Effective Preventive Regimens Research Articles

Pharmacological prevention strategy for capecitabine‐induced hand‐foot syndrome: A network meta‐analysis of randomized control trials

Capecitabine-induced hand-foot syndrome (HFS) is common in clinical practice. There are many regimens used to prevent HFS. However, the most effective preventive regimen has not yet been identified. Thus, we conducted a network meta-analysis to investigate the best preventive regimen for HFS. The PRISMA-NMA guidelines were used in this study. The PubMed, Cochrane, and Embase databases were searched. The main endpoint was set as HFS of National Cancer Institute grade 2 or more. We included only randomized control trials. The P-score was used to rank the regimens. Among all the regimens, topical silymarin had the best preventive ability compared with the placebo (OR: 0.08; 95% CI: 0.01-0.71). The other identified effective regimen included pyridoxine (400 mg) and celecoxib; compared with the placebo, the odds ratio was 0.27 (95% CI: 0.08-0.91) and 0.41 (95% CI: 0.18-0.95), respectively. Topical silymarin is the most useful regimen for preventing capecitabine-induced HFS.

Global Epidemiology of HIV/AIDS: A Resurgence in North America and Europe

We aimed to assess global trends in Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) and evaluate progress toward eradication since the inception of the pandemic. Data were extracted from the Global Burden of Disease 2019 update and the UNAIDS Data 2019. The datasets included annual figures from 1990 to 2019 for HIV/AIDS in 204 countries and all world regions. We analyzed rates and trends for prevalence, incidence, mortality and disability adjusted life years. Analysis of age and gender distribution in different regions was used to assess demographic changes. Forecasting was used to estimate disease burden up to 2040. Although many countries have witnessed a decrease in the incidence, for Russia, Ukraine, Portugal, Brazil, Spain and the United States, the rates of new cases are rising since 2010. This trend is present even in age-standardized analysis, indicating a rise in excess of population growth. Over 0.5% of the world’s population is infected. About 5000 new infections occur daily, of which 500 are children. Mortality rates are falling globally; currently at 11 deaths per 100,000 population, forecasted to decrease to 8.5 deaths by 2040. Prevalence continues to increase, with South Africa, Nigeria, Mozambique, India, Kenya and the United States having the highest burden. The total number as well as the rates of new HIV infections are rising every year in Europe, South America, North America and other regions over the last decade. Maternal-to-child transmission continues at high rates despite effective preventive regimens. There is an urgent need to develop programs to curb the rising incidence of HIV.

The Prevention of Tooth Wear

With adult dentitions being retained for longer, issues relating to the wear of teeth are increasingly becoming of relevance to the general dental practitioner. As with any treatment plan, prevention is a fundamental and an important stage in the management of tooth wear. This article outlines the contemporary preventive features that the general dental practitioner should be aware of when dealing with patients presenting with tooth wear or exhibiting a susceptibility to this. CPD/Clinical Relevance: An understanding of the factors relevant to the prevention of tooth wear will enable an effective preventive regimen to be prescribed. This will play an integral role in the management of tooth wear and its sequalae.

Microbiological Aspect in Dental Implants and Natural Teeth with the Impact of Aloe vera Gel

The health of peri-implant tissues is one of the most important aspects for the long-term success of dental implants. Thus the control of bacterial plaque which is the main etiological factor in peri-implant diseases by using an effective preventive regimen and a therapeutic agent is of vital importance in prevention of any irreversible pathological conditions of peri‑implant tissues. The purposeof this study wasto investigate and compare microbiological aspect of subgingival plaque at implants and contralateral natural teeth in the same patients with the impact of Aloe vera gel. 20 females aged 25- 45 year who exhibited the presence of one clinically stable implant carrying a full ceramic crown and one contralateral natural tooth were selected to be enrolled in a split-mouth study. All participants were apparently healthy with no history of any systematic diseases and they have been treated with a two-piece implant system which should be in function for at least 6 months. Samples of subgingival plaque were collected from implants and contralateral teeth for microbial analyses (Gram positive bacteria, Gram negative bacteria and Candida species) at base line and 2 weeks after the application of Aloe vera gel. Microbial analyses revealed no statistically significant difference (p> 0.05) in the counts of microorganisms between implants and teeth, although they were lower in implant than that in teeth. Finding also revealed a significant reduction (p< 0.01) in the count of Gram-positive bacteria and Candida speciesafter application of Aloe vera for both implants and teeth. On the other hand, the count of Gram-negative bacteria seems not to be affected by Aloe vera gel. No differences were found in microbiological analysis of subgingival plaque from dental implants and teeth in the same patient. Moreover, Aloe vera is a promising herb with antimicrobial activity that could be used as a beneficial agent in treatment and prevention of peri-implant diseases.

The Challenges to Improve Farm Animal Welfare in the United Kingdom by Reducing Disease Incidence with Greater Veterinary Involvement on Farm

Simple SummarySick cattle and sheep are often treated by farmers without prior veterinary examination and, as a consequence, incorrect diagnoses and inappropriate therapies are common, but these failings largely go undetected and unreported. Many farmers maintain that market forces render veterinary care of individual sick sheep and cattle too expensive. Delays in requesting veterinary attention are not uncommon causing unnecessary animal suffering and a poorer outcome. Incidence rates of endemic diseases in the United Kingdom are too high, causing animal welfare concerns, but these could be reduced by the implementation of proven veterinary flock/herd health programmes.The Cattle Health and Welfare Group of Great Britain report (CHAWG; 2012) lists the most important cattle diseases and disorders but fails to fully acknowledge the importance of animal mental health and; in so doing; misses the opportunity to further promote animal welfare. There are effective prevention regimens; including vaccination; husbandry and management strategies for all ten listed animal health concerns in the CHAWG report; however control measures are infrequently implemented because of perceived costs and unwillingness of many farmers to commit adequate time and resources to basic farm management tasks such as biosecurity; and biocontainment. Reducing disease prevalence rates by active veterinary herd and flock health planning; and veterinary care of many individual animal problems presently “treated” by farmers; would greatly improve animal welfare. Published studies have highlighted that treatments for lame sheep are not implemented early enough with many farmers delaying treatment for weeks; and sometimes even months; which adversely affects prognosis. Disease and welfare concerns as a consequence of sheep ectoparasites could be greatly reduced if farmers applied proven control strategies detailed in either veterinary flock health plans or advice available from expert veterinary websites. Recent studies have concluded that there is also an urgent need for veterinarians to better manage pain in livestock. Where proven treatments are available; such as blockage of pain arising from ovine obstetrical problems by combined low extradural injection of lignocaine and xylazine; these are seldom requested by farmers because the technique is a veterinary procedure and incurs a professional fee which highlights many farmers’ focus on economics rather than individual animal welfare.

Maintaining the dental implants: Importance in long-term success

Present paper aims to discuss and emphasize the importance of maintenance programs for oral implants among general dental practitioners for successful implant dentistry. Bacterial plaque accumulation around the endosseous dental implants results in inflammatory changes in the surrounding soft tissues and if not controlled, has shown to develop the progressive destruction of the supporting tissues, which may ultimately compromise its future. Maintaining the permucosal seal of soft tissue to implant surface and healthy tissue around oral implants is the prerequisite to its success and hence, it is important to introduce an effective preventive regimen and a therapeutic intervention should be initiated as early as possible when a pathological condition of peri-implant tissues is diagnosed.

Tacrolimus and “Mini” Methotrexate is an Effective Regimen for Prevention of Graft-Versus-Host-Disease In Children Undergoing Umbilical Cord Blood Transplant

Tacrolimus and “Mini” Methotrexate is an Effective Regimen for Prevention of Graft-Versus-Host-Disease In Children Undergoing Umbilical Cord Blood Transplant

A prospective randomized antiplatelet trial of cilostazol versus clopidogrel in patients with bare metal stent

Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary bare metal stent implantation for thrombosis and restenosis prevention. This prospective randomized and double blind trial was designed to investigate the safety and efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis. One hundred and twenty patients who underwent elective stent were randomly assigned to treatment group with cilostazol 200 mg/d (n = 60), clopidogrel 75 mg/d and aspirin 100 mg/d or to control group with clopidogrel treatment 75 mg/d (n = 60) and aspirin 100 mg/d. Follow-up coronary angiography was performed 6 - 9 months later. Nine months major adverse cardio-cerebral event (MACCE) were lower in treatment groups (P < 0.05). The quantitative coronary angiography (QCA) at 6 months follow-up showed that minimum lumen diameter (MLD) was higher in treatment group than that of control group [(2.14 +/- 0.52) mm vs (1.82 +/- 0.36) mm, P < 0.05]. Late lumen loss (LL) [(0.82 +/- 0.42) mm vs (1.31 +/- 0.58) mm; P < 0.01], restenosis rate (RR) (14% vs 32%; P < 0.05) and target lesion revascularizaion (TLR) rate (5% vs 17%; P < 0.05) were lower in treatment group than in control group. Cilostazol therapy is an effective regimen for prevention not only stent thrombosis but also RR and TLR through reducing MLD without the risk of increasing bleeding.

A Simple and Effective Regimen for Prevention of Radial Artery Spasm during Coronary Catheterization

Radial artery spasm occurs frequently during the transradial approach for coronary catheterization. Premedications with nitroglycerin and verapamil have been documented to be effective in preventing radial spasms. Verapamil is relatively contraindicated for some patients with left ventricular dysfunction, hypotension and bradycardia. We would like to know whether nitroglycerin alone is sufficient for the prevention of radial artery spasm. We conducted a randomized controlled trial to compare the spasmolytic effect between heparin alone, heparin plus nitroglycerin and heparin plus nitroglycerin and varapamil during transradial cardiac catheterization. In this study, a total of 406 patients underwent transradial cardiac catheterization and intervention. After successful cannulation and sheath insertion of radial arteries, 133 patients in group A received 3,000 units of heparin, 100 µg of nitroglycerin and 1.25 mg of verapamil via sheath, 135 patients in group B received 3,000 units of heparin and 100 µg of nitroglycerin, and 93 patients in group C received 3,000 units of heparin. Five patients in group A (3.8%), 6 patients in group B (4.4%) and 19 patients in group C (20.4%) showed radial spasms. There is no statistically significant difference between groups A and B (p = 0.804), but there are strong statistically significant differences between groups A and C (p = 0.001) and groups B and C (p = 0.003). Intra-arterial premedication with 100 µg nitroglycerin and 3,000 units of heparin is effective in preventing radial spasms during transradial cardiac catheterization.

Effect of Deguelin on UVB-Induced Skin Carcinogenesis

Nonmelanoma skin cancer afflicts more than one million people in the U.S. annually, highlighting the need for more effective preventive regimens. We have investigated the ability of deguelin, a plant-derived rotenoid with cancer chemopreventive activity, to inhibit UVB-induced skin carcinogenesis with the SKh-1 mouse model. Topically-applied deguelin significantly inhibited the multiplicity of UVBinduced skin tumors, indicating potential as a human skin cancer chemopreventive agent. Mechanistic studies to determine the potential of deguelin to block a number of established UVB-induced molecular events yielded negative results [including UVB-induced AP-1 DNA binding, c-fos and TNF? mRNA induction, arachidonic acid release and UVB-induced phosphorylation of mTOR (Ser2448), akt (Ser473) and erk (Thr202/Tyr204)]. These results are of interest as they contradict a major hypothesis for the mode of action of deguelin, i.e., a general down regulation of signal transduction based on inhibition of NADH dehydrogenase and depletion of ATP levels. In the current work, however, deguelin was found to activate 5' AMPactivated kinase (AMPK), a protein that acts as a cellular energy sensor. This is the first report of a chemopreventive agent having this effect and suggests a possible role for AMPK in cancer chemoprevention.

Dietary prevention of allergic diseases in infants and small children. Part III: Critical review of published peer-reviewed observational and interventional studies and final recommendations.

The role of primary prevention of allergic diseases has been a matter of debate for the last 40 years. In order to shed some light on this issue, a group of experts of the Section of Pediatrics EAACI reviewed critically the existing literature on the subject. An analysis of published peer-reviewed observational and interventional studies was performed following the statements of evidence as defined by WHO. The results of the analysis indicate that breastfeeding is highly recommended for all infants irrespective of atopic heredity. A dietary regimen is unequivocally effective in the prevention of allergic diseases in high-risk children. In these patients breastfeeding combined with avoidance of solid food and cow's milk for at least 4-6 months is the most effective preventive regimen. In the absence of breast milk, formulas with documented reduced allergenicity for at least 4-6 months should be used.

Interventions for replacing missing teeth: maintaining health around dental implants.

To maintain healthy tissues around dental implants it is important to institute an effective preventive regimen (supportive therapy). Different maintenance regimens have been suggested, however it is unclear which are the most effective. To test the null hypothesis of no difference between different interventions for maintaining healthy tissues around dental implants. We searched the Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Handsearching included several dental journals. We checked the bibliographies of the identified randomised controlled trials (RCTs) and relevant review articles for studies outside the handsearched journals. We wrote to authors of all identified RCTs, to more than 55 oral implant manufacturers and an internet discussion group to find unpublished or ongoing RCTs. No language restrictions were applied. The last electronic search was conducted on 2 February 2004. All randomised controlled trials of oral implants comparing agents or interventions for maintaining or recovering healthy tissues around dental implants. We carried out a quality assessment of the included RCTs in duplicate and contacted the authors for missing information. We independently extracted the data in duplicate. We followed the Cochrane Oral Health Group's statistical guidelines. Fourteen RCTs were identified. Five of these trials, which reported results from a total of 127 patients, were suitable for inclusion in the review. Two trials evaluated the efficacy of powered and sonic toothbrushes, respectively, when compared to manual toothbrushing and showed no statistically significant differences. One RCT compared Listerine versus placebo mouthwashes showing a reduction of 54% in plaque and 34% in marginal bleeding compared with the placebo. One trial compared self administered subgingival chlorhexidine irrigation versus chlorhexidine mouthwash. The group using chlorhexidine irrigation resulted in statistically significantly lower mean plaque scores and a marginal bleeding index than the group using chlorhexidine mouthwash, however the mouthwash was given at a suboptimal dosage. One study compared etching gel with mechanical debridement showing no statistical differences. Follow ups ranged between 6 weeks and 5 months. It was not possible to make any meta-analysis as each trial assessed different interventions. There is only little reliable evidence for which are the most effective interventions for maintaining health around peri-implant tissues. There was no evidence that the use of powered or sonic toothbrushes was superior to manual toothbrushing. There is weak evidence that Listerine mouthwash, used twice a day for 30 seconds, as adjunct to routine oral hygiene is effective in reducing plaque formation and marginal bleeding around implants. There was no evidence that phosphoric etching gel offered any clinical advantage over mechanical debridement. These findings are based on RCTs having short follow-up periods and few subjects. There is not any reliable evidence for the most effective regimens for long term maintenance. More RCTs should be conducted in this area. In particular, there is a definite need for trials powered to find possible differences, using primary outcome measures and with much longer follow up. Such trials should be reported according the CONSORT guidelines (http://www.consort-statement.org/).

Randomized comparison of cilostazol versus ticlopidine hydrochloride for antiplatelet therapy after coronary stent implantation for prevention of late restenosis

Background Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary stent implantation. However, its evaluation has not been established yet. Methods This prospective randomized trial was designed to investigate the efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis in comparison with ticlopidine hydrochloride. One hundred thirty consecutive patients, scheduled for elective coronary stenting, were randomly assigned to receive oral aspirin (81 mg/day) plus ticlopidine hydrochloride therapy (200 mg/day; group I) or aspirin plus cilostazol therapy (200 mg/day; group II). These medications were started at least 2 days before coronary intervention and continued until follow-up coronary angiography was performed 6 months later. Results Subacute stent thrombosis was observed in 2 patients of group I but in no patients of group II. Major cardiac events were similarly present in both groups. Elevated transaminase levels were observed more frequently in group I than in group II (P <.05). Each of the quantitative coronary angiography variables before and immediately after coronary stenting were similar in both groups. At follow-up angiography, however, late lumen loss (0.69 ± 0.79 mm vs 0.28 ± 0.40 mm; P <.01) and loss index (0.42 ± 0.56 vs 0.16 ± 0.27; P <.01) were smaller in group II than in group I. Restenosis rate (13% vs 31%; P <.05) and target lesion revascularization rate (7% vs 21%; P <.05) were both lower in group II than in group I. Conclusion Aspirin plus cilostazol therapy may be an effective regimen for prevention of not only stent thrombosis but also restenosis. (Am Heart J 2002;144:303-8.)

Interventions for replacing missing teeth: maintaining and re-establishing healthy tissues around dental implants.

To maintain healthy tissues around oral implants it is important to institute an effective preventive regimen (supportive therapy) and when a pathologic condition of the tissue around implants is diagnosed, an intervention should be initiated as soon as possible. Different maintenance regimens and treatment strategies for failing implants have been suggested, however it is unclear which are the most effective. To test the null hypothesis of no difference between different interventions for maintaining or re-establishing healthy tissues around dental implants. The Cochrane Oral Health Group Specialised Register, The Cochrane Controlled Trials Register, MEDLINE and EMBASE were searched. Hand searching included several dental journals. In addition, authors of all identified trials, fifty-five oral implant manufacturers and two extensive personal libraries (ME and AJ) were consulted. All randomised controlled trials of oral implants comparing agents or interventions for maintaining or re-establishing healthy tissues around dental implants. Data were independently extracted, in duplicate, by two reviewers (ME & HW). Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out. The Cochrane Oral Health Group's statistical guidelines were followed. Nine RCTs were identified. Five of these trials, which reported results from a total of 127 patients, were suitable for inclusion in the review. There is only a little reliable evidence for which are the most effective interventions for maintaining health around peri-implant tissues. There was no evidence that the use of powered or sonic toothbrushes was superior to manual toothbrushing. There is a weak evidence that Listerine mouthwash, used twice a day for 30 seconds, as adjunct to routine oral hygiene is effective in reducing plaque formation and marginal bleeding around implants. There was no evidence that phosphoric etching gel offered any clinical advantage over mechanical debridement. These findings are based on RCTs having short follow-up periods and few subjects. There is not any reliable evidence for the most effective regimens for long-term maintenance. For the treatment of failing implants (peri-implantitis) there is not any reliable evidence for preferring one therapeutic regimen over another. More RCTs should be conducted in this area. In particular, there is a definite need for trials investigating which is the most effective approach for the treatment of peri-implantitis and for trials with longer follow-up for maintenance. Such trials should be reported according the CONSORT guidelines (http://www.consort-statement.org/).

Prevention of Cytomegalovirus Disease in Recipients of Solid-Organ Transplants

The introduction and combination of more-potent immunosuppressive regimens, and the increased transplantation of organs into more severely ill patients, have again placed cytomegalovirus (CMV) disease in the spotlight of posttransplantation complications. Both direct and associated complications related to CMV need to be considered in understanding the pathogenesis of CMV infection after solid-organ transplantation. New diagnostic methods with higher sensitivity for the detection of CMV and the ability to quantify CMV indicate that low levels of CMV replication are present in many patients who don't have clinical symptoms ascribed to CMV infection. How these low levels of CMV replication impact the outcome of the transplanted graft remains unknown. In addition, there needs to be further study regarding whether only patients at high risk for developing CMV disease or, also, those with clinically asymptomatic levels of CMV replication should be the target of effective preventive regimens. This review summarizes our current knowledge of the pathogenesis of CMV infection after solid-organ transplantation, and it outlines different effective preventive regimens and approaches.

Age-related changes in bone mass, structure, and strength--effects of loading.

The incidence of vertebral fracture has increased three- to fourfold for women and more than fourfold for men during the last 30 years. These data are age-adjusted and therefore highlight the decrease in bone mass or bone quality from generation to generation. To arrest or reverse these increases in osteoporotic fractures, effective preventive regimens must be established. However, in order to do so, a basic understanding of age-related changes in the quality and strength of vertebral bone is crucial. In this study, the normal age-related changes in human bone have been investigated by using a combination of different techniques: normal histomorphometry, structural analyses, scanning electron microscopy (SEM), and biomechanical testing. It has been demonstrated that age by itself is the major determinant of vertebral bone strength, mass, and microarchitecture. When the sex-related differences are investigated, three different factors are disclosed: Men have, at the age of 20-30 years, a higher peak bone mass and strength than women. Men show an age-related compensatory increase in bone size (cross-sectional area of the vertebral bodies) which can not be found in women. There is, after the age of 50 years (menopause), a higher tendency for disconnection of the trabecular network in women than in men. Furthermore, it was shown that loading plays an important role in the maintenance of trabecular connectivity (through the remodeling process) and in the periosteal apposition and thereby increase in cross-sectional area (through the modeling process). Loading affects bone mass, microarchitecture, and size throughout life. Loading is therefore important for the maintenance of bone strength during normal aging--and exercise plays an important role in the prevention of osteoporotic fractures.

Analysis of rifapentine for preventive therapy in the Cornell mouse model of latent tuberculosis.

Rifapentine is a long-acting rifamycin which may be useful for intermittent drug therapy against tuberculosis. In this study we measured the efficacies of rifapentine-containing intermittent drug regimens for preventive therapy using the Cornell mouse model of latent tuberculosis. We infected groups of mice intravenously with Mycobacterium tuberculosis and then treated them with isoniazid and pyrazinamide for 12 weeks according to the Cornell latency development protocol. After a 4-week interval of no treatment, experimental preventive therapy was administered by esophageal gavage for 12 or 18 weeks. After equilibration and dexamethasone amplification treatment, mouse organs were analyzed by quantitative colony counts to measure the effectiveness of therapy. Our results showed that once-weekly isoniazid plus rifapentine combination therapy for 18 weeks was an effective preventive regimen with sterilizing potency and bacillary load reduction comparable to those of daily isoniazid therapy for 18 weeks. Monotherapy with rifapentine weekly or fortnightly or with rifampin twice weekly for up to 18 weeks did not offer advantages in reducing bacillary load or in sterilizing organs compared to the effects of a placebo. These results with the Cornell mouse model indicate that once-weekly, short-course preventive therapy with isoniazid plus rifapentine is effective and may warrant investigation in humans with latent tuberculosis infection.

Commentary on and Recommendations for the Proper Uses of Fluoride

Fluorosis has been associated with the fluoride concentration of drinking water, use of dietary fluoride supplements, early use of dentifrices, and prolonged use of infant formula. The literature, however, does not show associations between fluorosis and use of fluoride mouthrinses, professionally applied fluorides, bottled waters, carbonated beverages, and juices. It is unwise to issue laundry lists of items that may be implicated as problem-causing when, in fact, they may not be. Although usually classified without fluorosis, children in Dean's "questionable" category would be classified with the condition if the TFI or TSIF were used. Accordingly, Dean, in 1942, really reported only 52.8 percent of children without fluorosis in Kewanee, a community with 0.9 ppm fluoride in drinking water. Because the morbidity and sequelae of dental caries have declined, undue emphasis has been placed recently on the risks of using fluoride rather than on its profound beneficial effects. Although of paramount importance, conclusions cannot be drawn on whether fluoride protects against, contributes to, or has no effect on bone fractures or is valuable in treating osteoporosis. Careful thought is required before making recommendations that may reduce health benefits because of unfounded concerns about perceived risks. There should be greater regulation of extraneous fluoride sources, rather than reliance on educational efforts or recommendations to eliminate use of highly effective preventive regimens.

An Overview of Therapeutic Interventions in Myocardial Infarction

The high risk of subsequent mortality and morbidity following the occurrence of a myocardial infarction (MI) underlies the importance of instituting effective preventive regimens as part of the overall management of these patients. The aim of such treatment is to prolong survival by preventing sudden and non-sudden death and further major cardiovascular events. Currently available data from randomised, controlled clinical trials in MI patients indicate that early treatment with thrombolytic agents [streptokinase, anisolyated plasminogen streptokinase activator complex (APSAC) or recombinant tissue-type plasminogen activator (rt-PA)] in the first few hours after onset of symptoms significantly reduces the short term mortality following MI, with follow-up studies at 1 year indicating that the early benefits persist long term. The optimum time for initiation of thrombolytic therapy is within 6 hours of onset, but treatment started between 7 and 24 hours after onset can also be beneficial. Similarly, there is good evidence that beta-blockers (e.g. propranolol, timolol, metoprolol, atenolol) and aspirin are effective in reducing both the mortality and reinfarction rate following MI. With beta-blockers, a policy of starting treatment early intravenously and continuing orally for 2 to 3 years seems likely to save more lives than either strategy alone; however, contraindications to beta-blockade reduce the number of patients eligible to receive this treatment. In the case of aspirin, the optimum dosage has yet to be determined, but on the basis of present evidence, it seems reasonable to start treatment early with doses of 160 to 325 mg daily and continue for a year or 2 after recovery. Other studies have shown that long term oral anticoagulant therapy is also effective in reducing the mortality and reinfarction rate after MI. Subcutaneous heparin therapy given for 10 days in patients with acute anterior MI reduces the frequency of left ventricular mural thrombosis, while intravenous heparin given for greater than or equal to 4 days improves coronary artery patency rates following administration of a thrombolytic agent. In a comparison with low dose aspirin, intravenous heparin proved more effective in maintaining coronary artery patency rates after rt-PA thrombolysis. There is also evidence that oral nitrates may reduce mortality in MI patients, especially in those with heart failure. However, current data on the use of antiarrhythmic drugs do not support the routine of these drugs following MI. Similarly, with lipid-lowering agents, the evidence that lowering cholesterol is beneficial in reducing mortality after MI is at present inconclusive. Further studies with these groups of drugs are awaited with interest.(ABSTRACT TRUNCATED AT 400 WORDS)

George Lyman Duff memorial lecture. Persistent problems in the pathogenesis of atherosclerosis.

In concluding this eclectic review, I believe that we can say with certainty that coronary atherosclerosis has its origins in childhood, at least by age 10 and possibly earlier. Endothelial changes follow lipid accumulation, but, with present methods, there is no evidence that endothelial injury precedes lipid accumulation. Proliferation is a prominent feature of accelerated experimental atherosclerosis, but we do not see evidence that proliferation is a major feature of early naturally occurring human atherosclerosis. The prominence of the monocyte-macrophage in the earliest detectable lesions of atherosclerosis in childhood justifies the current interest in monocyte biology. Hyperlipidemia, in the sense of the average high levels common in our population, seems almost certain to contribute to accelerated atherogenesis in children, but conclusive proof is still lacking. Mild hypertension in children, or even the high range of normal blood pressure, may accelerate the transition of innocuous childhood fatty streaks to more ominous fibrous plaques. The putative relationship of adult coronary heart disease risk factors to the childhood lesions of atherosclerosis is largely based on extrapolation from adult data. Direct evidence bearing on these relationships, however difficult to obtain, would be helpful in designing and promoting effective preventive regimens for children.