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PubMed2006

Pregnancy-associated deaths: a 15-year retrospective study and overall review of maternal pathophysiology.

Pregnancy-related death is defined by the International Classification of Diseases, Tenth Revision (ICD-10) as the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death. In the year 2000, a collaborative effort involving World Health Organization (WHO), UNICEF, and UNFPA estimated 660 maternal deaths in the United States. This averages 11 maternal deaths per 100,000 live births reported. Many pregnancy-associated deaths are not easily identified as such since the presence of a recent or current pregnancy may not be listed on the death certificate. Thus, the WHO estimates that in the United States, the maternal mortality is approximately 17/100,000 pregnancies. This is significantly higher than the goal set by the US Department of Health and Human Services in Healthy People 2010, which sets the target for maternal mortality at less than 3.3/100,000 live births. The most common causes of maternal death vary somewhat from region to region in the United States. They include pulmonary thromboembolism, amniotic fluid embolism, primary postpartum uterine hemorrhage, infection, and complications of hypertension including preeclampsia and eclampsia. Pulmonary disease, complications of anesthesia, and cardiomyopathy also are significant contributors to maternal mortality in some populations. The death of a pregnant or recently pregnant individual poses a wide scope of challenges to the forensic pathologist and investigator. The pathologist must have a broad knowledge of the physiologic and biochemical changes that occur during pregnancy, as well as the clinical and pathological manifestation of these changes. Conditions that may be "benign" in the nonpregnant individual may be lethal in the puerperal period. In addition, it should be kept in mind that deaths during pregnancy may be due to unnatural causes. Accident, homicide, and suicide must be ruled out in each case. The authors reviewed all forensic cases referred for autopsy to the Forensic Section of the Medical University of South Carolina from January 1989 through December 2003. All decedents listed as pregnant or postpartum were analyzed as to maternal age, race, past medical history, previous pregnancies and outcome, prenatal care, gestational age, fetal or neonatal outcome, location of delivery, placental findings, maternal autopsy findings, toxicology, cause of death, manner of death, and fetal or neonatal autopsy findings. The authors present this retrospective study to better determine the factors leading to maternal demise and discuss the autopsy/ancillary techniques useful in determining the cause of death in this challenging area.

Adult↗

PubMed1971

Repair of injury in freeze-dried Salmonella anatum.

Repair of injury induced by freeze-drying Salmonella anatum in nonfat milk solids occurred rapidly after rehydration. Injury in surviving cells was defined as the inability to form colonies on a plating medium containing deoxycholate. Death was defined as inability to form colonies in the same medium without this selective agent. The rate of repair of injury was reduced by lowering the temperature from 35 C to 10 C and was extremely low at 1 C. Repair was independent of influence of pH between 6.0 and 7.0. Repair did not require synthesis of protein, ribonucleic acid, or cell wall mucopeptide, but did require energy in the form of adenosine triphosphate (ATP) synthesized through oxidative phosphorylation. The requirement for ATP was based on dinitrophenol or cyanide interference with repair. Dinitrophenol activity was pH-dependent; no repair occurred at pH 6.0 and some repair was observed at pH 6.5 and above. Injured cells were extremely sensitive to low concentrations of ethylenedinitrilotetraacetate. This indicated that freeze-drying injury of S. anatum may involve the lipopolysaccharide portion of the cell wall and that repair of this damage requires ATP synthesis.

Adenosine Triphosphate↗

PubMed2002

[Brain death determination algorithm].

The article overviews the summarized published data concerning determination of brain death in different countries. The paper is based on some foreign guidelines, as well as recent literature. Brain death has been discussed extensively for the last 30 years. Brain death is defined as cessation and irreversibility of all brains function, including brain stem. Brain death is equivalent to death of the individual, even though the heart continues to beat and spinal cord functions may persist. There are no internationally accepted guidelines for diagnosis of brain death. Different sets of criteria, based on the Harvard Medical School criteria (1968), are used in different countries, and have been revised and updated in the recent years. The exact identification of the preconditions is among the most important requirements. The cause of coma has to be known and sufficient to account for the irreversible loss of all brain functions. Coma and apnea must coexist as well as absence of brainstem function. Cultural differences can lead to fundamentally different approaches to brain death determination. Moral, ethical, religious as well as educational factors, including mass media are important in the determination brain death in different countries. Brain death is both a medically and legally important event. In some Western countries, the legal and medical systems have cooperated, while in others only the medical system is working. There are no medical criteria and no legal support in Egypt, many Islamic and African countries. Brain death can usually be diagnosed reliably by clinical criteria alone. However, there are special circumstances when these are not suitable and cannot be applied and confirmatory instrumental test is required for the diagnosis of brain death. In the paper is presented algorithm of the brain death determination developed according to the some foreign guidelines, as well as literature.

Algorithms↗

PubMed2001

Sudden cardiac death in the United States, 1989 to 1998.

BACKGROUND: Sudden cardiac death (SCD) is a major clinical and public health problem. METHODS AND RESULTS: United States (US) vital statistics mortality data from 1989 to 1998 were analyzed. SCD is defined as deaths occurring out of the hospital or in the emergency room or as "dead on arrival" with an underlying cause of death reported as a cardiac disease (ICD-9 code 390 to 398, 402, or 404 to 429). Death rates were calculated for residents of the US aged >/=35 years and standardized to the 2000 US population. Of 719 456 cardiac deaths among adults aged >/=35 years in 1998, 456 076 (63%) were defined as SCD. Among decedents aged 35 to 44 years, 74% of cardiac deaths were SCD. Of all SCDs in 1998, coronary heart disease (ICD-9 codes 410 to 414) was the underlying cause on 62% of death certificates. Death rates for SCD increased with age and were higher in men than women, although there was no difference at age >/=85 years. The black population had higher death rates for SCD than white, American Indian/Alaska Native, or Asian/Pacific Islander populations. The Hispanic population had lower death rates for SCD than the non-Hispanic population. From 1989 to 1998, SCD, as the proportion of all cardiac deaths, increased 12.4% (56.3% to 63.9%), and age-adjusted SCD rates declined 11.7% in men and 5.8% in women. During the same time, age-specific death rates for SCD increased 21% among women aged 35 to 44 years. CONCLUSIONS: SCD remains an important public health problem in the US. The increase in death rates for SCD among younger women warrants additional investigation.

Adult↗

PubMed2000

Apoptotic chondrocyte death in human osteoarthritis.

OBJECTIVE: To define apoptotic chondrocyte death and the expression of Bcl-2, Bax, and Fas in human osteoarthritis (OA) cartilage. METHODS: Cartilage samples were obtained from patients with knee OA at the time of joint replacement surgery and from normal autopsy cases. In OA, sections were obtained both from the lesional area, usually within 1 cm of bony exposure, and from the non-lesional area, which had macroscopically normal appearance or only mild surface irregularities. Apoptosis was verified by microscopic examination of hematoxylin and eosin stained specimens, TUNEL staining, electron microscopy, and DNA ladder analysis by electrophoresis. Immunohistochemistry was done to study the expression of Bcl-2, Bax, and Fas. Apoptotic cells and Bcl-2, Bax, and Fas positive cells were counted within defined microscopic fields. Expression of Bcl-2 and Bax was verified by Western blot. RESULTS: The percentage of apoptotic cells in the lesional area was significantly higher than in the non-lesional area in cartilage from the same patient with OA, while apoptotic cells were rarely seen in normal cartilage. This result was confirmed by TUNEL stain. Many chondrocytes with chromatin condensation were verified in electron microscopy, and DNA from OA lesional cartilage revealed a DNA ladder on electrophoresis. Bcl-2 and Fas expressions were significantly higher in the OA lesional area than in the non-lesional area. On the other hand, Bcl-2 expression in normal cartilage was significantly higher than in OA cartilage. There was no significant difference in Bax expression among normal, OA lesional, and OA non-lesional cartilage. CONCLUSION: These results show that apoptotic chondrocyte death occurs more frequently in OA compared to normal cartilage and in OA lesional compared to OA non-lesional cartilage. The different expression patterns of Bcl-2 and Fas in OA lesional and non-lesional cartilage suggest that they might be involved in the pathogenesis of OA.

Aged↗

PubMed1998

Anti-apoptotic oncogenes prevent caspase-dependent and independent commitment for cell death.

Apoptosis is a morphologically defined type of cell death associated with the activation of certain proteases belonging to the ICE/CED-3 family, known as caspases. Resistance to apoptosis has been implicated as one of the mechanisms that participates in oncogenesis. We found that the broad-spectrum peptide inhibitor of the caspases, zVAD-fmk, interferes in a dose-dependent way with all the morphological and biochemical changes associated with apoptosis induced by anti-CD95 mAb, staurosporine, VP-16 and Act-D. However, with the exception of anti-CD95-triggered apoptosis, the insulted cells lost their clonogenic potential, even when pre-treated with a high dose of zVAD-fmk. Under these circumstances, the dying cells displayed no signs of apoptosis, including activation of caspases, externalization of phosphatidylserine, nuclear condensation, or DNA fragmentation. Instead, this cell death was characterized by cytoplasmic and nuclear vacuolization followed by the loss of plasma membrane integrity. Thus, preventing the onset of apoptosis by blocking caspase activity did not rescue cells from dying in response to drugs such as staurosporine, VP-16 and Act-D. In comparison, ectopic expression of anti-apoptotic oncogenes such as bcl-2 and bcr-abl not only inhibited apoptosis but also preserved the clonogenic potential of the cells. Therefore, oncogenesis is promoted not by simply interfering with caspase-mediated apoptosis, but by preventing an upstream event which we define as the commitment point for cell death.

Amino Acid Chloromethyl Ketones↗

PubMed1997

The outcome of bacterial arthritis: a prospective community-based study.

OBJECTIVE: To assess the outcome and adverse prognostic factors of bacterial arthritis (BA). METHODS: In a prospective community survey of BA, data were collected at the time of diagnosis and at a mean of 2 years later. A poor patient outcome was defined as death due to BA or severe overall functional deterioration. A poor joint outcome was defined as amputation, arthrodesis, prosthetic surgery, or severe functional deterioration. Possible prognostic factors were analyzed by univariate analysis. RESULTS: BA was diagnosed in 154 patients, 121 adults and 33 children. One-half of the adults had a preexisting joint disease and 29% of the infected joints contained synthetic material. The patient outcome was poor in 21% of all patients, and the joint outcome was poor in 33% of the surviving patients. Adverse prognostic factors were an older age, preexisting joint disease, and an infected joint containing synthetic material. These factors were interrelated. There was no association between a poor outcome and young age, comorbidity, immunosuppressive medication, functional class, multiple infected joints, type of microorganism, or treatment delay. CONCLUSION: BA had a poor outcome in almost one-half of the patients. Patients who were older, had a preexisting joint disease, and/or had an infected joint containing synthetic material had the poorest prognosis.

Adult↗

PubMed1999

Innovative uses of a cardiothoracic database.

This report describes the activities of the Northern New England Cardiovascular Disease Study Group. The group consists of representatives from six institutions: Eastern Maine Medical Center in Bangor, and Maine Medical Center in Portland, ME; Optima Health Care in Manchester and Dartmouth-Hitchcock Medical Center in Lebanon, NH; Fletcher Allen Health Care in Burlington, VT; and Beth Israel-Deaconess Medical Center in Boston, MA. The Northern New England Cardiovascular Disease Study Group maintains a voluntary primary cardiac surgical database that has risk-stratified information on more than 60,000 consecutive patients who have undergone open heart surgical procedures in northern New England since 1987. In 1991, the group reported that significant variation in mortality rate existed between centers, a difference not explained by case mix. The finding led to a regional retrospective review of deaths in an effort to identify "mode of death." Mode of death is defined as that event that started the chain of events ultimately leading to the death of the patient. The most common mode of death was found to be low cardiac output syndrome. This information has led to a regional effort toward prevention, early recognition, and successful treatment of low cardiac output syndrome in the perioperative period.

Cardiac Output, Low↗

PubMed2003

Mortality in parents after death of a child in Denmark: a nationwide follow-up study.

BACKGROUND: Little is known about the effect of parental bereavement on physical health. We investigated whether the death of a child increased mortality in parents. METHODS: We undertook a follow-up study based on national registers. From 1980 to 1996, we enrolled 21062 parents in Denmark who had a child who had died (exposed cohort), and 293745 controls--ie, parents whose children were alive, and whose family structure matched that of the exposed cohort. Natural deaths were defined with ICD8 codes 0000-7969 and ICD10 codes A00-R99, and unnatural deaths with codes 8000-9999 and V01-Y98. We used Cox's proportional-hazards regression models to assess the mortality rate of parents up to 18 years after bereavement. FINDINGS: We observed an increased overall mortality rate in mothers whose child had died (hazards ratio 1.43, 95% CI 1.24-1.64; p<0.0001). An excess mortality from natural causes (1.44, 1.15-1.78; p<0.0001) was noted in mothers only during the 10th-18th year of follow-up. Mothers had increased mortality rates from unnatural causes throughout follow-up, with the highest rate recorded during the first 3 years (3.84, 2.48-5.88; p<0.0001). Bereaved fathers had only an early excess mortality from unnatural causes (1.57, 1.06-2.32; p=0.04). Mothers who lost a child due to an unnatural death or an unexpected death had a hazard ratio of 1.72 (1.38-2.15; p=0.0040) and 1.67 (1.37-2.03; p=0.0037), respectively. INTERPRETATION: The death of a child is associated with an overall increased mortality from both natural and unnatural causes in mothers, and an early increased mortality from unnatural causes in fathers.

Adolescent↗

PubMed1997

Postmenopausal hormone therapy and mortality.

BACKGROUND: Postmenopausal hormone therapy has both benefits and hazards, including decreased risks of osteoporosis and cardiovascular disease and an increased risk of breast cancer. METHODS: We examined the relation between the use of postmenopausal hormones and mortality among participants in the Nurses' Health Study, who were 30 to 55 years of age at base line in 1976. Data were collected by biennial questionnaires beginning in 1976 and continuing through 1992. We documented 3637 deaths from 1976 to 1994. Each participant who died was matched with 10 controls alive at the time of her death. For each death, we defined the subject's hormone status according to the last biennial questionnaire before her death or before the diagnosis of the fatal disease; this reduced bias caused by the discontinuation of hormone use between the time of diagnosis of a potentially fatal disease and death. RESULTS: After adjustment for confounding variables, current hormone users had a lower risk of death (relative risk, 0.63; 95 percent confidence interval, 0.56 to 0.70) than subjects who had never taken hormones; however, the apparent benefit decreased with long-term use (relative risk, 0.80; 0.67 to 0.96, after 10 or more years) because of an increase in mortality from breast cancer among long-term hormone users. Current hormone users with coronary risk factors (69 percent of the women) had the largest reduction in mortality (relative risk, 0.51; 95 percent confidence interval, 0.45 to 0.57), with substantially less benefit for those at low risk (13 percent of the women; relative risk, 0.89; 95 percent confidence interval, 0.62 to 1.28). CONCLUSIONS: On average, mortality among women who use postmenopausal hormones is lower than among nonusers; however, the survival benefit diminishes with longer duration of use and is lower for women at low risk for coronary disease.

Adult↗

PubMed2001

The role of alcohol in accident and violent deaths in Finland.

BACKGROUND: In Finland, the high rates of forensic autopsy and postmortem toxicology furnish a reliable base for nation-wide studies on alcohol-related violent deaths. MATERIAL AND METHODS: National mortality and population data within Finland, from 1987 to 1996, were used to analyze sex- and age-specific rates, proportions, and trends of violent deaths associated with alcohol. Deaths were defined as alcohol-related when alcohol was certified as a contributing factor to death. RESULTS: During the study period, 10,360 (23.3%) of the 45,544 violent deaths that occurred were alcohol-related. Among 15- to 64-year-olds, 28.6% of accidents, 30.5% of suicides, and 55.3% of homicides were associated with alcohol (alcohol-positive). Differences in epidemiologic patterns and trends for different types of violent death were observed between sexes and age groups. For instance, alcohol-positive accidents significantly decreased in males (-2.3%/year; CL95: -3.3, -1.2; p < 0.001), but not in females (+0.5%/year; CL95: -2.7, +3.7; p = 0.772), and alcohol-positive suicides increased slightly in females (+3.9%/year; CL95: +0.0, +7.9; p = 0.047), but not in males (-0.2%/year, CL95: -1.4, +1.0; p = 0.704). CONCLUSIONS: The victims of violent deaths have often consumed or abused alcohol before the fatal events. Especially in young adults, consumption of alcohol is likely one of the most serious risk factors in accidents and may decrease the threshold for suicide ideation and impulsive behaviors. Studies that explore the effects of sociodemographic and health factors on random populations with relevant control data will increase the understanding of the causal connection between alcohol and violent deaths.

Accidents↗

PubMed1992

[Circadian variations of sudden death].

Characteristics of the circadian variation for sudden death (SD), were studied by analyzing summary death certificates for the period of 1984 to 1986 in Niigata prefecture. SD was defined as death within 2 hours of onset of underlying cause (n = 4,362), and the time of onset of the cause was determined by subtracting the "time elapsed until death" from the "time of death." The periodicity for time of onset of the cause was analyzed in groups stratified by year, season, sex and age with Rogers' method utilized to check the statistical significance of the periodicity. SD, as a whole, showed a statistically significant circadian variation with a low incidence during 0 to 4 A.M. and a high incidence during 6 to 8 A.M. and 6 to 8 P.M. By season, no significant circadian variation was seen in the summer unlike for other seasons. When analyzed by age group, no significant circadian variation in SD was seen for the young to middle aged group (15-54 years old). On the other hand, there was a significant circadian variation for the senior (55 to 74 years old) and the elderly group (75 years old or older) with a low incidence during 0 to 4 A.M. and high incidence during 6 to 12 A.M. and 6 to 8 P.M.. For the old age group, the number of the cases increased so remarkably as to form an evening peak. The percentage of SD for young to middle cases was higher in the summer than in the other seasons which may be the reason for absence of significant circadian variation in the summer.

Adolescent↗

PubMed1993

The potential organ donor.

The source of most organs for transplantation is the brain-dead cadaveric donor. The realistic potential donor is one for whom mechanical ventilation and other support, to the point of brain death, is provided in the best interests of that patient, and not solely for the purpose of organ donation. Brain death secondary to spontaneous intracranial haemorrhage now exceeds traumatic head injury as a source of organ donors in Australia. There are now few medical exclusions to organ donation. Age limits rise constantly. No patient should be excluded without referral to the transplant coordinator. Adequate medical support of the potential donor is no more than should be provided to the severely brain-injured patient. Haemodynamic and other organ support are as logically appropriate as ventilation and must be continued until confirmation of brain death. Support should cease only if organ donation will not occur. Australian State laws define brain death as irreversible cessation of all function of the brain of the person, but do not dictate the methods of confirmation. The prospect of organ donation should not be raised until brain death is confirmed. The over-riding principle is that the family always has the right to be asked. There is no other way for the family's and patient's wishes about organ donation to be known and respected. It is vital that the person who will ask be experienced, competent and committed. A dedicated medical, nursing and allied health team providing care of the family throughout the period is essential.

Australia↗

PubMed1997

Years of potential life lost due to HIV infection in the United States.

OBJECTIVE: To compare premature mortality due to HIV infection with that from other causes of death in the United States, so as to provide a basis for allocating public health resources among causes of death that would be more useful than either total or age-specific mortality data. METHODS: Using death certificate data, we calculated years of potential life lost (YPLL) before age 65 years for each cause of death. We defined YPLL for an individual as the difference between 65 years and the age at death if the age was < 65 years, or zero if the age was > or = 65 years. The YPLL in the population was the sum of YPLL for individuals. RESULTS: In 1995, HIV infection was the fourth leading cause of YPLL nationally, accounting for 4.7 YPLL per 1000 population (all under age 65 years; 8.8% of the 53.9 YPLL from all causes per 1000 population). Among males, HIV infection ranked fourth (11.0% of YPLL) nationally and in 1994 was the top cause of YPLL in four states: New York (causing 22.7% of YPLL), Florida (18.1%), New Jersey (17.6%) and Maryland (13.9%); and in 51 cities of > or = 100,000 total population, where it caused 12.6-50.9% of YPLL. In 1995, among females, HIV ranked sixth (4.5% of YPLL) nationally and in 1994 was the leading cause of YPLL in 11 cities (11.6-31.4%). CONCLUSION: HIV infection has become the fourth leading cause of premature mortality, measured in terms of YPLL, in the United States and the leading cause in a sizeable number of United States cities.

Adult↗

PubMed2004

[Organizational aspects of organ harvesting in France].

Organ transplantation of kidneys, liver, heart, lungs and pancreas is a routine practice in numerous French surgical centers with very good long-term results. Tissue transplantation of cornea, blood vessels, bone, and cardiac valves has also shown its efficacity and these tissues should be harvested whenever possible. Brain death is defined as the complete and irreversible destruction of the brain stem and cerebral cortex. The diagnosis of brain death is largely clinical but must be confirmed by EEG and cerebral arteriography. The Law of Caillavet has established the concept of "presumed consent" and has defined the judicial framework to permit organ harvesting. Nevertheless, there is still a high level of refusal of organ donation (in a third of cases) by the family of the decedent. At local and regional levels, control and coordination are provided by trained teams in liaison with the French Establishment for Transplantation (Etablissement français de greffes). The number of organ harvests grows steadily (18/million inhabitants in 2001) yet remains insufficient to meet the needs of the ever lengthening list of patients awaiting transplant. The profile of potential donors has also changed with time and poses increasing problems with regard to the quality of harvested organs.

Brain Death↗

PubMed2000

Zidovudine (AZT) versus AZT plus didanosine (ddI) versus AZT plus zalcitabine (ddC) in HIV infected adults.

BACKGROUND: Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. The next two drugs to be developed were didanosine (ddI) and zalcitabine (ddC). OBJECTIVES: To assess the effects of zidovudine (AZT), zidovudine plus didanosine (ddI) and zidovudine plus zalcitabine (ddC) on HIV disease progression and survival. SEARCH STRATEGY: Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts. SELECTION CRITERIA: Randomised controlled trials comparing any two of AZT plus ddI, AZT plus ddC or AZT alone in participants with or without AIDS which collected information on deaths and new AIDS events. DATA COLLECTION AND ANALYSIS: Individual patient data with, wherever possible, follow-up obtained beyond that previously published were obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials. MAIN RESULTS: Six trials were included in the meta-analysis. During a median follow-up of 29 months, 2904 individuals progressed, of whom 1850 died. The addition of ddI to AZT delayed both progression (RR 0.74; 95% CI 0.67 to 0.82, P<0.0001) and death (RR 0.72; 95% CI 0.64 to 0.82, P<0.0001). Likewise, the addition of ddC to AZT also delayed progression (RR 0. 86; 95% CI 0.78 to 0.94, P=0.001) and death (RR 0.87; 95% CI 0.77 to 0.98, P=0.02). After 3 years the estimated percentages alive and without a new AIDS event were 53% for AZT+ddI, 49% for AZT+ddC and 44% for AZT alone; the percentages alive were 68%, 63% and 59% respectively. Five of the six trials involved randomised comparisons of AZT+ddI versus AZT+ddC: in these, the AZT+ddI regimen had greater effects on disease progression (P=0.004) and death (P=0.009). REVIEWER'S CONCLUSIONS: The use of ddI and, to a lesser extent, ddC delayed both HIV disease progression and death, at least when added to AZT.

Adult↗

PubMed2000

Immediate versus deferred zidovudine (AZT) in asymptomatic or mildly symptomatic HIV infected adults.

BACKGROUND: Zidovudine (AZT) monotherapy was the first antiretroviral drug to be tested widely. Subsequent trials in asymptomatic or early symptomatic HIV infection indicated short-term delays in disease progression with AZT, but not improved survival. OBJECTIVES: To assess the effects of immediate versus deferred zidovudine (AZT) on HIV disease progression and survival. SEARCH STRATEGY: Investigators and pharmaceutical companies were contacted, and MEDLINE searches were supplemented by searching conference abstracts. SELECTION CRITERIA: Randomised controlled trials comparing immediate versus deferred AZT in participants without AIDS which prospectively collected deaths and new AIDS events. DATA COLLECTION AND ANALYSIS: Individual patient data with, wherever possible, follow-up obtained beyond that previously published was obtained and checked for internal consistency and consistency with any published reports; any apparent discrepancies were resolved with the trialists. Time to death and to disease progression (defined as a new AIDS-defining event or prior death) were analysed on an intention to treat basis, stratified to avoid direct comparisons between participants in different trials. MAIN RESULTS: Nine trials were included in the meta-analysis. During a median follow-up of 50 months, 1908 individuals developed disease progression, of whom 1351 died. In the deferred group, 61% started antiretroviral therapy (median time to therapy 28 months, which was AZT monotherapy in 94%). During the first year of follow-up immediate AZT halved the rate of disease progression (P<0.0001), increasing the probability of AIDS-free survival at one year from 96% to 98%, but this early benefit did not persist: after 6 years AIDS-free survival was 54% in both groups, and at no time was there any difference in overall survival, which at 6 years was 64% with immediate and 65% with deferred AZT (rate ratio [RR] 1.04, 95% confidence interval [CI] 0. 94 to 1.15). REVIEWER'S CONCLUSIONS: Although immediate use of AZT halved disease progression during the first year, this effect was not sustained, and there was no improvement in survival in the short or long term.

Anti-HIV Agents↗

PubMed2004

Primary stent-supported angioplasty for treatment of below-knee critical limb ischemia and severe claudication: early and one-year outcomes.

OBJECTIVES: The objective of this study was an investigation of the safety and efficacy of primary below-knee stent-supported angioplasty (BKSSA) for restoring straight inline arterial flow in patients with critical limb ischemia (CLI) or lifestyle-limiting claudication (LLC). BACKGROUND: Surgical tibial bypass for CLI and severe LLC is associated with significant morbidity, mortality, and graft failure, whereas percutaneous angioplasty is suboptimal. METHODS: Below-knee stent-supported angioplasty was attempted in 82 patients (92 limbs) with either CLI (68%) or severe LLC (32%). Patients received daily aspirin, thienopyridine, and glycoprotein IIb/IIIa agents during the procedure. One-month major adverse events (MAEs) were defined as death, myocardial infarction, major unplanned amputation, need for surgical revascularization, or major bleeding. Clinical success was defined as improved resting ankle brachial index by > or =0.10, relief of resting pain, healing of ulceration or amputation, and improvement of claudication. RESULTS: Mean age of patients was 74 +/- 17 years. In 86 limbs, straight inline flow was restored to at least one tibial vessel. Technical success was 94% for de novo lesions and there were no MAEs. Ankle brachial indexes increased for all groups (CLI = 0.32 +/- 0.13 to 0.9 +/- 0.14 and LLC = 0.65 +/- 0.09 to 0.95 +/- 0.12; p < or = 0.0001, pre vs. post). Relief of rest pain and healing of ulcerations and amputations were seen in 96% (47 of 49) of patients with CLI who underwent successful intervention. CONCLUSIONS: Below-knee stent-supported angioplasty for CLI and LLC improves ankle brachial indexes comparable to tibial bypass, heals amputations and ulcerations, relieves rest pain, and improves ambulation. Because BKSSA is associated with minimal MAE, it may hold promise as an alternative therapy for patients with CLI and LLC.

Aged↗