Reaching Ambulatory Older Adults with Educational Tools: Comparative Efficacy and Cost of Varied Outreach Modalities in Primary Care.

BACKGROUND: Providing patients with access to health information that can be obtained outside of an office visit is an important part of education, yet little is known about the effectiveness of outreach modalities to connect older adults to online educational tools. The objective was to identify the effectiveness and cost of outreach modalities providing online information about advance care planning (ACP) for older adults. METHODS: Six different outreach modalities were utilized to connect patients to online educational tools (ACP video decision aids). Participants were 13,582 patients aged 65 and older of 185 primary care providers with appointments over a 30-month period within a large health system in the greater New York City area. Main outcome measures were number of online video views and costs per outreach for each modality. KEY RESULTS: There were 1150 video views for 21,407 remote outreach events. Text messages, sent to the largest volume of patients (8869), had the highest outcome rate (9.6%) and were the most economical ($0.09). Characterization of phone calls demonstrated 21.7% engagement in the topic of ACP but resulted in minimal video views (<1%) and incurred the highest cost per outreach ($2.88). In-office handouts had negligible results (<1%). CONCLUSIONS: Text was the most cost-effective modality to connect older adults to an online educational tool in this pragmatic trial, though overall efficacy of all modalities was low.

Testing of an oral dosing technique for double-crested cormorants, Phalacocorax auritus, laughing gulls, Leucophaeus atricilla, homing pigeons, Columba livia, and western sandpipers, Calidris mauri, with artificially weather MC252 oil.

Scoping studies were designed to determine if double-crested cormorants (Phalacocorax auritus), laughing gulls (Leucophaues atricilla), homing pigeons (Columba livia) and western sandpipers (Calidris mauri) that were gavaged with a mixture of artificially weathered MC252 oil and food for either a single day or 4-5 consecutive days showed signs of oil toxicity. Where volume allowed, samples were collected for hematology, plasma protein electrophoresis, clinical chemistry and electrolytes, oxidative stress and organ weigh changes. Double-crested cormorants, laughing gulls and western sandpipers all excreted oil within 30min of dose, while pigeons regurgitated within less than one hour of dosing. There were species differences in the effectiveness of the dosing technique, with double-crested cormorants having the greatest number of responsive endpoints at the completion of the trial. Statistically significant changes in packed cell volume, white cell counts, alkaline phosphatase, alanine aminotransferase, creatine phosphokinase, gamma glutamyl transferase, uric acid, chloride, sodium, potassium, calcium, total glutathione, glutathione disulfide, reduced glutathione, spleen and liver weights were measured in double-crested cormorants. Homing pigeons had statistically significant changes in creatine phosphokinase, total glutathione, glutathione disulfide, reduced glutathione and Trolox equivalents. Laughing gulls exhibited statistically significant decreases in spleen and kidney weight, and no changes were observed in any measurement endpoints tested in western sandpipers.

Deep intronic KRIT1 mutation in a family with clinically silent multiple cerebral cavernous malformations.

Loss-of-function mutations in CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10 genes are identified in the vast majority of familial cases with multiple cerebral cavernous malformations (CCMs). However, genomic DNA sequencing combined to large rearrangement screening fails to detect a mutation in 5% of those cases. We report a family in which CCM lesions were discovered fortuitously because of the investigation of a developmental delay in a boy. Three members of the family on three generations had typical multiple CCM lesions and no clinical signs related to CCM. No mutation was detected using genomic DNA sequencing and quantitative multiplex PCR of short fluorescent fragments (QMPSF). cDNA sequencing showed a 99-nucleotide insertion between exons 5 and 6 of CCM1, resulting from a mutation located deep into intron 5 (c.262+132_262+133del) that activates a cryptic splice site. This pseudoexon leads to a premature stop codon. These data highly suggest that deep intronic mutations explain part of the incomplete mutation detection rate in CCM patients and underline the importance of analyzing the cDNA to provide comprehensive CCM diagnostic tests. This kind of mutation may be responsible for apparent sporadic presentations due to a reduced penetrance.

Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium.

The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P< or =0.10 in a log-additive model: rs2740574 in CYP3A4 (P=0.011), rs1805386 in LIG4 (P=0.007), and rs3218536 in XRCC2 (P=0.095). Additional genotyping in other OCAC studies was undertaken and only the variant in CYP3A4, rs2740574, continued to show an association in the replication data among homozygous carriers: OR(homozygous(hom))=2.50 (95% CI 0.54-11.57, P=0.24) with 1406 cases and 2827 controls. Overall, in the combined data the odds ratio was 2.81 among carriers of two copies of the minor allele (95% CI 1.20-6.56, P=0.017, p(het) across studies=0.42) with 1969 cases and 3491 controls. There was no association among heterozygous carriers. CYP3A4 encodes a key enzyme in oestrogen metabolism and our finding between rs2740574 and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted.

Lethal and sub-lethal effects of Deepwater Horizon slick oil and dispersant on oyster (Crassostrea virginica) larvae.

In April 2010, crude oil was spilled from the Deepwater Horizon (DWH) oil platform for 87 days, coincident with the spawning season and recruitment of the oyster, Crassostrea virginica, in the Gulf of Mexico. Impacts of acute exposures to surface-collected DWH oil (HEWAF), dispersed oil (CEWAF) and dispersant alone (Corexit 9500A(®)) on planktonic larval stages of C. virginica (veliger, umbo and pediveliger) were tested in the laboratory. Exposures to HEWAF, CEWAF and dispersant were toxic to larvae impairing growth, settlement success and ultimately survival. Larval growth and settlement were reduced at concentrations of tPAH50 ranging from 1.7 to 106 µg L(-1) for HEWAF and 1.1-35 µg L(-1) for CEWAF, concentrations well within the range of water sampled during the DWH oil spill. Sublethal effects induced by oil and dispersant could have significant ecological implications on oyster populations and on the whole estuarine ecosystem.

PTEN mutation in endometrial cancers is associated with favorable clinical and pathologic characteristics.

Mutation of the PTEN tumor suppressor gene is a frequent event in endometrial cancers. In other types of cancers, PTEN mutation has been associated with metastatic behavior and advanced stage. To examine the relationship between PTEN mutation and clinical features of endometrial cancers, we screened 136 cases for mutations in the nine exons and intronic splice sites of the PTEN gene, using single-strand conformation analysis, and aberrant bands were sequenced. Mutations were noted in 44 of 136 (32%) endometrial cancers, and two mutations were present in 8 cases. There were 36 cases with mutations resulting in truncated protein products, 6 cases with missense mutations in the phosphatase domain, 1 case with an in-frame deletion, and 1 case with a large insertion. Mutation of the PTEN gene correlated most closely with endometrioid histology; mutations were seen in only 5% (1 of 21) of serous/clear cell cancers compared with 37% (43 of 115) of endometrioid cancers (P = 0.004). PTEN mutation was associated with early stage, nonmetastatic disease and more favorable survival in both the entire group of 136 cases and in the 115 endometrioid cases. In addition, PTEN mutation correlated with other molecular features associated with favorable clinical behavior, including microsatellite instability and absence of p53 overexpression. Microsatellite instability was found in 60% of cases with PTEN mutations compared with only 25% of cases without mutations (P = 0.004). Overexpression of p53 was seen in only 14% of cases with PTEN mutations compared to 39% of cases without mutations (P = 0.006). In conclusion, PTEN mutation is associated with endometrioid histology and other favorable pathological, clinical, and molecular features rather than with increased metastatic potential as has been noted in some other types of cancers.

Frequency of germline and somatic BRCA1 mutations in ovarian cancer.

Germline mutations in the BRCA1 tumor suppressor gene are thought to be the most common cause of hereditary ovarian cancer. The aim of this study was to explore further the role of BRCA1 alterations in the development of ovarian cancers. We sought to determine whether somatic BRCA1 mutations are ever present in ovarian cancers and whether mutation is always accompanied by loss of the wild-type allele. The entire coding region and intronic splice sites of BRCA1 were sequenced using genomic DNA samples from 103 unselected ovarian cancers. Thirteen clearly deleterious BRCA1 mutations and two variants of uncertain significance were found. Blood DNA was available in all but two cases and demonstrated that 4 of 13 mutations and both variants of uncertain significance were germline alterations, whereas in seven cases the mutation was a somatic change present only in the cancer. Using four microsatellite markers, loss of heterozygosity at the BRCA1 locus was found in all 15 ovarian cancers with BRCA1 sequence alterations, compared with only 58% of ovarian cancers that did not have BRCA1 mutations. BRCA1-associated ovarian cancers were characterized by serous histology and moderate histological grade. These data confirm prior reports suggesting that germline mutations in BRCA1 are present in about 5% of women with ovarian cancer. In addition, somatic mutations in BRCA1 occur in the development of some sporadic cases. The finding that both germline and somatic BRCA1 mutations are accompanied by loss of heterozygosity, suggests that loss of this tumor suppressor gene is a critical event in the development of these cancers.

Moving beyond the keg party: a daily process study of college student drinking motivations.

Theoretical models of alcohol consumption assert that young adults endorse multiple drinking motives, including drinking to cope with negative experiences and to enhance positive experiences. Social contacts may be important to both pathways. This study applied daily process methodology to determine the relationship between college student drinking in different contexts and daily social contacts and moods. Each afternoon for 3 weeks, 122 undergraduates (43% men, 57% women) logged onto a secure Web site during specified hours to report daily activities, moods, and contacts. Hierarchical linear modeling analyses provided support for motivational models and the context-specific nature of motivated drinking. Individual differences were revealed for each motivation. These findings highlight the importance of studying within-person processes using daily process designs.

Impacts of Deepwater Horizon oil and associated dispersant on early development of the Eastern oyster Crassostrea virginica.

The explosion of the Deepwater Horizon (DWH) oil platform resulted in large amounts of crude oil and dispersant Corexit 9500A® released into the Gulf of Mexico and coincided with the spawning season of the oyster, Crassostrea virginica. The effects of exposing gametes and embryos of C. virginica to dispersant alone (Corexit), mechanically (HEWAF) and chemically dispersed (CEWAF) DWH oil were evaluated. Fertilization success and the morphological development, growth, and survival of larvae were assessed. Gamete exposure reduced fertilization (HEWAF: EC201h=1650µg tPAH50L(-1); CEWAF: EC201h=19.4µg tPAH50L(-1); Corexit: EC201h=6.9mgL(-1)). CEWAF and Corexit showed a similar toxicity on early life stages at equivalent nominal concentrations. Oysters exposed from gametes to CEWAF and Corexit experienced more deleterious effects than oysters exposed from embryos. Results suggest the presence of oil and dispersant during oyster spawning season may interfere with larval development and subsequent recruitment.

Expression of C5a anaphylatoxin receptor in monoblastic cells involves facilitation of an adenosine 3',5'-monophosphate-dependent process.

We have previously reported a synergistic effect of 1,25-dihydroxyvitamin D [1,25-(OH)2D] and agents that elevate intracellular cAMP to induce the expression of the C5a complement receptor in U937 cells. In this report we examine the mechanism of this synergy, considering the hypothesis that the steroid hormone works by facilitating what is ultimately a cAMP-dependent process. We show that U937 cells cultured with 1,25-(OH)2D alone before culture with prostaglandin (PGE2) alone will express C5a receptor (an average of 55 +/- 4% of the receptors expressed with continuous exposure of cells to both agents; P less than 0.05). The reverse, PGE2 followed by 1,25-(OH)2D, causes very little receptor induction. This demonstrates the ability of 1,25-(OH)2D to induce changes in the state of the cell, such that activation of cAMP-dependent protein kinase has effects that are otherwise not seen, in other words 1,25-(OH)2D can prime the cell for the subsequent action of the cAMP messenger system. Furthermore, we are able to substitute, during the priming period, the protein synthesis inhibitor cycloheximide (CHX) for 1,25-(OH)2D. Cells cultured for 24 h with CHX will express C5a receptor when cultured for a second 2-day period with PGE2 at about 77 +/- 7% of the amount obtained with simultaneous exposure to 1,25-(OH)2D and PGE2. The CHX effect is time dependent and visible after 2 h. CHX is not synergistic with 1,25-(OH)2D. Other agents that can also substitute for 1,25-(OH)2D, but not for cAMP, in facilitating C5a receptor expression include retinoic acid and ionomycin, but with less potency. The 1,25-(OH)2D and PGE2 synergy is sensitive to the presence of isobutylmethylxanthine, implicating its dependence on the maintained elevation of intracellular cAMP levels. The synergy does not appear to be sensitive to changes in extracellular or intracellular calcium. We conclude from these results that 1,25-(OH)2D may promote the expression of C5a receptor in these cells in a fashion similar to that by which CHX potentiates other genes, i.e. that 1,25-(OH)2D increases levels of the mRNA encoding the C5a receptor. The mechanism of cAMP's subsequent and necessary action in the induction of C5a receptor expression is not yet clear.

S-adenosylmethionine and affective disorder.

Several open and double-blind studies suggest that SAMe may have an anti-depressant effect, and further studies are indicated. SAMe may exert a beneficial effect selectively on endogenous rather than neurotic depression. SAMe crosses the blood-brain barrier. SAMe is involved in several central enzyme pathways relating to transmethylation and folate and monoamine metabolism as well as in membrane function and neuro-transmission. The neuropharmacology of SAMe's effect on mood and the switch mechanism has yet to be fully explored. The actions of SAMe on the dopaminergic system are as yet unclear. SAMe is a physiologic substance that is non-toxic and relatively free of severe side effects (with the exception of mania, which may be a manifestation of the basic mood disorder.

Human ovarian cancer of the surface epithelium.

Epidemiologic studies have shown that the risk of cancer in the ovarian surface epithelium is decreased by factors that suppress ovulation, whereas uninterrupted ovulation has been associated with increased risk. This suggests that ovulation may play a critical role in ovarian carcinogenesis. More recently, molecular studies have demonstrated alterations in specific oncogenes and tumor suppressor genes in ovarian cancers. Overexpression of the HER-2/neu oncogene occurs in approximately 30% of ovarian cancers and correlates with poor survival. Although mutation of the K-ras oncogene has been found in some mucinous ovarian cancers, mutations in this gene appear to be more common in borderline ovarian tumors. Amplification of c-myc occurs in approximately 30% of ovarian cancers and is more frequently seen in serous cancers. Mutation of the p53 tumor suppressor gene, with resultant overexpression of mutant p53 protein, occurs in 50% of stage III/IV and 15% of stage I/II ovarian cancers. Most p53 mutations in ovarian cancers are transitions, which suggests that they arise spontaneously rather than due to exogenous carcinogens. In contrast to the acquired genetic alterations described above that are a feature of sporadic ovarian cancers, 5-10% of ovarian cancers probably arise due to inherited genetic defects. Recently, the BRCA1 tumor suppressor gene has heen identified and shown to be responsible for most cases of hereditary ovarian cancer. Further studies are needed to augment our understanding of the molecular pathogenesis of ovarian cancer.

A preliminary study of desipramine in the treatment of cocaine abuse in methadone maintenance patients.

Intravenous cocaine use is a major problem in methadone maintenance programs. In this pilot study of 16 cocaine-abusing methadone maintenance patients, 8 received desipramine and 8 received no medication other than methadone. During an 8-week open trial the desipramine patients reported significantly less cocaine craving and had less cocaine use than the other patients.

Intercostal artery laceration during thoracocentesis: increased risk in elderly patients.

Two cases of intercostal artery laceration following thoracocentesis are reported. Subsequent analysis of 29 thoracic aortograms demonstrated a definite trend toward increasing tortuosity of intercostal arteries with advancing age. Consequently, the amount of space available for safe insertion of the thoracocentesis needle tends to decrease with advancing age. As a result, elderly patients are more prone to intercostal artery laceration during thoracocentesis, and careful attention must be paid to the proper technique for performing this examination in such patients.

Epiretinal membranes in sickle cell retinopathy.

We examined the hospital records (including fundus photographs) of 769 patients (1486 eyes) with sickle cell disease from June 1978 to July 1985 for evidence of epiretinal membranes in the macula (51 eyes) or extramacular region (four eyes) of the posterior pole. The incidence of epiretinal membranes, seen in the eyes of patients with hemoglobin SC, SS, and SB+ thalassemia, was 3.7%. Most epiretinal membranes were mild, and visual acuity was 20/40 or better in 78.2% of these eyes. Severe macular pucker was occasionally noted following retinal detachment surgery. One patient with SC disease developed a macular epiretinal membrane that led to a macular hole and eventually to macular and extra-macular retinal detachment. Epiretinal membranes are a relatively common cause of maculopathy in patients with sickle cell disease.

Three-dimensional graphic reconstruction of the insect exoskeleton through confocal imaging of endogenous fluorescence.

The exoskeleton of the cockroach leg was imaged via confocal microscopy to generate digital graphic reconstructions of its three-dimensional structure. The cuticle is autofluorescent and can be visualized without staining, but is maximally imaged in aldehyde-fixed preparations viewed under krypton-argon laser illumination (yellow green (568 nm) excitation, commonly used in confocal microscopes). Images of the entire trochanteral segment of the leg were constructed as montages from optical sections taken as overlapping series that were coincident in the z-axis. Reconstructions of the exoskeleton from these images showed that strain sensing mechanoreceptors are located in association with buttresses and thickenings that form a consistent internal architecture in both juvenile and adult animals. Accuracy of reconstructions was gauged by embedding specimens in Spurr's resin and histologically sectioning them perpendicular to the optical plane of section (z-axis). Comparison of plastic sections with two-dimensional images generated by "resectioning" the software model showed that reconstructed exoskeleton had a high level of accuracy. Imaging of older and larger animals was limited by the sclerotization and increased thickness of the cuticle. Surface extraction algorithms were used to generate vector graphic files in CAD format for export to software used in engineering and design. Among other potential uses, these models have been studied by Finite Element Analysis to examine the distribution of mechanical strains in the exoskeleton that occur during posture and locomotion. The advantages and limitations of the techniques are discussed. These methods may be used in studying the exoskeleton and the anatomy of cuticular mechanoreceptors of other arthropods to similar advantage.

Cesarean childbirth and psychosocial outcomes: a meta-analysis.

A comprehensive literature review with meta-analysis examines the differences between vaginal and cesarean delivery on 23 psychosocial outcomes of childbirth. The most robust findings suggest that cesarean mothers, compared with mothers who delivered vaginally, expressed less immediate and long-term satisfaction with the birth, were less likely ever to breast-feed, experienced a much longer time to first interaction with their infants, had less positive reactions to them after birth, and interacted less with them at home. Some differences were also found between unplanned and planned cesarean sections; none were found between birthing methods for maternal confidence for infant caretaking soon after birth, maternal anxiety in the hospital and at home, maternal stress at home, maternal return to work, and continuation of breast-feeding once begun. Implications of these findings for theory, research, and childbirth practice are discussed.

Clopenthixol decanoate in schizophrenia.

Clopenthixol decanoate was given to 20 chronic schizophrenic patients for 11 months in doses ranging from 100 mg initially up to 1000 mg 3-weekly subsequently, according to clinical response and the occurrence of adverse effects. A further 3 patients received the depot injections for periods of 6 to 9 months. Improvement in individual symptoms was rated on a 4-point scale. Unwanted effects were recorded on a checklist and routine biochemical and haematological tests were carried out at the beginning and end of the treatment period. There were highly significant improvements in the mean overall symptom score and in the 5 single symptom scores (hallucinations, delusions, depression, aggressive behaviour and non-aggressive behaviour disturbance). The 2 'negative' symptoms of apathy and social withdrawal showed improvement up to 16 weeks but not at 11 months. The incidence of depression was less at the end of the study than at the time fo entry. Three patients stopped the drug after the sixth month because of extrapyramidal symptoms (2) or drowsiness (1). Three others developed severe extra-pyramidal side-effects. Unwanted effects, though recorded in 70% of patients--drowsiness and extrapyramidal symptoms were the commonest--were for the most part trivial, and were fewer and less severe than they were on entry to the study. There was no evidence of toxicity. It was considered that on the basis of this experience the drug was an effective, safe antipsychotic agent, warranting more extensive clinical trial.

Positive and negative daily events, perceived stress, and alcohol use: a diary study.

Using daily diary methodology, the authors examined over 60 days the within-person associations among positive and negative daily experiences, perceptions of stress, desire to drink, and alcohol consumption in a sample of 83 regular drinkers. Multilevel regression analyses indicated that days on which individuals reported more positive and negative nonwork events were also days they reported higher levels of desire to drink and actual consumption. Days on which individuals reported more negative work events were also days they reported a greater desire to drink, and days on which individuals reported more positive and negative health events were also days they reported lower levels of desire to drink and actual consumption. Weak evidence was found for the mediating effects of perceived stress in these associations. Several of the within-person associations varied as a function of gender, neuroticism, and drinking to cope; no moderating effects were found for extraversion.

Mood and alcohol consumption: an experience sampling test of the self-medication hypothesis.

In this investigation the authors applied the experience sampling method to prospectively test the self-medication hypothesis. In vivo reports gathered in the context of daily life demonstrated that nervousness was the only negative mood state to predict increases in alcohol consumption later in the course of the day. Further examination of this within-person relationship demonstrated that men were more likely to consume alcohol when nervous than were women, but this association was unrelated to family history of alcoholism, problem drinking patterns, or trait anxiety and depression. Consistent with the self-medication hypothesis, cross-sectional analyses also confirmed that alcohol consumption was generally associated with lower levels of nervousness; this effect varied by several demographic and clinical variables. These findings are discussed in terms of the diversity of reasons for alcohol consumption and their potential for explaining problem drinking.