Determinants of non-vaccination against seasonal influenza during pregnancy.

OBJECTIVE: The objective of this study was to identify the determinants of influenza non-vaccination during pregnancy in Canada. METHODS: Biological mothers of children born between December 2018 and March 2019 were surveyed about vaccinations they had received during pregnancy, reasons for non-vaccination, obstetrical history, and demographics. Simple and multiple logistic regression models were used to measure associations between various sociodemographic factors as well as obstetrical history, and non-vaccination against influenza. We analyzed data from 2361 mothers. RESULTS: Factors associated with non-vaccination included being followed during pregnancy by a midwife compared to by an obstetrician-gynecologist (OR 2.02; 95% CI, 1.17‒3.50); having two or more past live births compared to none (OR 1.58; 95% CI, 1.01‒2.49); having an education level below high school diploma compared to a bachelor's degree or above (OR 2.50; 95% CI, 1.06‒5.90); and having a household income below $60,000 (OR 2.46; 95% CI, 1.42‒4.24) or between $60,000 and $99,999 (OR 2.77; 95% CI, 1.70‒4.52) compared to a household income of $140,000 or more. The province or territory of prenatal care proved to be an important factor in non-vaccination, with statistically significant odds ratios for certain provinces: OR 7.50 (95% CI, 1.40‒40.26) for Ontario, 8.23 (95% CI, 1.53‒44.23) for Newfoundland and Labrador, and 11.39 (95% CI, 2.14‒60.60) for Quebec, as compared to the territories. CONCLUSION: Despite universal access to influenza vaccines in Canada during pregnancy, regional variations and socioeconomic disparities in non-vaccination are still observable.

RéSUMé: OBJECTIF: Identifier les déterminants de la non-vaccination contre la grippe pendant la grossesse au Canada. MéTHODES: Notre étude porte sur 2 361 mères biologiques d'enfants nés entre décembre 2018 et mars 2019 qui ont été interrogées sur les vaccins reçus pendant leur grossesse, les raisons de non-vaccination, leurs antécédents obstétricaux, et leurs caractéristiques démographiques. Des modèles de régression logistique simple et multiple ont été utilisés pour mesurer les associations entre divers facteurs sociodémographiques, les antécédents obstétricaux, et la non-vaccination contre l'influenza. RéSULTATS: Les facteurs associés à la non-vaccination comprennent le suivi de grossesse par une sage-femme par rapport à un obstétricien-gynécologue (RC 2,02; IC 95% : 1,17‒3,50); avoir eu deux naissances vivantes ou plus par rapport à aucune (RC 1,58; IC 95% : 1,01‒2,49); avoir une scolarité inférieure au diplôme d'études secondaires par rapport à un baccalauréat ou plus (RC 2,50; IC 95% : 1,06‒5,90); et avoir un revenu du ménage inférieur à 60 000 $ (RC 2,46; IC 95% : 1,42‒4,24) ou entre 60 000 $ et 99 999 $ (RC 2,77; IC 95% : 1,70‒4,52) par rapport à un revenu ménager de 140 000 $ ou plus. La province ou le territoire de soins prénataux s'est avéré un facteur important de la non-vaccination avec des rapports de cote statistiquement significatifs pour certaines provinces : RC 7,50 (IC 95% : 1,40‒40,26) pour l'Ontario, 8,23 (IC 95% : 1,53‒44,23) pour Terre-Neuve-et-Labrador, et 11,39 (IC 95% : 2,14‒60,60) pour le Québec, comparativement aux territoires. CONCLUSION: Malgré l'accès universel aux vaccins antigrippaux au Canada durant la grossesse, des variations régionales et des disparités socioéconomiques en non-vaccination persistent.

Pertussis Non-Vaccination During Pregnancy Despite Advice From Prenatal Care Providers.

OBJECTIVE: The purpose of this study was to measure the proportion of non-vaccination for pertussis in mothers in Canada who had been advised by their prenatal care provider to get vaccinated, and to identify sociodemographic factors and beliefs associated with non-vaccination. METHODS: The Survey on Vaccination during Pregnancy (part of childhood National Immunization Coverage Survey) included biological mothers of children born from September 2018 to March 2019. This analysis was restricted to 2657 mothers who had been advised by their prenatal care provider to get vaccinated against pertussis during pregnancy and knew whether or not they had been vaccinated. RESULTS: Of those who had been advised to get vaccinated against pertussis, 21% were not. This rate varied across provinces and territories, ranging from 9% in Prince Edward Island to 32% in Newfoundland and Labrador. Factors independently associated with pertussis non-vaccination included lower household income, having had past live births, and having received prenatal care from an obstetrician-gynecologist or a midwife compared to a family doctor. The risk of pertussis non-vaccination despite prenatal care advice was higher for those who disagreed that the baby would be at greater risk of pertussis if the mother did not get vaccinated. It was also higher for those who disagreed with statements regarding perceived benefits of vaccination. Conversely, disagreement with statements on perceived barriers was negatively associated with pertussis non-vaccination. CONCLUSION: These findings highlight the underlying factors associated with non-vaccination against pertussis despite prenatal care provider recommendation. Some inaccurate beliefs about pertussis and vaccination during pregnancy persist, leading to non-vaccination.

Pertussis Vaccination in Canadian Pregnant Women, 2018-2019.

OBJECTIVE: This study was undertaken to measure the uptake of pertussis vaccination during pregnancy in Canada and to identify sociodemographic factors associated with non-vaccination. METHODS: A total of 5091 biological mothers of children born between September 2, 2018, and March 1, 2019, were interviewed about pertussis vaccination during their pregnancy. RESULTS: Among 4607 mothers who recalled whether they had been vaccinated for pertussis, 43% had been vaccinated and 57% had not. The main reason given by mothers for not having been vaccinated was not being aware that pertussis vaccination was recommended. Factors independently associated with non-vaccination were being born outside Canada, lower household income, living in a province or territory where pertussis vaccination was not provided free of charge, having had previous live births, and having received maternity care from a midwife. CONCLUSION: Advice from the maternity care provider is an important driver of pertussis vaccination during pregnancy.

Genetic spectrum in a Canadian cohort of apparently sporadic pheochromocytomas and paragangliomas: New data on multigene panel retesting over time.

OBJECTIVE: Pheochromocytomas (PHEOs) and paragangliomas (PGLs), collectively known as PPGLs, are tumours with high heritability. The prevalence of germline mutations in apparently sporadic PPGLs varies depending on the study population. The objective of this study was to determine the spectrum of germline mutations in a cohort of patients with apparently sporadic PPGLs over time. DESIGN: We performed a retrospective review of patients with apparently sporadic PPGLs who underwent genetic testing at our referral centre from 2005 to 2020. PATIENTS: We included patients with apparently sporadic PPGLs who underwent genetic testing at our referral center. MEASUREMENTS: Genetic analysis included sequential gene sequencing by Sanger method or next generation sequencing (NGS) with a multigene panel. RESULTS: The prevalence of germline mutations was 26.2% (43/164); 40.0% (30/75) in PGLs and 14.6% (13/89) in PHEOs. We identified four novel pathogenic variants (two SDHB and two SDHD). Patients carrying germline mutations were younger (38.7 vs. 49.7 years old) than patients with no identified germline mutations. From 2015 to 2020, we performed NGS with a multigene panel on 12 patients for whom the initial genetic analysis was negative. Germline mutations in previously untested genes were found in four (33.3%) of these patients (two MAX and two SDHA), representing 9.3% (4/43) of the mutation carriers. CONCLUSION: The prevalence of germline mutations in our cohort of patients with apparently sporadic PPGLs was 26.2%. Genetic re-evaluation over time using multigene sequencing by NGS assay in a subgroup of patients leads to an increase in the detection of mutations.

Measuring functional outcome in Dupuytren's disease: A systematic review of patient-reported outcome measures.

BACKGROUND: Functional impairments related to Dupuytren's disease (DD) can be assessed using patient-reported outcome measures (PROMs). A systematic review was published in 2013 on outcome measures for assessing treatment in individuals with DD; however, several articles have since been published on this matter. PURPOSE: To conduct a systematic review to analyze the quality and content of the evidence on the psychometric properties of PROMs used in individuals with DD. STUDY DESIGN: Systematic review. METHODS: CINAHL, EBM reviews, Embase, Medline, and Web of Science were searched to identify studies evaluating the psychometric properties of PROMs used with individuals with DD. All studies retained were appraised by two independent assessors using two validated critical appraisal tools. RESULTS: Fifteen articles on the psychometric properties of 10 PROMs were included. Construct validity and responsiveness were the most studied. Eighty percent of the studies were of good to very good methodological quality according to MacDermid's Critical appraisal checklist for psychometric articles, whereas 67% of the studies comported risks of bias according to the COSMIN checklist. Of the 10 PROMs, three were specifically developed for DD but remain mostly under-studied for their psychometric properties (≤ 2 studies for the SDSS and DIF-CHUM). The QuickDASH, MHQ, BriefMHQ, and URAM present moderate to good convergent validity. Test-retest reliability was found to be good for the MHQ, briefMHQ, URAM, SDSS, SF-36, and the multi-attribute of the HUI-3. The MHQ and BriefMHQ are highly responsive. CONCLUSION: There is a need for more psychometric studies on the PROMs used with individuals with DD. However, to date, the results included in this systematic review support that the MHQ and briefMHQ are the PROMs with the most acceptable psychometric properties.

Homeless youth with first-episode psychosis: A 2-year outcome study.

BACKGROUND: Psychosis augments the risk of homelessness, the latter is associated with increased morbidity and mortality. Young adults experiencing first-episode psychosis (FEP) are increasingly recognized as being vulnerable to homelessness. However, data on homeless in youth with FEP are sparse. OBJECTIVES: To compare symptomatic and functional outcomes in homeless v. never homeless FEP, at admission and two years after admission to an Early Psychosis Intervention Service (EIS). METHOD: From October 2005 to April 2011, 167 FEP consecutive admissions (aged 18-30 years old), were recruited in a 2-year prospective longitudinal study in an inner city EIS in Montreal, Canada. Socio-demographic characteristics, symptomatic and functional outcomes, as well as treatments and service use data were collected at admission and annually. RESULT: 26% of FEP were homeless, prior or during the follow-up. Attrition rate was similar among the two groups. At baseline, the homeless group were more likely to have childhood abuse, forensic history, non-affective psychosis, negative symptoms, substance use disorder and cluster B personality. Despite the intensive care of EIS, the similarity of illness severity at baseline and medication adherence rate, homeless FEP had poorer 2-year symptomatic and functional outcomes, although having more long-acting injectable antipsychotics (LAI) (vs oral antipsychotics), community treatment order and hospitalizations. CONCLUSION: Homelessness is a serious and prevalent phenomenon among FEP youth associated with worse symptomatic and functional outcomes. More studies on interventions focusing on potentially modifiable factors (e.g. substance use disorders, social support) are warranted.

Psychosocial Factors of Health Professionals' Intention to Use a Decision Aid for Down Syndrome Screening: Cross-Sectional Quantitative Study.

BACKGROUND: Decisions about prenatal screening for Down syndrome are difficult for women, as they entail risk, potential loss, and regret. Shared decision making increases women's knowledge of their choices and better aligns decisions with their values. Patient decision aids foster shared decision making but are rarely used in this context. OBJECTIVE: One of the most promising strategies for implementing shared decision making is distribution of decision aids by health professionals. We aimed to identify factors influencing their intention to use a DA during prenatal visit for decisions about Down syndrome screening. METHODS: We conducted a cross-sectional quantitative study. Using a Web panel, we conducted a theory-based survey of health professionals in Quebec province (Canada). Eligibility criteria were as follows: (1) family physicians, midwives, obstetrician-gynecologists, or trainees in these professions; (2) involved in prenatal care; and (3) working in Quebec province. Participants watched a video depicting a health professional using a decision aid during a prenatal consultation with a woman and her partner, and then answered a questionnaire based on an extended version of the theory of planned behavior, including some of the constructs of the theoretical domains framework. The questionnaire assessed 8 psychosocial constructs (attitude, anticipated regret, subjective norm, self-identity, moral norm, descriptive norm, self-efficacy, and perceived control), 7 related sets of behavioral beliefs (advantages, disadvantages, emotions, sources of encouragement or discouragement, incentives, facilitators, and barriers), and sociodemographic data. We performed descriptive, bivariate, and multiple linear regression analyses to identify factors influencing health professionals' intention to use a decision aid. RESULTS: Among 330 health professionals who completed the survey, 310 met the inclusion criteria: family physicians, 55.2% (171/310); obstetrician-gynecologists, 33.8% (105/310); and midwives, 11.0% (34/310). Of these, 80.9% were female (251/310). Mean age was 39.6 (SD 11.5) years. Less than half were aware of any decision aids at all. In decreasing order of importance, factors influencing their intention to use a decision aid for Down syndrome prenatal screening were as follows: self-identity (beta=.325, P<.001), attitude (beta=.297, P<.001), moral norm (beta=.288, P<.001), descriptive norm (beta=.166, P<.001), and anticipated regret (beta=.099, P=.003). Underlying behavioral beliefs significantly related to intention were that the use of a decision aid would promote decision making (beta=.117, 95% CI 0.043-0.190), would reassure health professionals (beta=.100, 95% CI 0.024-0.175), and might require more time than planned for the consultation (beta=-.077, 95% CI -0.124 to -0.031). CONCLUSIONS: We identified psychosocial factors that could influence health professionals' intention to use a decision aid about Down syndrome screening. Strategies should remind them of the following: (1) using a decision aid for this purpose should be a common practice, (2) it would be expected of someone in their societal role, (3) the experience of using it will be satisfying and reassuring, and (4) it is likely to be compatible with their moral values.

Use of a patient decision aid for prenatal screening for Down syndrome: what do pregnant women say?

BACKGROUND: Patient decision aids (PtDAs) help people make difficult, values-sensitive decisions. Prenatal screening for assessing the risk of genetic conditions in the fetus is one such decision and patient decision aids are rarely used in this clinical context. We sought to identify factors influencing pregnant women's use of a patient decision aid for deciding about prenatal screening for Down syndrome (DS). METHODS: This qualitative study was embedded in a sequential mixed-methods research program whose main aim is to implement shared decision-making (SDM) in the context of prenatal screening for DS in the province of Quebec, Canada. We planned to recruit a purposive sample of 45 pregnant women with low-risk pregnancy consulting for prenatal care at three clinical sites. Participating women watched a video depicting a prenatal care follow-up during which a pregnant woman, her partner and a health professional used a PtDA to decide about prenatal screening for DS. The women were then interviewed about factors that would influence the use of this PtDA using questions based on the Theoretical Domains Framework (TDF). We performed content analysis of transcribed verbatim interviews. RESULTS: Out of 216 eligible women, 100 agreed to participate (46% response rate) and 46 were interviewed. Regarding the type of health professional responsible for their prenatal care, 19 participants (41%) reported having made a decision about prenatal screening for DS with an obstetrician-gynecologist, 13 (28%) with a midwife, 12 (26%) with a family physician, and two (4%) decided on their own. We identified 54 factors that were mapped onto nine of the 12 TDF domains. The three most frequently-mentioned were: opinion of the pregnant woman's partner (n = 33, 72%), presentation of the PtDA by health professional and a discussion (n = 27, 72%), and not having encountered a PtDA (n = 26, 57%). CONCLUSION: This study allowed us to identify factors influencing pregnant women's use of a PtDA for prenatal screening for DS. Use of a PtDA by health professionals and patients is one step in providing the needed decision support and our study results will allow us to design an effective implementation strategy for PtDAs for prenatal screening for DS.

Role of Psychosocial Factors and Health Literacy in Pregnant Women's Intention to Use a Decision Aid for Down Syndrome Screening: A Theory-Based Web Survey.

BACKGROUND: Deciding about undergoing prenatal screening is difficult, as it entails risks, potential loss and regrets, and challenges to personal values. Shared decision making and decision aids (DAs) can help pregnant women give informed and values-based consent or refusal to prenatal screening, but little is known about factors influencing the use of DAs. OBJECTIVE: The objective of this study was to identify the influence of psychosocial factors on pregnant women's intention to use a DA for prenatal screening for Down syndrome (DS). We also added health literacy variables to explore their influence on pregnant women's intention. METHODS: We conducted a survey of pregnant women in the province of Quebec (Canada) using a Web panel. Eligibility criteria included age >18 years, >16 weeks pregnant, low-risk pregnancy, and having decided about prenatal screening for the current pregnancy. We collected data based on an extended version of the Theory of Planned Behavior assessing 7 psychosocial constructs (intention, attitude, anticipated regret, subjective norm, descriptive norm, moral norm, and perceived control), 3 related sets of beliefs (behavioral, normative, and control beliefs), 4 health literacy variables, and sociodemographics. Eligible women watched a video depicting the behavior of interest before completing a Web-based questionnaire. We performed descriptive, bivariate, and ordinal logistic regression analyses. RESULTS: Of the 383 eligible pregnant women who agreed to participate, 350 pregnant women completed the Web-based questionnaire and 346 were retained for analysis (completion rate 350/383, 91.4%; mean age 30.1, SD 4.3, years). In order of importance, factors influencing intention to use a DA for prenatal screening for DS were attitude (odds ratio, OR, 9.16, 95% CI 4.02-20.85), moral norm (OR 7.97, 95% CI 4.49-14.14), descriptive norm (OR 2.83, 95% CI 1.63-4.92), and anticipated regret (OR 2.43, 95% CI 1.71-3.46). Specific attitudinal beliefs significantly related to intention were that using a DA would reassure them (OR 2.55, 95% CI 1.73-4.01), facilitate their reflections with their spouse (OR 1.55, 95% CI 1.05-2.29), and let them know about the advantages of doing or not doing the test (OR 1.53, 95% CI 1.05-2.24). Health literacy did not add to the predictive power of our model (P values range .43-.92). CONCLUSIONS: Implementation interventions targeting the use of a DA for prenatal screening for DS by pregnant women should address a number of modifiable factors, especially by introducing the advantages of using the DA (attitude), informing pregnant women that they might regret not using it (anticipated regret), and presenting the use of DAs as a common practice (descriptive norm). However, interventions on moral norms related to the use of DA should be treated with caution. Further studies that include populations with low health literacy are needed before decisive claims can be made.

What factors influence health professionals to use decision aids for Down syndrome prenatal screening?

BACKGROUND: Health professionals are expected to engage pregnant women in shared decision making to help them make informed values-based decisions about prenatal screening. Patient decision aids (PtDAs) foster shared decision-making, but are rarely used in this context. Our objective was to identify factors that could influence health professionals to use a PtDA for decisions about prenatal screening for Down syndrome during a clinical pregnancy follow-up. METHODS: We planned to recruit a purposive sample of 45 health professionals (obstetrician-gynecologists, family physicians and midwives) involved in the care of pregnant women in three clinical sites (15 per site). Participating health professionals first watched a video showing two simulated consecutive prenatal follow-up consultations during which a pregnant woman, her partner and a health professional used a PtDA about Down syndrome prenatal screening. Participants were then interviewed about factors that would influence their use of the PtDA. Questions were based on the Theoretical Domains Framework. We performed content analyses of transcribed verbatim interviews. RESULTS: Out of 42 eligible health professionals approached, 36 agreed to be interviewed (86 % response rate). Of these, 27 were female (75 %), nine were obstetrician-gynecologists (25 %), 15 were family physicians (42 %), and 12 were midwives (33 %), with a mean age of 42.1 ± 11.6 years old. We identified 35 distinct factors reported by 20 % or more participants that were mapped onto 10 of the 12 of the Theoretical Domains Framework domains. The six most frequently mentioned factors influencing use of the PtDA were: 1) a positive appraisal (n = 29, 81 %, beliefs about consequences domain); 2) its availability in the office (n = 27, 75 %, environmental context and resources domain); 3) colleagues' approval (n = 27, 75 %, social influences domain); 4) time constraints (n = 26, 72 %, environmental context and resources domain); 5) finding it a relevant source of information (n = 24, 67 %, motivation and goals domain); and 6) not knowing any PtDAs (n = 23, 64 %, knowledge domain). CONCLUSIONS: Appraisal, PtDA availability, peer approval, time concerns, evidence and PtDA awareness all affect whether health professionals are likely to use a PtDA to help pregnant women make informed decision about Down syndrome screening. Implementation strategies will need to address these factors.

Health literacy in pregnant women facing prenatal screening may explain their intention to use a patient decision aid: a short report.

BACKGROUND: It has been suggested that health literacy may impact the use of decision aids (DAs) among patients facing difficult decisions. Embedded in the pilot test of a questionnaire, this study aimed to measure the association between health literacy and pregnant women's intention to use a DA to decide about prenatal screening. We recruited a convenience sample of 45 pregnant women in three clinical sites (family practice teaching unit, birthing center and obstetrical ambulatory care clinic). We asked participating women to complete a self-administered questionnaire assessing their intention to use a DA to decide about prenatal screening and assessed their health literacy levels using one subjective and two objective scales. RESULTS: Two of the three scales discriminated between levels of health literacy (three numeracy questions and three health literacy questions). We found a positive correlation between pregnant women's intention to use a DA and subjective health literacy (Spearman coefficient, Rho 0.32, P = 0.04) but not objective health literacy (Spearman coefficient, Rho 0.07, P = 0.65). Hence subjective health literacy may affect the intention to use a DA among pregnant women facing a decision about prenatal screening. CONCLUSION: Special attention should be given to pregnant women with lower health literacy levels to increase their intention to use a DA and ensure that every pregnant women can give informed and value-based consent to prenatal screening.

ARMC5 mutations in a large French-Canadian family with cortisol-secreting ß-adrenergic/vasopressin responsive bilateral macronodular adrenal hyperplasia.

BACKGROUND: Bilateral macronodular adrenal hyperplasia (BMAH) is a rare cause of Cushing's syndrome (CS) and its familial clustering has been described previously. Recent studies identified that ARMC5 mutations occur frequently in BMAH, but the relation between ARMC5 mutation and the expression of aberrant G-protein-coupled receptor has not been examined in detail yet. METHODS: We studied a large French-Canadian family with BMAH and sub-clinical or overt CS. Screening was performed using the 1-mg dexamethasone suppression test (DST) in 28 family members. Screening for aberrant regulation of cortisol by various hormone receptors were examined in vivo in nine individuals. Sequencing of the coding regions of ARMC5 gene was carried out. RESULTS: Morning ambulating cortisol post 1 mg DST were >50 nmol/l in 5/8 members in generation II (57-68 years old), 9/22 in generation III (26-46 years old). Adrenal size was enlarged at different degrees. All affected patients increased cortisol following upright posture, insulin-induced hypoglycemia and/or isoproterenol infusion. ß-blockers led to the reduction of cortisol secretion in all patients with the exception of two who had adrenalectomies because of ß-blockers intolerance. We identified a heterozygous germline variant in the ARMC5 gene c.327_328insC, (p.Ala110Argfs*9) in nine individuals with clinical or subclinical CS, in four out of six individuals with abnormal suppression to dexamethasone at initial investigation and one out of six individuals with current normal clinical screening tests. CONCLUSIONS: Systematic screening of members of the same family with hereditary BMAH allows the diagnosis of unsuspected subclinical CS associated with early BMAH. The relation between the causative ARMC5 mutation and the reproducible pattern of aberrant ß-adrenergic and V1-vasopressin receptors identified in this family remains to be elucidated.

Synthesis, gelation and topochemical polymerization of meta-linked oligophenylenebutadiynylene derivatives.

Rational design of meta-linked oligophenylbutadiynylene (OPBD) derivatives was conducted in order to gain insight into their gelation properties and reactivity toward topochemical polymerization to yield polydiacetylenes (PDAs). Different structural parameters influencing the gel formation such as the presence of peripheral 2-hydroxyethoxy side chains and the position of amide functionalities, responsible for intermolecular hydrogen bonds, were studied. Topochemical polymerization of butadiyne units contained within the OPBDs was performed and the resulting PDAs were characterized by electron microscopy and spectroscopy.

Rigid organic nanotubes obtained from phenylene-butadiynylene macrocycles.

Rigid organic nanotubes were prepared from six-membered phenylene-butadiynylene macrocycles through topochemical polymerization in the xerogel state. All six butadiyne units underwent polymerization, thus creating rigid nanotubes with six polydiacetylene chains lying parallel, one relative to each other.

Mass-action model analysis of the apparent molar volume and heat capacity of pluronics in water and liposome suspensions at 25 °C.

Pluronics are block copolymers composed of a central block of polypropylene oxide and two side chains of polyethylene oxide. They are used in water to generate aggregates and gels or added to phospholipid suspensions to prepare microparticles for drug delivery applications. The structure of these systems has been widely investigated. However, little is known about the mechanisms leading to these structures. This investigation compares the apparent molar volumes and heat capacities of Pluronics F38, F108, F127, P85, P104, and P103 at 25 °C in water and in the presence of lecithin liposomes. The changes in molar volumes, heat capacities, and enthalpies generated by a mass-action model are in good agreement with the loss of hydrophobic hydration of the polypropylene oxide central block of the Pluronics. However, the molecularity of the endothermic transitions is much smaller than the aggregation numbers reported in the literature for the same systems. It is suggested that Pluronics go through dehydration of their central block to form unimolecular or small entities having a hydrophobic polypropylene oxide core. In water, these entities would assemble athermally to form larger aggregates. In the presence of liposomes, they would be transferred into the hydrophobic lecithin bilayers of the liposomes. Light transmission experiments suggest that the liposome suspensions are significantly altered only when the added Pluronics are in the dehydrated state.

On the interaction of acetone with electrophilic metallocavitands having extended cavities.

We report the synthesis and characterization of tantalum-boronate trimetallic clusters of general formula {[Cp*Ta](3)(µ(2)-RB(O)(2))(3)(µ(2)-OH)(µ(2)-O)(2)(µ(3)-OH)} (R= 4-(C(6)H(5))(C(6)H(4)) (Ta(3)-4Ph), 4-(C(6)H(5)O)(C(6)H(4)) (Ta(3)-4OPh), 4-(C(7)H(7)O)(C(6)H(4)) (Ta(3)-4OBn), 4-(C(8)H(5))(C(6)H(4)) (Ta(3)-4PhEt), and 4-(C(12)H(7))(C(6)H(4)) (Ta(3)-4Napht)). All complexes have been characterized by NMR spectroscopy and X-ray diffraction. The trimetallic species feature a large Lewis acid type cavity allowing for substrate binding in both the solid and the liquid state using a unique electrostatic interaction and a hydrogen bond. ΔH° and ΔS° values for association of acetone with the complexes vary between -2.0 and -4.1 kcal·mol(-1) and -3 and 2 cal·mol(-1)·K(-1), respectively, showing weaker binding than smaller cavitands of the same type. The barrier for acetone exchange at equilibrium is similar for all complexes, and ΔH(‡) values vary between 8.2 and 11.4 kcal·mol(-1).

Impact of hemolysis during sample collection: how different is drug concentration in hemolyzed plasma from that of normal plasma?

Hemolysis is a common phenomenon in clinical studies. Despite the growing interest in hemolysis matrix effect, how hemolysis impacts the representability of hemolyzed plasma samples was rarely evaluated. The purpose of this research is to perform such an evaluation by theoretical consideration and experiment. A formula for estimating the impact is proposed, which includes the degree of hemolysis and the drug's red blood cell (RBC): plasma concentration ratio. The impact of hemolysis on the representability of hemolyzed plasma samples is compound-dependant. Given the same degree of hemolysis, the stronger a drug binds to RBCs, the more significant the impact of hemolysis. For a drug with high affinity to RBCs, the results of hemolyzed plasma samples may not be useful even though they are accurate. There is an overall agreement between theoretical predication and experimental results. Among the ten different drug compounds tested, only methazolamide, which binds strongly to RBCs, showed significant change in plasma concentration due to hemolysis.

Analyte and internal standard cross signal contributions and their impact on quantitation in LC-MS based bioanalysis.

Cross signal contributions between an analyte and its internal standard (IS) are very common due to impurities in reference standards and/or isotopic interferences. Despite the general awareness of this issue, how exactly they affect quantitation in LC-MS based bioanalysis has not been systematically evaluated. In this research, such evaluations were performed first by simulations and then by experiments using a typical bioanalytical method for tiagabine over the concentration range of 1-1000 ng/mL in human EDTA K(3) plasma. The results demonstrate that when an analyte contributes to IS signal, linearity and accuracy can be affected with low IS concentration. Thus, minimum IS concentrations have been obtained for different combinations of concentration range, percentage of cross contribution, and weighting factor. Moreover, while impurity in analyte reference standard is a factor in cross signal contribution, significant systematic errors could exist in the results of unknown samples even though the results of calibration standards and quality controls are acceptable. How these systematic errors would affect stability evaluation, method transfer, and cross validation has also been discussed and measures to reduce their impact are proposed. On the other hand, the signal contribution from an IS to the analyte causes shifting of a calibration curve, i.e. increase of intercept, and theoretically, the accuracy is not affected. The simulation results are well supported by experimental results. For example, good inter-run (between-run) accuracy (bias: -2.70 to 5.35%) and precision (CV: 2.07-10.50%) were obtained when runs were extracted with an IS solution containing 1-fold of the lower limit of quantitation.

The right lateral position for laparoscopic diaphragmatic hernia repair in pregnancy: technique and review of the literature.

Maternal diaphragmatic hernia is a rare disorder of pregnancy. Laparoscopic repair of diaphragmatic hernias is gaining more and more consideration among the surgical community. To date, only a few centers have reported using the laparoscopic approach for diaphragmatic hernias occurring in pregnancy. As congenital diaphragmatic hernias occur mostly on the left side, a right lateral position would theoretically facilitate the surgery and would render an eventual simultaneous left thoracoscopy feasible without repositioning the patient. However, such a position in a pregnant woman has serious implications because of possible inferior vena cava compression by the gravid uterus. We performed a laparoscopic reduction and repair of a left foramen of Bochdalek hernia in a 26-week-pregnant patient, using a right lateral position. The right lateral position facilitated the procedure, without any adverse outcome for the fetus or the mother. This approach should be considered for any left diaphragmatic hernia repair occurring in pregnancy.

Laparoscopic appendectomy in pregnant patients: a review of 45 cases.

BACKGROUND AND OBJECTIVES: Laparoscopic surgery in pregnancy remains debated, especially in cases of suspected appendicitis. Cases of suspected appendicitis treated by the laparoscopic approach in a single institution over a 10-year period were reviewed (1997-2007). The objectives were to evaluate the immediate complications of the procedure and the outcome of pregnancies including foetal loss and preterm delivery. RESULTS: Retrospective analysis of 45 consecutive cases of suspected appendicitis during pregnancy was carried out. Forty-two patients (93%) had a preoperative ultrasound, of which 13 (33%) confirmed an acute appendicitis. Out of 45 cases, 15 (33%) had the surgical procedure during the first trimester, 22 (49%) in the second and 8 (18%) in the third. Two (4%) patients had major complications (intra-abdominal abscess and uterine perforation) and two others (4%) had minor complications (cystitis and ileus). No patients underwent delivery in the month following surgery and there was no foetal loss in the follow-up. Three (8.1%) patients delivered prior to 35 weeks' gestation and 18.1% delivered before term (<37 weeks). As previously reported, a high rate of normal appendix (33%) was found at surgery. No significant differences were found in rates of preterm delivery, adverse outcome or operative time between trimesters of pregnancy at the time of surgery. Mean operative time was 49 +/- 19 min. DISCUSSION: This large series from a single institution shows a low rate of preterm delivery and absence of foetal loss after laparoscopic appendectomy. Regardless of trimester, the low rate of complication makes it a valuable option for pregnant patients with suspicion of acute appendicitis. The rate of normal appendectomies remaining high, efforts have to be made towards new diagnostic modalities to lower the negative appendectomy rate in this specific population.