Generalizability of predictive models for Clostridioides difficile infection, severity and recurrence at an urban safety-net hospital.

INTRODUCTION: Predictive models for Clostridioides difficile infection can identify high-risk patients and aid clinicians in preventing infection. Issues of generalizability regarding current predictive models have been acknowledged but, to the authors' knowledge, have never been quantified. METHODS: C. difficile infection, severity and recurrence predictive models were created using multi-variate logistic regression through case-control sampling from an urban safety-net hospital. Models were validated using five-fold cross-validation, and inverse probability weights (IPW) based on two different catchment area definitions were used to improve external validity. Akaike Information Criterion (AIC), area under the receiver operating characteristic curve (AUROC), and sensitivity and specificity with bootstrapped confidence intervals (CI) were used to assess and compare model fit and performance. RESULTS: Changes in performance before and after weighting were small across all models, although differences were more apparent after weighting the recurrence model (AUROC values of 0.78, 0.76 and 0.71 for the unweighted and two weighted models, respectively). Overall, the infection model performed the best (AUROC 0.82, 95% CI 0.78-0.85), followed by the recurrence model (AUROC 0.78, 95% CI 0.69-0.86) and then the severity model (AUROC 0.70, 95% CI 0.63-0.78). CONCLUSIONS: The performance of the models after weighting did not change drastically, suggesting that the models predicting C. difficile infection, severity and recurrence may not be impacted by patient selection factors. However, other researchers may wish to consider addressing these catchment forces using IPW.

Evaluating a neonatal intensive care unit MRSA surveillance programme using agent-based network modelling.

BACKGROUND: Surveillance for meticillin-resistant Staphylococcus aureus (MRSA) in neonatal intensive care units (NICUs) is a commonplace infection prevention strategy, yet the optimal frequency with which to monitor the unit is unknown. AIM: To compare various surveillance frequencies using simulation modelling. METHODS: One hundred NICU networks of 52 infants were simulated over a six-month period to assess MRSA transmission. Unit-wide surveillance occurred every N weeks where N={1,2,3,4}, and was compared with the current NICU policy of dynamic surveillance (i.e. weekly when at least one positive screen, otherwise every three weeks). For each surveillance period, colonized infants received a decolonization regimen (56% effective) and were moved to isolation rooms, if available. FINDINGS: As the surveillance frequency increased, the mean number of MRSA-colonized infants decreased, from a high of 2.9 (four-weekly monitoring) to a low of 0.6 (weekly monitoring) detected per episode. The mean duration of colonization decreased from 307 h (four-weekly monitoring) to 61 h (weekly monitoring). Meanwhile, the availability of isolation rooms followed an inverse relationship: as surveillance frequency increased, the availability of isolation rooms decreased (61% isolation success rate for four-weekly monitoring vs 49% success rate for weekly monitoring). The dynamic policy performed similar to a biweekly programme. CONCLUSIONS: An effective MRSA surveillance programme needs to balance resource availability with potential for harm due to longer colonization periods and opportunity for development of invasive disease. While more frequent monitoring led to greater use of a decolonization regimen, it also reduced the likelihood of isolation rooms being available.

Density of day cares in relation to reported pertussis incidence in Philadelphia.

OBJECTIVES: Reported pertussis incidence has increased markedly in recent years. In addition to the documented increase in under-immunization and waning immunity, the increase may be related to the more frequent use of child care services by parents over the last few decades. Additionally, clustering of outbreaks may be related to neighborhood characteristics not previously identified. STUDY DESIGN: We conducted a citywide case-control study of children in Philadelphia aged birth through six years, between 2001 and 2013. Cases were reported as probable pertussis diagnoses to the Health Department. Controls were sampled from the city's immunization information system and matched to the cases by date of birth. METHODS: Multilevel logistic regression was used to isolate the independent contributions of individual and neighborhood risk factors and the corresponding relative odds of pertussis. The density of day cares in each neighborhood served as the main exposure and reported incident cases of confirmed and probable pertussis was the main outcome. RESULTS: Between 2001 and 2013, 410 cases of confirmed and probable pertussis were included with four controls matched per case yielding a final sample of 2050 children from 45 Philadelphia neighborhoods. There was a 30% increase in the risk of pertussis based solely on the neighborhood where the children resided (median odds ratio 1.3, 95% credible interval 1.1, 1.6). The density of day cares in each neighborhood was unrelated to the distribution of pertussis cases. CONCLUSIONS: Pertussis clustering was observed at the neighborhood level in Philadelphia, but was unrelated to the neighborhood's day care density. From a Health Department perspective, the highest risk neighborhoods should be targeted for vaccine campaigns and further research to identify the etiologic risk factors.

Characteristics of late-onset sepsis in the NICU: does occupancy impact risk of infection?

OBJECTIVE: Infants in neonatal intensive care units (NICUs) are vulnerable to a variety of infections, and occupancy in the unit may correlate with risk of infection. STUDY DESIGN: A retrospective cohort of infants admitted to the NICUs between 1997 and 2014. Survival analysis was used to model the relative hazard of sepsis infection in relation to two measures of occupancy: 1) the average census and 2) proportion of infants <32 weeks gestation in the unit. RESULT: There were 446 (2.3%) lab-confirmed cases of bacterial or fungal sepsis, which steadily declined over time. For each additional percentage of infants <32 weeks gestation, there was an increased hazard of 2% (hazard ratio 1.02, 95% confidence interval: 1.00, 1.03) over their NICU hospitalization. Census was not associated with risk for infection. CONCLUSION: During times of a greater proportion of infants <32 weeks gestation in the NICU, enhanced infection-control interventions may be beneficial to further reduce the incidence of infections.

Decreased adiponectin links elevated adipose tissue autophagy with adipocyte endocrine dysfunction in obesity.

BACKGROUND/OBJECTIVES: Adipose tissue (AT) autophagy gene expression is elevated in human obesity, correlating with increased metabolic risk, but mechanistic links between the two remain unclear. Thus, the objective of this study was to assess whether elevated autophagy may cause AT endocrine dysfunction, emphasizing the putative role of adiponectin in fat-liver endocrine communication. SUBJECTS/METHODS: We utilized a large (N=186) human AT biobank to assess clinical associations between human visceral AT autophagy genes, adiponectin and leptin, by multivariate models. A broader view of adipocytokines association with elevated autophagy was assessed using adipocytokine array. Finally, to establish causality, ex vivo studies utilizing a murine AT-hepatocyte cell line co-culture system was used. RESULTS: Circulating high-molecular-weight adiponectin and leptin levels were associated with human omental-AT expression of ATG5 mRNA, associations that remained significant (ß=-0.197, P=0.011; ß=0.267, P<0.001, respectively) in a multivariate model adjusted for age, sex, body mass index and interleukin-6 (IL-6). A similar association was observed with omental-AT LC3A mRNA levels. Bafilomycin-A1 (Baf A) pretreatment of AT explants from high-fat-fed (HFF) mice had no effect on the secretion of some AT-derived endocrine factors, but partially or fully reversed obesity-related changes in secretion of a subset of adipocytokines by >30%, including the obesity-associated upregulation of IL-6, vascular endothelial growth factor, tumor necrosis factor alpha (TNFα) and certain insulin-like growth factor-binding proteins, and the HFF-induced downregulated secretion of IL-10 and adiponectin. Similarly, decreased adiponectin and increased leptin secretion from cultured adipocytes stimulated with TNFα+IL-1ß was partially reversed by small interfering RNA-mediated knockdown of ATG7. AT explants from HFF mice co-cultured with Hepa1c hepatoma cells impaired insulin-induced Akt and GSK3 phosphorylation. This effect was significantly reversed by pretreating explants with Baf A, but not if adiponectin was immunodepleted from the conditioned media. CONCLUSIONS: Reduced secretion of adiponectin may link obesity-associated elevated AT autophagy/lysosomal activity with adipose endocrine dysfunction.

Helicobacter pylori infection in patients with selective immunoglobulin a deficiency.

Selective immunoglobulin A (IgA) deficiency (IgAD) is the most common primary immunodeficiency in the western world. The aim of the study was to investigate the prevalence and clinical characteristics of Helicobacter pylori-infected dyspeptic patients with IgAD. Case samples were drawn from all subjects ≥ 12 years of age (n = 104729) who had undergone serum total IgA measurements during 2004-14 for any reason at Leumit Healthcare Services (Israel) and had serum total IgA < 0·07 g/l. The control group was comprised of a random sample of remaining patients with a case-control ratio of 10 controls for each case. The dyspeptic diseases were identified and retrieved from Leumit Health Care Services electronic database using specific ICD-9-CM diagnostic codes. The case group included 347 subjects and the control group 3470 subjects. There were no significant differences in the prevalence of patients with dyspepsia [84 (24·2%) versus 821 (23·6%) for cases and controls, respectively]. Additionally, there was no difference in a proportion of dyspeptic H. pylori-positive subjects [59 (17·1%) versus 524 (15·1%)] between the case and control groups. Only 59 (17%) among the 347 IgAD patients underwent gastroscopy. A significantly larger proportion of case subjects experienced several forms of gastritis [13 (61·9%) versus 38 (21·6%), P < 0·001), duodenal ulcers [seven (33·3%) versus 19 (10·8%); P = 0·01] and nodular lymphoid hyperplasia (NLH) [two (9·5%) versus none; P = 0·011]. IgAD is not associated with increased prevalence of H. pylori-associated dyspepsia; nevertheless, H. pylori-infected dyspeptic IgAD subjects experience more EGD-proved gastritis, duodenal ulcers and NLH.

Blood-brain barrier unlocked.

The brain is protected by a physiological blood-brain barrier (BBB) against toxins and some metabolites circulating in the blood. At the same time, the BBB limits penetration into the brain of many neuroactive drugs. Efficient ways to increase BBB permeability for delivery of drugs of different chemical nature into the brain are unknown. This work deals with delivery into the brain of 10(-2) M dopamine, a substance that does not penetrate the BBB under normal circumstances. It was studied in two independent experiments: (i) penetration of (3)H-labeled dopamine from its mixture with 10(-5) M H2O2 into hypothalamus and striatum structures of intact rat brain, and (ii) effect of unlabeled dopamine from a mixture with H(2)O(2) on the rat motor activity in a haloperidol catalepsy model. It was shown that (i) at the third minute after nasal application of the dopamine + H(2)O(2) mixture, the dopamine level increases 45-fold in the hypothalamus and almost 30-fold in the striatum and (ii) motility of animals in the catalepsy haloperidol model is recovered 90 sec after intranasal introduction of dopamine. No such effects were observed after replacement of H(2)O(2) by 0.9% NaCl solution. Thus, it was shown on the example of dopamine that its introduction into the nasal cavity simultaneously with H(2)O(2) provides for rapid delivery of the drug into the brain. These results expand our knowledge concerning the biological role of exoROS in modulating BBB permeability and may contribute to the development of a new therapeutic strategy for neurological diseases.

Electronic health records and adverse drug events after patient transfer.

BACKGROUND: Our objective was to examine the frequencies of medication error and adverse drug events (ADEs) at the time of patient transfer in a system with an electronic health record (EHR) as compared with a system without an EHR. It was hypothesised that the frequencies of these events would be lower in the EHR system because of better information exchange across sites of care. METHODS: 469 patients transferred between seven nursing homes and three hospitals in New York and Connecticut between 1999 and 2005 were followed retrospectively. Two groups of patients were compared: US Veterans Affairs (VA) patients, with an EHR, and non-VA patients, without an EHR, on the following measures: (1) medication prescribing discrepancies at nursing home/hospital transfer, (2) high-risk medication discrepancies and (3) ADEs caused by medication discrepancies according to structured medical record review by pairs of physician and pharmacist raters. RESULTS: The overall incidence of ADE caused by medication discrepancies was 0.20 per hospitalisation episode. After controlling for demographic and clinical covariates, there were no significant differences between VA and non-VA groups in medication discrepancies (mean difference 0.02; 95% CI -0.81 to 0.85), high-risk medication discrepancies (-0.18; 95%CI -0.22 to 0.58) or occurrence of an ADE caused by a medication discrepancy (OR 0.96; 95% CI 0.18 to 5.01). CONCLUSIONS: There was no difference, with and without an EHR, in the occurrence of medication discrepancies or ADEs caused by medication discrepancies at the time of transfer between sites of care. Reducing such problems may require specialised computer tools to facilitate medication review.

Prescribing discrepancies likely to cause adverse drug events after patient transfer.

BACKGROUND: Medication-prescribing discrepancies are used as a quality measure for patients transferred between sites of care. The objective of this study was to quantify the rate of adverse drug events (ADEs) caused by prescribing discrepancies and the discrimination of an index of high-risk transition drug prescribing. METHODS: We examined medical records of patients transferred between seven nursing homes and three hospitals between 1999 and 2005 in New York and Connecticut for transfer-associated prescribing discrepancies. ADEs caused by discrepancies were determined by two clinician raters. We calculated the fraction of medication discrepancies that caused ADEs in each of 22 drug classes by calculating positive predictive values (PPVs). We calculated the discrimination of a count of high-risk drug discrepancies, selected from published lists of high-risk medications and using observed PPVs. RESULTS: 208 patients were hospitalised 304 times. Overall, 65 of 1350 prescribing discrepancies caused ADEs, for a PPV of 0.048 (95% CI 0.037 to 0.061). PPVs by drug class ranged from 0 to 0.28. Drug classes with the highest PPVs were opioid analgesics, metronidazole, and non-opioid analgesics. Patients with 0, 1-2 and >/=3 high-risk discrepancies had a 13%, 23% and 47% chance of experiencing a discrepancy-related ADE, respectively. CONCLUSIONS: Discrepancies in certain drug classes more often caused ADEs than other types of discrepancies in hospitalised nursing-home patients. Information about ADEs caused by medication discrepancies can be used to enhance measurement of care quality, identify high-risk patients and inform the development of decision-support tools at the time of patient transfer.

A mutation analysis of the phenylalanine hydroxylase (PAH) gene in the Israeli population.

Hyperphenylalaninemia (HPA) is a group of diseases characterized by a persistent elevation of phenylalanine levels in tissues and biological fluids. The most frequent form is phenylalanine hydroxylase deficiency, causing phenylketonuria (PKU). Among 159 Israeli patients (Jews, Muslim and Christian Arabs and Druze) with HPA, in whom at least one of the mutations was characterized, a total of 43 different mutations were detected, including seven novel ones. PKU was very rare among Ashkenazi Jews and relatively frequent among Jews from Yemen, the Caucasian Mountains, Bukhara and Tunisia. The mutations responsible for the high frequency were: exon3del (Yemenite Jews), L48S (Tunisian Jews) and E178G, P281L and L48S (Jews from the Caucasian Mountains and Bukhara). Among the non-Jewish Israeli citizens, the disease was relatively frequent in the Negev and in the Nazareth vicinity, and in many localities a unique mutation was detected, often in a single family. While marked genetic heterogeneity was observed in the Arab and Jewish populations, only one mutation A300S, was frequent in all of the communities. Several of the other frequent mutations were shared by the non-Ashkenazi Jews and Arabs; none were mutual to Ashkenazi Jews and Arabs.

Meaning-Making of a Group of South Africans in their Experience of Living with HIV : a Phenomenological study

With the primary focus of disease specific studies on the medical and biological transmission and progression of HIV/AIDS; the lived experience and meaning-making of individuals who live with this disease; is a literary scarcity. Similarly; the idiosyncratic meaning-making of middle class citizens diagnosed with HIV/AIDS appears largely unexplored. Addressing these concerns; the aim of this article is to explore the lived experience and meaning-making of four middle-class South Africans diagnosed with HIV. Open-ended questions were formulated and used to elicit the rich idiosyncratic meaning of the complex experiences of the participants. The research indicates that HIV/AIDS is experienced as an intrusive violation of one's way of being-in-the-world in relation to one's self and others and involves a complex process consisting of overwhelming and intense feelings. The research also indicates that; in the experience of living with HIV/AIDS; a space is created for the rediscovery of spirituality; religion and compassion. Consequently; an appreciation for life; a need for belongingness; community; and also a transcendence of the mundane by positive embrace of one's time on earth is facilitated in the experience of living with this disease. This positive shift in what it means to live with HIV/AIDS in South Africa might have important implications for the helping professions and from which many therapeutic benefits might derive

Allergic rhinitis due to house dust mites: evaluation of the efficacy of specific sublingual immunotherapy.

BACKGROUND: The efficacy and safety of sublingual immunotherapy (SLIT) in patients with chronic rhinitis related to sensitization to house dust mites are still controversial. METHODS: After application of an anti-mite mattress cover, patients were only included in the study when the cumulative symptom score over a fortnight was greater than 70 out of a possible total of 168. Thirty-two of the 120 patients selected were randomized to receive SLIT for 2 years: 17 received placebo and 15 received the Dermatophagoides pteronyssinus and D. farinae 50/50 allergen extract. RESULTS: Significant between-group differences were observed after 1 year and persisted at the end of the second year for the rhinitis total score (P < 0.02), blocked nose score (P < 0.01) and nasal itching score (P < 0.01). Skin reactivity to house dust mites was significantly reduced in the group receiving house dust mite extract (P < 0.03). No statistical difference was observed between the two groups for medication scores, but a low medication consumption was observed in all patients. No serious and no systemic adverse reactions were reported. CONCLUSION: This study indicates the superiority of active treatment vs. placebo, evaluated on efficacy criteria (rhinitis score) or objective criteria (skin reactivity). The availability of a solid form (tablet) could represent a progress in terms of patient acceptability.

Proximal small-bowel mucosal villous intraepithelial lymphocytes.

Small-bowel biopsies are routinely obtained from adult patients as a screening tool to evaluate the possibility of gluten sensitivity (GS). Previous morphological criteria of GS including completely flattened villi are usually absent. In the context of screening for GS, an altered distribution density pattern of villous intraepithelial lymphocytes (IELs) is probably the most sensitive morphological feature to suggest the possibility of GS and prompt the initiation of further medical evaluation. Altered villous IEL density distribution is a more sensitive screening feature than villous IEL counts. With increased small-bowel GS screening biopsies, occasional adults without GS with complete villous flattening and numerous villous IELs are encountered. These patients are usually incorrectly diagnosed with GS. However, they do not respond to a gluten-free diet and slowly improve over months.

Workshop on partial breast irradiation: state of the art and the science, Bethesda, MD, December 8-10, 2002.

Breast conserving surgery followed by radiation therapy has been accepted as an alternative to mastectomy in the management of patients with early-stage breast cancer. Over the past decade there has been increasing interest in a variety of radiation techniques designed to treat only the portion of the breast deemed to be at high risk for local recurrence (partial-breast irradiation [PBI]) and to shorten the duration of treatment (accelerated partial-breast irradiation [APBI]). To consider issues regarding the equivalency of the various radiation therapy approaches and to address future needs for research, quality assurance, and training, the National Cancer Institute, Division of Cancer Treatment and Diagnosis, Radiation Research Program, hosted a Workshop on PBI in December 2002. Although 5- to 7-year outcome data on patients treated with PBI and APBI are now becoming available, many issues remain unresolved, including clinical and pathologic selection criteria, radiation dose and fractionation and how they relate to the standard fractionation for whole breast irradiation, appropriate target volume, local control within the untreated ipsilateral breast tissue, and overall survival. This Workshop report defines the issues in relation to PBI and APBI, recommends parameters for consideration in clinical trials and for reporting of results, serves to enhance dialogue among the advocates of the various radiation techniques, and emphasizes the importance of education and training in regard to results of PBI and APBI as they become emerging clinical treatments.

Reactive oxygen species as essential components of ambient air.

In this review evidence for the presence of the anion radical O2(-*) in atmospheric air is considered, and the biological activity of superoxide and negative air ions is compared. Various aspects of the biological effect of superoxide and other reactive oxygen species contained in air at the cell, tissue, and organism levels are discussed. The results of the therapeutic use of exogenous gaseous superoxide and low doses of H2O2 for the treatment of bronchial asthma, pain, and Parkinson's disease are reported. A hypothesis on the mechanism of physiological action of exogenous reactive oxygen species is discussed.

Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties.

Abnormalities in cellular differentiation are frequent occurrences in human cancers. Treatment of human melanoma cells with recombinant fibroblast interferon (IFN-beta) and the protein kinase C activator mezerein (MEZ) results in an irreversible loss in growth potential, suppression of tumorigenic properties and induction of terminal cell differentiation. Subtraction hybridization identified melanoma differentiation associated gene-7 (mda-7), as a gene induced during these physiological changes in human melanoma cells. Ectopic expression of mda-7 by means of a replication defective adenovirus results in growth suppression and induction of apoptosis in a broad spectrum of additional cancers, including melanoma, glioblastoma multiforme, osteosarcoma and carcinomas of the breast, cervix, colon, lung, nasopharynx and prostate. In contrast, no apparent harmful effects occur when mda-7 is expressed in normal epithelial or fibroblast cells. Human clones of mda-7 were isolated and its organization resolved in terms of intron/exon structure and chromosomal localization. Hu-mda-7 encompasses seven exons and six introns and encodes a protein with a predicted size of 23.8 kDa, consisting of 206 amino acids. Hu-mda-7 mRNA is stably expressed in the thymus, spleen and peripheral blood leukocytes. De novo mda-7 mRNA expression is also detected in human melanocytes and expression is inducible in cells of melanocyte/melanoma lineage and in certain normal and cancer cell types following treatment with a combination of IFN-beta plus MEZ. Mda-7 expression is also induced during megakaryocyte differentiation induced in human hematopoietic cells by treatment with TPA (12-O-tetradecanoyl phorbol-13-acetate). In contrast, de novo expression of mda-7 is not detected nor is it inducible by IFN-beta+MEZ in a spectrum of additional normal and cancer cells. No correlation was observed between induction of mda-7 mRNA expression and growth suppression following treatment with IFN-beta+MEZ and induction of endogenous mda-7 mRNA by combination treatment did not result in significant intracellular MDA-7 protein. Radiation hybrid mapping assigned the mda-7 gene to human chromosome 1q, at 1q 32.2 to 1q41, an area containing a cluster of genes associated with the IL-10 family of cytokines. Mda-7 represents a differentiation, growth and apoptosis associated gene with potential utility for the gene-based therapy of diverse human cancers.

[Overuse of antibiotics with upper respiratory tract infections in a primary care clinic].

UNLABELLED: In the majority of cases upper respiratory tract infections (URI's) are caused by viruses. Nonetheless, in many instances, patients with URI's are over-treated with antibiotics. In order to evaluate the use of antibiotic therapy in patients with URI's, we recorded medications prescribed for URI's in 394 young adults seeking care in a primary care clinic. The following parameters were assessed: rhinnorhea, cough, sore throat, dysphagia, tonsillar exudates, tonsillar enlargement and cervical lymphadenopathy. Throat cultures were taken from all the patients. RESULTS: Antibiotic therapy was prescribed for 99 of the 370 patients (26.8%) with URI's and negative throat cultures. Among these patients, a high prevalence of the following findings was evident: tonsillar enlargement (66.7%), tonsillar exudates (48.5%), cervical lymphadenopathy (42.4%), lack of rhinorrhea (40.4%), lack of cough (32.0%) and fever (31.3%). CONCLUSIONS: Excess antibiotic therapy was prescribed for patients with URI's. Possible explanations are: clinical findings that suggest a diagnosis of follicular tonsillitis, early antibiotic treatment that is not based on throat cultures or antigen detection tests, and multiple treating physicians. RECOMMENDATIONS: We recommend that in cases of patients with URI's, antibiotics should not be prescribed unless diagnosis of a streptococcal infection is supported by results of throat cultures or antigen detection tests. Furthermore, in primary care clinics with a number of physicians, treatment should guarantee appropriate medical follow-up.

A surrogate-based approach for post-genomic partner identification.

BACKGROUND: Modern drug discovery is concerned with identification and validation of novel protein targets from among the 30,000 genes or more postulated to be present in the human genome. While protein-protein interactions may be central to many disease indications, it has been difficult to identify new chemical entities capable of regulating these interactions as either agonists or antagonists. RESULTS: In this paper, we show that peptide complements (or surrogates) derived from highly diverse random phage display libraries can be used for the identification of the expected natural biological partners for protein and non-protein targets. Our examples include surrogates isolated against both an extracellular secreted protein (TNFbeta) and intracellular disease related mRNAs. In each case, surrogates binding to these targets were obtained and found to contain partner information embedded in their amino acid sequences. Furthermore, this information was able to identify the correct biological partners from large human genome databases by rapid and integrated computer based searches. CONCLUSIONS: Modified versions of these surrogates should provide agents capable of modifying the activity of these targets and enable one to study their involvement in specific biological processes as a means of target validation for downstream drug discovery.

A review and update on the practice of evaluating Miranda comprehension.

This article summarizes recent developments in constitutional law relevant to the Miranda warning. We describe the origins of the warning, concerns about the use of the Miranda warning, perspectives on the utility of the warning, and the relevance of the warning. We describe how the warning has changed over time, requirements for administering the warning, and procedures that police use in delivering the warning and obtaining confessions. We review case law relevant to "coerced" Miranda waivers and confessions, changes over time in the court's interpretation of what constitutes "coercion," use of the warning with special populations, and the recent focus in case law on individual factors that might impair Miranda comprehension. We review empirical research on factors associated with deficits in Miranda comprehension. We integrate case law rulings and empirical research into suggested approaches to forensic assessment of Miranda comprehension.

Preadolescent adjudicative competence: methodological considerations and recommendations for practice standards.

This article examines developmental and legal issues directed toward a downward age extension of forensic evaluation practice standards for preadolescent defendants whose competence is questioned. Existing research and practice standards were developed for cases involving adolescents and adults, but they lack sufficient application to evaluations of young children because of the ways in which legal parameters affect young children. We review practice implications of the legal role of "immaturity" for adjudicative competence, alterations of Dusky in some juvenile courts, and the role of parens patriae in competence hearings held in juvenile court. We examine competence abilities in a developmental framework. Examining practice standards is timely because adjudicative competence in preadolescent defendants has taken on recent significance. The last decade saw changes in the stringency of delinquency statutes, increased emphasis on adversarial approaches to juvenile proceedings, and a de-emphasis on rehabilitation and parens patriae protections. Statutory changes and increased referrals have heightened inquiry into the meaning of preadolescent adjudicative competence.