Background
Studies validating indirect methods to identify nonadherence in chronic patients who visit pharmacies are lacking. The aim of this study was to validate self-reported adherence and assess ...the variables associated with both overestimation and underestimation of good adherence when using this method.
Materials and methods
An observational, cross-sectional study was undertaken to validate self-reported adherence in 132 community pharmacies throughout Spain in 6237 chronic patients. The Morisky-Green test was used as the validation method and through a 2 × 2 table, the validity indicators, predictive values, and likelihood ratios were calculated. To assess the variables associated with both overestimation and underestimation of good adherence, multivariate logistic regression analysis and calculation of the area under the ROC curve were used to evaluate discriminatory capacity.
Results
Sensitivity was 27.8% (95% CI: 26.2–29.4) and specificity was 93.9% (95% CI: 93.1–94.7). Discrepancy analysis obtained a significant overestimation of good adherence (
p
< 0.001). The factors associated with overestimating good adherence were performing a mnemonic trick (
p
< 0.001), not self-medicating (
p
< 0.001), a high level of physical activity (
p
< 0.001), and an older age (
p
= 0.014). Factors associated with underestimation were self-medication (
p
< 0.001), desiring more information (p < 0.001), smoking (
p
= 0.014), not engaging in physical activity in the low (
p
= 0.006) or high (
p
< 0.001) categories, having a younger mean age (
p
= 0.007), and taking two to three (
p
= 0.029) or four or more (
p
< 0.001) chronic treatments.
Conclusion
Self-reported adherence has good specificity but poor sensitivity. The associated profiles of the discrepancies were obtained to identify both good and poor adherence.
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•GHEP-MIX06 collaborative exercise makes an evaluation of mixture profiles reports.•25 forensic genetic laboratories from 8 different countries have participated.•Reports issued, with ...a page number range of 1–11, do not completely fit to ISO/IEC 17025:2017 requirements.•Most of laboratories use the same software (LRmixStudio), but with an important LR values dispersion.•All laboratories that express LR in conclusions make a correct verbalization.
One of the main goals of the Spanish and Portuguese-Speaking Group of the International Society for Forensic Genetics (GHEP-ISFG) is to promote and contribute to the development and dissemination of scientific knowledge in the field of forensic genetics. Due to this fact, GHEP-ISFG holds different working commissions that are set up to develop activities in scientific aspects of general interest. One of them, the Mixture Commission of GHEP-ISFG, has organized annually, since 2009, a collaborative exercise on analysis and interpretation of autosomal short tandem repeat (STR) mixture profiles. Until now, six exercises have been organized. At the present edition (GHEP-MIX06), with 25 participant laboratories, the exercise main aim was to assess mixture profiles results by issuing a report, from the proposal of a complex mock case.
One of the conclusions obtained from this exercise is the increasing tendency of participating laboratories to validate DNA mixture profiles analysis following international recommendations. However, the results have shown some differences among them regarding the edition and also the interpretation of mixture profiles. Besides, although the last revision of ISO/IEC 17025:2017 gives indications of how results should be reported, not all laboratories strictly follow their recommendations.
Regarding the statistical aspect, all those laboratories that have performed statistical evaluation of the data have employed the likelihood ratio (LR) as a parameter to evaluate the statistical compatibility. However, LR values obtained show a wide range of variation. This fact could not be attributed to the software employed, since the vast majority of laboratories that performed LR calculation employed the same software (LRmixStudio). Thus, the final allelic composition of the edited mixture profile and the parameters employed in the software could explain this data dispersion. This highlights the need, for each laboratory, to define through internal validations its criteria for editing and interpreting mixtures, and to continuous train in software handling.
Marine organisms with a short pelagic larval duration (PLD) are assumed to display significant population structure given low long-distance dispersal ability. For the wider Caribbean, theoretical and ...empirical considerations suggest that species with short PLDs inhabiting each of the following areas should be genetically distinct: Costa Rica (CR), Mexico (MX), and Florida Keys (FL-K), USA. This study tested the hypothesis of significant genetic differentiation in Maguimithrax spinosissimus populations across the wider Caribbean using a combination of biophysical modeling and population genetics. Biophysical modeling predicted dissimilar connectivity patterns among CR, MX, and FL-K depending upon assumed PLD. Eight days of dispersal only provided rare connections from MX to FL-K, and low likelihood multi-generational connections between CR and FL-K. In turn, 12 d of dispersal was sufficient to connect MX to FL-K through direct and indirect routes in biophysical models, but CR and FL-K remained connected only through multiple generational steps. After 16 d of dispersal, direct connections between CR and FL-K may occur, and by 20 d of dispersal, connections are likely between all sampled patches. Population genetic analyses based on partial sequences of the mtDNA 12S, 16S, and COI genes denoted the existence of a single, relatively high-frequency haplotype shared among all 3 populations, which suggests a longer PLD than predicted by laboratory study. In turn, an analysis of molecular variance and pairwise FST values demonstrated significant genetic differentiation among the studied populations. Altogether, the above information suggests low to moderate connectivity among populations in M. spinosissimus. Subpopulation split predictions suggest multi-generational or stepping-stone connectivity between CR and both MX and FL-K, and provides a framework for understanding the structure of M. spinosissimus metapopulations throughout the region. Overall, this study agrees with the notion of significant population structure in marine species with lower dispersal ability.
•An automatic DVH-based dose verification system with contour propagation was developed.•Thirty-one breast cancer patients were used to benchmark the dose verification system against the TPS.•Strong ...agreement in DVH parameters were found between the dose verification system and the TPS.•Uncertainties derived from the dose verification system, with and without automatic contour propagation, were quantified.
Image guided radiotherapy (IGRT) strategies allow detecting and monitoring anatomical changes during external beam radiotherapy (EBRT). However, assessing the dosimetric impact of anatomical changes is not straightforward. In current IGRT strategies dose volume histograms (DVH) are not available due to lack of contours and dose recalculations on the cone-beam CT (CBCT) scan. This study investigates the feasibility of using automatically calculated DVH parameters in CBCTs using an independent dose calculation engine and propagated contours.
A prospective study (NCT03385031) of thirty-one breast cancer patients who received additional CBCT imaging (N = 70) was performed. Manual and automatically propagated contours were generated for all CBCTs and an automatic dose recalculation was performed. Differences between planned and CBCT-derived DVH parameters (mean and maximum dose to targets, 95% volume coverage to targets and mean heart dose (MHD)) were calculated using the dose verification system with manual and propagated contours and, in both cases, benchmarked against DVH differences quantified in the TPS using manually contoured CBCTs.
Differences in DVH parameters between the TPS and dose verification system with propagated contours were −1.3% to 0.7% (95% CI) for mean dose to the target volume, −0.3 to 0.2 Gy (95% CI) in MHD and −3.9% to 2.9% (95% CI) in target volume coverage.
The use of an independent fully automatic dose verification system with contour propagation showed to be feasible and sufficiently reliable to recalculate CBCT based DVHs during breast EBRT. Volume coverage parameters, i.e. V95%, proved to be especially sensitive to contouring differences.
Dose-guided adaptive radiation therapy (DGART) is the systematic evaluation and adaptation of the dose delivery during treatment for an individual patient. The aim of this study is to define ...quantitative action levels for DGART by evaluating changes in 3D dose metrics in breast cancer and correlate them with clinical expert evaluation.
Twenty-three breast cancer treatment plans were evaluated, that were clinically adapted based on institutional IGRT guidelines. Reasons for adaptation were variation in seroma, hematoma, edema, positioning or problems using voluntary deep inspiration breath hold. Sixteen patients received a uniform dose to the breast (clinical target volume 1; CTV1). Six patients were treated with a simultaneous integrated boost to CTV2. The original plan was copied to the CT during treatment (re-CT) or to the stitched cone-beam CT (CBCT). Clinical expert evaluation of the re-calculated dose distribution and extraction of dose-volume histogram (DVH) parameters were performed. The extreme scenarios were evaluated, assuming all treatment fractions were given to the original planning CT (pCT), re-CT or CBCT. Reported results are mean ± SD.
DVH results showed a mean dose (Dmean) difference between pCT and re-CT of -0.4 ± 1.4% (CTV1) and -1.4 ± 2.1% (CTV2). The difference in V95% was -2.6 ± 4.4% (CTV1) and -9.8 ± 8.3% (CTV2). Clinical evaluation and DVH evaluation resulted in a recommended adaptation in 17/23 or 16/23 plans, respectively. Applying thresholds on the DVH parameters: D
CTV, V95% CTV, D
, mean lung dose, volume exceeding 107% (uniform dose) or 90% (SIB) of the prescribed dose enabled the identification of patients with an assumed clinically relevant dose difference, with a sensitivity of 0.89 and specificity of 1.0. Re-calculation on CBCT imaging identified the same plans for adaptation as re-CT imaging.
Clinical expert evaluation can be related to quantitative DVH parameters on re-CT or CBCT imaging to select patients for DGART.
Summary
Background
Diagnostic methods for the study of allergic reactions to Anisakis simplex (A.s.) based on whole‐body extracts of the larva are clearly insufficient.
Objectives
To study the ...allergenicity of the proteins secreted by the parasite. Comparison with somatic antigens and determination of their clinical importance in allergic patients were also addressed.
Methods
An excretory/secretory (E/S) extract was produced by culturing third‐stage A.s. larvae. It was used to perform immediate skin tests and to determine specific IgE in 10 patients diagnosed with allergy to A.s. Both tests were compared with the results obtained with the whole‐body extract (somatic (S)). The molecular weight (MW) of their allergens was determined by immunoblotting, and a single‐blind placebo‐controlled oral challenge with E/S proteins was performed. Finally, allergens' resistance to gastric pepsin and acid pH was explored.
Results
A.s. larvae secreted allergens more potent than those present in the S extract. The skin prick test wheal area produced by E/S molecules and the absorbance obtained in the determination of specific IgE with these allergens (ELISA) were 5.8 times bigger than those obtained with S extract. MW allergens of 72 and 56 kDa in E/S extracts and those of 56, 48 and 43 kDa in S extract were recognized by more than 50% of the patients. Partial cross‐reactivity between them was revealed by immunoblotting inhibition studies. Oral challenge with E/S extract (up to 479 μg) was negative in all the patients. Treatment of E/S proteins with gastric pepsin inhibited the binding of the E/S allergens for specific IgE. The acid pH did not affect the overall binding of IgE to E/S extract. It decreased by 15.23% and 19.96% at pH 4 and 2, but the difference was not statistically significant.
Conclusion
A.s. secretes allergens more potent than somatic antigens and should be used in the diagnostic procedures. These allergens are inactivated by the pepsin, which supports the theory that live larva is necessary to induce an allergic reaction in most of the patients.
To contrast the initial suspected etiology of anaphylaxis with the postworkup diagnosis in patients attended at the emergency department (ED) of a tertiary-level hospital in Spain and to investigate ...the incidence, causes, and management of anaphylaxis.
We performed an observational study of patients aged more than 15 years who came to the ED with anaphylaxis between 2009 and 2010. All clinical records from the ED were reviewed. We recorded data on clinical management, the etiology proposed by the attending emergency physician, and the cause reported by the patient. The findings were compared with the diagnosis reached after the allergy workup.
The incidence of anaphylaxis was 0.08%. The most common manifestation was skin-mucosal symptoms (98.3%). Anaphylaxis was diagnosed in the ED in only 44% of the cases, regardless of severity. Only 39.7% received epinephrine, which was administered more frequently when the ED physician diagnosed anaphylaxis, regardless of severity. A total of 60 patients were subsequently seen at the allergy department. The final etiology differed from the initial suspicion in the ED in 45% of cases. The frequency of anaphylaxis of uncertain origin decreased from 33.3% to 13.3%. After the allergy workup, drugs (41.7%) were considered the main cause of anaphylaxis, followed by food (25%).
The incidence of anaphylaxis (0.08%) was double that estimated in the ED. Anaphylaxis is underdiagnosed. A correct diagnosis conditions the administration of epinephrine, regardless of the severity of symptoms. The real etiology of anaphylaxis should only be proposed after an allergy workup, which is recommended in all cases, as the real cause can differ considerably from the initial impression in the ED.
There are no previous Spanish guidelines or consensus statements on bradykinin-induced angioedema.
To draft a consensus statement on the management and treatment of angioedema mediated by bradykinin ...in light of currently available scientific evidence and the experience of experts. This statement will serve as a guideline to health professionals.
The consensus was led by the Spanish Study Group on Bradykinin-Induced Angioedema, a working group of the Spanish Society of Allergology and Clinical Immunology. A review was conducted of scientific papers on different types of bradykinin-induced angioedema (hereditary and acquired angioedema due to C1 inhibitor deficiency, hereditary angioedema related to estrogens, angioedema induced by angiotensin-converting enzyme inhibitors). Several discussion meetings were held to reach the consensus.
Treatment approaches are discussed, and the consensus reached is described. Specific situations are addressed, namely, pregnancy, contraception, travelling, blood donation, and organ transplantation.
A review of and consensus on treatment of bradykinin-induced angioedema is presented.
One of the main goals of sex allocation theory is understanding sex ratio evolution. However, theoretical studies predicting sex ratios in species with unusual sexual systems, such as protandric ...simultaneous (PS) hermaphroditism, are rare. In PS hermaphrodites, juveniles first develop into functional males that mature into simultaneous hermaphrodites later in life. Here, we report on the sex ratio (males/males + hermaphrodites) in the PS hermaphroditic shrimp Exhippolysmata oplophoroides. A 2-year study demonstrated that hermaphrodites dominated the population in two different bays. This skewed sex ratio may be explained by limited encounter rates among conspecifics. In agreement with this idea, the density of shrimps was extremely low (≤1 shrimp km⁻²) at the two study sites. Size at sex phase change and sex ratios remained relatively stable through time at the two bays. The stability of these parameters might be explained by the rather steady population structure of this species during the study period. A review of sex ratios in PS hermaphroditic shrimps (Lysmata and Exhippolysmata) revealed considerable variation; some species have male- and others hermaphrodite-skewed sex ratios. The conditions explaining inter- and intra-specific sex ratio variation in protandric simultaneous hermaphroditic species remain to be addressed.
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