The preferences of women with ovarian cancer for oral versus intravenous recurrence regimens.

OBJECTIVE: To assess preferences of women with ovarian cancer regarding features of available anti-cancer regimens for platinum-resistant, biomarker-positive disease, with an emphasis on oral PARP inhibitor and standard intravenous (IV) chemotherapy regimens. METHODS: A discrete-choice-experiment preferences survey was designed, tested, and administered to women with ovarian cancer, with 11 pairs of treatment profiles defined using seven attributes (levels/ranges): regimen (oral daily, IV weekly, IV monthly); probability of progression-free (PFS) at 6 months (40%-60%); probability of PFS at 2 years (10%-20%); nausea (none, moderate); peripheral neuropathy (none, mild, moderate); memory problems (none, mild); and total out-of-pocket cost ($0 to $10,000). RESULTS: Of 123 participants, 38% had experienced recurrence, 25% were currently receiving chemotherapy, and 18% were currently taking a PARP inhibitor. Given attributes and levels, the relative importance weights (sum 100) were: 2-year PFS, 28; cost, 27; 6-month PFS, 19; neuropathy,14; memory problems, nausea, and regimen, all ≤5. To accept moderate neuropathy, participants required a 49% (versus 40%) chance of PFS at 6 months or 14% (versus 10%) chance at 2 years. Given a 3-way choice where PFS and cost were equal, 49% preferred a monthly IV regimen causing mild memory problems, 47% preferred an oral regimen causing moderate nausea, and 4% preferred a weekly IV regimen causing mild memory and mild neuropathy. CONCLUSIONS: These findings challenge the assumption that oral anti-cancer therapies are universally preferred by patients and demonstrate that there is no "one size fits all" regimen that is preferable to women with ovarian cancer when considering recurrence treatment regimens.

Dose-response assessment for impaired memory from chronic exposure to domoic acid among native American consumers of razor clams.

Domoic acid (DA) is a marine neurotoxin that accumulates in filtering shellfish during harmful algal blooms. A health protection limit of 20 ppm DA in razor clams (RC) has been set based principally upon an episode of acute DA toxicity in humans that included Amnesic Shellfish Poisoning among survivors. The objective of this study was to determine the dose-response relationship between estimated DA exposure through RC consumption and memory loss in Washington state Native Americans from 2005 to 2015. Results from total learning recall (TLR) memory scores were compared before and after the highest DA exposures. A decrease in TLR was related to DA dose (p < 0.01) regardless whether the effect was assumed to be transient or lasting, and whether the dose was expressed as an average daily dose or an average dose per meal. Benchmark dose modeling identified BMDL10 values of 167 ng/kg-day and 2740 ng/kg-meal assuming a transient effect, and 196 ng/kg-day and 2980 ng/kg-meal assuming no recovery of function occurs. These DA dose thresholds for a measurable memory function reduction observed in this study of clam consumers are well below the safe acute dose underpinning the current regulatory DA limit of 20 ppm (ca. 60 µg/kg).

Patient emergency assessment following deliberate self-poisoning with benzodiazepines: Can cognitive markers predict recall of the psychiatric interview? A pilot study.

STUDY HYPOTHESIS: In cases of deliberate self-poisoning (DSP), patients often ingest benzodiazepines (BZDs), known to alter memory. Experts recommend recovery of the patient's cognitive capacity before psychiatric assessment. Unfortunately, there is no validated tool in common practice to assess whether sufficient cognitive recovery has occurred after DSP with BZDs to ensure patient memory of the assessment. OBJECTIVE: The aim of the study was to identify cognitive functions and markers which predict preserved memory of the mental health care plan proposed at the emergency department after DSP. METHODS: We recruited patients admitted for DSP with BZDs and control patients. At the time of the psychiatric assessment, we performed cognitive tests and we studied the relationship between these tests and the scores of a memory test performed 24 h after. RESULTS: In comparison with the control group, we found memory impairment in the BZD group. We found significant impairment on the Trail Making Test A (TMT A) in the BZD group in comparison with the control group, while TMT A and Wechsler Adult Intelligence Scale (WAIS) Coding test scores were significantly correlated with memory scores. CONCLUSIONS: Attentional functions tested by WAIS Coding test and TMT A were correlated with memory score. It could be profitable to assess it in clinical practice prior to a psychiatric interview.

Validity of self-reported concentration and memory problems: Relationship with neuropsychological assessment and depression.

BACKGROUND: This study investigated the validity of self-reported concentration and memory problems (CMP) in residents environmentally exposed to manganese (Mn). METHOD: Self-report of CMP from a health questionnaire (HQ) and the Symptom Checklist-90-Revised (SCL-90-R) was compared to neuropsychological assessment (Trails A&B; Digit Span; Digit Symbol; Similarities; Auditory Consonant Trigrams, ACT; NAB Memory; Rey-Osterrieth, Rey-O, Delayed). Participants included 146 residents from Ohio exposed to air-Mn, with a modeled average concentration of 0.55 µg m-3 (range = 0.01-4.58). RESULTS: Residents were primarily White (94.5%), aged 30-64 years (M = 51.24), with a minimum of 10 years of residence (range = 10-64). Ninety-four (65.3%) participants reported concentration problems, and 107 residents (73.3%) reported memory problems. More participants endorsed CMP on the SCL-90-R than on the HQ. The prevalence of self-reported CMP was higher for women than for men (88.4% vs. 68.3%). Point-biserial and Pearson's correlations between self-reported CMP and neuropsychological test scores were nonsignificant and weak for both the HQ (rpb = -.20 to rpb = .04) and the SCL-90-R (r = -.12 to r = .007). Greater levels of depression, anxiety, and female sex predicted having more self-reported CMP on both the HQ and the SCL-90-R. Air-Mn and blood-Mn were not associated with self-reported CMP. Residential distance from the Mn source accounted for a small proportion of variance (sr2 = .04), although depression remained the largest predictor (sr2 = .21). CONCLUSION: These results indicate that self-report of CMP in Mn-exposed residents appear to be invalid when compared to neuropsychological test scores. The participants' misperception of having CMP is associated with less education and higher levels of depression. Neuropsychological assessment is recommended to attain valid results.

Low-level prenatal lead exposure alters auditory recognition memory in 2-month-old infants: an event-related potentials (ERPs) study.

This study used event-related potentials (ERPs) to assess effects of low-level prenatal lead exposure on auditory recognition memory in 2-month-old infants. Infants were divided into four groups according to cord-blood lead concentration: (1) <2.00 µ g/dL, (2) 2.00-2.99 µ g/dL, (3) 3.0-3.7 µ g/dL, and (4) ≥3.7 µ g/dL. The first group showed the normally expected differences in P2, P750, and late slow wave (LSW) amplitudes elicited by mothers' and strangers' voices. These differences were not observed for one or more ERP components in the other groups. Thus, there was electrophysiological evidence of poorer auditory recognition memory at 2 months with cord-blood lead ≥2.00 µ g/dL.

Investigation of the neuroprotective action of saffron (Crocus sativus L.) in aluminum-exposed adult mice through behavioral and neurobiochemical assessment.

In the present study, the possible reversal effects of saffron against established aluminum (Al)-toxicity in adult mice, were investigated. Control, Al-treated (50 mg AlCl(3)/kg/day diluted in the drinking water for 5 weeks) and Al+saffron (Al-treatment as previously plus 60 mg saffron extract/kg/day intraperitoneally for the last 6 days), groups of male Balb-c mice were used. We assessed learning/memory, the activity of acetylcholinesterase [AChE, salt-(SS)/detergent-soluble(DS) isoforms], butyrylcholinesterase (BuChE, SS/DS isoforms), monoamine oxidase (MAO-A, MAO-B), the levels of lipid peroxidation (MDA) and reduced glutathione (GSH), in whole brain and cerebellum. Brain Al was determined by atomic absorption spectrometry, while, for the first time, crocetin, the main active metabolite of saffron, was determined in brain after intraperitoneal saffron administration by HPLC. Al intake caused memory impairment, significant decrease of AChE and BuChE activity, activation of brain MAO isoforms but inhibition of cerebellar MAO-B, significant elevation of brain MDA and significant reduction of GSH content. Although saffron extract co-administration had no effect on cognitive performance of mice, it reversed significantly the Al-induced changes in MAO activity and the levels of MDA and GSH. AChE activity was further significantly decreased in cerebral tissues of Al+saffron group. The biochemical changes support the neuroprotective potential of saffron under toxicity.

Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABA(A) [corrected] receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function.

The aim of the present paper was to study the effects of GABAA receptor-positive modulators (L-838417 and NS11394) showing a preference for α2/3 subunits of the GABAA receptor, in models of pain, anxiety, learning, memory and motor function. These compounds have been suggested to have a favourable therapeutic profile over nonselective compounds such as diazepam. In this study, we tested both compounds for their effects in rat models of formalin-induced pain, spinal nerve-ligation-induced mechanical allodynia, plus maze, open field, rotarod, balance beam walking, contextual fear conditioning and Morris water maze. Both compounds exerted analgesic, but no anxiolytic effects. However, they induced motor side-effects, and learning and memory impairment at similar doses. Therefore, the anxiolytic effect and the lack of side-effects of these compounds, as described in the literature, could not be confirmed in the present study.

Teenage drinking, alcohol availability and pricing: a cross-sectional study of risk and protective factors for alcohol-related harms in school children.

BACKGROUND: There is a lack of empirical analyses examining how alcohol consumption patterns in children relate to harms. Such intelligence is required to inform parents, children and policy relating to the provision and use of alcohol during childhood. Here, we examine drinking habits and associated harms in 15-16 year olds and explore how this can inform public health advice on child drinking. METHODS: An opportunistic survey of 15-16 year olds (n = 9,833) in North West England was undertaken to determine alcohol consumption patterns, drink types consumed, drinking locations, methods of access and harms encountered. Cost per unit of alcohol was estimated based on a second survey of 29 retail outlets. Associations between demographics, drinking behaviours, alcohol pricing and negative outcomes (public drinking, forgetting things after drinking, violence when drunk and alcohol-related regretted sex) were examined. RESULTS: Proportions of drinkers having experienced violence when drunk (28.8%), alcohol-related regretted sex (12.5%) and forgetting things (45.3%), or reporting drinking in public places (35.8%), increased with drinking frequency, binge frequency and units consumed per week. At similar levels of consumption, experiencing any negative alcohol-related outcome was lower in those whose parents provided alcohol. Drunken violence was disproportionately associated with being male and greater deprivation while regretted sex and forgetting things after drinking were associated with being female. Independent of drinking behaviours, consuming cheaper alcohol was related to experiencing violence when drunk, forgetting things after drinking and drinking in public places. CONCLUSION: There is no safe level of alcohol consumption for 15-16 year olds. However, while abstinence removes risk of harms from personal alcohol consumption, its promotion may also push children into accessing drink outside family environments and contribute to higher risks of harm. Strategies to reduce alcohol-related harms in children should ensure bingeing is avoided entirely, address the excessively low cost of many alcohol products, and tackle the ease with which it can be accessed, especially outside of supervised environments.

Post-marketing assessment of the safety of strontium ranelate; a novel case-only approach to the early detection of adverse drug reactions.

AIMS: Post licensing, the evaluation of drug safety relies heavily on the collation of sporadic, spontaneous reports on adverse effects. The aim was to assess the potential utility of a more systematic approach to the detection of adverse events that utilizes routinely collected clinical data from a large primary care population. METHODS: We used the UK General Practice Research Database to assess the risk of several recently reported adverse events linked to the use of strontium ranelate for osteoporosis in postmenopausal women. The self-controlled case-series method was used to minimize the potential for biases in the quantification of risk estimates. RESULTS: Age-adjusted rate ratios for venous thromboembolism, gastrointestinal disturbance, minor skin complaint and memory loss were 1.1 [95% confidence interval (CI) 0.2, 5.0], 3.0 (95% CI 2.3, 3.8), 2.0 (95% CI 1.3, 3.1) and 1.8 (95% CI 0.2, 14.1), respectively. No cases of osteonecrosis of the jaw, toxic-epidermal necrosis, Stevens-Johnson syndrome or drug rash with eosinophilia and systemic symptoms were found. CONCLUSIONS: Although we confirmed the association between strontium ranelate and adverse events identified in the Phase III publications, there was no evidence of an association between strontium ranelate and the aforementioned potentially life-threatening adverse events. Our study demonstrates the relative ease with which this method can assess a variety of adverse events associated with a new drug in actual clinical practice. We believe this technique could be more widely adopted to assess the safety profile of new drugs.