Fragile X syndrome clinical trials: exploring parental decision-making.

BACKGROUND: The objective of this research was to understand parental proxy decision-making for drug trial participation for children with Fragile X syndrome (FXS). Specifically, we aimed to capture preferences, motivations, influencing factors and barriers related to trial involvement among trial joiners and decliners and describe ease of trial decision-making and decisional regret. METHODS: Interviews were conducted with parents from two groups: those who chose to enrol their child with FXS in a trial (N = 16; Joiners) and those who declined trial participation (N = 15; Decliners). Data were coded and interpreted through inductive content analysis. RESULTS: Prominent decisional factors included attitudes about medicating FXS symptoms, potential for direct benefit (primarily evaluated through the degree of match between target outcomes and child symptomatology and drug mechanism), logistical convenience and perceived risks of side effects. The ultimate motivation for participation was potential for direct benefit. None of the parents reported decisional regret, and ease of decision-making ranged from easy to difficult for our participants. CONCLUSIONS: Therapeutic optimism was high among those who elected participation. Parents may benefit from an explanation of the rationale behind chosen outcome variables and may be more interested in trials that target or measure as an exploratory outcome the symptoms they find most concerning. Our findings reinforce the need for future trials to reduce participant inconvenience. Our results contrast with what has previously been observed in parents of children with life-threatening conditions; parents of children with FXS may be more trial risk averse and find trial decisions to be harder. Parents of children with FXS considering trials may benefit from a decisional intervention aimed at deliberating motivations and barriers.

Defining personal utility in genomics: A Delphi study.

BACKGROUND: Individual genome sequencing results are valued by patients in ways distinct from clinical utility. Such outcomes have been described as components of "personal utility," a concept that broadly encompasses patient-endorsed benefits, that is operationally defined as non-clinical outcomes. No empirical delineation of these outcomes has been reported. AIM: To address this gap, we administered a Delphi survey to adult participants in a National Institute of Health (NIH) clinical exome study to extract the most highly endorsed outcomes constituting personal utility. MATERIALS AND METHODS: Forty research participants responded to a Delphi survey to rate 35 items identified by a systematic literature review of personal utility. RESULTS: Two rounds of ranking resulted in 24 items that represented 14 distinct elements of personal utility. Elements most highly endorsed by participants were: increased self-knowledge, knowledge of "the condition," altruism, and anticipated coping. DISCUSSION: Our findings represent the first systematic effort to delineate elements of personal utility that may be used to anticipate participant expectation and inform genetic counseling prior to sequencing. The 24 items reported need to be studied further in additional clinical genome sequencing studies to assess generalizability in other populations. Further research will help to understand motivations and to predict the meaning and use of results.

Preferences for results from genomic microarrays: comparing parents and health care providers.

Chromosomal microarray (CMA) testing is now performed frequently in paediatric care. Although CMAs improve diagnostic yields, they increase detection of variants of unknown and uncertain clinical significance (VUS). Understanding parents', paediatricians' and genetic health professionals' (GHPs) views regarding variant disclosure may reduce the potential for communication of unwanted information. A questionnaire was designed to compare disclosure preferences of these three groups in Australia. One hundred and forty-seven parents, 159 paediatricians and 69 GHPs hold similar views with at least 89% of respondents certainly or probably favouring disclosure of all categories of variants. However, some differences were observed between health care providers (HCPs: paediatricians and GHPs) and parents, who were less sure of their disclosure preferences. There was consensus among respondent groups that knowledge of a variant of certain clinical significance would provide more practical and emotional utility compared to VUS. Compared to HCPs, parents placed more emphasis on using knowledge of a VUS when considering future pregnancies (p < 0.001). This study may help HCPs anticipate parents' preferences for genomic testing. As whole exome/genome sequencing is integrated into clinical practice, the potential for differing views of parents and HCPs should be considered when developing guidelines for result disclosure.

Multiple-locus variable-number tandem-repeat analysis for discriminating within Salmonella enterica serovar Typhimurium definitive types and investigation of outbreaks.

The discriminatory power of multiple-locus variable-number tandem-repeat analysis (MLVA) needs to be evaluated for all Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium) phage types so that the power of this methodology is understood and results can be interpreted correctly during outbreak investigations. We evaluated the ability of MLVA to characterize four definitive phage types (DT) problematic in New Zealand. MLVA discriminated between DT104 isolates although there was very limited variation in the MLVA profiles for isolates with an RDNC phage type (reacts but does not conform to a recognized Typhimurium phage pattern) first observed in New Zealand's Enteric Reference Laboratory in May 2006. Most DT101 isolates had indistinguishable MLVA profiles or profiles that differed at one or two loci. This was also observed in DT160 isolates. MLVA may not identify all common-source outbreaks although it provided valuable data when applied to case isolates from two S. Typhimurium outbreaks.

Characterization of Escherichia coli O157:H7 in New Zealand using multiple-locus variable-number tandem-repeat analysis.

Recently, multiple-locus variable-number tandem-repeat analysis (MLVA) has been proposed as an alternative to pulsed-field gel electrophoresis (PFGE) for characterization of Escherichia coli O157:H7. In this study we characterized 118 E. coli O157:H7 isolates from cases of gastrointestinal disease in New Zealand using XbaI PFGE profiles and a MLVA scheme that assessed variability in eight polymorphic loci. The 118 isolates characterized included all 80 E. coli O157:H7 referred to New Zealand's Enteric Reference Laboratory in 2006 and 29 phage-type 2 isolates from 2005. When applied to these isolates the discriminatory power of PFGE and MLVA was not significantly different. However, MLVA data may be more epidemiologically relevant as isolates from family clusters of disease had identical MLVA profiles, even when the XbaI PFGE profiles differed slightly. Furthermore, most isolates with indistinguishable XbaI PFGE profiles that did not appear to be epidemiologically related had distinct MLVA profiles.

An examination of antecedent traumas and psychiatric comorbidity among male inmates with PTSD.

Despite substantially higher rates of posttraumatic stress disorder (PTSD) among male inmates than among men in the general population, there is a dearth of research on PTSD among incarcerated men. The current study addresses traumatic events that precede PTSD and psychiatric disorders that are comorbid with PTSD in an inmate sample. Seeing someone seriously injured or killed, being sexually abused, and being physically assaulted were the three most commonly reported antecedent traumas to PTSD. Lifetime and current rates of mood disorders, anxiety disorders, and antisocial personality disorder were elevated among inmates with a diagnosis of PTSD. Two hundred and thirteen inmates participated in the study. Sixty-nine participants (33%) met lifetime DSM-III-R criteria for PTSD, and 45 (21%) met current criteria. The findings are compared with general population samples, and implications of the findings are discussed.