The COVID-19 pandemic and children with PANS/PANDAS: an evaluation of symptom severity, telehealth, and vaccination hesitancy.

The current study assessed the impact of the COVID-19 pandemic on children with PANS/PANDAS, a condition characterized by sudden-onset obsessive-compulsive, tic, or restrictive eating symptoms following infection. We conducted an anonymous survey between February and June 2021 of 254 self-reported caregivers of minors with PANS/PANDAS. Caregivers answered questions regarding PANS/PANDAS symptoms, telehealth care, and intention to vaccinate their child against COVID-19. PANS/PANDAS symptoms during COVID-19 infections were assessed when applicable. Children's OCD symptoms and coercive behaviors towards caregivers, along with the caregivers' mental health, relationship satisfaction, and burden, were assessed using standardized questionnaires. A majority of respondents endorsed a negative impact on their child's friendships, relationships with extended family, hobbies, and academic skills due to the pandemic. Children with suspected or diagnosed COVID-19 experienced new or worsened psychiatric symptoms, particularly mood lability, OCD, and anxiety. Telehealth care was the preferred treatment modality if the child had mild symptoms of PANS/PANDAS. A majority of caregivers reported high levels of relationship dissatisfaction and caregiver burden. As expected, these data suggest an overall negative impact of the COVID-19 pandemic on children with PANS/PANDAS and their caregivers.

Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine.

BACKGROUND: The RTS,S/AS01 vaccine targets the circumsporozoite protein of Plasmodium falciparum and has partial protective efficacy against clinical and severe malaria disease in infants and children. We investigated whether the vaccine efficacy was specific to certain parasite genotypes at the circumsporozoite protein locus. METHODS: We used polymerase chain reaction-based next-generation sequencing of DNA extracted from samples from 4985 participants to survey circumsporozoite protein polymorphisms. We evaluated the effect that polymorphic positions and haplotypic regions within the circumsporozoite protein had on vaccine efficacy against first episodes of clinical malaria within 1 year after vaccination. RESULTS: In the per-protocol group of 4577 RTS,S/AS01-vaccinated participants and 2335 control-vaccinated participants who were 5 to 17 months of age, the 1-year cumulative vaccine efficacy was 50.3% (95% confidence interval [CI], 34.6 to 62.3) against clinical malaria in which parasites matched the vaccine in the entire circumsporozoite protein C-terminal (139 infections), as compared with 33.4% (95% CI, 29.3 to 37.2) against mismatched malaria (1951 infections) (P=0.04 for differential vaccine efficacy). The vaccine efficacy based on the hazard ratio was 62.7% (95% CI, 51.6 to 71.3) against matched infections versus 54.2% (95% CI, 49.9 to 58.1) against mismatched infections (P=0.06). In the group of infants 6 to 12 weeks of age, there was no evidence of differential allele-specific vaccine efficacy. CONCLUSIONS: These results suggest that among children 5 to 17 months of age, the RTS,S vaccine has greater activity against malaria parasites with the matched circumsporozoite protein allele than against mismatched malaria. The overall vaccine efficacy in this age category will depend on the proportion of matched alleles in the local parasite population; in this trial, less than 10% of parasites had matched alleles. (Funded by the National Institutes of Health and others.).

International outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder - USA and Canada, 2013-2014.

Salmonella is a leading cause of bacterial foodborne illness. We report the collaborative investigative efforts of US and Canadian public health officials during the 2013-2014 international outbreak of multiple Salmonella serotype infections linked to sprouted chia seed powder. The investigation included open-ended interviews of ill persons, traceback, product testing, facility inspections, and trace forward. Ninety-four persons infected with outbreak strains from 16 states and four provinces were identified; 21% were hospitalized and none died. Fifty-four (96%) of 56 persons who consumed chia seed powder, reported 13 different brands that traced back to a single Canadian firm, distributed by four US and eight Canadian companies. Laboratory testing yielded outbreak strains from leftover and intact product. Contaminated product was recalled. Although chia seed powder is a novel outbreak vehicle, sprouted seeds are recognized as an important cause of foodborne illness; firms should follow available guidance to reduce the risk of bacterial contamination during sprouting.

A pan-Canadian practice guideline and algorithm: screening, assessment, and supportive care of adults with cancer-related fatigue.

PURPOSE: The purpose of the present systematic review was to develop a practice guideline to inform health care providers about screening, assessment, and effective management of cancer-related fatigue (crf) in adults. METHODS: The internationally endorsed adapte methodology was used to develop a practice guideline for pan-Canadian use. A systematic search of the literature identified a broad range of evidence: clinical practice guidelines, systematic reviews, and other guidance documents on the screening, assessment, and management of crf. The search included medline, embase, cinahl, the Cochrane Library, and other guideline and data sources to December 2009. RESULTS: Two clinical practice guidelines were identified for adaptation. Seven guidance documents and four systematic reviews also provided supplementary evidence to inform guideline recommendations. Health professionals across Canada provided expert feedback on the adapted recommendations in the practice guideline and algorithm through a participatory external review process. CONCLUSIONS: Practice guidelines can facilitate the adoption of evidence-based assessment and interventions for adult cancer patients experiencing fatigue. Development of an algorithm to guide decision-making in practice may also foster the uptake of a guideline into routine care.

Feasibility of direct venous inoculation of the radiation-attenuated Plasmodium falciparum whole sporozoite vaccine in children and infants in Siaya, western Kenya.

PfSPZ Vaccine, composed of radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, is administered by direct venous inoculation (DVI) for maximal efficacy against malaria. A critical issue for advancing vaccines that are administered intravenously is the ability to efficiently administer them across multiple age groups. As part of a pediatric safety, immunogenicity, and efficacy trial in western Kenya, we evaluated the feasibility and tolerability of DVI, including ease of venous access, injection time, and crying during the procedure across age groups. Part 1 was an age de-escalation, dose escalation trial in children aged 13 months-5 years and infants aged 5-12 months; part 2 was a vaccine efficacy trial including only infants, using the most skilled injectors from part 1. Injectors could use a vein viewer, if needed. A total of 1222 injections (target 0.5 mL) were initiated by DVI in 511 participants (36 were 5-9-year-olds, 65 were 13-59-month-olds, and 410 infants). The complete volume was injected in 1185/1222 (97.0%) vaccinations, 1083/1185 (91.4%) achieved with the first DVI. 474/511 (92.8%) participants received only complete injections, 27/511 (5.3%) received at least one partial injection (<0.5 mL), and in 10/511 (2.0%) venous access was not obtained. The rate of complete injections by single DVI for infants improved from 77.1% in part 1 to 92.8% in part 2. No crying occurred in 51/59 (86.4%) vaccinations in 5-9-year-olds, 25/86 (29.1%) vaccinations in 13-59-month-olds and 172/1067 (16.1%) vaccinations in infants. Mean administration time ranged from 2.6 to 4.6 minutes and was longer for younger age groups. These data show that vaccination by DVI was feasible and well tolerated in infants and children in this rural hospital in western Kenya, when performed by skilled injectors. We also report that shipping and storage in liquid nitrogen vapor phase was simple and efficient. (Clinicaltrials.gov NCT02687373).

In-vivo efficacy of amodiaquine-artesunate in children with uncomplicated Plasmodium falciparum malaria in western Kenya.

OBJECTIVES: To assess the efficacy of amodiaquine-artesunate in an area with high chloroquine resistance in western Kenya. METHODS: Twenty-eight day in-vivo efficacy trial of amodiaquine-artesunate in 103 children aged 6-59 months in western Kenya with smear-confirmed uncomplicated Plasmodium falciparum malaria. RESULTS: The 28-day uncorrected adequate clinical and parasitological response (ACPR) was 69.0%, with 15.5% Late Clinical Failure and 15.5% Late Parasitologic Failure rates. The PCR-corrected 28-day ACPR was 90.2%. Clinical risk factors for recurrent infection (recrudescences and reinfections) were lower axillary temperature at enrollment and low weight-for-age Z-score. The presence of single nucleotide polymorphisms pfcrt 76T and pfmdr1 86Y at baseline was associated with increased risk of recurrent infections, both reinfections and recrudescences. CONCLUSION: Although artemether-lumefantrine (Coartem) is the first line ACT in Kenya, amodiaquine-artesunate is registered as an option for treatment of uncomplicated P. falciparum and remains an effective alternative to Coartem in western Kenya. Continued amodiaquine monotherapy in the private sector may jeopardize the future use of amodiaquine-artesunate as an alternative artemisinin-based combination therapy.

Daily trimethoprim-sulfamethoxazole prophylaxis rapidly induces corresponding resistance among intestinal Escherichia coli of HIV-infected adults in Kenya.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMZ) has been recommended by World Health Organization (WHO) as daily prophylaxis for Africans with AIDS to prevent opportunistic infections. Daily TMP-SMZ may reduce its susceptibility to commensal intestinal Escherichia coli (E coli), increasing the burden of TMP-SMZ-resistant pathogens. METHODS: Participants received either daily TMP-SMZ (CD4 <350 cells/mm(3)) or daily multivitamins (MVIs; CD4 > or =350 cells/mm(3)) for 6 months. Stool was collected at baseline, 2 weeks, 2 months, and 6 months. A random E coli was tested for susceptibility. RESULTS: Baseline prevalence of TMP-SMZ resistance ranged from 71% to 81% and was not different across CD4 strata. At 2 weeks, prevalence of TMP-SMZ-resistant E coli increased significantly from 78% to 98% (P < .001) among persons taking daily TMP-SMZ and did not change among persons taking MVIs. CONCLUSIONS: Daily prophylaxis with TMP-SMZ induced in vivo resistance to the drug after 2 weeks. Empiric therapy for diarrhea with agents other than TMP-SMZ should be considered for HIV-infected persons receiving daily TMP-SMZ prophylaxis.

[Exercise therapy in the treatment of chronic back pain. An integral part of interdisciplinary therapy]. / Medizinische Trainingstherapie beim chronischen Rückenschmerz. Ein integraler Bestandteil der interdisziplinären Therapie.

Chronic low back pain requires interdisciplinary and biopsychosocial treatment. Apart from the medical, psychological, and physiotherapeutic aspects of therapy, exercise therapy is an important component. Together with"work hardening," it represents the elements for reconditioning. The isolated effect is scientifically difficult to specify with the available data, but in most analytical studies, exercise therapy is an important component in an interdisciplinary setting. A nonspecific, diversified training program is superior to exercise solely of the trunk muscles. The primary tasks are to recover load capacity and diminish pain-avoidance behaviors, with consideration of the principles of"functional restoration." Thorough information and cooperation with the patient, continuous motivation, ratio control, a systematic increase in load, and permanent feedback are necessary. Close communication within the team makes immediate accompanying interventions of other specialized groups possible.

["Work hardening" for chonic back pain. An integral component of multimodal therapy programs]. / "Work hardening" bei chronischen Rückenschmerzen. Ein integraler Bestandteil multimodaler Therapieprogramme.

Work hardening is aimed at a reestablishment of the potentials needed in occupational everyday life. Fundamental motor abilities, such as strength, stability, flexibility and persistence, are restored and merged into the everyday life so that psychological contents, such as fear avoidance behavior will be positively affected. The design of work hardening is interdisciplinary in the sense of a holistic approach to back pain. Handling the pain under load requires sophisticated treatment and the training demands a high degree of individual design. A trusting and mutual agreement between therapist and patient is essential. Work hardening represents an important part of the therapy of chronic back pain and greatly supports regaining confidence in the physical efficiency and the ability to control the body.

Causes of deaths using verbal autopsy among adolescents and adults in rural western Kenya.

OBJECTIVE: To establish causes and patterns of deaths among adolescents and adults (age >11 years) using verbal autopsy (VA) in a rural area of western Kenya where malaria and HIV are common. METHODS: Village reporters reported all deaths in Asembo and Gem (population 135 000), an area under routine demographic surveillance. After an interval of >/=1 month, a trained interviewer used a structured questionnaire to ask the caretaker about signs and symptoms that preceded death. Three clinical officers independently reviewed the interviews and assigned two unranked causes of death; a common cause was designated as the cause of death. RESULTS: In 2003, 1816 deaths were reported from residents; 48% were male and 72% were between 20 and 64 years of age. Most residents (97%) were ill before death, with 60% of illnesses lasting more than 2 months; 87% died at home. Care was sought by 96%; a health facility was the most common source, visited by 73%. For 1759 persons (97%), a common cause of death was designated. Overall, 74% of deaths were attributed to infectious causes. HIV (32%) and tuberculosis (TB) (16%) were the most frequent, followed by malaria, respiratory infections, anaemia and diarrhoeal disease (approximately 6% each). Death in a health facility was associated with young age, higher education, higher SES, a non-infectious disease cause and a shorter duration of illness. CONCLUSION: In this area, the majority of adult and adolescent deaths were attributed to potentially preventable infectious diseases. Deaths in health facilities were not representative of deaths in the community. Programmes to prevent HIV and TB infection and to decrease mortality have started. Their impact can be evaluated against this baseline information.

Patient characteristics associated with care by a cardiologist among adults hospitalized with severe congestive heart failure. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

OBJECTIVES: The goal of this study was to determine factors associated with receiving cardiologist care among patients with an acute exacerbation of congestive heart failure. BACKGROUND: Because cardiologist care for acute cardiovascular illness may improve care, barriers to specialty care could impact patient outcomes. METHODS: We studied 1,298 patients hospitalized with acute exacerbation of congestive heart failure who were cared for by cardiologists or generalist physicians. Using multivariable logistic models we determined factors independently associated with attending cardiologist care. RESULTS: Patients were less likely to receive care from a cardiologist if they were black (adjusted odds ratio [AOR] 0.53, 95% confidence interval [CI] 0.35, 0.80), had an income of less than $11,000 (AOR 0.65, 95% CI 0.45, 0.93) or were older than 80 years of age (AOR 0.23, 95% CI 0.12, 0.46). Patients were more likely to receive cardiologist care if they had college level education (AOR 1.89, 95% CI 1.02, 3.51), a history of myocardial infarction (AOR 1.59, 95% CI 1.17, 2.16), a serum sodium less than 133 on admission (AOR 1.96, 95% CI 1.30, 2.95) or a systolic blood pressure less than 90 on admission (AOR 1.97, 95% CI 1.20, 3.24). Patients who stated a desire for life extending care were also more likely to receive care from a cardiologist (AOR 1.40, 95% CI 1.04, 1.90). CONCLUSIONS: After adjusting for severity of illness and patient preferences for care, patient sociodemographic factors were strongly associated with receiving care from a cardiologist. Future investigations are required to determine whether these associations represent unmeasured preferences for care or inequities in our health care system.

An overview of foodborne outbreaks in Canada reported through Outbreak Summaries: 2008-2014.

BACKGROUND: Enteric outbreak investigation in Canada is performed at the local, provincial/territorial (P/T) and federal levels. Historically, routine surveillance of outbreaks did not occur in all jurisdictions and so the Public Health Agency of Canada, in partnership with P/T public health authorities, developed a secure, web-based Outbreak Summaries (OS) Reporting System to address this gap. OBJECTIVE: This analysis summarizes the foodborne outbreak investigations reported to the OS Reporting System between 2008 and 2014. METHODS: Finalised reports of investigations between 2008 and 2014 for all participating jurisdictions in Canada were extracted and descriptive analysis was carried out for foodborne outbreaks on etiological agent, severity of illness, outbreak duration, exposure setting and outbreak source. RESULTS: There were 115 reported foodborne outbreaks included in the analysis. This represents 11.2% of all outbreaks reported in the enteric module of the OS Reporting System between 2008 and 2014. Salmonella was the most commonly reported cause of foodborne outbreak (40.9%) and Enteritidis was the most common serotype reported. Foodborne outbreaks accounted for 3,301 illnesses, 225 hospitalizations and 30 deaths. Overall, 38.3% of foodborne outbreaks were reported to have occurred in a community and 32.2% were associated with a food service establishment. Most foodborne outbreak investigations (63.5%) reported a specific food associated with the outbreak, most frequently meat. CONCLUSION: The OS Reporting System supports information sharing and collaboration among Canadian public health partners and offers an opportunity to obtain a national picture of foodborne outbreaks. This analysis has demonstrated the utility of the OS Reporting System data as an important and useful source of information to describe foodborne outbreak investigations in Canada.

Clinical and methodological factors related to reliability of the best-estimate diagnostic procedure.

OBJECTIVE: The reliability and accuracy of the best-estimate diagnostic procedure were examined, and factors associated with reliability were determined. METHOD: The subjects were 134 members of large multigenerational pedigrees densely affected by bipolar disorders or schizophrenia. Three best-estimate diagnoses were derived: first, by a research psychiatrist and research assistant unblind to the relatives' diagnoses; second, by two blind independent psychiatrists; third, by a panel of four blind psychiatrists. The subjects were characterized on several clinical and methodological variables, which were used to compare the agreements of two types of best-estimate diagnoses with the disagreements. RESULTS: There was satisfactory agreement between the unblind and blind consensus best-estimate diagnoses and between the two blind independent psychiatrists. Latent class analyses revealed that limited sensitivity was the main source of imperfect reliability. Confusability analyses revealed that the most problematic diagnostic distinctions involved schizoaffective disorder, which was confused with schizophrenia, bipolar I disorder, and schizophreniform disorder. Blindness significantly affected diagnostic outcome in latent class analyses. Moreover, for diagnostic disagreements, unblind diagnoses had greater continuity with the most predominant diagnosis in the pedigree than did blind diagnoses. Diagnostic disagreements were associated with the presence of mixed affective and psychotic symptoms, less diagnostic certainty, and shorter duration of illness. CONCLUSIONS: These results suggest that it is possible to identify cases that are more likely to lead to diagnostic disagreements in family and epidemiological studies and that blind diagnoses may help to prevent false positive diagnoses, which may be particularly detrimental to genetic linkage analyses.

Solid-phase antigen density and avidity of antibodies detected in anti-group B streptococcal type III IgG enzyme immunoassays.

Two enzyme immunoassays which measure anti-group B streptococcal type III capsular carbohydrate IgG antibodies were compared. One utilised poly-L-lysine conjugated coating antigen while the other used tyraminated coating antigen. Both carbohydrate antigens appeared to be antigenically identical but the poly-L-lysine based assay gave significantly lower values for some sera. Sera were identified which had low and high avidity anti-group B streptococcal type III IgG antibodies by the thiocyanate elution method. These antibodies gave results on a dilution range of coating concentrations consistent with their relative avidity. Comparison of dilution ranges of the two conjugates used for coating suggests that the poly-L-lysine conjugate coats with a ten-fold lower efficiency than the tyramine conjugate and therefore detects only higher avidity antibodies. Four fractions containing different relative avidities of affinity-purified IgG were produced from a single serum. These fractions behaved in the same manner as sera containing antibodies of different avidities. The results of this study suggest that the method of polysaccharide conjugation in enzyme immunoassays may affect the antigen concentration on the solid phase and thence the detection of antibodies of various avidities.

A comparison of generalist and pulmonologist care for patients hospitalized with severe chronic obstructive pulmonary disease: resource intensity, hospital costs, and survival. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatment.

PURPOSE: Both generalist and pulmonologist physicians care for patients with severe chronic obstructive pulmonary disease (COPD). We studied patients hospitalized with severe COPD to explore whether supervision of care by pulmonologists is associated with greater costs or better survival. SUBJECTS AND METHODS: We studied 866 adults with severe COPD enrolled in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT), a prospective study at five academic medical centers. Patients were admitted to the hospital or transferred to an intensive care setting for treatment of severe COPD, defined by hypoxia (PaO2 <60 mm Hg) and hypercapnia (PaCO2 >50 mm Hg) or hypercapnia alone if on supplemental oxygen. Resource intensity was measured using a modified version of the Therapeutic Intervention Scoring System and estimated hospital costs. To account for differences in the patient case mix, propensity scores were developed to represent each patient's probability of having a pulmonologist as attending physician and each patient's probability of being in an intensive care unit (ICU) at study admission. RESULTS: Of the 866 patients studied, 512 had generalists and 354 pulmonologists as their attending physicians. The median patient age was 70 years; 52% were male; 14% died within 30 days. After adjusting for baseline differences in patient characteristics, there were no differences in resource intensity and hospital costs in those treated by pulmonologists or generalists. Adjusted average resource intensity scores for the entire hospitalization were 16.5 for pulmonologists and 17.0 for generalists (P = 0.34). Estimated hospital costs were the same ($6,400) for patients treated by pulmonologists and generalists (P = 0.99). Patients with pulmonologists as attending physicians did not experience better survival. Comparing patients of pulmonologists to patients of generalists, the adjusted hazard ratio for 30-day mortality was 1.6 (95% confidence interval: 0.98, 2.5); the hazard ratio for 180-day mortality was 1.2 (0.9, 1.7). CONCLUSIONS: Our findings suggest that for patients hospitalized with exacerbation of severe COPD, those with pulmonologist attending physicians do not have higher hospital resource use or better survival than those with generalist attending physicians.

Outcomes and cost-effectiveness of ventilator support and aggressive care for patients with acute respiratory failure due to pneumonia or acute respiratory distress syndrome.

PURPOSE: Many patients with acute respiratory failure die despite prolonged and costly treatment. Our objective was to estimate the cost-effectiveness of providing rather than withholding mechanical ventilation and intensive care for patients with acute respiratory failure due to pneumonia or acute respiratory distress syndrome. SUBJECTS AND METHODS: We studied 1,005 patients enrolled in a five-center study of seriously ill patients (the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments [SUPPORT]) with acute respiratory failure (pneumonia or acute respiratory distress syndrome and an Acute Physiology Score > or =10) who required ventilator support. We estimated life expectancy based on long-term follow-up of SUPPORT patients. Utilities were estimated using time-tradeoff questions. Costs (in 1998 dollars) were based on hospital fiscal data and Medicare data. RESULTS: Of the 963 patients who received ventilator support, 48% survived for at least 6 months. At 6 months, survivors reported a median of 1 dependence in activities of daily living, and 72% rated their quality of life as good, very good, or excellent. Among the 42 patients in whom ventilator support was withheld, the median survival was 3 days. Among patients whose estimated probability of surviving at least 2 months from the time of ventilator support ("prognostic estimate") was 70% or more, the incremental cost per quality-adjusted life-year (QALY) saved by providing rather than withholding ventilator support and aggressive care was $29,000. For medium-risk patients (prognostic estimate 51% to 70%), the incremental cost-effectiveness was $44,000 per QALY, and for high-risk patients (prognostic estimate < or =50%), it was $110,000 per QALY. When assumptions were varied from 50% to 200% of baseline estimates, the results ranged from $19,000 to $48,000 for low-risk patients, from $29,000 to $76, 000 for medium-risk patients, and from $67,000 to $200,000 for high-risk patients. CONCLUSIONS: Ventilator support and intensive care for acute respiratory failure due to pneumonia or acute respiratory distress syndrome are relatively cost-effective for patients with >50% probability of surviving 2 months. However, for patients with an expected 2-month survival < or =50%, the cost per QALY is more than threefold greater at >$100,000.

Patient race and decisions to withhold or withdraw life-sustaining treatments for seriously ill hospitalized adults. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

PURPOSE: Patient race is associated with decreased resource use for seriously ill hospitalized adults. We studied whether this difference in resource use can be attributed to more frequent or earlier decisions to withhold or withdraw life-sustaining therapies. SUBJECTS AND METHODS: We studied adults with one of nine illnesses that are associated with an average 6-month mortality of 50% who were hospitalized at five geographically diverse teaching hospitals participating in the Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT). We examined the presence and timing of decisions to withhold or withdraw ventilator support and dialysis, and decisions to withhold surgery. Analyses were adjusted for demographic characteristics, prognosis, severity of illness, function, and patients' preferences for life-extending care. RESULTS: The mean (+/- SD) age of the patients was 63 +/- 16 years; 16% were African-American, 44% were women, and 53% survived for 6 months or longer. Of the 9,076 patients, 5,349 (59%) had chart documentation that ventilator support had been considered in the event the patient's condition required such a treatment to sustain life, 2,975 charts (33%) had documentation regarding major surgery, and 1,293 (14%) had documentation of discussions about dialysis. There were no significant differences in the unadjusted rates of decisions to withhold or withdraw treatment among African-Americans compared with non-African-Americans: among African-Americans, 33% had a decision made to withhold or withdraw ventilator support compared with 35% among other patients, 14% had a decision made to withhold major surgery compared with 12% among other patients, and 25% had a decision made to withhold or withdraw dialysis compared with 30% among other patients (P >0.05 for all comparisons). After adjustment for demographic characteristics, prognosis, illness severity, function, and preferences for care, there were no differences in the timing or rate of decisions to withhold or withdraw treatments among African-Americans compared with non-African-American patients. CONCLUSION: Patient race does not appear to be associated with decisions to withhold or withdraw ventilator support or dialysis, or to withhold major surgery, in seriously ill hospitalized adults.

Outcomes, preferences for resuscitation, and physician-patient communication among patients with metastatic colorectal cancer. SUPPORT Investigators. Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments.

PURPOSE: To describe characteristics, outcomes, and decision making in patients with colorectal cancer metastatic to the liver, and to examine the relationship of doctor-patient communication with patient understanding of prognosis and physician understanding of patients' treatment preferences. PATIENTS AND METHODS: The Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments (SUPPORT) was a prospective cohort study conducted at five teaching hospitals in the United States between 1989 and 1994. Participants in this study were hospitalized patients 18 years of age or older with known liver metastases who had been diagnosed with colorectal cancer at least 1 month earlier. Data were collected by patient interview and chart review at study entry; patients were interviewed again at 2 and 6 months. Data collected by physician interview included estimates of survival and impressions of patients' preferences for cardiopulmonary resuscitation (CPR). Patients and physicians were also asked about discussions about prognosis and resuscitation preferences. RESULTS: We studied 520 patients with metastatic colorectal cancer (median age 64, 56% male, 80% white, 2-month survival 78%, 6-month survival 56%). Quality of life (62% "good" to "excellent") and functional status (median number of disabilities = 0) were high at study entry and remained so among interviewed survivors at 2 and 6 months. Of 339 patients with available information, 212 (63%) of 339 wanted CPR in the event of a cardiopulmonary arrest. Factors independently associated with preference for resuscitation included younger age, better quality of life, absence of lung metastases, and greater patient estimate of 2-month prognosis. Of the patients who preferred not to receive CPR, less than half had a do-not-resuscitate note or order written. Patients' self-assessed prognoses were less accurate than those of their physicians. Physicians incorrectly identified patient CPR preferences in 30% of cases. Neither patient prognostication nor physician understanding of preferences were significantly better when discussions were reported between doctors and patients. CONCLUSIONS: A majority of patients with colorectal cancer have preferences regarding end of life care. The substantial misunderstanding between patients and their physicians about prognosis and treatment preferences appears not to be improved by direct communication. Future research focused on enhancing the effectiveness of communication between patients and physicians about end of life issues is needed.

A novel high throughput screening assay for HCV NS3 helicase activity.

A novel assay for measurement of Hepatitis C virus (HCV) NS3 helicase activity was developed using Flashplate technology. This assay involves the use of a DNA duplex substrate and recombinant HCV NS3 produced in Escherichia coli. The DNA duplex consisted of a pair of oligonucleotides, one biotinylated, the other radiolabeled at their respective 5' termini. This DNA duplex was immobilized, via the biotin molecule, on the surface of a neutravidin-coated SMP103 Flashplate (NEN Life Science Products). Helicase activity results in the release of the radiolabeled oligonucleotide, which translates in signal reduction with respect to control wells. Biochemical characterization of the HCV NS3 helicase activity was performed using this assay. We demonstrated that the NS3-mediated unwinding is proportional to both the amount of DNA substrate in the well, and to the NS3 concentration in the reaction. Most of the NS3-mediated unwinding was achieved in the initial 60 min of incubation. As expected the reactions were ATP-dependent and found to be affected by the concentration of MgCl(2), MnCl(2), KCl, EDTA, and by pH. We found this assay to be highly reproducible since only slight variation was observed when a total of 68 helicase reactions were performed on one plate. Therefore, this Flashplate helicase assay is fast, convenient and reproducible. These criteria make it suitable for high throughput screening of potential NS3 helicase inhibitors.

Elderly persons' last six months of life: findings from the Hospitalized Elderly Longitudinal Project.

BACKGROUND: Few studies describe the end of life in very old people. OBJECTIVES: To characterize the last 6 months of life and dying in patients 80 years and older by describing demographic characteristics, functional state and quality of life, symptoms, preferences, use of life-sustaining treatments, satisfaction with care, and family burden. DESIGN: A retrospective analysis for patients enrolled in a prospective cohort study. SETTING: Four teaching hospitals who participated in the Hospitalized Elderly Longitudinal Project (HELP). SUBJECTS: 417 patients who died within 1 year of their enrollment hospitalization. MEASUREMENTS: Chart reviews and interview data with patients and surrogates at several points in time. We constructed four observational time windows backward in time beginning with the patients' death. RESULTS: Before hospitalization, two out of three patients reported fair quality of life, and patients averaged 2.4 impairments in activities of daily living. Seventy percent preferred comfort care on the third day of hospitalization. During the last month of life, three of five patients interviewed in the hospital and four of five interviewed out of the hospital preferred not to be resuscitated. At the time of death, four of five patients had a do not resuscitate (DNR) order and two of five had an order to withhold a ventilator. During the last month of life, one out of four patients reported severe pain. CONCLUSIONS: Patients reported increasing functional impairments and limited quality of life. The majority preferred comfort care. The number of patients in severe pain was substantial. Before death, the majority had measures in place to limit aggressive care.