The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia. An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Benefit and risk of heparin for maintaining peripheral venous catheters in neonates: a placebo-controlled trial. S100 protein and its relation to cerebral microemboli in on-pump and off-pump coronary artery bypass surgery. Comparison of a high and a low intensity smoking cessation intervention in a dentistry setting in Sweden: a randomized trial. Neuromonitoring and neurocognitive outcome in off-pump versus conventional coronary bypass operation. Pain reducing effect of three types of transcutaneous electrical nerve stimulation in patients with chronic pain: a randomized crossover trial. The role of prostanoid in hepatic damage during hepatectomy. A randomized phase II study of a new tick-borne encephalitis vaccine using three different doses and two immunization regimens. Low molecular weight heparin (Alfa LHWH) compared with unfractionated heparin in prevention of deep-vein thrombosis after hip fractures. Can low molecular weight heparin replace unfractionated heparin during peripheral arterial reconstruction? An open label prospective randomized controlled trial.
Heparin can induce heparin-induced thrombocytopenia (HIT). The combined effect of type of surgery (major vs minor) and heparin on this prothrombotic immune reaction to platelet factor 4 (PF4)/heparin was analyzed. In a randomized, double-blind study, trauma patients receiving low-molecular-weight (LMWH) or unfractionated heparin (UFH) for thrombosis prophylaxis were assessed for PF4/heparin-antibody seroconversion, HIT, and thrombosis according to type of surgery. The risk for seroconversion was higher than major versus minor surgery odds ratio, 7.98 [95% confidence interval, 2.06-31.00], P = .003, controlled for potential confounders, as was the risk for HIT (2.2% [95% confidence interval, 0.3%-4.1%] vs 0.0%, P = .010). During LMWH compared with UFH thromboprophylaxis, HIT (1 of 298 vs 4 of 316; P = .370) and PF4/heparin seroconversion (1.7% vs 6.6%; P = .002) were less frequent, driven by differences in patients undergoing major surgery (incidence of HIT: LMWH 0.8% vs UFH 4.0%; P = .180; seroconversion rates: 4.0% vs 17.0%; P = .001). After minor surgery, no case of HIT occurred. The severity of trauma and the need for major surgery strongly influence the risk of an anti-PF4/heparin immune response, which is then increased by UFH. In major trauma certoparin may be safer than UFH because it induces HIT-antibody seroconversion, and the corresponding risk of HIT, less frequently. Diagnosis of immune heparin-induced thrombocytopenia (HIT) is usually based on a fall in platelet count below 150 x 109/L (standard definition of thrombocytopenia). However, this definition may be inappropriate for postoperative patients who often develop postoperative thrombocytosis. We sought to determine an improved definition of thrombocytopenia indicating HIT in postoperative orthopedic patients, including its impact on frequency and thrombotic risk of HIT.
                We performed a secondary analysis of a clinical trial of 665 patients who received unfractionated or low-molecular-weight heparin following elective hip arthroplasty. Daily platelet counts and objective studies for deep vein thrombosis were performed in all patients. Laboratory detection of HIT antibodies from a 362-patient subgroup was used to define sensitivity and specificity of various definitions of thrombocytopenia to indicate HIT.
                The improved definition of HIT was a 50% or greater platelet count fall from the postoperative peak, as this definition had greater sensitivity (50% vs 25%) and similar high specificity (99.1% vs 99.4%) for detecting HIT-IgG compared with the standard definition. Patients with HIT who were identified using the improved definition had a higher frequency of thrombosis than patients without HIT (72.2% vs 17.3%; P<.001). The improved definition showed an even greater absolute difference in frequency of HIT between unfractionated and low-molecular-weight heparin (4.8% vs 0.6%; P<.001) compared with the standard definition (2.7% vs 0%; P =.002).
                A 50% or greater fall in the platelet count from the postoperative peak is a sensitive definition indicating possible HIT that is associated with an increased risk of thrombosis. Heparin addition to infusion fluids is used to prolong catheter patency in newborns. Heparin may also induce adverse effects such as bleeding complications and immune-mediated heparin-induced thrombocytopenia (HIT). One objective was peripheral venous catheter patency with heparinization of continuous infusions (0.5 IU/mL). Secondary objectives were incidences of bleeding, clinically manifest HIT, HIT antibodies, and catheter-related complications.
                Inclusion criteria were anticipated need for intravenous peripheral infusion (>or=5 days for HIT-related endpoints) and postnatal age <28 days at study entry. Exclusion criteria were bodyweight <1000 g, congenital malformation, need for therapeutic anticoagulation or mechanical ventilation, and severe bleeding. HIT antibodies were assessed by enzyme-linked immunosorbent assay.
                A total of 145 infants received heparin, and 151 infants received saline. Patient characteristics, number of additional drugs, duration of treatment, and location and size of catheters did not differ. Patency of catheters was 7.4 hours longer in the heparin group (33.8 hours vs 26.4 hours, P<.0001), but the total numbers of catheters did not differ (565 vs 692, P=.3). No infant developed HIT antibodies. Incidences of bleeding complications and thrombocytopenia were comparable between groups.
                Balancing the benefits against the risks of heparin addition and the rare complication of HIT, we will not use 0.5 IU/mL heparin addition to parenteral fluids. S100 protein has been used as a marker for cerebral injury. Studies have reported lower levels in off-pump coronary artery surgery (CABG) compared to on-pump surgery. However, most of these are flawed as S100 from extracerebral sources was included (e.g. blood from cardiotomy suckers). Microemboli (high-intensity transient signals or HITS) during CABG have been implicated as a cause of postoperative neurocognitive dysfunction. The aim of this study was to compare the number of HITS during on-pump and off-pump CABG, measure S100 accurately by excluding extracerebral sources, and assess whether any changes in S100 were related to HITS.
                Thirty-five patients admitted for CABG were randomised to on-pump (n=20) or off-pump (n=15) surgery. Bilateral transcranial Doppler ultrasonography was performed on the middle cerebral artery to detect HITS. S100 was measured preoperatively, at termination of bypass in on-pump surgery, at completion of anastomoses in off-pump surgery, and 48 h postoperatively. A cell saver was used instead of cardiotomy suction in the on-pump group in order to limit extracerebral contamination of the S100 assay.
                The number of HITS was 2016+/-1897 during on-pump and 16+/-21 during off-pump surgery (P<0.0001). In on-pump surgery S100 increased from 0.05+/-0.03 to 0.50+/-0.28 microg/l (P<0.0001) at termination of bypass. In off-pump surgery S100 increased from 0.08+/-0.05 to 0.35+/-0.20 microg/l (P<0.0001) at completion of anastomoses. The mean intraoperative S100 in the on-pump group was 1.6 times greater compared to that in the off-pump group (95% CI 0.88-2.8; P=0.01). There was no evidence of a relationship between S100 and HITS in both groups. By 48 h S100 decreased to 0.22+/-0.14 microg/l in the on-pump and 0.21+/-0.09 microg/l in the off-pump group (P<0.0001, compared to the preoperative value).
                We have demonstrated a significantly higher number of cerebral microemboli in patients undergoing on-pump compared to off-pump CABG. By limiting contamination from extracerebral sources, we have shown S100 beta levels during on-pump CABG one and a half times greater than that in off-pump, although this did not reach statistical significance. In addition, we have shown no correlation between S100 beta and the total microemboli count, possibly because of the small numbers in this study. Tobacco is still the number one life style risk factor for ill health and premature death and also one of the major contributors to oral problems and diseases. Dentistry may be a potential setting for several aspects of clinical public health interventions and there is a growing interest in several countries to develop tobacco cessation support in dentistry setting. The aim of the present study was to assess the relative effectiveness of a high intensity intervention compared with a low intensity intervention for smoking cessation support in a dental clinic setting.
                300 smokers attending dental or general health care were randomly assigned to two arms and referred to the local dental clinic for smoking cessation support. One arm received support with low intensity treatment (LIT), whereas the other group was assigned to high intensity treatment (HIT) support. The main outcome measures included self-reported point prevalence and continuous abstinence (> or = 183 days) at the 12-month follow-up.
                Follow-up questionnaires were returned from 86% of the participants. People in the HIT-arm were twice as likely to report continuous abstinence compared with the LIT-arm (18% vs. 9%, p = 0.02). There was a difference (not significant) between the arms in point prevalence abstinence in favour of the HIT-protocol (23% vs. 16%). However, point prevalence cessation rates in the LIT-arm reporting additional support were relatively high (23%) compared with available data assessing abstinence in smokers trying to quit without professional support.
                Screening for willingness to quit smoking within the health care system and offering smoking cessation support within dentistry may be an effective model for smoking cessation support in Sweden. The LIT approach is less expensive and time consuming and may be appropriate as a first treatment option, but should be integrated with other forms of available support in the community. The more extensive and expensive HIT-protocol should be offered to those who are unable to quit with the LIT approach in combination with other support.
                Trial registration number: NCT00670514. Cardiopulmonary bypass seems to be a major cause for both intraoperative microemboli and cerebral hypoperfusion. This study investigates high intensive transient signals (HITS) in transcranial Doppler ultrasound (TCD) and serum levels of the neurobiochemical marker protein S-100 in patients who underwent coronary artery bypass operation without cardiopulmonary bypass (off-pump CABG) in comparison with the conventional procedure using cardiopulmonary bypass (CPB). The results are related to the neuropsychologic outcome in both surgical groups.
                Forty patients were randomized in 2 groups (20 conventional and 20 off-pump CABG). Neurocognitive status was assessed preoperatively and postoperatively. Venous serum levels of S-100 protein were measured before and after coronary operation, HITS were measured in the middle cerebral artery during the operation.
                The median value of HITS was 394.5 (0 to 2217) in the conventional versus 11 (0 to 50) in the off-pump group, p less than 0.0001. Postoperative S-100 serum levels were: 3.76 (0.13 to 11.2) microg/L (conventional) versus 0.13 (0.04 to 1.01) microg/L (off-pump), p less than 0.0001. Postoperative cognitive testing showed significantly different results with a postoperative impairment of 90% of the patients in the conventional group versus no impairment in the off-pump group.
                Cognitive impairment seems to be strongly associated to CPB and the occurrence of micro-emboli. The off-pump technique appears to be promising in order to eliminate the source of these neuropyschologic impairments following CABG operation. Transcutaneous electrical nerve stimulation (TENS) is a frequently applied therapy in chronic pain although evidence for effectiveness is inconclusive. Several types of TENS, based on different combinations of frequency, pulse duration and intensity, exist. The precise mechanism of action and the relevance of combinations of stimulus parameters are still unclear. To compare the effectiveness of three types of TENS we conducted a randomized, single blinded crossover trial. Patients received two times a 2-week period of daily TENS treatment, separated by a washout period of 2 weeks. In total, 180 chronic pain patients were randomized into three groups. In group 1, high frequency, low intensity TENS (HFT) was compared with high frequency, high intensity TENS (HIT). In groups 2 and 3, HFT and HIT were compared with a control TENS (COT). The order of applying the different modalities of TENS in each group was also randomized. Primary outcome was the patient's overall assessment of effectiveness and pain reduction (VAS). No differences were found in patient's assessment or pain reducing effect between the three groups, indicating no superiority of one type of TENS. In total, 56% continued TENS after the 2-week treatment period. At 6 months, 42% of all patients still used TENS. We concluded that there were no differences in effectiveness for the three types of TENS used in this study. Because no placebo group was included, no definite conclusions on effectiveness of TENS in general in the treatment of chronic pain could be made. The aim of this study in hepatectomy is to investigate whether or not hepatic ischemia elevates the serum prostanoid levels, and whether or not thromboxane A2 (TXA2) synthetase inhibitor (OKY 046) improves hepatic damage.
                The prostanoid levels were measured in 22 hepatectomy cases. The beneficial effects of thromboxane A2 synthetase inhibitor were examined in cases who underwent hepatectomy under hemihepatic vascular control. The total prostanoid levels (6-keto PG Fla+ PGE2 + TXB2) were measured in 22 cases before and after hepatectomy. The hepatic ischemic time (HIT) was defined as the time required to perform a hepatic mobilization plus the right hemihepatic vascular control technique.
                The total prostanoid levels increased after hepatectomy (P < 0.01). The changes in the total prostanoid levels positively correlated with the HIT (P < 0.01). The 17 cases who underwent hepatectomy with the HIT were randomly divided into 2 groups; the OKY group (n = 9), OKY 046 (0.2 mg/kg/hr), the control group (n = 8); no drug was given. The OKY 046 administration reduced the TXB2 levels (P < 0.01), without any changes in the PGE2, or 6-keto PGF1a levels. The serum glutamic oxaloacetic transaminase levels after operation were lower, and the hepaplastin tests were higher in the OKY group than those of the control (P < 0.05).
                These results demonstrated that hepatectomy under ischemia elevated the prostanoid levels. OKY 046 significantly reduced the TXB2 levels and the degree of hepatic damage in hepatectomy under ischemia. A new, highly purified inactivated tick-borne encephalitis (TBE) vaccine (FSME-Vaccine Behring, BI 71.061) was recently registered in Germany. A multinational phase II study was performed in seven centres located in areas endemic for TBE. A total of 379 healthy adults were randomly allocated into three dosage groups (1.0, 1.5 and 2.0 micrograms antigen per dose, respectively) and into two immunization schedules [vaccination with one dose of 0.5 ml intramuscularly on days 0, 7 and 21 (abbreviated schedule), or on days 0, 28 and 300 (conventional schedule)]. Antibody response to vaccination was assayed by enzyme-linked immunosorbent assay (ELISA), haemagglutination inhibition test (HIT) and neutralization test (NT). Seroconversion rates in the different groups 28 days after one single dose were 75.3-83.5% in ELISA, 35.8-50.6% in HIT, and 100% in NT. All vaccinees showed seroconversion in all tests on day 42 in the conventional schedule and on day 35 in the abbreviated schedule, with the exception of one subject, who remained seronegative in HIT only. Geometric mean titres (GMT) of about 3000 in ELISA were achieved by two vaccinations in the conventional schedule and showed a booster increase to 5500-8000 GMT after revaccination on day 300. Overall frequency of adverse events (related and unrelated) was 37% (conventional schedule) and 46% (abbreviated schedule) after the first, 9% and 21% after the second, and 5% and 15% after the third vaccination, respectively. Generally, side effects were mild and transient, including mainly headache, fever, malaise and local irritation. Serious, vaccine-related side effects did not occur.(ABSTRACT TRUNCATED AT 250 WORDS) Efficacy and safety of a low molecular weight heparin (Alfa LMWH) was compared with unfractionated heparin (UFH) in the prevention of post-operative venous thromboembolism after hip fractures. Forty-nine patients were randomized to treatment with Alfa LMWH 7500 anti-Xa coagulometric units twice daily or with UFH 5000 IU t.i.d. Screening for thrombosis was performed with 125-I-fibrinogen leg scanning and strain-gauge plethysmography. Positive results were confirmed by venography. Five patients in the Alfa LMWH group (20 per cent) developed venographycally proven deep vein thrombosis (DVT) versus seven (29 per cent) in the UFH group. One pulmonary embolism and two deaths occurred in the UFH group and none in the LMWH group. No differences in haemorrhagic complications and blood loss indices were observed. Alfa LMWH appears to be a promising drug for prevention of venous thromboembolism after orthopaedic surgery. A "flexible" schedule of administration is proposed on the basis of the results of plasma anti-Xa assays. This study was undertaken to evaluate the effect of low molecular weight heparin (LMWH) compared with unfractionated heparin (UFH) on the rate of occlusion and bleeding during peripheral vascular surgery.
                The study was an open label, prospective, randomized trial, carried out by 20 Swedish surgical and vascular surgical departments that report to the Swedish Vascular Registry (SWEDVASC). Study subjects included patients undergoing peripheral vascular procedures, except carotid surgery. Of the 849 patients included, 817 were followed up to 30 days. LMWH (40 mg of enoxaparin) or UFH (5000 IU heparin) was given intravenously immediately before clamping. The same formulation in diluted form was used for vascular rinsing. Main outcome measures included patent reconstruction at day 1, perioperative blood loss, and the percentage of patients requiring protamin. Further, 30-day data for mortality, repeat operation, and recurrent occlusion are reported.
                The mortality rate at 30 days was 2.7%, with no difference between groups. The patency rate at 1 day was 91.2% to 98.4%, depending on diagnosis and type of reconstruction. No difference was recorded between study groups (0.6 < P < 1.0). At 30 days the patency rate was 83.1% to 100% (0.2 < P <.9). Median blood loss was 350 mL (interquartile range [IQR], 200-800 mL) in the LMWH group and 425 mL (IQR, 200-900 mL) in the UFH group (P =.02). Protamin was given to significantly fewer patients in the LMWH group (P =.001). LMWH was comparable to UFH during peripheral vascular reconstruction in terms of 1-day and 30-day graft patency, operative blood loss, and hemorrhagic complications. Protamine was required less often after LMWH. In this randomized trial LMWH was as effective as UFH in preventing thrombosis without excess bleeding or hemorrhagic complications.
There was a lower incidence of HIT and HIT complicated by VTE in postoperative patients undergoing thromboprophylaxis with LMWH compared with UFH. This is consistent with the current clinical use of LMWH over UFH as front-line heparin therapy. However, conclusions are limited by a scarcity of high quality evidence. We did not expect the paucity of RCTs including HIT as an outcome as heparin is one of the most commonly used drugs worldwide and HIT is a life-threatening adverse drug reaction. To address the scarcity of clinically-relevant information on the topic of HIT as a whole, HIT should be included as an outcome in future RCTs of heparin, and HIT as an adverse drug reaction should be considered in clinical recommendations regarding monitoring of the platelet count for HIT.