Characterization of associations and development of atazanavir resistance after unplanned treatment interruptions.

OBJECTIVES: Although current guidelines recommend resistance testing prior to antiretroviral therapy (ART) reinitiation after treatment interruptions, virological failure of first-line ritonavir-boosted, protease-inhibitor (PI/r)-containing ART is associated with low emergent PI resistance. In patients experiencing unscheduled treatment interruptions (UTrIs) on ritonavir-boosted atazanavir (ATV/r) ART regimens, we hypothesized low emergence of PI mutations conferring resistance to ATV/r. METHODS: In a retrospective assessment of HIV-infected patients initiating ATV/r-containing ART, using logistic regression we determined factors associated with UTrI, the prevalence of emergent resistance mutations and virological response after ART reinitiation. RESULTS: A total of 202 patients [median age 33 years (interquartile range (IQR) 29-40 years); 52% female; median CD4 count 184 cells/µL (IQR 107-280 cells/µL); median HIV RNA 4.6 log10 HIV-1 RNA copies/mL (IQR 3.2-5.1 copies/mL)] initiated ATV/r between 2004 and 2009; 80 (43%) were ART naïve. One hundred and ten patients (55%) underwent 195 UTrIs after a median (IQR) 25 (10-52) weeks on ART, with a median (IQR) UTrI duration of 10 (3-31) weeks. Fifty-four of 110 patients (49%) underwent more than one UTrI. The commonest reasons for UTrI were nonadherence (52.7%) and drug intolerance (20%). Baseline HIV RNA > 100 000 copies\mL [odds ratio (OR) 3.6; 95% confidence interval (CI) 1.3-9.95] and being HCV positive, an injecting drug user or on methadone (OR 2.4; 95% CI 1.3-4.4) were independently associated with UTrI. In 39 patients with at least two resistance assays during UTrIs, 72 new mutations emerged; four nucleoside reverse transcriptase inhibitor (NRTI), two nonnucleoside reverse transcriptase inhibitor (NNRTI) and 66 protease inhibitor (PI) resistance mutations. All emergent PI resistance mutations were minor mutations. At least 65% of patients were re-suppressed on ATV/r reinitiation. CONCLUSIONS: In this PI-treated cohort, UTrIs are common. All emergent PI resistance mutations were minor and ATV/r retained activity and efficacy when reintroduced, even after several UTrIs, raising questions regarding the need for routine genotypic resistance assays in PI/r-treated patients prior to ART reinitiation after UTrI.

3D isotropic high-resolution diffusion-weighted MRI of the whole brain with a motion-corrected steady-state free precession sequence.

The main obstacle to high-resolution (<1.5 mm isotropic) 3D diffusion-weighted MRI is the differential motion-induced phase error from shot-to-shot. In this work, the phase error is addressed with a hybrid 3D navigator approach that corrects motion-induced phase in two ways. In the first, rigid-body motion is corrected for every shot. In the second, repeatable nonrigid-body pulsation is corrected for each portion of the cardiac cycle. These phase error corrections were implemented with a 3D diffusion-weighted steady- state free precession pulse sequence and were shown to mitigate signal dropouts caused by shot-to-shot phase inconsistencies compared to a standard gridding reconstruction in healthy volunteers. The proposed approach resulted in diffusion contrast more similar to the contrast observed in the reference echo-planer imaging scans than reconstruction of the same data without correction. Fractional anisotropy and Color fractional anisotropy maps generated with phase-corrected data were also shown to be more similar to echo-planer imaging reference scans than those generated without phase correction.

Model for the correction of motion-induced phase errors in multishot diffusion-weighted-MRI of the head: are cardiac-motion-induced phase errors reproducible from beat-to-beat?

In diffusion-weighted imaging, multishot acquisitions are problematic due to intershot inconsistencies of the phase caused by motion during the diffusion-encoding gradients. A model for the motion-induced phase errors in diffusion-weighted-MRI of the brain is presented, in which rigid-body and nonrigid-body motion are separated. In the model, it is assumed that nonrigid-body motion is due to cardiac pulsation, and that the motion patterns are repeatable from beat-to-beat. To test the validity of this assumption, the repeatability of nonrigid-body motion-induced phase errors is quantified in three healthy volunteers. Nonrigid-body motion-induced phase was found to significantly correlate (P < 0.05) with pulse-oximeter waveforms in ~83% of the pixels tested across all slices and subjects.

[The intercontinental schizophrenia outpatient health outcomes study (IC-SOHO): initial 6 month findings of the sample in Latin America]. / Estudio observacional intercontinental de los resultados de salud en pacientes ambulatorios con esquizofrenia (IC-SOHO): hallazgos iniciales de 6 meses de la muestra en Latinoamérica.

The IC-SOHO study was designed to supply information on antipsychotic treatments in the real clinical practice by assessment of a large and diverse sample population with schizophrenia. This document describes the findings of the first 6 months of IC-SOHO in Latin America. To date, this is the largest observational study of its type in this region. In this observational and prospective study, those out-patients with schizophrenia, who require a change or initiation of antipsychotic medication are hospitalized. Effectiveness was evaluated using the Clinical Global Impression-Seriousness (CGI-S) grading scale. Tolerability was assessed by questionnaires on adverse events and weight measurements. Herein, the comparisons between olanzapine (monotherapy), risperidone (monotherapy) and conventional antipsychotics (monotherapy and combined therapy) are presented. As a whole, 7,658 patients participated in the ICSOHO; n=2,671 from 11 countries of Latin America that were included in this report. At 6 months, the proportion of patients who responded to olanzapine was significantly greater than those who responded to risperidone or conventional antipsychotics (p<0.001). Patients from the olanzapine group had greater improvements in all the symptom domains, including general, positive, negative, depressive and cognitive symptoms in comparison with risperidone (p<0.05) or conventional antipsychotics (p < 0.001). Extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) decreased from baseline in the groups treated with olanzapine and risperidone, but increased in the conventional group. The adverse events related with the sexual function were more prominent in the conventional group. Weight gain was observed in each treatment group, although the patients from the olanzapine group had greater weight grain followed by those of risperidone and then by those of conventional antipsychotics. Our findings in this population of the Latin American sample emulate the results of other studies in different samples, where it was found that olanzapine was more effective and better tolerated than risperidone or conventional antipsychotics.

Estudio observacional intercontinental de los resultados de salud en pacientes ambulatorios con esquizofrenia (IC-SOHO): hallazgos iniciales de 6 meses de la muestra en Latinoamérica / The intercontinental schizophrenia outpatient health outcomes study (IC-SOHO): initial 6 month findings of the sample in Latin America

El estudio IC-SOHO se diseñó para aportar información sobre los tratamientos antipsicóticos en la práctica clínica real mediante la evaluación de una población de muestra grande y diversa con esquizofrenia. Este documento describe los hallazgos de los primeros 6 meses del IC-SOHO en Latinoamérica. A la fecha éste es el estudio observacional más grande de su tipo en esta región. En este estudio observacional y prospectivo se ingresaron aquellos pacientes ambulatorios con esquizofrenia que requirieron un cambio o un inicio de medicación antipsicótica. La efectividad se evaluó utilizando la escala de Calificación de Impresión Clínica Global-Gravedad (CGI-S). La tolerabilidad se evaluó mediante cuestionarios de efectos adversos y mediciones de peso. Se presentan aquí las comparaciones entre olanzapina (monoterapia), risperidona (monoterapia) y antipsicóticos convencionales (monoterapia y terapia combinada). En conjunto, participaron 7.658 pacientes en el IC-SOHO; n=2.671 provenientes de 11 países de Latinoamérica se incluyeron en este informe. A los 6 meses la proporción de pacientes que respondieron a la olanzapina fue significativamente mayor que los que respondieron a la risperidona o los antipsicóticos convencionales (p < 0,001). Los pacientes del grupo de olanzapina tuvieron mejorías mayores en todos los dominios de síntomas, incluyendo los síntomas generales, positivos, negativos, depresivos y cognoscitivos, en comparación con la risperidona (p<0,05) o los antipsicóticos convencionales (p<0,001). Los síntomas extrapiramidales (SEP) y la discinesia tardía (DT) disminuyeron desde la línea basal en los grupos tratados con olanzapina y risperidona, pero aumentaron en el grupo convencional. Los efectos adversos relacionados con la función sexual fueron más prominentes en el grupo convencional. Se observó ganancia de peso en cada grupo de tratamiento, aunque los pacientes del grupo de olanzapina aumentaron más de peso, seguidos por los de risperidona y después por los de antipsicóticos convencionales. Nuestros hallazgos en esta población de muestra latinoamericana emulan los resultados de otros estudios en muestras diferentes, donde se encontró que la olanzapina fue más efectiva y mejor tolerada que la risperidona o los antipsicóticos convencionales

The IC-SOHO study was designed to supply information on antipsychotic treatments in the real clinical practice by assessment of a large and diverse sample population with schizophrenia. This document describes the findings of the first 6 months of IC-SOHO in Latin America. To date, this is the largest observational study of its type in this region. In this observational and prospective study, those out-patients with schizophrenia, who require a change or initiation of antipsychotic medication are hospitalized. Effectiveness was evaluated using the Clinical Global Impression- Seriousness (CGI-S) grading scale. Tolerability was assessed by questionnaires on adverse events and weight measurements. Herein, the comparisons between olanzapine (monotherapy), risperidone (monotherapy) and conventional antipsychotics (monotherapy and combined therapy) are presented. As a whole, 7,658 patients participated in the ICSOHO; n=2,671 from 11 countries of Latin America that were included in this report. At 6 months, the proportion of patients who responded to olanzapine was significantly greater than those who responded to risperidone or conventional antipsychotics (p<0.001). Patients from the olanzapine group had greater improvements in all the symptom domains, including general, positive, negative, depressive and cognitive symptoms in comparison with risperidone (p<0.05) or conventional antipsychotics (p < 0.001). Extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) decreased from baseline in the groups treated with olanzapine and risperidone, but increased in the conventional group. The adverse events related with the sexual function were more prominent in the conventional group. Weight gain was observed in each treatment group, although the patients from the olanzapine group had greater weight grain followed by those of risperidone and then by those of conventional antipsychotics. Our findings in this population of the Latin American sample emulate the results of other studies in different samples, where it was found that olanzapine was more effective and better tolerated than risperidone or conventional antipsychotics

Microbiological influences in 'blue water' copper corrosion.

AIMS: To investigate the influence of micro-organisms associated with copper corrosion on 'blue water' corrosion in drinking water. METHODS AND RESULTS: Laboratory rigs comprising of polycarbonate containers attached to annealed copper plumbing tubes were filled with Melbourne drinking water and sterilized by autoclaving. The copper tubes were inoculated with sterile or nonsterile extracts obtained from corroding copper and allowed to stand for 7 days. The extracts were drained and the tubes flushed and filled with sterile water from the rig. The water within the tubes was removed weekly for analysis and the tubes were refilled with freshly aerated water. The tube water sampled was analysed for pH, total copper and the presence of micro-organisms. Sterile rigs and rigs containing nonsterile water, both without tube inoculums, were used as controls. The results demonstrated that tubes inoculated with nonsterile corrosion extracts showed statistically higher copper release compared with the other rigs. Copper release as blue water was only observed after a lag period of 9 weeks. The internal surfaces of tubes releasing copper showed significant amounts of corrosion products and the presence of biofilm. Bacteria isolated from the corroding tubes included Acidovorax spp. and Sphingomonas sp. CONCLUSIONS: The results demonstrate a microbial role in blue water, as corrosion was induced in new copper tubes by exposure to nonsterile copper corrosion products. SIGNIFICANCE AND IMPACT OF THE STUDY: The potential for micro-organisms present in corrosion products to initiate blue water corrosion presents significant implications for the management of corrosion in distribution systems.

Asphyxial death during prone restraint revisited: a report of 21 cases.

Determining the cause of death when a restrained person suddenly dies is a problem for death investigators. Twenty-one cases of death during prone restraint are reported as examples of the common elements and range of variation in these apparently asphyxial events. A reasonable diagnosis of restraint asphyxia can usually be made after ruling out other causes and collecting supportive participant and witness statements in a timely fashion. Common elements in this syndrome include prone restraint with pressure on the upper torso; handcuffing, leg restraint, or hogtying; acute psychosis and agitation, often stimulant drug induced; physical exertion and struggle; and obesity. Establishing a temporal association between the restraint and the sudden loss of consciousness/death is critical to making a correct determination of cause of death.

Age and sex-related variation in hyoid bone morphology.

Although the relationship between hyoid bone shape and fracture pattern figures prominently in forensic investigations of strangulation, few quantitative data exist on age and sex differences in hyoid morphology. An image analysis system was used to take a series of 30 measurements on digitized radiographs of 315 hyoid bones from people of known age and sex. The degree of fusion of the greater cornua to the hyoid body was also recorded. Statistical analysis of these data shows that there is a continuous distribution of hyoid bone shapes and the most bones are highly symmetrical. Based on smaller samples, previous researchers have suggested that non-fusion is more common in women than in men. In contrast, our data suggest that men and women have similar non-fusion rates. Analysis of sexual dimorphism shows that the greatest length differences are in the greater cornua. There are also significant sex differences in hyoid shape. For example, the distal ends of the greater cornua of women are significantly longer than those of men.

Child abuse reports in families with sudden infant death syndrome.

This study investigates the relation between sudden infant death syndrome (SIDS) cases and reports to public child protection service (CPS) agencies of suspected child abuse or neglect prior to the sudden deaths. SIDS data were collected from the Ventura County Medical Examiner's death investigation records of 1981 through 1995. Names of deceased infants, their parents, and any other caretakers who might have been with the infant near the time of death were submitted to the county CPS, where they were referenced for reports of abuse or neglect. A control population of non-SIDS infants and their caretakers were checked in a similar manner. The 150 infants from the control group were compared with 157 SIDS infants; no significant statistical difference was found between groups in the incidence or type of CPS referrals. These findings suggest that screening CPS records for previous referrals is an ineffective method by which to detect infanticides misdiagnosed as SIDS and may cast unwarranted suspicion on otherwise typical SIDS cases.

Restraint asphyxiation in excited delirium.

Eleven cases of sudden death of men restrained in a prone position by police officers are reported. Nine of the men were hogtied, one was tied to a hospital gurney, and one was manually held prone. All subjects were in an excited delirious state when restrained. Three were psychotic, whereas the others were acutely delirious from drugs (six from cocaine, one from methamphetamine, and one from LSD). Two were shocked with stun guns shortly before death. The literature is reviewed and mechanisms of death are discussed.

An accidental death related to cocaine, cocaethylene, and caffeine.

Cocaethylene is often found in body fluids after concurrent use of alcohol and cocaine. Current research is showing that cocaethylene is more toxic than cocaine. The case presented here involves a death that is due to cocaine, cocaethylene, and caffeine. The cocaethylene concentrations found were 0.16 mg/L (blood) and 1.85 mg/L (gastric). Caffeine concentrations were 16.40 mg/L (blood) and 15.40 mg/L (gastric). Cocaine was found only in the gastric sample at a level of 0.45 mg/L. The blood alcohol of the subject was 10 mg/dL. From the case investigation it was determined that the death was accidental but related to the ingestion of cocaine and caffeine tablets. With the combination of alcohol and cocaine use rising, it is becoming evident that the routine screening of medical examiner cases for cocaethylene should be performed.

Autoerotic fatalities with power hydraulics.

We report two cases in which men used the hydraulic shovels on tractors to suspend themselves for masochistic sexual stimulation. One man developed a romantic attachment to a tractor, even giving it a name and writing poetry in its honor. He died accidentally while intentionally asphyxiating himself through suspension by the neck, leaving clues that he enjoyed perceptual distortions during asphyxiation. The other man engaged in sexual bondage and transvestic fetishism, but did not purposely asphyxiate himself. He died when accidentally pinned to the ground under a shovel after intentionally suspending himself by the ankles. We compare these cases with other autoerotic fatalities involving perceptual distortion, cross-dressing, machinery, and postural asphyxiation by chest compression.

Death by embolization of prosthetic aortic valve.

This report describes a case in which a young woman died from embolization of her prosthetic aortic valve. The discussion includes the embolization's association with chronic intravenous narcotism, recurrent bacterial endocarditis, and acute cocaine toxicity.

Autoerotic asphyxial death following television broadcast.

How individuals who engage in autoerotic asphyxial activities first become aware of its purported erotic potential is debated. The case of an adult male who died from autoerotic asphyxiation shortly after watching a television show that discussed sexual asphyxiation is reported. A request is made that medical examiners and coroners report other accidental autoerotic deaths that are temporally associated with this television broadcast.

Age and ossification of the hyoid bone: forensic implications.

Hyoid bones from a medical examiner population were visually and radiographically examined to determine the presence or absence of bony fusion of the greater cornua to the central body. Fusion was found to increase in frequency with age. Hyoid bones fused more frequently in males than in females. Females showed an especially high frequency of unilateral nonfusion.

Three fatalities in flash fire with variable dental charring.

The deaths of three teenagers in an automobile crash and flash fire are presented. The inability to draw valid conclusions about whether the victims were dead prior to the fire based on dental examination is discussed.