Comparative effectiveness of gonadotropins used for ovarian stimulation during assisted reproductive technologies (ART) in France: A real-world observational study from the French nationwide claims database (SNDS).

This comparative non-interventional study using data from the French National Health Database (Système National des Données de Santé) investigated real-world (cumulative) live birth outcomes following ovarian stimulation, leading to oocyte pickup with either originator recombinant human follicle-stimulating hormone (r-hFSH) products (alfa or beta), r-hFSH alfa biosimilars, or urinaries including mainly HP-hMG (menotropins), and marginally u-hFSH-HP (urofollitropin). Using data from 245,534 stimulations (153,600 women), biosimilars resulted in a 19% lower live birth (adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76-0.86) and a 14% lower cumulative live birth (adjusted hazard ratio (HR) 0.86, 95% CI 0.82-0.89); and urinaries resulted in a 7% lower live birth (adjusted OR 0.93, 95% CI 0.90-0.96) and an 11% lower cumulative live birth (adjusted HR 0.89, 95% CI 0.87-0.91) versus originator r-hFSH alfa. Results were consistent across strata (age and ART strategy), sensitivity analysis using propensity score matching, and with r-hFSH alfa and beta as the reference group.

Formal evaluation of PYNK: Breast Cancer Program for Young Women-the patient perspective.

PURPOSE: The aim of the present study was to assess patient satisfaction with pynk: Breast Cancer Program for Young Women so as to determine how the program might be improved and to provide feedback to donors. METHODS: All pynk patients who had consented to have their information entered in our database and who supplied us with their e-mail address were invited to complete a 58-item online questionnaire consisting of multiple choice and open-ended questions. Domains included demographics, provision of written and spoken information, support, infertility risk, research awareness, attitudes toward discharge, and general feedback. RESULTS: Of 120 pynk patients approached, 61 (51%) participated. More than 90% were satisfied or very satisfied with the timing, usefulness, and clarity of spoken and written information given, and 69% found the service and support provided by the nurse navigator to be the most helpful component of the program. Of those who had received systemic therapy, 93% recalled a health care provider initiating a discussion of the risk of treatment-related infertility, and 67% were referred to a fertility clinic. On the negative side, 11%-27% were unaware of various services provided by pynk, and 11% were unaware of pynk's ongoing research. One third of patients were unhappy or ambivalent about the prospect of discharge from the program. CONCLUSIONS: Patient satisfaction with this novel program for young women with breast cancer is high. This study highlights the critical role that the nurse navigator plays in patient support and dissemination of information. In contrast to other reported surveys of young cancer patients, pynk patients are routinely given the opportunity to undergo fertility preservation.

Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: updated overall survival and biomarker analyses.

BACKGROUND: Tecemotide is a MUC1-antigen-specific cancer immunotherapy. The phase III START study did not meet its primary end point but reported notable survival benefit with tecemotide versus placebo in an exploratory analysis of the predefined patient subgroup treated with concurrent chemoradiotherapy. Here, we attempted to gain further insight into the effects of tecemotide in START. PATIENTS AND METHODS: START recruited patients who did not progress following frontline chemoradiotherapy for unresectable stage III non-small-cell lung cancer. We present updated overall survival (OS) data and exploratory analyses of OS for baseline biomarkers: soluble MUC1 (sMUC1), antinuclear antibodies (ANA), neutrophil/lymphocyte ratio (NLR), lymphocyte count, and HLA type. RESULTS: Updated OS data are consistent with the primary analysis: median 25.8 months (tecemotide) versus 22.4 months (placebo) (HR 0.89, 95% CI 0.77-1.03, P = 0.111), with ∼20 months additional median follow-up time compared with the primary analysis. Exploratory analysis of the predefined subgroup treated with concurrent chemoradiotherapy revealed clinically relevant prolonged OS with tecemotide versus placebo (29.4 versus 20.8 months; HR 0.81, 95% CI 0.68-0.98, P = 0.026). No improvement was seen with sequential chemoradiotherapy. High sMUC1 and ANA correlated with a possible survival benefit with tecemotide (interaction P = 0.0085 and 0.0022) and might have future value as biomarkers. Interactions between lymphocyte count, NLR, or prespecified HLA alleles and treatment effect were not observed. CONCLUSION: Updated OS data support potential treatment benefit with tecemotide in patients treated with concurrent chemoradiotherapy. Exploratory biomarker analyses suggest that elevated sMUC1 or ANA levels correlate with tecemotide benefit. CLINICALTRIALSGOV NUMBER: NCT00409188.

Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) or its methylester [methyl-5-aminolaevulinate (MAL) or 5-amino-4-oxopentanoate] was recently ranked as first-line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF-200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration. OBJECTIVES: To evaluate the efficacy and safety of PDT of AKs with BF-200 ALA in comparison with a registered MAL cream and with placebo. METHODS: The study was performed as a randomized, multicentre, observer-blind, placebo-controlled, interindividual trial with BF-200 ALA, a registered MAL cream and placebo in a ratio of 3:3:1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3months after treatment, PDT was repeated. RESULTS: PDT with BF-200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P<0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P<0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment-related adverse events were observed for the narrow- and broad-spectrum light sources. CONCLUSIONS: BF-200 ALA is a very effective, well-tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used.

The relation between law and morality: children's reasoning about socially beneficial and unjust laws.

This study investigated children's reasoning about laws and legal compliance. A total of 72 children, 24 each at 6, 8, and 10 years of age, made judgments of law evaluation ("Is it a good or bad law?"), legitimacy of legal regulation ("Is it OK or not for government to make a law?"), and law violation ("Is it OK or not for people to break the law?") for three socially beneficial laws (a traffic law, a vaccination law, and a law requiring compulsory education for children under 16) and three unjust laws (denial of education to a class of persons, denial of medical care to the poor, and age discrimination). Participants also evaluated the application of laws in conflict scenarios in which a socially beneficial law infringed on individual freedom. Results showed that children considered a number of factors in their judgments, including the perceived justice of the law, its socially beneficial purpose, and its potential for infringement on individual freedoms and rights. The findings showed that children apply moral concepts of harm, rights, and justice to evaluate laws and to inform their judgments of legal compliance.

Children's judgements of psychological harm in normal and noncanonical situations.

This study investigated children's (3-, 5-, and 7-year-olds) and adults' (total N = 92) integration of information about intentions, acts, and outcomes in moral judgments of psychological harm. Behavioral and emotional predictions and judgments of act acceptability and punishment were made under normal and noncanonical causal conditions. Participants at all ages judged it wrong to inflict negative psychological reactions of fear or embarrassment on unwilling participants, even when these reactions were idiosyncratic or noncanonical. When assigning punishment, younger children tended to use an outcome rule, whereas older participants were more likely to use an intention rule or a conjunction rule (if outcome is negative and intention is negative, then punish). The results show that children as young as 3 years are able to take into account other people's idiosyncratic perspectives when making moral judgments of psychological harm.

Children's judgements about psychological harm in social context.

72 children, ages 6 to 11 years, were presented with a series of stories involving psychological harm (name-calling) in a game context. Situations were presented in which intentions, consequences, and game context were varied, along with order of story presentation. Comparison between acts of physical and psychological harm were also conducted. Although responses in some conditions were influenced by order of presentation, age differences were found in children's evaluations of agents' actions and recipients' reactions for psychological harm in game contexts. Younger children were more likely to ignore intentions and consequences or the recipient's perspective and to focus on contextual features (e.g. game rules). Older children were more likely to base their evaluations on intentions, or both intentions and consequences, and to take into account the recipient's perspective. Game context interacted differentially with psychological and physical harm at all ages. Evaluations of acts of physical harm were more likely than acts of psychological harm to be transformed by game context.

Adolescents' and young adults' conceptions of civil liberties: freedom of speech and religion.

This study examined adolescents' and young adults' conceptions of freedom of speech and religion (civil liberties). 48 adolescents and young adults in 3 grade levels (mean ages 12-8, 16-10, and 19-6) were administered a structured interview containing assessments of civil liberties in general, in straightforward (unconflicted) applications, and in conflict with other social and moral concerns, including law, physical and psychological harm, and equality of opportunity. Freedom of speech and religion were conceptualized as universal rights and applied to social events in unconflicted contexts at all ages. A diverse array of rationales, differentiated according to type of freedom, were used at all ages to ground conceptions of universal freedoms. Judgments of civil liberties in conflicts exhibited several sources of variation, including developmental differences, situational or contextual variation determined by the particular types of issues in conflict, and individual differences. Results are consistent with the proposition that judgments of civil liberties reflect age-related patterns of coordination of delimited social and moral concepts rather than general orientations.

The spatial attributes of stimulus frequency in the median sagittal plane and their role in sound localization.

Stimulus cues used to locate sounds in the median sagittal plane were investigated. Listeners first were required to report the location of noise bands 1.0 kHz wide whose center frequencies ranged from 4.0 through 14.0 kHz. It was found that the apparent locations of the stimuli depended on their frequency compositions, not their places of origin. As the center frequency was increased from 4.0 to about 12.0 kHz, the apparent location of the sound moved from in front of the subject to the rear. Then, at center frequencies of around 13.0 kHz, the sounds again appeared to come from the front. The authors infer that different frequency regions within the sound's spectrum possess specific spatial referents along the median sagittal plane. When the bandwidth was increased to 4.0 kHz, listeners could locate the stimuli with reasonable proficiency only for the sectors of the median sagittal plane that were represented by the spatial referents inherent in the frequency composition of the stimulus. Finally, a stimulus comprising all audible frequencies above 4.0 kHz could be located proficiently, and it is concluded that this sound, unlike the others, contained all spatial referents for the median sagittal plane, hence the superior performance on the localization task.

Evaluation of the relative effectiveness of methylphenidate and cognitive behavior modification in the treatment of kindergarten-aged hyperactive children.

This study of kindergarten-aged hyperactive children evaluated the effects of three modes of treatment in relation to an untreated control group. The treatments were administered over a 3-month period and included cognitive behavior modification, methylphenidate, and the two treatments combined. A follow-up assessment was done approximately 1 year later at the end of the first grade. Analyses of psychological, rating scale observational, and interview data showed that hyperactive children became less symptomatic over time; the data did not provide evidence indicating that any of the treatments studied was more effective than any other or than no treatment at all.