in children: experiences and attitudes of family physicians in Newfoundland and Labrador.

OBJECTIVE: To determine the experiences of family physicians in Newfoundland and Labrador with parents' use of natural health products (NHPs) for their children and to assess physicians' attitudes toward use of NHPs in children. DESIGN: A survey using the Dillman approach. SETTING: Newfoundland and Labrador. PARTICIPANTS: All family physicians in the province. MAIN OUTCOME MEASURES: Physician demographic characteristics; whether physicians inquire about the use of NHPs in children; the degree to which they think patients disclose use of NHPs in children; whether they counsel parents about the potential benefits or harms of NHPs; their own opinions about the usefulness of NHPs; whether they recommend NHPs in children and for what reasons; and the particular NHPs they have seen used in children and for what reasons. RESULTS: A total of 159 (33.1%) family physicians responded; 65.4% were men, 71.7% were Canadian medical graduates, and 46.5% practised in rural areas. Overall, 18.8% of family physicians said they regularly or frequently asked about NHP use; 24.7% counseled patients about potential harms. Only 1.9% of physicians believed NHPs were usually beneficial, but a similarly small number (8.4%) thought they were usually harmful. Most respondents were somewhat neutral; 59.7% said they never recommend NHPs for children, and a further 37.0% said they would only "sometimes" recommend NHPs. CONCLUSION: Most physicians believed that NHPs were probably of little benefit but not likely to be harmful. Most NHPs used were vitamins and minerals. Physicians recognized that NHPs were often used by parents for children, but in general they believed NHPs had little effect on their day-to-day medical practices. Thirty-eight (24.7%) of the 154 physicians had at least once recommended an NHP (including vitamins) for their pediatric patients. Physicians believed that parents did not often disclose use of NHPs for their children, but at the same time physicians generally did not actively inquire.

Use of natural health products in children: survey of parents in waiting rooms.

OBJECTIVE: To determine how common it is for parents to give natural health products (NHPs) to their children, which NHPs are being used, why they are being used, and parents' assessments of the benefits and side effects of NHPs. DESIGN: Survey. SETTING: Newfoundland and Labrador. PARTICIPANTS: Parents waiting in their family doctors' offices. MAIN OUTCOME MEASURES: Parent and child demographic characteristics; pediatric chronic medical conditions affecting the children; prescribed medications, over-the-counter medications, and NHPs used by the children; why the medications and NHPs were being used, the dose, and parents' assessments of the effectiveness and side effects; and where parents had heard about the NHPs, whether they had told their physicians that the children were taking the products, and where they had obtained the products. RESULTS: A total of 202 (53.4%) of the 378 eligible adults who were approached completed the survey. This represented 333 children. Mean (SD) age of the children was 5.1 (3.3) years. Overall, 28.7% of parents reported using nonvitamin NHPs for their children. A total of 137 children (41.1%) had taken NHPs (including vitamins); 61.1% of the NHPs being used were vitamins. The remainder fell under teas (primarily chamomile and green teas), echinacea, fish or omega-3 oils, and a large category of "other" products. These NHPs were most commonly used to improve general health, improve immunity, and prevent colds and infections. Approximately half of the parents (51.7%) believed their children had benefited from taking NHPs, and 4.4% believed their children had experienced adverse side effects. Slightly less than half of the parents (45.0%) had informed their physicians that their children were taking NHPs. CONCLUSION: Overall, 45.5% of parents attending physicians' offices reported using NHPs in their children. If vitamins are not included in the definition of NHPs, this rate drops to 28.7%. Parents most commonly use NHPs to maintain the general health of their children, to prevent colds, and to boost children's immune systems. About half of the parents believed the NHPs helped, very few had noticed any side effects, and approximately half had informed their physicians that they were giving their children NHPs.

Use of natural health products in children: qualitative analysis of parents' experiences.

OBJECTIVE: To gain a more thorough understanding of why parents choose to give their children natural health products (NHPs), parents' sources of information about NHPs, and the extent of disclosure and conversation with family doctors about the use of NHPs. DESIGN: Qualitative study. SETTING: Newfoundland and Labrador. PARTICIPANTS: Parents of children who were using NHPs (N = 20). METHODS: Individual, semistructured interviews were carried out with parents to obtain a better understanding of the reasoning behind the use of NHPs. Key themes emerging from the qualitative data were identified according to a number of criteria, including relevance to the research objectives, frequency with which a theme was mentioned, relative importance of the themes based on the amount of text taken up to address an issue, and emphasis (eg, emphatic or emotional speech). MAIN FINDINGS: The types of NHPs used by parents participating in this study varied, except for the use of multivitamins. In addition, use of the products themselves was variable and inconsistent. Parents reported few concerns about the use of NHPs. The most commonly reported source of information about NHPs was family and friends. Most participants had not spoken to their family doctors about the use of NHPs. CONCLUSION: Participants considered NHPs to be "natural" and seemed to equate this assessment with safety. This might explain why these parents sought advice and information from family and friends rather than from their family doctors and often failed to disclose the use of NHPs to their children's family doctors.

Single nucleotide polymorphisms in C-reactive protein (CRP) predict response to adjunctive celecoxib treatment of resistant bipolar depression.

Background: Affective illness has been associated with a proinflammatory state, and it is generally accepted that the immune system plays a key role in the pathophysiology of mood disorders. Since inflammatory biomarkers are elevated in bipolar disorder, anti-inflammatory combination therapies may enhance response and reverse treatment resistance. Purpose: In the present study we investigated the possible impact of single nucleotide polymorphisms (SNPs) within the CRP gene on CRP blood levels, treatment response and level-of-stress perception in our cohort of treatment-resistant bipolar-depressed patients receiving escitalopram and celecoxib, or escitalopram and placebo, as previously reported (Halaris et al., 2020). Methods: Study design, clinical findings, and CRP blood levels have been reported previously (Halaris et al., 2020; Edberg et al., 2018). In this follow-up study we extracted DNA from blood cells collected at baseline. Genome-wide genotyping was performed for all subjects using the Infinium Multi-Ethnic Global-8 v1.0 Kit. Based on reports in the literature indicating possible associations with psychiatric conditions, ten previously reported CRP gene polymorphisms were evaluated in a preliminary analysis. We focused on rs3093059 and rs3093077 were in complete LD. Carriers were defined as those possessing at least one C allele for rs3093059, or at least one G allele for rs3093077. Additionally, we determined blood levels of the medications administered. Results: Non-carriers of rs3093059 and rs3093077 had significantly lower baseline CRP blood levels than carriers (p = 0.03). Increased rates of HAM-D17 response (p = 0.21) and remission (p = 0.13) and lower PSS-14 scores (p = 0.13) were observed in non-carriers among subjects receiving celecoxib but they did not reach statistical significance. When examining all subjects, nominally significant associations between carrier-status and remission (p = 0.04) and PSS-14 scores (p = 0.04) were observed after correcting for treatment arm. Non-carriers receiving celecoxib had the highest rates of response and remission, and the lowest stress scores. Conclusions: Carriers of the CRP SNPs may have higher baseline CRP levels, although non-carriers appear to benefit more from celecoxib co-therapy. Determination of the carrier status in conjunction with pretreatment blood CRP level measurement may contribute to personalized psychiatric practice, but replication of the present findings is needed.