Infection Risk-Adjusted Antibiotic Prophylaxis Strategies in Arthroplasty: Low-Dose Single vs. High-Dose Dual Antibiotic-Loaded Bone Cement

Aims Patients receiving cemented hemiarthroplasties after hip fracture have a significant risk of deep surgical site infection (SSI). Standard UK practice to minimize the risk of SSI includes the use of antibiotic-loaded bone cement with no consensus regarding type, dose, or antibiotic content of the cement. This is the protocol for a randomized clinical trial to investigate the clinical and cost-effectiveness of high dose dual antibiotic-loaded cement in comparison to low dose single antibiotic-loaded cement in patients 60 years and over receiving a cemented hemiarthroplasty for an intracapsular hip fracture. Methods The WHiTE 8 Copal Or Palacos Antibiotic Loaded bone cement trial (WHiTE 8 COPAL) is a multicentre, multi-surgeon, parallel, two-arm, randomized clinical trial. The pragmatic study will be embedded in the World Hip Trauma Evaluation (WHiTE) (ISRCTN 63982700). Participants, including those that lack capacity, will be allocated on a 1:1 basis stratified by recruitment centre to either a low dose single antibiotic-loaded bone cement or a high dose dual antibiotic-loaded bone cement. The primary analysis will compare the differences in deep SSI rate as defined by the Centers for Disease Control and Prevention within 90 days of surgery via medical record review and patient self-reported questionnaires. Secondary outcomes include UK Core Outcome Set for hip fractures, complications, rate of antibiotic prescription, resistance patterns of deep SSI, and resource use (more specifically, cost-effectiveness) up to four months post-randomization. A minimum of 4,920 patients will be recruited to obtain 90% power to detect an absolute difference of 1.5% in the rate of deep SSI at 90 days for the expected 3% deep SSI rate in the control group. Conclusion The results of this trial will provide evidence regarding clinical and cost-effectiveness between low dose single and high dose dual antibiotic-loaded bone cement, which will inform policy and practice guidelines such as the National Institute for Health and Care Excellence guidance on management of hip fractures. Cite this article: Bone Jt Open 2021;2(2):72–78.

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Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100127906 ◽

1987 ◽

Vol 45 ◽

pp. 718-719

Author(s):

G.A. Miranda ◽

M.A. Arroyo ◽

C.A. Lucio ◽

M. Mongeotti ◽

S.S. Poolsawat

Keyword(s):

Low Dose ◽

Fetal Liver ◽

Late Pregnancy ◽

Toxic Chemicals ◽

Control Group ◽

High Dose ◽

Over The Counter ◽

Liver And Kidney ◽

Neonatal Liver ◽

Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

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Evaluation of hippocampus in rhesus monkeys after chronic (1-year) inhalation exposure to marijuana: I. Electron microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159539 ◽

1990 ◽

Vol 48 (3) ◽

pp. 398-399

Author(s):

A.M. Andrews ◽

S.W. Wilson ◽

A.C. Scallet ◽

S.F. Ali ◽

J. Bailey ◽

...

Keyword(s):

Synaptic Vesicles ◽

Rhesus Monkeys ◽

Low Dose ◽

Inhalation Exposure ◽

Synaptic Cleft ◽

High Dose ◽

Withdrawal Time ◽

Treatment Groups ◽

Ultrastructural Evidence ◽

Male Rhesus

Exposure of rhesus monkeys (Macaca mulatta) to marijuana via inhalation or to intravenous delta-9-tetrahydrocannabinol (THC), reportedly caused ultrastructural evidence of increased synaptic width. Chronic marijuana smoke in a single rhesus monkey examined after a six month withdrawal time caused ultrastructure changes in the septal, hippocampal and amygdala regions; the synaptic cleft was widened, electron opaque material was found in the cleft and in the pre- and postsynaptic regions, with some clumping of the synaptic vesicles. The objective of our study was to assess neuropathological alterations produced by chronic inhalation of marijuana smoke.Nineteen male rhesus monkeys, 3-5 years of age and weighing 3-8 kg, were divided into four treatment groups: a) sham control, b) placebo smoke (7 days/ week) c) low dose marijuana (2 times/week with 5 days/week sham) and d) high dose marijuana (7 times/week). A smoke exposure consisted of smoke from one cigarette (2.6% THC) burned down to 10 mm butt length. Smoke was administered via smoke generator (ADL II, Arthur D. Little, Inc. Cambridge, MA) and nose-mouth only masks (local production) equipped with one-way valves.

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Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648180 ◽

1991 ◽

Vol 65 (05) ◽

pp. 504-510 ◽

Cited By ~ 20

Author(s):

Raffaele De Caterina ◽

Rosa Sicari ◽

Walter Bernini ◽

Guido Lazzerini ◽

Giuliana Buti Strata ◽

...

Keyword(s):

Platelet Function ◽

Low Dose ◽

Bleeding Time ◽

Ex Vivo ◽

Stable Coronary Artery Disease ◽

High Dose ◽

Single Drug ◽

Before And After ◽

Serum Thromboxane ◽

Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

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Intensive Initial Oral Anticoagulation and Shorter Heparin Treatment in Deep Vein Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1661195 ◽

1984 ◽

Vol 52 (03) ◽

pp. 276-280 ◽

Cited By ~ 17

Author(s):

Sam Schulman ◽

Dieter Lockner ◽

Kurt Bergström ◽

Margareta Blombäck

Keyword(s):

Deep Vein Thrombosis ◽

Oral Anticoagulation ◽

Dose Group ◽

Low Dose ◽

Clinical Signs ◽

Coagulation Factor ◽

High Dose ◽

Vein Thrombosis ◽

Heparin Treatment ◽

Deep Vein

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

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Effects of Aspirin and Sulfinpyrazone on Thromboxane and Prostacyclin Synthesis in Rabbits

10.1055/s-0038-1665775 ◽

1979 ◽

Author(s):

J McDonald ◽

A Cerskus ◽

M Ali

Keyword(s):

Arachidonic Acid ◽

Platelet Aggregation ◽

Low Dose ◽

High Dose ◽

Prostacyclin Synthesis

Arachidonic acid (AA) or collagen were infused into rabbits causing intravascular platelet aggregation with thrombocytopenia, hypotension and death. Thromboxane and prostacyclin synthesis were measured by radioimmunoassay of plasma TXB2 and 6-keto-PGF1α. The effects of pretreatement with aspirin (ASA) or sulfinpyrazone(SPZ) were assessed.Death in drug-treated rabbits was always associated with elevations of plasma TXB2(1-40 ng/ml) and of 6-keto-PGF1α(1-20 ng/ml). Collagen produced only small elevations of plasma TXB2 compared to AA but protection by ASA correlated better with inhibition of TXB2 and 6-keto-PGF1α synthesis than with inhibition of aggregation. Low dose ASA produced less inhibition of prostacyclin synthesis than high dose ASA but was less effective in preventing thromboxane synthesis and death.

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