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PubMed2002

Adverse cardiac events in emergency department patients with chest pain six months after a negative inpatient evaluation for acute coronary syndrome.

OBJECTIVE: To evaluate the impact of the diagnostic test setting-inpatient versus outpatient-on adverse cardiac events (ACEs) after six months in emergency department (ED) patients with chest pain who were admitted to the hospital and subsequently had a negative evaluation for acute coronary syndrome (ACS). METHODS: The authors retrospectively studied a consecutive sample of ED patients with chest pain over a nine-month period. All patients were admitted to the hospital and underwent negative evaluations for ACS, defined as the absence of diagnostic changes on serial electrocardiograms or cardiac markers (creatine kinase-MB and troponin T), and a negative diagnostic cardiac study. Subjects were classified according to cardiac diagnostic study setting-either inpatient or outpatient. Diagnostic testing included exercise treadmill, angiography, stress echocardiography, or stress thallium scans. Acute cardiac events at six months were defined as cardiac death, myocardial infarction, unstable angina, cardiac arrest, or emergent revascularization. RESULTS: The six-month rate of ACEs among 157 subjects was 14%, with 2% cardiac mortality. The outpatient group had higher ACE risk when compared with the inpatient group using multivariate logistic regression, both for the entire cohort (OR 3.5, p < 0.03) and for a subgroup excluding patients with prior coronary artery disease (OR 6.7, p < 0.05). The outpatient group included 19 of 52 (37%) noncompliant subjects who did not receive a diagnostic study. CONCLUSIONS: Long-term cardiac morbidity of patients after a negative ACS evaluation may be higher than previously thought. Risk of ACE is significantly higher in subjects scheduled for outpatient diagnostic tests. Inpatient diagnostic testing is justified for subjects at risk for poor compliance.

Adult↗

PubMed1997

A prospective study of oral lesions and their predictive value for progression of HIV disease.

OBJECTIVE: This report evaluates and compares individual oral lesions and combinations of lesions in predicting progression-free survival in a seroprevalent cohort of men and women with HIV infection. DESIGN: This was a prospective study of HIV-infected patients, initially AIDS-free, followed for approximately 30 months. SETTING: Patients were volunteers examined at an academic medical center and at an inner-city hospital in New York. Participants identified themselves as homosexual men or as injection drug users (IDU). OUTCOME MEASURES: The primary outcome being assessed is time from a baseline oral examination until the development of an AIDS-defining condition or death from any cause within 12 months of the last study visit. Correlation is measured by relative risk (RR). RESULTS: While oral lesions were not predictive of progression among subjects with CD4 > or = 200, they were highly predictive of progression among those with CD4 < 200. For subjects with CD4 < 200, the only individual lesion that was significantly associated with progression-free survival was oral candidiasis (RR = 4.12, P = 0.009). Positivity for one or more lesions in a set demonstrated greater prognostic value among those with CD4 < 200, with RR's of 6.03 (P = 0.018) for the set consisting of oral candidiasis, hairy leukoplakia, and necrotizing ulcerative gingivitis (NUG), and 8.77 (P = 0.036) for the set consisting of the above lesions plus linear gingival erythema (LGE). Analysis by cohort suggested that the improvement in correlation was stronger in homosexual men than in IDU, but this question could not be resolved conclusively with these data. CONCLUSIONS: Lesion sets might be better prognosticators of progression-free survival than individual lesions among HIV-infected subjects with CD4 < 200. Prognostic value of the core lesion set (oral candidiasis and hairy leukoplakia) was enhanced by the addition of other lesions (NUG and LGE) not usually included in HIV staging systems. These results suggest that staging systems for HIV might be improved by the inclusion of other, survival-related oral lesions.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Androgens prevent normally occurring cell death in a sexually dimorphic spinal nucleus.

The spinal nucleus of the bulbocavernosus (SNB) contains many more motoneurons in adult male rats than in females. Androgens establish this sex difference during a critical perinatal period, which coincides with normally occurring cell death in the SNB region. Sex differences in SNB motoneuron number arise primarily because motoneuron loss is greater in females than in males during the early postnatal period. Perinatal androgen treatment in females attenuates cell death in the SNB region, reducing motoneuron loss to levels typical of males. The results suggest that steroid hormones determine sex differences in neuron number by regulating normally occurring cell death and that the timing of this cell death may therefore define critical periods for steroid effects on neuron number.

Androgens↗

PubMed1979

Intoxication of cells from different-aged embryos by diphtheria toxin.

Different methods were used to assay diphtheria toxin sensitivity of fibroblast and heart cell cultures from chicken embryos of various ages. As defined by inhibition of protein synthesis, fibroblasts from 18-day and younger embryos respond more rapidly to toxin than fibroblasts from older embryos. The response of heart cells cultures is independent of the age of the embryos and is similar to the response of fibroblasts from 18-day embryos. Since the EF-2 content is 10-fold less in fibroblasts from 21-day-old embryos, the different responses of protein synthesis to intoxication appear to reside at the membrane level. Cytotoxicity assays in cell culture and in vivo toxin sensitivity assays show that cells from both young and old embryos, as well as whole embryos, are equally sensitive to toxin. Thus, short-term (5-h) measurements of inhibition of protein synthesis are insufficient for determining the relative sensitivity of cells to intoxication as defined by cell death.

Animals↗

PubMed1997

Role of early and late replication events in induction of apoptosis by baculoviruses.

Autographa californica nuclear polyhedrosis virus (AcMNPV) mutants that lack the apoptotic suppressor gene p35 cause apoptosis in Spodoptera frugiperda SF21 cells. To identify a viral signal(s) that induces programmed cell death, we first defined the timing of apoptotic events during infection. Activation of a P35-inhibitable caspase, intracellular fragmentation of host and AcMNPV DNA, and cell membrane blebbing coincided with the initiation of viral DNA synthesis between 9 and 12 h after infection and thus suggested that apoptotic signaling begins at or before this time. Virus entry was required since binding of budded virus to host cell receptors alone was insufficient to induce apoptosis. To therefore determine the contribution of early and late replication events to apoptotic signaling, we used the AcMNPV mutant ts8 with a temperature-sensitive lesion in the putative helicase gene p143. At the nonpermissive temperature at which viral DNA synthesis was conditionally blocked, ts8 caused extensive apoptosis of the SF21 cell line p3576D, which dominantly interferes with anti-apoptotic function of viral P35. Confirming that apoptosis can be induced in the absence of normal viral DNA synthesis, parental SF21 cells also underwent apoptosis when infected with a ts8 p35 deletion mutant at the nonpermissive temperature. However, maximum levels of ts8 p35 deletion mutant-induced apoptosis required a temperature-sensitive event(s) that included the initiation of viral DNA synthesis. Collectively, these data suggested that baculovirus-induced apoptosis can be triggered by distinct early (pre-DNA synthesis) and late replicative events, including viral DNA synthesis or late gene expression.

Animals↗

PubMed1994

HIV disease progression in 854 women and men infected through injecting drug use and heterosexual sex and followed for up to nine years from seroconversion. Italian Seroconversion Study.

OBJECTIVE: To compare the progression of HIV-1 infection in men and women followed up for up to nine years after an accurately estimated date of seroconversion. DESIGN: Prospective observational study. SETTING: 16 HIV outpatient clinics across Italy. SUBJECTS: 321 women and 533 men infected with HIV through injecting drug use or heterosexual sex and with accurately estimated dates of seroconversion. MAIN OUTCOME MEASURES: Progression to severe CD4 lymphocytopenia (CD4 lymphocyte count < 200 x 10(6)/l), development of AIDS defining diseases, and death from AIDS. RESULTS: Thirty two women and 67 men developed AIDS at Kaplan-Meier progression rates of 25% (95% confidence interval 13.8% to 35.5%) and 23% (15.6% to 30.4%), respectively, 7 years after seroconversion. In a Cox proportional hazards model the relative hazard was 0.93 (that is, a slightly lower hazard in women) before and 1.10 (0.70 to 1.72) after adjusting for age, HIV exposure group, and year of seroconversion. When CD4 lymphocytopenia and death from AIDS were used as end points the results were similar, with adjusted relative hazards of 0.95 (0.63 to 1.42) and 0.72 (0.48 to 1.79) respectively. In both women and men the risk of developing AIDS before the CD4 lymphocyte count had declined below 200 x 10(6)/l was small (3% in women, 6% in men). The estimated median count at which AIDS developed in women (34 x 10(6)/l; 10 x 10(6) to 44 x 10(6)) was similar to that for men (44 x 10(6)/l; 22 x 10(6) to 60 x 10(6)). CONCLUSION: There seems to be little evidence for appreciable differences in the natural course of HIV infection between men and women followed up from the time of seroconversion.

Acquired Immunodeficiency Syndrome↗

PubMed2002

Systematic review of long term effects of advice to reduce dietary salt in adults.

OBJECTIVE: To assess the long term effects of advice to restrict dietary sodium in adults with and without hypertension. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Cochrane library, Medline, Embase, and bibliographies. STUDY SELECTION: Unconfounded randomised trials that aimed to reduce sodium intake in healthy adults over at least 6 months. Inclusion decisions, validity and data extraction were duplicated. Random effects meta-analysis, subgrouping, sensitivity analysis, and meta-regression were performed. OUTCOMES: Mortality, cardiovascular events, blood pressure, urinary sodium excretion, quality of life, and use of antihypertensive drugs. RESULTS: Three trials in normotensive people (n=2326), five trials in those with untreated hypertension (n=387), and three trials in people being treated for hypertension (n=801) were included, with follow up from six months to seven years. The large high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported. There were 17 deaths, equally distributed between intervention and control groups. Systolic and diastolic blood pressures were reduced (systolic by 1.1 mm Hg, 95% confidence interval 1.8 to 0.4 mm Hg; diastolic by 0.6 mm Hg, 1.5 to -0.3 mm Hg) at 13 to 60 months, as was urinary 24 hour sodium excretion (by 35.5 mmol/24 hours, 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related. CONCLUSIONS: Intensive interventions, unsuited to primary care or population prevention programmes, provide only small reductions in blood pressure and sodium excretion, and effects on deaths and cardiovascular events are unclear. Advice to reduce sodium intake may help people on antihypertensive drugs to stop their medication while maintaining good blood pressure control.

Adolescent↗

PubMed1994

Serious paracetamol poisoning and the results of liver transplantation.

Paracetamol poisoning is the most common cause of fulminant liver failure in the United Kingdom. An accurate assessment of prognosis at the time of referral will allow the appropriate application of liver transplantation in this setting. The outcome of 92 patients consecutively admitted to a specialist liver unit with severe poisoning has been examined. In patients who did not have a transplant, a fatal outcome was seen for 26/82 (32%), and was associated with late presentation, coma grade, prothrombin time prolongation, metabolic acidosis, and renal dysfunction. Cerebral oedema, and sepsis were responsible for most deaths. Prognostic criteria defined at King's College Hospital seemed to predict the outcome of patients who did not have a transplant managed on the Birmingham liver unit. Seventeen patients were listed for transplantation, 10 had liver transplantation, and seven of 10 survived. Seven were listed but not transplanted, and one of seven survived. Psychological rehabilitation of patients who had a transplant has not proved difficult. These results suggest a role for liver transplantation in the management of selected patients with paracetamol poisoning.

Acetaminophen↗

PubMed2005

Roller coaster related fatalities, United States, 1994--2004.

OBJECTIVE: To determine the number of fatalities related to roller coasters and examine factors common to multiple incidents. METHODS: A case was defined as the death of a person, which was associated with a roller coaster in the United States between 15 May 1994 and 14 May 2004. Cases were identified from four DATA SOURCES: (1) Consumer Product Safety Commission, (2) Lexis-Nexis, (3) Medline, and (4) Safer parks. RESULTS: Forty people, ranging in age from 7 to 77 years, were killed in 39 separate incidents. Twenty nine (73%) deaths occurred among roller coaster patrons. Eleven fatalities resulted from external causes related to injuries from falls or collisions. Eighteen people died from medical conditions that might have been caused or exacerbated by riding a roller coaster; 15 were the result of intracranial hemorrhages or cardiac problems. Eleven (28%) deaths involved employees; all were caused by injuries. CONCLUSIONS: Approximately four deaths annually in the United States are associated with roller coasters. Prevention of roller coaster fatalities is dependent on establishing an effective surveillance system for amusement ride injuries, engineering rides to better protect both patrons and employees, improving training and supervision of employees regarding safety precautions, and posting cautionary notices near roller coasters for people with specified medical conditions. Further research is needed on roller coaster related deaths resulting from intracranial hemorrhages and cardiac problems.

Accidents, Occupational↗

PubMed2002

Comparison of short (3-day) hospitalization followed by home care treatment and conventional (10-day) hospitalization for acute ischemic stroke.

This prospective randomized controlled study was designed to compare the treatment efficacy, safety and quality of life of ischemic stroke patients treated with conventional (10-day) hospitalization or short (3-day) hospitalization followed by home care treatment. One hundred and two patients with acute ischemic stroke who arrived within 48 h after symptom onset and met the inclusion criteria were studied. Patients were randomly assigned to either of two groups of treatment. Patients in the 'hospitalization' group were hospitalized for 10 days, whereas those in the 'home care' group were admitted only for the first 3 days and were followed at home under the home care program. The baseline characteristics were similar in the two groups. There was no difference in the number of deaths or dependency defined by the Modified Rankin scale more than or equal to 3 between the two groups at 6 months. The relative risk was 0.85 with a 95% confidence interval between 0.35 and 2.04. There was also no difference in the number of patients who had good outcome (NIHSS between 0 and 2 and Barthel index between 75 and 100) at 6 months. One patient in the home care group died due to massive intracerebral hemorrhage. Seventy-nine percent of patients in the home care group were satisfied with the home treatment program.

Adult↗

PubMed2004

Treatment of left anterior descending coronary artery disease with sirolimus-eluting stents.

BACKGROUND: Revascularization strategies often hinge on the presence and degree of left anterior descending coronary artery (LAD) stenosis. A decision for bypass surgery is often based on the durability of surgical LAD revascularization compared with percutaneous approaches. By decreasing restenosis, drug-eluting stents may have reduced the "reintervention gap" between surgery and percutaneous intervention, making the percutaneous route preferable. METHODS AND RESULTS: Of the 1101 patients in the SIRIUS trial, 459 with an LAD stenosis were randomized to percutaneous intervention with either sirolimus-eluting or bare-metal stents. Baseline demographic, clinical, and angiographic data were obtained. Patients had 1-year clinical and 8-month angiographic follow-up. Baseline characteristics were similar in both groups. The majority of lesions were tubular type B lesions (69.7%) with a mean diameter of 2.73 mm and a mean length of 14.0 mm. The binary in-stent restenosis rate was 2% for the sirolimus stent group and 41.6% for the bare-metal arm (relative risk, 0.05; 95% CI, 0.02 to 0.1; P<0.001). One-year major adverse events (defined as cardiac death, Q-wave and non-Q-wave myocardial infarction, or target vessel revascularization) was decreased 59% in the sirolimus-stent group (9.8% versus 24.9%; relative risk, 0.39; 95% CI, 0.26 to 0.61; P<0.001). Subgroup analysis of 135 patients with proximal LAD lesions showed similar benefits. In-stent restenosis was 0 in the proximal LAD sirolimus-eluting group (n=67), compared with 38% in the bare-metal arm (n=68), and major adverse events demonstrated a similar trend, with a 50% decrease compared with control patients (10.4% versus 20.6%, P=NS). CONCLUSIONS: Sirolimus-eluting stents significantly decrease revascularization rates in LAD lesions. At 1 year, sirolimus-eluting stent revascularization rates are comparable to historic single vessel bypass surgery revascularization rates.

Aged↗

PubMed1995

Effect of thromboxane A2 blockade on clinical outcome and restenosis after successful coronary angioplasty. Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART II)

BACKGROUND: Antithromboxane therapy with aspirin reduces acute procedural complications of coronary angioplasty (PTCA) but has not been shown to prevent restenosis. The effect of chronic aspirin therapy on long-term clinical events after PTCA is unknown, and the utility of more specific antithromboxane agents is uncertain. The goal of this study was to assess the effects of aspirin (a nonselective inhibitor of thromboxane A2 synthesis) and sulotroban (a selective blocker of the thromboxane A2 receptor) on late clinical events and restenosis after PTCA. METHODS AND RESULTS: Patients (n = 752) were randomly assigned to aspirin (325 mg daily), sulotroban (800 mg QID), or placebo, started within 6 hours before PTCA and continued for 6 months. The primary outcome was clinical failure at 6 months after successful PTCA, defined as (1) death, (2) myocardial infarction, or (3) restenosis associated with recurrent angina or need for repeat revascularization. Neither active treatment differed significantly from placebo in the rate of angiographic restenosis: 39% (73 of 188) in the aspirin-assigned group, 53% (100 of 189) in the sulotroban group, and 43% (85 of 196) in the placebo group. In contrast, aspirin therapy significantly improved clinical outcome in comparison to placebo (P = .046) and sulotroban (P = .006). Clinical failure occurred in 30% (49 of 162) of the aspirin group, 44% (73 of 166) of the sulotroban group, and 41% (71 of 175) of the placebo group. Myocardial infarction was significantly reduced by antithromboxane therapy: 1.2% in the aspirin group, 1.8% in the sulotroban group, and 5.7% in the placebo group (P = .030). CONCLUSIONS: Thromboxane A2 blockade protects against late ischemic events after angioplasty even though angiographic restenosis is not significantly reduced. While both aspirin and sulotroban prevent the occurrence of myocardial infarction, overall clinical outcome appears superior for aspirin compared with sulotroban. Therefore, aspirin should be continued for at least 6 months after coronary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed1998

Personality, disease severity, and the risk of long-term cardiac events in patients with a decreased ejection fraction after myocardial infarction.

BACKGROUND: Patients with myocardial infarction (MI) with a decreased left ventricular ejection fraction (LVEF) have a poor prognosis, but the role of emotional stress in prognosis is not known. We hypothesized that emotional stress in these patients (1) is unrelated to the severity of cardiac disorder, (2) predicts cardiac events, and (3) is a function of basic personality traits. METHODS AND RESULTS: Eighty-seven patients with MI (age, 41 to 69 years) with an LVEF of < or =50% underwent psychological assessment at baseline. Patients and their families were contacted after 6 to 10 years (mean, 7.9 years); cardiac events were defined as cardiac death or nonfatal MI. Emotional distress was unrelated to the severity of cardiac disorder. At follow-up, 21 patients had experienced a cardiac event (13 fatal events). These events were related to LVEF of < or =30%, poor exercise tolerance, previous MI, anxiety, anger, and depression (all P< or =.02). Patients with a distressed personality (type D; ie, the tendency to suppress negative emotions) were more likely to experience an event over time compared with non-type D patients (P=.00005). Cox proportional hazards analysis yielded LVEF of < or =30% (relative risk, 3.0; 95% confidence interval, 1.2 to 7.7; P=.02) and type D (relative risk, 4.7; 95% confidence interval, 1.9 to 11.8; P=.001) as independent predictors. Anxiety, anger, and depression did not add to the predictive power of type D; these negative emotions were highly correlated and reflected the personality domain of negative affectivity. CONCLUSIONS: Personality influences the clinical course of patients with a decreased LVEF. Emotional distress in these patients is unrelated to disease severity but reflects individual differences in personality. Clinical trials should take a broad view of the target of intervention; assessment of LVEF and personality may identify patients at risk.

Adult↗

PubMed2006

B-type natriuretic peptide predicts adverse cardiovascular events in pediatric outpatients with chronic left ventricular systolic dysfunction.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) levels are elevated in adults with heart failure and correlate with functional classification and prognosis. The range and predictive power of BNP concentrations in children with chronic heart failure, however, are not known. METHODS AND RESULTS: Whole blood BNP concentrations were measured in 53 consecutive patients with chronic left ventricular (LV) systolic dysfunction (biventricular hearts, ejection fraction < 50%, > 3 months since diagnosis). Children who had been hospitalized within 3 months before potential enrollment and those < 2 months or > 21 years of age were excluded. BNP concentrations were measured with the Triage assay (Biosite Diagnostics, Inc, San Diego, Calif). Echocardiographers and clinicians were blinded to BNP levels. An adverse cardiovascular event was defined as cardiac death, cardiac-related hospitalization, or listing for cardiac transplantation. The median age of patients with LV dysfunction was 9.3 years (interquartile range [IQR], 2.7 to 15.1 years). BNP levels were elevated in children with LV dysfunction compared with healthy controls (median, 78 pg/mL [IQR, 22 to 551 pg/mL] versus median, 7 pg/mL [IQR, 5 to 11 pg/mL]; P < 0.0001). Whole blood BNP concentrations were increased in patients who had a 90-day adverse cardiovascular event compared with those who did not (median, 735 pg/mL [IQR, 685 to 1510 pg/mL] versus median, 37 pg/mL [IQR, 14 to 92 pg/mL]; P < 0.001). Patients with a BNP concentration > or = 300 pg/mL were at increased risk of death, hospitalization, or listing for cardiac transplantation (adjusted hazard ratio, 63.6; P < 0.0001). CONCLUSIONS: BNP concentrations are elevated in children with chronic LV systolic dysfunction and predict the 90-day composite end point of death, hospitalization, or listing for cardiac transplantation.

Adolescent↗

PubMed2005

In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells.

Due to its relatively slow clinical progression, B cell chronic lymphocytic leukemia (B-CLL) is classically described as a disease of accumulation rather than proliferation. However, evidence for various forms of clonal evolution suggests that B-CLL clones may be more dynamic than previously assumed. We used a nonradioactive, stable isotopic labeling method to measure B-CLL cell kinetics in vivo. Nineteen patients drank an aliquot of deuterated water (2H2O) daily for 84 days, and 2H incorporation into the deoxyribose moiety of DNA of newly divided B-CLL cells was measured by gas chromatography/mass spectrometry, during and after the labeling period. Birth rates were calculated from the kinetic profiles. Death rates were defined as the difference between calculated birth and growth rates. These analyses demonstrated that the leukemic cells of each patient had definable and often substantial birth rates, varying from 0.1% to greater than 1.0% of the entire clone per day. Those patients with birth rates greater than 0.35% per day were much more likely to exhibit active or to develop progressive disease than those with lower birth rates Thus, B-CLL is not a static disease that results simply from accumulation of long-lived lymphocytes. Rather, it is a dynamic process composed also of cells that proliferate and die, often at appreciable levels. The extent to which this turnover occurs has not been previously appreciated. A correlation between birth rates and disease activity and progression appears to exist, which may help identify patients at risk for worsening disease in advance of clinical deterioration.

Aged↗

PubMed2003

Care for perinatal illness in rural Nepal: a descriptive study with cross-sectional and qualitative components.

BACKGROUND: Maternal, perinatal and neonatal mortality rates remain high in rural areas of developing countries. Most deliveries take place at home and care-seeking behaviour is often delayed. We report on a combined quantitative and qualitative study of care seeking obstacles and practices relating to perinatal illness in rural Makwanpur district, Nepal, with particular emphasis on consultation strategies. METHODS: The analysis included a survey of 8798 women who reported a birth in the previous two years [of whom 3557 reported illness in their pregnancy], on 30 case studies of perinatal morbidity and mortality, and on 43 focus group discussions with mothers, other family members and health workers. RESULTS: Early pregnancy was often concealed, preparation for birth was minimal and trained attendance at birth was uncommon. Family members were favoured attendants, particularly mothers-in-law. The most common recalled maternal complications were prolonged labour, postpartum haemorrhage and retained placenta. Neonatal death, though less definable, was often associated with cessation of suckling and shortness of breath. Many home-based care practices for maternal and neonatal illness were described. Self-medication was common.There were delays in recognising and acting on danger signs, and in seeking care beyond the household, in which the cultural requirement for maternal seclusion, and the perceived expense of care, played a part. Of the 760 women who sought care at a government facility, 70% took more than 12 hours from the decision to seek help to actual consultation. Consultation was primarily with traditional healers, who were key actors in the ascription of causation. Use of the government primary health care system was limited: the most common source of allopathic care was the district hospital. CONCLUSIONS: Major obstacles to seeking care were: a limited capacity to recognise danger signs; the need to watch and wait; and an overwhelming preference to treat illness within the community. Safer motherhood and newborn care programmes in rural communities, must address both community and health facility care to have an impact on morbidity and mortality. The roles of community actors such as mothers-in-law, husbands, local healers and pharmacies, and increased access to properly trained birth attendants need to be addressed if delays in reaching health facilities are to be shortened.

Journal Article↗

PubMed1982

Effect of inbreeding on juvenile mortality in some small mammal species.

In breeding records for 12 species of small mammals from 9 families in 3 orders, individuals with an inbreeding coefficient of 0 were classified as non-inbred, those with inbreeding coefficients greater than 0 as inbred. Juvenile mortality was defined as all deaths prior to 1/2 of the age of sexual maturity for each species. It was significantly higher for inbred than for noninbred animals in 11 of the 12 species using a 1-tailed sign test, and by Fisher's exact test in 3 species. Monodelphis domestica, Wiedomys pyrrhorhinos and and Dolichotis salinicola. The higher mortality of inbred young of the species with the largest sample size, Elephantulus rufescens, was irrespective of litter size and of the parity of the dam.

Age Factors↗

PubMedDate not supplied

A randomized clinical trial comparing nelfinavir and ritonavir in patients with advanced HIV disease (CPCRA 042/CTN 102).

PURPOSE: To compare the long-term clinical efficacy and toxicity of initial strategies of nelfinavir (NFV) or ritonavir (RTV) in patients with CD4+ cells below 200/mm3. METHOD: This was an open-label randomized multicenter trial (CPCRA, CTN). Patients were naïve to protease inhibitor use except for hard gel saquinavir. Patients who were intolerant to their assigned therapy were allowed to switch arms (later RTV-intolerant patients could switch to indinavir). The primary objective was to compare the regimens for AIDS-defining conditions and death (AIDS/death) using intent-to-treat analysis. Hazard ratios (HR) for NFV and RTV were estimated using Cox's proportional hazards models. Kaplan-Meier life table summaries were also used to compare the two groups. RESULTS: There were 775 patients who were randomized beginning in January 1997 and followed through December 2001. At entry, mean CD4+ cell count was 58 cells/mm3 and HIV RNA level averaged 4.9 log copies/mL. After a median follow-up of 52 months, rates of AIDS/death were 12.7 and 11.0 per 100 person years for the NFV and RTV groups, respectively (HR=1.16; 95% CI, 0.92-1.46; p=.21). Discontinuations occurred earlier in the RTV group (p=.0001). CONCLUSION: There are moderate differences in efficacy and large differences in tolerability between a strategy of initial NFV or RTV in patients with advanced disease. Finding the right balance between potency and tolerability remains a challenge.

Adult↗