Standardizing Electronic Health Record Data on AD/ADRD to Accelerate Health Equity in Prevention, Detection, and Treatment.

Improving the prevention, detection, and treatment of Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) across racial, ethnic, and other diverse populations is a national priority. To this end, this paper proposes the development of the Standard Health Record for Dementia (SHRD, pronounced "shared") for collecting and sharing AD/ADRD real-world data (RWD). SHRD would replace the current unstandardized, fragmented, or missing state of key RWD with an open source, consensus-based, and interoperable common data standard. This paper describes how SHRD could leverage the best practices of the Minimal Common Oncology Data Elements (mCODETM) initiative to advance prevention, detection, and treatment; gain adoption by clinicians and electronic health record (EHR) vendors; and establish sustainable business and governance models. It describes a range of potential use cases to advance equity, including strengthening public health surveillance by facilitating AD/ADRD registry reporting; improving case detection and staging; and diversifying participation in clinical trials.

Patient decision aid based on multi-criteria decision analysis for disease-modifying drugs for multiple sclerosis: prototype development.

BACKGROUND: Since decision making about treatment with disease-modifying drugs (DMDs) for multiple sclerosis (MS) is preference sensitive, shared decision making between patient and healthcare professional should take place. Patient decision aids could support this shared decision making process by providing information about the disease and the treatment options, to elicit the patient's preference and to support patients and healthcare professionals in discussing these preferences and matching them with a treatment. Therefore, a prototype of a patient decision aid for MS patients in the Netherlands-based on the principles of multi-criteria decision analysis (MCDA) -was developed, following the recommendations of the International Patient Decision Aid Standards. MCDA was chosen as it might reduce cognitive burden of considering treatment options and matching patient preferences with the treatment options. RESULTS: After determining the scope to include DMDs labelled for relapsing-remitting MS and clinically isolated syndrome, users' informational needs were assessed using focus groups (N = 19 patients) and best-worst scaling surveys with patients (N = 185), neurologists and nurses (N = 60) to determine which information about DMDs should be included in the patient decision aid. Next, an online format and computer-based delivery of the patient decision aid was chosen to enable embedding of MCDA. A literature review was conducting to collect evidence on the effectiveness and burden of use of the DMDs. A prototype was developed next, and alpha testing to evaluate its comprehensibility and usability with in total thirteen patients and four healthcare professionals identified several issues regarding content and framing, methods for weighting importance of criteria in the MCDA structure, and the presentation of the conclusions of the patient decision aid ranking the treatment options according to the patient's preferences. Adaptations were made accordingly, but verification of the rankings provided, validation of the patient decision aid, evaluation of the feasibility of implementation and assessing its value for supporting shared decision making should be addressed in further development of the patient decision aid. CONCLUSION: This paper aimed to provide more transparency regarding the developmental process of an MCDA-based patient decision aid for treatment decisions for MS and the challenges faced during this process. Issues identified in the prototype were resolved as much as possible, though some issues remain. Further development is needed to overcome these issues before beta pilot testing with patients and healthcare professionals at the point of clinical decision-making can take place to ultimately enable making conclusions about the value of the MCDA-based patient decision aid for MS patients, healthcare professionals and the quality of care.

Health benefits of a physical exercise program for inpatients with mental health; a pilot study.

The positive effect of exercise on human health and the relationship between physical activity, health, and wellbeing are well studied and extensively documented in the literature. However, considerably less attention is devoted to the impact of exercise on mental health and wellbeing for people experiencing a mental illness, in general, and in particular for inpatients in the mental health care system. Here, we determine the clinical feasibility and effects of short-term (up to three months) vs long-term (up to six months) group-based exercise program for inpatients with chronic mental health. Changes in psychiatric symptoms, well-being, empathy, and physiological fitness factor (e.g., fasting blood glucose, lipid profile, hemoglobin A1C, and BMI) were monitored before, during and following the physical exercise program. Here, we demonstrated that long-term physical activity improved negative symptoms, but not positive symptoms, while improvement in the severity of the illness as measured by the BPRS questionnaire was found to be independent of the training time. We additionally showed that the empathic ability of patients who exercised for more than three months was significantly improved as compared to the other experimental groups. No significant differences were found in wellbeing, mood, satisfaction, and functioning between exercise groups and the control group. Furthermore, physical activity did not improve any of the physiological parameters that were measured in this study. Together, these data indicate that exercise for at least 3 months seems to improve the overall patient mental state, but not his or her physiological parameters, while improvement in negative symptoms and patient's empathy may occur only after a long-term physical exercise activity.

The influence of immune activation at early vs late gestation on fetal NRG1-ErbB4 expression and behavior in juvenile and adult mice offspring.

Maternal inflammation during pregnancy is associated with a higher incidence of mental disorders (e.g. schizophrenia and autism) in the offspring. In our study, we investigate the involvement of the NRG-ErbB signaling pathway in rodent fetal brains four hours following maternal immune activation (MIA) insult at two different gestational days (i.e. early vs late). Furthermore, we test the long-term behavioral alteration of the exposed MIA mice at juvenile and adulthood. We demonstrate that MIA at late, but not at early gestation day, altered the expression of NRG1, its receptor ErbB4, and the dopamine D2 receptor four hours post injection of viral or bacterial mimic material in fetal brain. At the behavioral levels, adult late-MIA-exposed female offspring, but not juvenile, display lack preference to a novel object. While working memory alteration observed only in adult male MIA-exposed offspring at late gestation day. In addition, we found that adult females MIA-exposed mice spent more time in the center of the open field than female-saline groups. On the other hand, juvenile male offspring exposed to MIA at early, but not late, gestation day displayed a significant alteration in social interaction. Our results suggest that MIA during late gestation immediately influences the expression levels of the NRG1 and ErbB4 genes, and affects long-term behavioral changes at adulthood. These behavioral changes are time related and sex-specific. Thus, immune activation at late stages of the embryonic brain development initiates the activation of the NRG1-ErbB4 pathway and this disturbance might result in cognitive dysfunction in adulthood.

Protective self-presentation style: association with disordered eating and anorexia nervosa mediated by sociocultural attitudes towards appearance.

OBJECTIVE: We tested the hypothesis that a protective self-presentation style (Lennox and Wolfe, 1984) is associated with eating pathology and anorexia nervosa (AN) and that this association is mediated by sociocultural attitudes towards appearance emphasizing the thin ideal. METHOD: We compared the protective-presentation style of women with AN (N=17), partially recovered women (N=110), fully recovered women (N=73), and female controls (N=374). RESULTS: Ill women had a more protective self-presentation style than partially or fully recovered women, who in turn had a more protective self-presentation style than controls. Sociocultural attitudes towards appearance fully mediated the association between protective self-presentation and disordered eating. CONCLUSIONS: Protective self-presentation may therefore be a risk factor for AN and/or a prognostic factor. Implications for therapy and prevention are discussed.

Effect of peripheral retinal ablation with cryotherapy versus diode laser photocoagulation on axial length in the growing rabbit eye.

AIMS: To evaluate and compare the effects of peripheral retinal cryotherapy and diode laser photocoagulation on axial length, anterior chamber depth, and lens thickness in developing rabbit eyes. METHODS: 26 eyes of 6 week old Abbit rabbits were randomly assigned to undergo laser photocoagulation or cryotherapy of the peripheral retina. Eight eyes of four untreated rabbits served as controls. Biometric and intraocular pressure measurements were performed at 0, 5, and 10 weeks after treatment. RESULTS: Five rabbits died, leaving 10 rabbits (20 eyes) in the study group and two (four eyes) in the control group. Average axial lengths for the control, laser treated, and cryo treated eyes were 15.72 mm, 16.08 mm, and 16.11 mm, respectively, at baseline and 17.48 mm, 18.09 mm, and 19.4 mm, respectively, at 10 weeks after treatment (p = 0.028, paired Wilcoxon test). Anterior chamber depth increased from 2.2 mm to 2.5 mm in both treatment groups, and from 2.14 mm to 2.28 mm in the control group. Lens thickness averaged 5.11 mm in the control group and 5.38 mm in the treatment groups before treatment, and 6.34 mm, 6.31 mm, and 6.38 mm, respectively, 10 weeks after treatment. CONCLUSIONS: Peripheral retinal cryotherapy causes a significantly greater elongation of the eye compared to diode laser photocoagulation in a rabbit model.

Transmission disequilibrium and haplotype analyses of the G72/G30 locus: suggestive linkage to schizophrenia in Palestinian Arabs living in the North of Israel.

Association of the G72/G30 locus with schizophrenia was recently reported in French Canadian, Russian, and Ashkenazi populations using case-control studies. In the present study we hypothesize the existence of a G72/G30 risk allele over-transmitted to affected sibs in Palestinian Arab families. A total of 223 Palestinian Arab families that included an affected offspring and parents were genotyped with 11 SNPs encompassing the G72/G30 genes. The families were recruited from three regions of Israel: 56 from the North (Afula), 136 from the central hill region (Bethlehem, Palestinian Authority), and 31 from the South (Beersheva). Individual SNP analyses disclosed a risk allele in SNP rs3916970 by both haplotype relative risk (HRR: chi(2) = 5.59, P = 0.018) and transmission disequilibrium test (TDT: chi(2) = 6.03, P = 0.014) in the Afula families. Follow-up multilocus analysis using family-based association tests (FBAT: z = 2.197, P = 0.028) exposed the adjacent haplotype. SNP rs3916970 is located about 8 kb from the linkage disequilibrium block that was reported to be associated with schizophrenia in Ashkenazi Jews. Excess of similar haplotypes of this region was observed in the Palestinian Arabs and the Ashkenazi patients. These data suggest a common risk factor for schizophrenia susceptibility in the G72/G30 locus among Ashkenazi Jews and Palestinian Arabs. The results strengthen previous reports on the role of this locus in the etiology of schizophrenia.

Cornea recipients: are their opinions and attitudes toward organ donation different from those of the general population?

BACKGROUND: Cornea transplantation provides a second chance for people with poor visual function. Unfortunately, there is a major shortage of donor cornea tissue. The purpose of this study was to evaluate the attitudes and willingness to donate organs among cornea transplant recipients. METHODS: Sixty-eight patients who underwent cornea transplantation between January 2002 and May 2003 were asked to complete a questionnaire dealing with their attitudes toward cornea and organ donation, and willingness to donate an organ. RESULTS: Religion was a contributing factor for a negative decision to donate organs. Only 29% of participants, most of whom were nonreligious were carrying a signed donation card. Fifty-eight percent of the patients knew that the cornea graft is derived from a deceased person; most of these patients were of European or American origin. Seventy-three percent knew that donation requires the agreement of a family member. Age, gender, marital status, and education were not significantly associated with attitude toward donation. CONCLUSION: Stronger efforts are needed by transplant coordinators, physicians, and nurses to improve the education and knowledge of patients and their families about the basic aspects of transplantation. Greater public awareness may increase the willingness to donate organs.

Keratometry measurements in preterm and full term newborn infants.

AIM: To evaluate the relation between postconceptional age and birth weight with keratometric values in preterm and full term infants. METHODS: A prospective cross sectional study was performed. The cohort included 99 infants (198 eyes) admitted to the Neonatal and Neonatal Intensive Care Units at Schneider Children's Medical Center of Israel from February to September 2002. Keratometry in the horizontal and vertical meridians was performed in both eyes of each infant by two ophthalmologists using an autokeratometer. The results were evaluated according to: postconceptual age (<32 weeks, 32-36 weeks, >36 weeks) and birth weight (<1500 g, 1501-2500 g, >2501 g). RESULTS: Corneal curvature measurements decreased progressively with both postconceptual age and birth weight. At <32 weeks, mean (standard deviation) readings were 63.3 (3.2) diopters (D) for the horizontal meridian and 57.3 (2.6) D for the vertical meridian; corresponding values at >36 weeks were 54.0 (3.0) D and 50.7 (2.4) D. In the <1500 g group, mean (SD) readings were 61.3 (3.9) D for the horizontal meridian and 56.0 (2.9) D for the vertical meridian; corresponding values in the >2501 g group were 51.3 (2.1) D and 48.6 (1.8) D. CONCLUSIONS: There is an inverse relation of horizontal and vertical keratometric values with both postconceptional age and birth weight. Highest readings were noted in the babies with the lowest birth weight and youngest postconceptional age. The decrease in corneal dioptric power to normal values is linear and is apparently part of the normal ocular maturation.

Family-based and case-control study of catechol-O-methyltransferase in schizophrenia among Palestinian Arabs.

COMT is a ubiquitous enzyme crucial to catechol metabolism. The molecular basis of COMT thermolability, that leads to three to fourfold differences in enzyme activity, is due to a substitution of valine with methionine in the Val158/108Met polymorphism. Of special interest is the role of this gene in major psychoses especially since a microdeletion (22q11) containing the COMT gene (velo-cardio-facial syndrome) also carries with it several types of behavioral disorders, including an increased prevalence of schizophrenia. Almost 20 genetic studies have examined the role of COMT in schizophrenia with ambiguous results. Towards clarifying the role of this polymorphism in conferring risk for psychosis, we examined a large group of culturally and ethnically akin Palestinian Arab schizophrenic triads (N = 276) using both a case-control and family-based study. In 194 informative triads with at least one heterozygote parent, no preferential transmission of either COMT allele was observed in this sample (TDT statistic chi-square = 0.14 NS; 131 COMT valine alleles were transmitted and 125 alleles not transmitted). However, using a case-control design a significant increase (Likelihood ratio = 3.935, P = 0.047) in the valine allele was observed in the group of schizophrenic patients (N = 276) compared to an ethnically matched control group (N = 77). The association was stronger in female patients (P = 0.012) similar to other studies showing that some COMT behavioral effects are gender sensitive. In summary, by case-control design but not by a family-based study, there is a weak effect in female patients of the high activity COMT allele in conferring risk for schizophrenia.

Hepatitis B vaccination: long-term follow-up of the immune response of preterm infants and comparison of two vaccination protocols.

BACKGROUND: We conducted a 3-year follow-up study of long-term antibody persistence following vaccination of low-risk preterm infants with recombinant hepatitis B vaccine (HBV). Two three-dose protocols were compared: vaccination beginning within 24 h of birth to initial vaccination delayed until a weight of 2,000 g was reached. SUBJECTS AND METHODS: The study population included 136 children, divided into three groups: children born prematurely (< or = 35 weeks, n = 57), children born at term (> or = 37 weeks, n = 39), both groups receiving the first dose of HBV within 24 h of birth, and children born prematurely (< or = 35 weeks, n = 40), who received the first dose of HBV when a weight of 2,000 g was reached. All infants received the second hepatitis vaccination 1 month after the first, and the third dose 6 months after the first. Hepatitis B surface antibody (AntiHBs) was measured at an age of 3-3.5 years (at least 2.5 years after completion of the three-dose HBV series). An AntiHBs level of > or = 10 IU/l was considered positive. RESULTS: At 3-3.5 years of age, a higher percentage of the premature-delayed vaccination group had a positive AntiHBs level (92.5%) compared to both the premature (54.4%, p < 0.001) and full-term groups (71.8%, p < 0.05) vaccinated soon after birth. The premature-delayed vaccination group also had a significantly higher geometric mean concentration (GMC) (119 vs 14.2 IU/l, p < 0.001 and 119 vs 32.7 IU/l, p < 0.005, respectively). CONCLUSION: Delaying vaccination of premature infants against hepatitis B until a weight of 2,000 g was reached resulted in both a significantly higher percentage of children with positive antibody levels and a significantly higher GMC at 3-3.5 years of age as compared to early-vaccinated preterm and full-term infants. The known short-term advantage of delayed vaccination of preterm infants was shown to persist for at least the first 3 years of life.

No evidence for linkage by transmission disequilibrium test analysis of microsatellite marker D22S278 and schizophrenia in a Palestinian Arab and in a German population.

Linkage for a schizophrenia susceptibility locus on chromosome region 22q12-q13 was initially suggested by independent studies from two groups and confirmed in a combined analysis of data for the microsatellite marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. In addition to these reports of linkage to schizophrenia on chromosome 22, bipolar disorder has also been linked to markers in this chromosomal region. We now report results from an analysis of 223 Palestinian Arab trios from three different centers in Israel and Palestine using the allele-wise extended transmission disequilibrium test for multiallelic markers. No evidence for linkage is observed in the entire group or in any of the three centers (entire group: chi-square = 5.59, P = 0.78, df = 9; Afula: chi-square = 6.51, P = 0.48, df = 7; Bethlehem: chi-square = 14.11, P = 0.12, df = 9; Beersheva: chi-square = 7.04, P = 0.32, df = 6). Additionally, we examined D22S278 in a group of 114 schizophrenic German triads and failed to observe evidence for linkage (chi-square = 8.13, P = 0.42, df = 8df).

A family-based study of the Cys23Ser 5HT2C serotonin receptor polymorphism in schizophrenia.

The 5HT2C receptor has a high affinity for clozapine, a nontypical neuroleptic, and has therefore been postulated to play a role in mediating negative symptoms and neuroleptic response in schizophrenia. In the current study, the Cys23Ser 5HT2C serotonin receptor polymorphism was examined for linkage to schizophrenia by genotyping 207 nuclear families consisting of both parents and schizophrenic child and using the transmission disequilibrium test to examine possible preferential transmission of these alleles from 68 heterozygous mothers to their ill child. No evidence was obtained for preferential transmission of the Cys23Ser 5HT2C alleles in schizophrenia in either of the two main ethnic groups examined (German and Palestinian Arab) or in the combined cohort (TDT chi-square = 0.00, NS).

Pretreatment with recombinant Flt3 ligand partially protects against progressive cutaneous leishmaniasis in susceptible BALB/c mice.

Dendritic cells are potent antigen-presenting cells that also produce interleukin-12 (IL-12) during innate and adaptive cellular immune responses and that thereby promote the differentiation of gamma interferon (IFN-gamma)-producing Th1-type CD4(+) T lymphocytes. We hypothesized that expanded dendritic-cell populations in mice pretreated with the hematopoietic cytokine Flt3L would protect against cutaneous Leishmania major infection. Pretreatment of disease-susceptible BALB/c mice with 10 microg of recombinant Flt3L (rFlt3L) for 9 to 10 days before infection increased lymph node IL-12 p40 productive capacity 20-fold compared to that of saline-injected controls. Furthermore, 9 of 22 (40.9%) rFlt3L-pretreated BALB/c mice resolved their cutaneous infections, whereas none of the 22 control BALB/c mice healed. Healed, rFlt3L-pretreated mice did not develop disease following reinfection. Flt3L pretreatment also reduced parasite numbers 1,000-fold in the cutaneous lesions at 2 weeks after infection relative to numbers in lesions of untreated controls. However, Flt3L pretreatment did not significantly alter L. major-induced IFN-gamma and IL-4 production in lymph node culture at 1, 2, and 4 weeks after infection. Despite the lack of Th immune deviation, Flt3L ligand-pretreated lymph nodes expressed up to 10-fold higher levels of IL-12 p40 and inducible (type 2) nitric oxide synthase mRNA at 7 days after infection. In contrast, treatment with rFlt3L after infection failed to protect against disease despite comparable expansions of dendritic cells and IL-12 p40 productive capacity in both infected and uninfected BALB/c mice treated with rFlt3L. We conclude that rFlt3L pretreatment before infection with L. major reduces parasite load and promotes healing of cutaneous lesions without stable cytokine deviation towards a dominant Th1 cytokine phenotype.

No association between the dopamine D3 receptor Bal I polymorphism and schizophrenia in a family-based study of a Palestinian Arab population.

Several recent meta-analyses appear to show a weak but significant effect of both forms of the gly/ser DRD3 polymorphism in conferring risk for schizophrenia. Since most studies have employed the artifact-prone case-control design, we thought it worthwhile to examine the role of this polymorphism using a robust family-based strategy in an ethnic group not previously systematically studied in psychiatric genetics, Palestinian Arabs. We failed to obtain any evidence in 129 Palestinian triads, using the haplotype relative risk (allele frequency: Pearson chi-square = 0.009, P > 0.1, df = 1, n = 258 alleles) or transmission disequilibrium test design (chi-square = 0.38, P > 0.1, n = 86 families) for association/linkage (or increased homozygosity) of the DRD3 Bal I polymorphism to schizophrenia in our sample. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:778-780, 2000.

Diode laser treatment of posterior retinopathy of prematurity.

AIMS: To study the efficacy of infrared diode laser for the treatment of posterior retinopathy of prematurity (ROP). METHODS: 48 eyes of 25 premature babies (mean birth weight 779 (SD 127.7) g; mean gestational age 25.5 (SD 1.47) weeks) with threshold ROP in zone I and posterior zone II were treated by the indirect infrared (810 nm) diode laser. Confluent burns were applied to the avascular retina. In 18 eyes, an additional row of laser burns was added posterior to the ridge. RESULTS: Favourable anatomical results were noted in 41 eyes (85.4%). ROP stage 5 developed in two eyes, ROP stage 4A developed in four eyes, and ROP stage 4B in one eye. Three of the eyes with stage 4A eyes were successfully buckled; the fourth was not operated on and remained demarcated by laser scars. No complications were noted. CONCLUSION: In this series, the diode laser was found to be a safe and effective treatment for posterior ROP.

Confirmation of an excess of the high enzyme activity COMT val allele in heroin addicts in a family-based haplotype relative risk study.

A previous case control study by Vandenbergh et al. [1997: Am J Med Genet 74:439-442] showed an association between the high activity catechol O-methyltransferase (COMT) polymorphism and polysubstance abuse in a group of North American subjects. In the current study we confirm these results by genotyping 38 Israeli heroin addicts and both parents using a robust family-based haplotype relative risk (HRR) strategy. There is an excess of the val COMT allele (likelihood ratio = 4.48, P = 0.03) and a trend for an excess of the val/val COMT genotype (likelihood ratio = 4.97, P = 0.08, 2 df) in the heroin addicts compared to the HRR control group. We also genotyped an additional 101 nonrelated heroin addicts and 126 control subjects using a case control design and found no significant difference in COMT val allele frequency (25.4% vs. 29.7%, likelihood ratio = 1.04, P = 0.31). A significant difference is observed in COMT allele frequency among the three principal Israeli ethnic groups (Ashkenazi Jewish, non-Ashkenazi Jewish, and Palestinian Arab) in a large group of control subjects we have so far examined (chi-square = 7.9, P = 0.019, df = 2, n = 1,422 alleles) suggesting that population stratification is responsible for our failure to observe an excess of the COMT val allele when using the case-control design.

Intradermal granulocyte-macrophage colony-stimulating factor alters cutaneous antigen-presenting cells and differentially affects local versus distant immunization in humans.

We hypothesized that intradermal delivery of granulocyte-macrophage colony-stimulating factor (GM-CSF) would alter the number and differentiation state of local antigen-presenting cells and thereby alter immunization strength at that site in humans. GM-CSF or placebo was administered intradermally on consecutive days prior to contact sensitization at that site. In GM-CSF-treated skin, epidermal CD1a(+)S100(+) Langerhans cells were reduced in number and had altered morphology, while the number of dermal CD1a(+), HLA-DR(+), and S100(+) cells was increased. In the deep dermis CD68(+) macrophages were increased. Expression of the APC activation markers CD40 and ICAM-1 was also increased in the dermis. Subjects were sensitized to DNCB through GM-CSF- or placebo-pretreated skin and to DPCP through untreated skin. Subjects immunized through GM-CSF-treated sites exhibited 64% greater elicitation responses to DNCB than placebo-treated subjects. GM-CSF-treated subjects also showed 43% lower responses to DPCP than placebo-treated subjects. The difference between DNCB (local) and DPCP (distant) responses was significantly greater for GM-CSF-treated subjects than for placebo responses (n = 8, P < 0.05). Therefore, local immunization site pretreatment with intradermal GM-CSF enhances immunization efficiency at that site.