Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials.

BACKGROUND: Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment. METHODS: A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics. RESULTS: Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID-19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials. CONCLUSIONS: Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy.

High HIV-1 incidence in young women masked by stable overall seroprevalence among childbearing women in Kinshasa, Zaïre: estimating incidence from serial seroprevalence data.

OBJECTIVE: To describe the dynamics of the HIV-1 epidemic in childbearing women in Kinshasa, Zaïre, by estimating incidence from serial seroprevalence studies. METHODS: In 1986 and 1989, 5937 and 4623 pregnant women, respectively, were screened for HIV-1 in Kinshasa. We estimated age-specific incidence from two seroprevalence surveys by using a birth-year cohort analysis and adjusting for differences in mortality and fertility between HIV-1-infected and uninfected women. Mortality and fertility data were measured in a cohort of women recruited from the survey in 1986 and followed until 1989. RESULTS: While the overall HIV-1 seroprevalence changed little (5.8% in 1986 and 6.5% in 1989; P = 0.17), the prevalence increased in birth-year cohorts of women under 25 years of age in 1989 from 3.2 to 6.2% (P < 0.001), but decreased for women above 25 years of age from 6.9 to 6.7% (P = 0.7). In addition, new HIV infections between 1986 and 1989 were balanced by a higher mortality and lower fertility observed in HIV-infected women. After adjusting for these effects, we estimated an overall 3-year cumulative HIV-1 incidence of 2.8 per 100 uninfected women [95% confidence interval (CI), 1.4-4.2]. The highest incidence, 5.7 per 100 (95% CI, 3.5-8.0), was in women aged 20-24 years in 1989. CONCLUSION: Despite an overall relatively stable HIV-1 prevalence in childbearing women in Kinshasa between 1986 and 1989, approximately 40% of all HIV-1 infections detected in the 1989 survey occurred between 1986 and 1989, and 60% occurred in women under 25 years of age in 1989.

Human immunodeficiency virus infection and stroke in young patients.

OBJECTIVE: To determine the association between human immunodeficiency virus (HIV) infection and stroke among young persons. DESIGN: Retrospective case-control study. SETTING: Large, inner-city public hospital. PARTICIPANTS: All patients aged 19 to 44 years with a diagnosis of stroke, whose HIV status was determined, admitted from January 1990 through June 1994. Controls matched for age and sex were selected from patients who were admitted during the same period for status asthmaticus whose HIV status was known. MAIN OUTCOME MEASURE: The associations of HIV infection with all strokes and with cerebral infarction, after adjustment for other cerebrovascular risk factors, were evaluated by Mantel-Haenszel stratified analyses. The subtypes and causes of stroke in HIV-infected patients were compared with HIV-seronegative patients. RESULTS: The HIV infection was associated with stroke (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.0-5.3) and cerebral infarction (OR, 3.4; 95% CI, 1.1-8.9), after adjustment for other cerebrovascular risk factors. Among patients with stroke, cerebral infarction was more frequent in HIV-infected patients than in HIV-seronegative patients (20 [80%] of 25 vs 48 [56%] of 88, P = .04). The frequency of cerebral infarctions associated with meningitis (P < .001) and protein S deficiency (P = .06) was higher in HIV-infected patients than in seronegative patients. CONCLUSIONS: Our study suggests that HIV infection is associated with an increased risk of stroke, particularly cerebral infarction in young patients. This risk is probably mediated by increased susceptibility of HIV-infected patients to meningitis and protein S deficiency.

The geographic and ethnic diversity of AIDS incidence trends in homosexual/bisexual men in the United States.

We examined geographic and racial/ethnic variation in acquired immune deficiency syndrome (AIDS) incidence in homosexual and bisexual men (i.e., men who report sex with men: MSWM) not using i.v. drugs in the United States. The AIDS incidence in these men has continued to increase in the United States. Incidence increased much less rapidly after 1986 in the three metropolitan statistical areas (MSAs) with the most cases, New York City, Los Angeles, and San Francisco, and may have reached a plateau in these areas. This change in incidence occurred in non-Hispanic black and Hispanic MSWM as well as in non-Hispanic whites in these MSAs, but earlier in whites. There have been similar changes in incidence (but later in time) in all other MSAs with a population of at least 1,000,000 combined, with more tendency toward a plateau in whites than in non-whites. In contrast, incidence increased linearly through 1989 in MSAs with a population less than 1,000,000 and in rural areas, with no change in trend after 1986. Changes in human immunodeficiency virus (HIV) infection incidence before 1985, better therapy and medical care, and migration all contributed to these changes in incidence, as may have changes in reporting. Continued HIV seroconversions among MSWM show that efforts to prevent HIV infection must be continued in all areas of the United States.

The projected incidence of AIDS and estimated prevalence of HIV infection in the United States.

Planning for health and social services and for prevention programs requires predicting the number of AIDS cases likely to be diagnosed during the next several years and estimating the prevalence of HIV infection. Extrapolating from recent AIDS incidence data, we estimate that 365,000 AIDS cases will be diagnosed in the United States through 1992 (68% prediction interval, 205,000 to 440,000). Both recent HIV seroprevalence surveys and historical AIDS incidence are consistent with the U.S. Public Health Service estimate that 1.0 to 1.5 million persons in the United States are now infected with human immunodeficiency virus (HIV). Although current estimates of future AIDS cases and of current prevalence of HIV infection are somewhat uncertain, better statistical estimation procedures are being developed, and current surveys will provide additional data on HIV prevalence in the United States within the next several years.

Changes in AIDS incidence trends in the United States.

Estimating the current prevalence of human immunodeficiency virus (HIV) and projecting the future incidence of AIDS require that trends in incidence be analyzed and interpreted. We analyzed AIDS incidence trends in the United States by exposure category and selected demographic factors. In 1987, the trend in United States AIDS incidence changed as growth in the number of cases diagnosed per quarter began to decline. The slowing in growth is due in large part to a plateau in quarterly incidence in men who have sex with men in the New York City, San Francisco, and Los Angeles metropolitan statistical areas (MSAs), and in injecting drug users in the New York City MSA and New Jersey. Incidence has also reached a plateau in both adult/adolescent and pediatric blood and blood product recipients. Quarterly U.S. AIDS incidence was roughly constant during 1990, but appears to have increased to a higher level during the first half of 1991. The variation in incidence trends among subgroups suggests that several factors have affected the trend in total incidence and that the burden of severe symptomatic HIV disease may be shifting.

Impact of the 1987 revision of the case definition of acquired immune deficiency syndrome in the United States.

To measure the impact of the 1987 expansion of the definition of acquired immune deficiency syndrome on the number and characteristics of cases in the United States, we reviewed the 28,920 cases diagnosed since the revision and reported through 1988. The proportion meeting only new criteria was 28% overall, with a range of 0 to 82% in different states and territories. This proportion was 26% in the last quarter of 1987 and increased to 31% in the last quarter of 1988. It was higher in heterosexual intravenous drug abusers (IVDAs) (43%) and lower in homosexual male non-IVDAs (21%) than in other groups. The new criteria, but not earlier (pre-1985) criteria, generally require a positive test for human immunodeficiency virus (HIV) infection; however, use of HIV testing varies among states, as demonstrated by differences in the percentage of pre-1985-criteria cases with a reported HIV test (39 to greater than 95%). The revision has changed the distribution of characteristics of cases (e.g., heterosexual IVDAs composed 18% of cases meeting old criteria, 35% of cases meeting only new criteria, and 23% of all cases). Interpretation of trends in both the number and characteristics of cases should take into account the variable impact of the revision on reporting.

The seroepidemiology of human immunodeficiency virus in the United States household population: NHANES III, 1988-1991.

To provide an estimate of the seroprevalence of human immunodeficiency virus (HIV) in a representative sample of the U.S. household population, serum samples from participants in the third National Health and Nutrition Examination Survey (NHANES III) were tested for HIV antibody. The testing was performed anonymously on 5,430 individuals 18-59 years old from phase 1 of NHANES III conducted from 1988 to 1991. Twenty-nine individuals were HIV positive. The total weighted prevalence was 0.39%. The population estimate of infected individuals was 547,000, with a 95% confidence interval of 299,000-1,020,000 infected persons. Black participants were four times more likely to be HIV positive than white/other individuals and three times more likely than Mexican Americans. Men were three times more likely to be infected than women. Higher nonresponse to the survey and to phlebotomy was observed in young white men; therefore these data provide a conservative estimate of HIV infection in the general household population. This estimate does not include individuals who do not live in households and who may be at higher risk of infection, such as persons in penal institutions, the homeless, or certain hospitalized patients.

The completeness, validity, and timeliness of AIDS surveillance data.

PURPOSE: To assess the completeness, validity, and timeliness of the AIDS surveillance system after the 1993 change in the surveillance case definition. METHODS: To assess completeness of AIDS case reporting, three study sites conducted a comparison of their AIDS surveillance registries with an independent source of information. To evaluate validity, the same sites conducted record reviews on a sample of reported AIDS cases, we then compared agreement between the original report and the record review for sex, race, and mode of transmission. To evaluate timeliness, we calculated the median delay from time of diagnosis to case report, before and after the change in case definition, in each of the three study sites. RESULTS: After expansion of the case definition, completeness of AIDS case reporting in hospitals (> or = 93%) and outpatient settings (> or = 90%) was high. Agreement between the information provided on the original case report and the medical record was > 98% for sex, > 83% for each race/ethnicity group; and > 67% for each risk group. The median reporting delay after the change was four months, but varied by site from three to six months. CONCLUSIONS: The completeness, validity, and timeliness of the AIDS surveillance system remains high after the 1993 change in the surveillance case definition. These findings might be useful for programs implementing integrated HIV and AIDS surveillance systems.

Autoradiography of protein turnover in subcrestal versus supracrestal fibre tracts of the developing mouse periodontium.

Eighteen-day-old C57Bl mice were injected with 5 muCi/g body weight [3H]-proline and killed at intervals of 4 h to 7 wk later. Grain counts in three fibre tracts revealed that (1) half-lives of labelled protein in the developing periodontium were much shorter than those found previously for the mature periodontium , and (2) the half-life of labelled protein in the dento-gingival region was longer than the half-lives in the trans-septal and dento-alveolar fibre tracts (half-lives: dento-alveolar = 2.5 days, trans-septal = 3.8 days; dento-gingival = 7.9 days). Eight mice were given injections of [3H]-proline on days 11, 13, 15 and 17, which encompasses the formation of the three fibre tracts, and killed 4 h, 2.5, 5 and 8 wk after the last injection. All label incorporated during the formation of the periodontium had been lost by 5 wk post-injection, showing that a stable core fibre (i.e. one which is not metabolized) was not present.

The Young Men's Survey: methods for estimating HIV seroprevalence and risk factors among young men who have sex with men.

Traditional sampling methods are unsuitable for determining the levels of human immunodeficiency virus type I infection and related behavioral risk factors among young men who have sex with men. Most surveys of this hard-to-reach population have used nonprobability samples of young men in clinical or public settings. While these studies have revealed high rates of HIV infection and risk behaviors, their findings are not generalizable to broader populations of young men who have sex with men. To better understand the epidemiology of HIV within this population, the Centers for Disease Control and Prevention, in collaboration with state and local health departments, has developed a venue-based probability survey of young men who have sex with men. Conducted in seven metropolitan areas in the United States, the Young Men's Survey combines outreach techniques with standard methods of sample surveys to enumerate, sample, and estimate prevalence outcomes of a population of young men who frequent public venues and who have sex with other men. Venues where young men who have sex with men are sampled include dance clubs, bars, and street locations. At sampled venues, young men are enumerated, consecutively approached, and offered enrollment if they are determined eligible. Young men who agree to participate in the Young Men's Survey are interviewed, counseled, and tested for human immunodeficiency virus, hepatitis B, and syphilis in vans parked near sampled venues. The Young Men's Survey provides data on the locations and times at which demographic and behavioral subgroups of young men who have sex with men may be targeted for prevention activities. Behaviors and psychosocial factors associated with human immunodeficiency virus infection can be used to design culturally relevant and age-specific prevention activities for young men who have sex with men.

A simulation model of AIDS in San Francisco: II. Simulations, therapy, and sensitivity analysis.

The HIV and AIDS incidences each year for homosexual men in San Francisco are estimated from data. A computer simulation model for HIV transmission dynamics and progression to AIDS is used to reconstruct the HIV epidemic. Using some a priori parameter estimates, simulations are found that give good fits to the incidence data. In the stimulations the populations is divided into risk groups whose sexual activities are found to be strongly connected. There is saturation in the high-risk group, but changes in sexual behavior are more important in obtaining adequate fits. The simulation modeling yields useful parameter estimates, but the remaining uncertainty in parameter values implies that the simulation forecasts are also uncertain. Changes in HIV incidence lead to changes in AIDS incidence about 6-10 years later. Simulation models with and without zidovudine treatment both fit the incidence data; thus the effects of therapy on AIDS incidence are unclear. The fits of the simulation model are most sensitive to the yearly migration rate, the number of stages in the progression to AIDS, and the average number of new sexual partners per month; thus better estimates of these parameters would be desirable.

Human immunodeficiency virus infection in rural areas and small cities of the southeast: contributions of migration and behavior.

The design of education and prevention strategies to stem the spread of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in rural areas depends on having accurate patterns of risk behavior and transmission in local areas. Interviews were conducted with people in rural areas and small cities in Delaware, Florida, Georgia and South Carolina who were at least 18 years old and infected with HIV in order to describe demographic characteristics, migration patterns and risk behaviors. Interviews were conducted with 608 people. Most respondents were male (66 percent), black (63 percent of men, 85 percent of women) and had been infected through sexual contact (67 percent of men, 66 percent of women). Most (65 percent) had lived away from a rural area or small city for at least one month; of those, 71 percent had moved from an urban area. Twenty-seven percent of respondents indicated they had been infected locally. People with a history of injection drug use were less likely to have been infected locally than those who had no history of injection drug use (6 percent vs. 26 percent among men, 3 percent vs. 40 percent among women, P < 0.001). Further understanding of the role of socioeconomic factors in HIV transmission in rural areas and small cities is needed. Programs designed to prevent HIV acquisition among people living in rural areas and small cities in the Southeast should focus on sexual behavior.

Functional properties of mesothelial cells after prolonged exposure to dialysate effluent.

The authors tested in vitro the effect of glucose-based and amino acid-based dialysate effluent on the function of human peritoneal mesothelial cells. After 9 days of exposure to the tested effluents with medium (1:1 v/v) or to a medium supplemented with 10% fetal calf serum (FCS) (control), several functional properties of the cells were studied. The synthesis of DNA measured by incorporation of 3H-methyl-thymidine was higher in mesothelial-cell monolayers exposed to the dialysates than in the controls. Synthesis of hyaluronic acid was similar in all three groups, but after stimulation with Il-1 the cells exposed to the dialysates produced more hyaluronic acid. Synthesis of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) was higher in the control cells. However, after stimulation with IL-1, the cells exposed to the dialysate showed greater synthesis of PAI-1 than of t-PA. Also, procoagulant activity of the control cells was higher than that of the cells exposed to the dialysates. We have concluded that the functional properties of the mesothelial cells may be altered in vitro during prolonged exposure to the dialysate, something that may also occur in vivo.

[Vesico-uterine fistula as a complication after the second cesarean section]. / Przetoka pecherzowo-maciczna jako powiklanie u kobiety po drugim cieciu cesarskim.

The case of vesico-uterine fistula after second Cesarean section is presented. The diagnosis was based on history data, urine examination, histerosalpingography and cystoscopy. Transvesical fistulectomy with good results was performed 6 month after Cesarean section.

[Pregnancy induced changes in lipid-lipoprotein serum profile in women and newborn birth weight]. / Zmieniony ciaza profil lipidowo-lipoproteinowy surowicky kobiet a urodzeniowa masa noworodka.

The pregnancy is associated with hyperlipoproteinemia including an increased level of total cholesterol, LDL-cholesterol, HDL2 and HDL3-cholesterol and triglycerides. The mechanism of pregnancy associated hyperlipoproteinemia remain unclear. The aim of the study was to estimate the relationship between the newborn body mass at delivery and changed by pregnancy lipid-lipoprotein blood profile in women. Studies were carried out in the cases of 67 women. Blood samples were studied at 25 week of pregnancy, during the labor, and at 5th day after delivery. No influence of the pregnancy-changed lipid-lipoprotein pattern of the mothers on the body mass of newborns was found in any of the investigated period.

[The type of material primary hyperlipoproteinemia and newborn birth weight]. / Typ hiperlipoproteinemii pierwotnej matki a masa urodzeniowa noworodka.

Twenty four cases of hyperlipoproteinemia were reported in the investigated group of 67 mother, which delivered behind 38 and 41 week of pregnancy newborns above 2500 g body mass. They were characterized as IIa and IV types according to the WHO classification. Fifteen mothers had HLP of IV type. The average delivery body mass of newborns of these mothers was 3550 g. Nine mothers had HLP of IIa type and these mothers delivered the lightest newborns, average delivery body mass was 3117 g while the average of with normolipidemia mothers was 3238 g. The chi 2 test indicated that the delivery body mass of the newborns is related to the type of hyperlipoproteinemia of mother (p < 0.05).

[Lipid-lipoprotein serum profile of the newborn and its birth weight]. / Profil lipidowo-lipoproteinowy surowicy noworodka a jego masa urodzeniowa.

The sixty-seven newborns were investigated. The umbilical cord blood samples were used to determine following indices: total cholesterol, LDL, HDL2, HDL3-cholesterol, total phospholipids, LDL, HDL-phospholipids, triglycerides and apolipoprotein B. The chi 2 test indicated correlations between increased levels of triglycerides, phospholipids LDL and cholesterol HDL2 and decreased level of cholesterol LDL in the group of newborns with the lowest delivery body mass.

[Spontaneous splenic rupture as a complication of infectious mononucleosis]. / Samoistne pekniecie sledziony w przebiegu mononukleozy zakaznej.

Spontaneous splenic rupture as a complication of infectious mononucleosis in 17-years old man was described. Clinical manifestations of infectious mononucleosis were typical without any sign of the splenic rupture. At the end of third week of the disease sonographic investigation revealed subcapsular hematoma of the spleen without overt rupture. The patient was observed. Five days later in the next sonographic investigation the second hematoma of the spleen appeared. Patient was treated underwent splenectomy and he remain alive and well. Authors suggest that in cases with subcapsular hematoma of the spleen splenectomy remains the treatment of choice. Mononucleosis patients with significant enlarged spleen should be observed very carefully. Authors propose control sonographic investigation in 3rd or 4th week of the disease in those cases.

[Verification of KTG recording in states of perinatal partial asphyxia using fetal capillary blood pH]. / Weryfikacja zapisu KTG w stanach zagrozenia niedotlenieniem okoloporodowym oznaczaniem pH krwi wlosniczkowej plodu.

We analysed 91 cases of pH-metric verifications of pre-pathological and pathological cardiotocograms, which suggested imminent perinatal partial asphyxia. In 50% of cases there was no need for medical intervention, this groups of patients delivered vaginally and newborns were in good condition. In 80% pH value well correlated with state of newborn at birth. Pre-pathological cardiotocograms showed mainly variable decelerations, pH value didn't show acidosis and afterbirth umbilical cord collision was stated. In pathological cardiotocograms we observed mainly late decelerations, pH value showed fetal acidosis which coexisted with placental insufficiency in prolonged gestation.