Treatment of periodontal disease for glycaemic control in people with diabetes

Background: Glycaemic control is a key issue in the care of people with diabetes mellitus (DM). Some studies have suggested a bidirectional relationship between glycaemic control and periodontal disease. Objectives: To investigate the relationship between periodontal therapy and glycaemic control in people with diabetes and to identify the appropriate future strategy for this question. Search strategy: A comprehensive approach was adopted employing handsearching; searching of electronic databases including the Cochrane Oral Health Group’s Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL, ZETOC, ISI Web of Knowledge and LILACS; contact with appropriate non‐English language healthcare professionals; authors and organizations. The final date for searching for studies was 24 March 2010. Selection criteria: This review studied randomized controlled trials of people with Type 1 or 2 diabetes mellitus (DM) with a diagnosis of periodontitis. Suitable interventions included mechanical periodontal therapy with or without adjunctives and oral hygiene education. Data collection and analysis: The titles and abstracts of 690 papers were examined by two review authors independently. Ultimately, seven studies were included and 19 excluded after full text scrutiny. All trials were assessed for risk of bias. Main results: Three studies had results pooled into a meta‐analysis. The effect for the mean percentage difference in HbA1c for scaling/root planing and oral hygiene (+/? antibiotic therapy) versus no treatment/usual treatment after 3–4 months was ?0.40% (95% confidence interval (CI) fixed effect ?0.78% to ?0.01%), representing a statistically significant reduction in HbA1c (P = 0.04) for scaling/root planing. One study was assessed as being at low risk of bias with the other two at moderate to high risk of bias. A subgroup analysis examined studies without adjunctive antibiotics ?0.80% (one study: 95% CI ?1.73% to 0.13%; P = 0.09), with adjunctive antibiotics in the test group ?0.36% (one study: 95% CI ?0.83% to 0.11%; P = 0.14), and with antibiotics in both test and control groups after 3/4 months ?0.15% (one study: 95% CI ?1.04% to 0.74%; P = 0.74). Authors’ conclusions: There is some evidence of improvement in metabolic control in people with diabetes, after treating periodontal disease. There are few studies available and individually these lacked the power to detect a significant effect. Most of the participants in the study had poorly controlled Type 2 DM with little data from randomized trials on the effects on people with Type 1 DM.     

Early drug distribution: a generally neglected aspect of pharmacokinetics of particular relevance to intravenously administered anesthetic agents

There is considerable variability in response to intravenously administered anesthetic drugs (e.g., hypnotics, benzodiazepines, and narcotics) that have a rapid onset of effect (such as hypnosis, anxiolysis, and analgesia) and a low margin of safety (because of cardiovascular or respiratory depression, etc.). Although the onset of effect for these drugs occurs seconds to minutes after injection, traditional pharmacokinetic models are based on blood samples that are first obtained after drug effects have peaked. As a result, many studies have failed to provide a pharmacokinetic rationale for dosage adjustments of these drugs.     

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005

Swift PGF, Skinner TC, de Beaufort CE, Cameron FJ, Åman J, Aanstoot H‐J, Castaño L, Chiarelli F, Daneman D, Danne T, Dorchy H, Hoey H, Kaprio EA, Kaufman F, Kocova M, Mortensen HB, Njølstad PR, Phillip M, Robertson KJ, Schoenle EJ, Urakami T, Vanelli M, Ackermann RW, Skovlund SE for the Hvidoere Study Group on Childhood Diabetes. Target setting in intensive insulin management is associated with metabolic control: the Hvidoere Childhood Diabetes Study Group Centre Differences Study 2005. Objective: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. Methods: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. Results: A total of 2062 adolescents completed questionnaires (age 14.4 ± 2.3 yr; diabetes duration 6.1 ± 3.5 yr). Mean HbA 1c = 8.2 ± 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). Conclusions: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.     

Effect of direct-acting oral anticoagulants (DOACs) on bleeding and blood product usage in cardiac surgery compared to warfarin and controls

In this retrospective, single-centre, observational study, we assessed (i) use of anticoagulant and antiplatelet (AP) therapy, (ii) the duration of direct-acting oral anticoagulant (DOAC) discontinuation, (iii) renal function and (iv) PT and APTT as predictors of bleeding and blood product usage; in adults (>18 years) undergoing major cardiac surgery from 01.01.2015 to 31.12.2018. Comparisons were made between each treatment group (warfarin, DOAC and DOAC + AP) and untreated controls, and between warfarin and DOAC. A total of 2928 patients were included for analysis. Median (range) of DOAC discontinuation prior to surgery was five days (1–22) for DOAC and five days (2–7) for DOAC + AP. There were no differences in bleeding between anticoagulant groups versus control, or DOAC versus warfarin. There were no differences in blood product use between DOAC and warfarin patients. The duration of DOAC discontinuation but not the creatinine clearance influenced bleeding and blood products use. Thrombosis occurred in 0·7% and 3·1% in controls and patients on warfarin respectively (P = 0·099) with none among patients on DOAC or DOAC + AP. The PT/APTT had no predictive value. Median five-day discontinuation of DOAC +/− AP irrespective of renal function prevents an increase in bleeding compared to patients on warfarin or controls with no increase in thrombosis.     

DLA-identical bone marrow grafts after low-dose total body irradiation: effects of high-dose corticosteroids and cyclosporine on engraftment

Previous studies found that marrow allografts from DLA-identical littermates resulted in survival of 60% of recipient dogs after an otherwise lethal dose of 450 cGy of total body irradiation (TBI), either because of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after allograft rejection. The current study asked whether allogeneic engraftment could be enhanced and survival improved by treating allograft recipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in group 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kilogram orally twice daily. All five dogs rejected their allografts; three died early with marrow aplasia and two showed endogenous marrow recovery. Nine dogs received CSP from day -6 to day -1 before transplantation at a dose of 20 mg/kg/d intravenously administered in divided doses. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally from day -1 to day 35. All seven had sustained allografts (two mixed chimeras and five complete donor-type chimeras) and became healthy long-term survivors without graft-versus-host disease. These results extend previous observations and confirm that grafts of marrow from DLA-identical littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP administered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after transplantation resulted in successful allografts and event-free survival in all cases.     

乳酸水平监测在治疗早期重症监护患者中的指导作用

背景和目的:乳酸水平增高与患者的致病率和病死率显著相关.该研究探讨了在危重患者的早期治疗中,监测乳酸水平是否可以改善患者的预后及其效果.方法:将入住ICU时血乳酸水平≥3.0 mmol/L(3.0 mEq/L)的患者随机分为2组,乳酸组以乳酸水平指导治疗,使患者在最初8h内乳酸水平每2h 下降20%以上;对照组仅有基线乳酸水平,不进行乳酸水平监测.     

Isoflurane Alters the Recirculatory Pharmacokinetics of Physiologic Markers

Background: Earlier studies have demonstrated that physiologic marker blood concentrations in the first minutes after administration, when intravenous anesthetics exert their maximum effect, are determined by both cardiac output and its distribution. Given the reported vasodilating properties of isoflurane, we studied the effects of isoflurane anesthesia on marker disposition as another paradigm of altered cardiac output and regional blood flow distribution.

Methods: The dispositions of markers of intravascular space and blood flow (indocyanine green), extracellular space and free water diffusion (inulin), and total body water and tissue perfusion (antipyrine) were determined in four purpose-bred coonhounds. The dogs were studied while awake and while anesthetized with 1.7%, 2.6%, and 3.5% isoflurane (1.15, 1.7, and 2.3 minimum alveolar concentration, respectively) in a randomized order determined by a Latin square experimental design. Marker dispositions were described by recirculatory pharmacokinetic models based on very frequent early, and less frequent later, arterial blood samples. These models characterize the role of cardiac output and regional blood flow distribution on drug disposition.

Results: Isoflurane caused a significant and dose-dependent decrease in cardiac output. Antipyrine disposition was profoundly affected by isoflurane anesthesia, during which nondistributive blood flow was maintained despite decreases in cardiac output, and the balance between fast and slow tissue volumes and blood flows was altered.