Standard Medical Intervention Research Articles

A Functional Restoration Program for Active Duty Service Members With Chronic Pain: Examining the Impact of Co-occurring PTSD on Treatment Response.

Standard medical intervention for chronic pain may be less effective in the presence of co-occurring PTSD. Functional restoration programs (FRPs), which combine psychological interventions and progressive exercise rehabilitation, represent an alternative to standard medical intervention for chronic pain. The objective of the current study is to evaluate a FRP serving Active Duty Service Members with chronic pain and to examine whether co-occurring PTSD symptoms are associated with differential treatment response. This is a retrospective observational study of data previously collected at Naval Medical Center San Diego approved by the Naval Medical Center San Diego Institutional Review Board. The study included 81 Active Duty Service Members, primarily Sailors and Marines, who completed a FRP, and examined pre- to post-treatment changes in Pain Impact Score-a composite measure of pain intensity, pain interference, and physical functioning-as well as measures of mental health and pain cognitions. Co-occurring PTSD symptoms were examined as a potential moderator of treatment response. Twenty-three patients (28.4%) screened positive for PTSD during baseline assessments. Repeated measures analysis of variance showed statistically significant improvement in Pain Impact Score for the full sample (P <.001). Although no significant interactions with probable PTSD were demonstrated for measures of pain intensity and physical functioning (both Ps >.05), patients screening positive for PTSD demonstrated a lesser decrease in pain interference compared to patients screening negative for PTSD (P <.01). Improvements in measures of mental health and pain cognitions were also statistically significant for the full sample (all P values <.05) and did not differ as a function of PTSD symptoms (all P values >.05). This FRP primarily serving Sailors and Marines contributed to broad overall improvements in the domains of pain and functioning as well as mental health and pain cognitions. Co-occurring PTSD symptoms were not associated with poorer treatment response on most measured outcomes.

Controlled ovarian stimulation in cancer patients under 18 years old; a case series

BackgroundFertility preservation for adolescent pubescent girls is a concern of the healthcare system and parents. Oocyte cryopreservation is regarded as a standard medical intervention for patients with a minimum age of 18 years. Evidence suggests that mature oocyte cryopreservation is possible for adolescent pubescent girls, although, ovarian stimulation for these patients remains a challenge.Cases presentationThis case series is the first report regarding ovarian stimulation with oocyte cryopreservation in younger than 18 years cancerous girls, who refer to ROYAN institute, Tehran, Iran, prior to the start of the treatment of cancer (November 2015 to February 2021). The oocyte cryopreservation was carried out in the 7 patients (five patients with Hodgkin lymphoma, one patient with Ewing sarcoma, and one patient with osteogenic tumor), the embryo cryopreservation in one patient with dysgerminoma, and the oocyte and embryo cryopreservation in one patient with germ cell tumor. No oocytes were retrieved after ovarian stimulation in the patient with medulloblastoma. For one of the patients with Hodgkin lymphoma, half of the tissues of one ovary were cryopreserved prior to ovarian stimulation.ConclusionsOocyte cryopreservation is a feasible option of fertility preservation in the adolescent’s patients with cancer. However, only if reported acceptable fertilization rates, as well as the successful cases of live birth from oocyte cryopreservation at the ages under 18, this option of preserving fertility can be applied to this age range.

Chinese Expert Consensus on Management of Special Adverse Effects Associated with Lorlatinib

间变性淋巴瘤激酶（anaplastic lymphoma kinase, ALK）融合基因是非小细胞肺癌（non-small cell lung cancer, NSCLC）中第二常见的肿瘤驱动基因。作为新型的第三代ALK酪氨酸激酶抑制剂（tyrosine kinase inhibitor, TKI），洛拉替尼对多种ALK激酶域突变具有广谱且高效的临床活性，并具有强大的穿透血脑屏障效力。洛拉替尼的总体耐受性良好，其独特的不良反应或不良事件包括高脂血症与中枢神经系统反应等，多为轻至中度，通常经剂量调整和/或标准医疗干预即可管理。对于ALK阳性晚期NSCLC，开始洛拉替尼治疗前应充分评估患者基线特征与既往用药状况，预先告知患者可能经历的用药相关不良反应，并定期监测以实现药物临床获益的最大化。同时，多学科专家团队对于建立全面的诊断和治疗策略是至关重要的。

HDL functionality in type 1 diabetes: enhancement of cholesterol efflux capacity in relationship with decreased HDL carbamylation after improvement of glycemic control

BackgroundReduced cholesterol efflux capacity (CEC) of HDLs is likely to increase cardiovascular risk in type 1 diabetes (T1D). We aimed to assess whether improvement of glycemic control in T1D patients is associated with changes in CEC in relation with changes in carbamylation of HDLs.MethodsIn this open-label trial, 27 uncontrolled T1D patients were given a three-month standard medical intervention to improve glycemic control. HDL fraction was isolated from plasma, and CEC was measured on THP-1 macrophages. Carbamylation of HDLs was evaluated by an immunoassay. Control HDLs from healthy subjects were carbamylated in vitro with potassium cyanate.ResultsHbA1c decreased from 11.4% [10.2–12.9] (median [1st–3rd quartiles]) at baseline to 8.1% [6.6–9.0] after the three-month intervention (P < 0.00001). The CEC of HDLs increased after intervention in 19 (70%) patients (P = 0.038). At the same time, the carbamylation of HDLs decreased in 22 (82%) patients after intervention (P = 0.014). The increase in CEC significantly correlated with the decrease in carbamylated HDLs (r = −0.411, P = 0.034), even after adjustment for the change in HbA1c (β = −0.527, P = 0.003). In vitro carbamylation of control HDLs decreased CEC by 13% (P = 0.041) and 23% (P = 0.021) using 1 and 10 mmol/L of potassium cyanate, respectively.ConclusionsThe improvement of CEC in relation to a decrease in the carbamylation of HDLs may likely contribute to the beneficial cardiovascular effect of glycemic control in T1D patients.Trial registration: NCT02816099 ClinicalTrials.gov.

Effect of Tratak (Yogic Ocular Exercises) on Intraocular Pressure in Glaucoma: An RCT.

Introduction:In healthy subjects, the intraocular pressure (IOP) is maintained by a dynamic equilibrium between continuous production of aqueous humor by ciliary bodies and continuous outflow through the two drainage pathways: trabecular meshwork and uveoscleral outflow. Here, we hypothesized that yogic ocular exercises, including extraocular muscles exercise, and modified Tratak Kriya (mTK), might reduce the IOP as well as stress and improve quality of life (QoL) in patients with glaucoma.Methodology:A parallel two-arm randomized controlled trial (RCT) was conducted in glaucoma patients (Control group and Intervention group). Control group patients were on standard medical treatment and intervention group patients practiced a Yoga-based lifestyle intervention (YBLI) for 4 weeks as add-on therapy with their standard medical treatment. All Participants were assessed at baseline day 1, day 14 (D14), and day 28 (D28). A minimum of 30 patients were recruited in each group.Results:We did not observe any statistically significant different mean IOP of right (IOP-r) or, left eyes at any time point as well as cortisol level and QoL between the two groups. However, with in intervention group, there was a reduction in IOP-r at D14 (15.54 ± 2.81 mmHg) and D28 (15.24 ± 3.1 mmHg), P = 0.006 and 0.001, respectively, compared to their baseline IOP (16.26 ± 2.98).Conclusion:Based on the present RCT, yoga-based ocular exercises practiced here cannot be recommended for management of raised IOP in glaucoma patients. Further larger studies are warranted with yoga-based interventions in patients with glaucoma.Clinical Trial Registration Number:CTRI/2016/03/006703

The Proton Pump Inhibitor Nonresponder: a Behavioral Approach to Improvement and Wellness.

Gastroesophageal reflux disease (GERD) is a difficult to treat medical condition, where nearly 40% of patients are refractory to standard medical intervention, which typically begins with a proton pump inhibitor (PPI). These PPI nonresponders represent a population of patients, where treatment planning must be individualized; multidisciplinary and psychiatric comorbidities should be considered. This review highlights treatment options that include neuromodulators, lifestyle, and psychological interventions for the PPI nonresponder. Mental health specialists in the field of psychogastroenterology can aid in the management of esophageal hypersensitivity, which can drive the symptom experience of a PPI nonresponder. Considerations for comorbid anxiety and depression in this population require careful assessment and treatment. Physicians are encouraged to create realistic expectations for symptom management and offer multidisciplinary options for treatment early in care. Patients will frequently benefit from working with a GI psychologist and find value in behavioral interventions.

Chinese Classical Formula Sijunzi Decoction and Chronic Atrophic Gastritis: Evidence for Treatment Approach?

Objective This aim is to evaluate the effect of Sijunzi decoction (SJZD) treating chronic atrophic gastritis (CAG). Methods We performed searches in seven databases. The randomized controlled trials (RCTs) comparing SJZD with standard medical care or inactive intervention for CAG were enrolled. Combined therapy of SJZD plus conventional therapies compared with conventional therapies alone was also retrieved. The primary outcome included the incidence of gastric cancer and the improvement of atrophy, intestinal metaplasia, and dysplasia based on the gastroscopy and pathology. The secondary outcomes were Helicobacter pylori clearance rate, quality of life, and adverse event/adverse drug reaction. Results Six RCTs met the inclusion criteria. The research quality was low in the trials. For the overall effect rate, pooled analysis from 4 trials showed that modified SJZD plus conventional medications exhibited a significant improvement (OR = 4.86; 95% CI: 2.80 to 8.44; P < 0.00001) and without significant heterogeneity compared with the conventional medications alone. None reported the adverse effect. Conclusions Modified SJZD combined with conventional western medicines appears to have benefits for CAG. Due to the limited number and methodological flaw, the beneficial and harmful effects of SJZD for CAG could not be identified. More high-quality clinical trials are needed to confirm the results.

Effects of Exercise and Sertraline on Measures of Coronary Heart Disease Risk in Patients With Major Depression: Results From the SMILE-II Randomized Clinical Trial.

To assess the effects of supervised and home-based aerobic exercise training, and antidepressant pharmacotherapy (sertraline) on coronary heart disease (CHD) risk factors in a sample of participants with major depressive disorder (MDD). The Standard Medical Intervention versus Long-term Exercise (SMILE)-II study randomized 202 adults (153 women, 49 men) diagnosed as having MDD to one of four interventions, each of 4-month duration: supervised exercise, home-based exercise, antidepressant medication (sertraline, 50-200 mg daily), or placebo pill. Patients underwent a structured clinical interview for depression and completed the Hamilton Depression Rating Scale. CHD risk factors included brachial artery flow-mediated dilation, carotid intima-media thickness, serum lipids, and 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Compared with placebo, active treatment of depression (supervised exercise, home-based exercise, sertraline therapy) was associated with an improvement in CHD risk factors (improved flow-mediated dilation [p = .032], reduced progression of intima-media thickness [p = .037], and a reduction in 10-year ASCVD [p = .049]). The active treatments did not differ from each other in their effects on the CHD risk outcomes. Both exercise and antidepressant medication improved CHD risk factors and lowered ASCVD risk in patients with MDD. Because MDD is associated with increased risk for CHD events, treatment of depression with exercise or sertraline may reduce the risk of developing CHD in patients with MDD. Clinical Trials Government Identifier: NCT-00331305.

Outcomes of modified endoscopic Lothrop in aspirin-exacerbated respiratory disease with nasal polyposis.

Patients with aspirin-exacerbated respiratory disease (AERD) and chronic rhinosinusitis with nasal polyps (CRSwNP) are often reported to be recalcitrant to standard medical and surgical intervention. Failure rates of standard endoscopic sinus surgery in these patients are reported to be as high as 90%. We review the outcomes for our cohort of AERD patients undergoing endoscopic sinus surgery and endoscopic modified Lothrop procedure (EMLP). Data was collected prospectively between January 2001 and December 2013. Information including demographics, asthma status, aspirin sensitivity, 22-item Sino-Nasal Outcome Test (SNOT-22), Lund-Mackay scores, and endoscopic ostium assessment were collected for up to 5 years. Minimum follow-up was 6 months. A total of 31 AERD patients underwent complete sphenoethmoidectomy, maxillary antrostomy and EMLP during the study period with an average follow-up of 36 months. Polyp recurrence was seen in a total of 18 patients (58%). Seven patients required revision EMLP following initial surgery demonstrating a failure rate of 22.5%. AERD patients had a statistically significant increased risk of both nasal polyps recurrence and need for revision surgery. Revision EMLP was needed due to recurrence of nasal polyps in 6 cases and frontal ostium stenosis in a single case. Time to revision EMLP was similar between the groups. Complete sphenoethmoidectomy, maxillary antrostomy, and EMLP is successful in a significant majority of patients with AERD and CRSwNP. It is well tolerated with a low complication rate and facilitates successful ongoing medical management of the condition in patients with AERD.

Impact of Sleep Complaints and Depression Outcomes Among Participants in the Standard Medical Intervention and Long-Term Exercise Study of Exercise and Pharmacotherapy for Depression

The aim of this study was to examine the effects of exercise and sertraline on disordered sleep in patients with major depressive disorder (MDD). Methods The Standard Medical Intervention and Long-term Exercise study randomized the patients with MDD (n = 202) to one of four arms: a) supervised exercise, b) home-based exercise, c) sertraline therapy, and d) placebo pill. Sleep disturbance was assessed with three sleep-related items from the Hamilton Rating Scale for Depression (HAM-D) before and after 4 months of treatment. The patients were followed for 12 months to assess the prognostic value of sleep disturbance on MDD relapse and recovery.Results Comparison of the active treatment and placebo groups showed no treatment differences in HAM-D sleep complaints after 4 months (p = 0.758). However, residual insomnia symptoms after treatment were strongly associated with elevated depressive symptoms assessed by the HAM-D after 4 months (β = 0.342, p < 0.0001) and MDD relapse (odds ratio, 1.55; 95% confidence interval, 1.15-2.10; p = 0.004) assessed at 1-year follow-up (16 months after randomization). Neither exercise nor sertraline was associated with greater improvements in sleep disturbance compared with the placebo controls. However, residual symptoms of insomnia after successful treatment of MDD predicted relapse, highlighting the clinical importance of addressing insomnia in patients with MDD.

Massive transfusion: An overview of the main characteristics and potential risks associated with substances used for correction of a coagulopathy

Massive transfusion (MT) is an empiric mode of treatment advocated for uncontrolled bleeding and massive haemorrhage, aiming at optimal resuscitation and aggressive correction of coagulopathy. Conventional guidelines recommend early administration of crystalloids and colloids in conjunction with red cells, where the red cell also plays a critical haemostatic function. Plasma and platelets are only used in patients with microvascular bleeding with PT/APTT values >1.5 times the normal values and if PLT counts are below 50×109/L.Massive transfusion carries a significant mortality rate (40%), which increases with the number of volume expanders and blood components transfused. Controversies still exist over the optimal ratio of blood components with respect to overall clinical outcomes and collateral damage. While inadequate transfusion is believed to be associated with poor outcomes but empirical over transfusion results in unnecessary donor exposure with an increased rate of sepsis, transfusion overload and infusion of variable amounts of some biological response modifiers (BRMs), which have the potential to cause additional harm. Alternative strategies, such as early use of tranexamic acid are helpful. However in trauma settings the use of warm fresh whole blood (WFWB) instead of reconstituted components with a different ratio of stored components might be the most cost effective and safer option to improve the patient’s survival rate and minimise collateral damage. This manuscript, after a brief summary of standard medical intervention in massive transfusion focuses on the main characteristics of various substances currently available to overcome massive transfusion coagulopathy. The relative levels of some BRMs in fresh and aged blood components of the same origin are highlighted and some myths and unresolved issues related to massive transfusion practice are discussed.In brief, the coagulopathy in MT is a complex phenomenon, often complicated by chronic activation of coagulation, platelets, complement and vascular endothelial cells, where haemolysis, microvesiculation, exposure of phosphatidyl serine positive cells, altered red cells with reduced adhesive proteins and the presence of some BRM, could play a pivotal role in the coagulopathy and untoward effects. The challenges of improving the safety of massive transfusion remain as numerous and as varied as ever. The answer may reside in appropriate studies on designer whole blood, combined with new innovative tools to diagnosis a coagulopathy and an evidence based mode of therapy to establish the optimal survival benefit of patients, always taking into account the concept of harm reduction and reduction of collateral damage.

Medical officers in Acute Care Settings: Their Views on Medically Assisted Hydration at the end of Life

This study explored the perceptions of doctors in acute care settings regarding the use of medically assisted hydration (MAH) in end-of-life care. The use of MAH at the end of life is controversial, and practice varies across health care settings. A qualitative study using discourse analysis was carried out. Eight medical practitioners in the acute care setting were interviewed individually. MAH has been associated with care, comfort, and standard medical intervention to save lives. Medical officers have some concerns about the benefits or adverse effects of MAH at the end of life. In acute care settings, it can be difficult to recognize and diagnose dying. Often, family discussions regarding end-of-life care do not occur due to pursuit of cure and, therefore, continuation of futile and burdensome treatment such as MAH can occur in the last few days of life.

Axitinib for the Management of Metastatic Renal Cell Carcinoma

In recent years, targeted agents have changed the treatment landscape for patients with advanced renal cell carcinoma (RCC), greatly improving treatment outcomes. Several targeted agents are now licensed for the treatment of metastatic RCC (mRCC), and a number of new agents are under investigation. Axitinib, a small molecule indazole derivative is an oral, potent multitargeted tyrosine kinase receptor inhibitor, which selectively inhibits vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 at subnanomolar concentrations, in vitro. In various nonclinical models, axitinib has demonstrated in vivo target modulation and antiangiogenesis. In pharmacokinetic studies, axitinib administered orally with food at the proposed regimen of 5mg twice daily continuous daily dosing, is rapidly absorbed, reaching peak concentrations within 2–6 hours. Axitinib is metabolized primarily in the liver via the cytochrome P450 (CYP) system with less than 1% of the administered drug passing unchanged in the urine. The pharmacokinetics of axitinib do not appear to be altered by coadministered chemotherapies, and antacids do not have a clinically significant effect. However, coadministration with CYP3A4 and 1A2 inducers is contraindicated. In addition, proton pump inhibitors reduce the rate of axitinib absorption. Increased axitinib exposure is associated with higher efficacy indicated by decreased tumor perfusion and volume. In three phase II clinical trials in patients with advancedRCCpreviously treated with cytokines, chemotherapy or targeted agents, axitinib has demonstrated antitumor activity with a favorable noncumulative toxicity profile. In one study of Western patients with cytokine-refractory mRCC, an objective response rate (ORR) of 44.2% (95% CI 30.5, 58.7) was achieved. The median time to progression was 15.7 months (95%CI 8.4, 23.4) and the median overall survival (OS) was 29.9 months (95%CI 20.3, not estimable). In the second study of patients with sorafenib-refractory mRCC, ORR was 22.6% (95% CI 12.9, 35.0). The median progression-free survival (PFS) was 7.4 months (95% CI 6.7, 11.0) and a median OS of 13.6 months (95% CI 8.4, 18.8) was achieved. Results from the third study in Japanese patients with cytokine-refractory mRCC reported an ORR of 55% and median PFS of 12.9 months (95% CI 9.8, 15.6).In the three studies, themost common adverse events reported were fatigue, hypertension, hand-foot syndrome (HFS), and gastrointestinal toxicity, which were generally manageable with standard medical intervention. Of note, the incidence of HFS and proteinuria in the Japanese study was higher than that reported in the Western study in cytokine-refractory mRCC patients.An observed association between diastolic blood pressure ≥90 mmHg and increased efficacy suggests potential use as a prognostic biomarker. However, this requires further investigation. Two randomized phase III clinical trials are ongoing to determine the efficacy of axitinib in patients with mRCC in the first- and second-line setting. These results will help to determine the place of axitinib in the mRCC treatment algorithm.

Sunitinib for the management of advanced renal cell carcinoma

Targeted agents, such as sunitinib (SUTENT®) have become central to the management of advanced and/or metastatic renal cell carcinoma (mRCC). Sunitinib is an oral, multitargeted receptor tyrosine kinase inhibitor that has demonstrated efficacy for the treatment of mRCC in multiple clinical trials. In a Phase III trial in previously untreated patients with mRCC, sunitinib was associated with median progression-free survival of 11 months, which was more than double that observed with interferon-α (5 months; p < 0.001). As a result, sunitinib is recommended in international treatment guidelines and is considered a reference standard of care in the first-line setting for patients at favorable or intermediate prognostic risk. Sunitinib is generally well tolerated with a predictable adverse-event profile; the majority of adverse events can be managed with standard medical intervention. This paper presents an overview of data supporting the use of sunitinib for mRCC, and considers the optimal management of sunitinib in clinical practice.

Psychological Treatments for Pediatric Functional Gastrointestinal Disorders

Our objective was to systematically review and evaluate behavioral and psychological treatments applied to pediatric functional gastrointestinal disorders. Electronic searches were conducted in bibliographic databases including PubMed, PsychInfo, and Medline. Psychological and behavioral interventions were classified into the following 5 primary treatment modalities: psychoeducation, behavior therapy/contingency management, relaxation-based therapies (including biofeedback and hypnotherapy), and cognitive-behavioral therapy (including cognitive-behavioral family therapy). There was a wide variation in the quality and quantity of studies within each treatment category. Effective interventions generally involved multiple therapeutic components and included elements of both individual and family treatment. Psychological interventions that combine psychoeducation, relaxation-based therapies, and cognitive-behavioral therapy appear superior to standard care (reassurance or dietary manipulation) in the elimination of pain and reduction in functional disability. Although many psychological treatments demonstrated evidence of positive effects, few well-designed randomized controlled trials of psychological treatments for functional gastrointestinal disorders exist. More work is needed to determine the most potent, essential elements of psychological treatments alone or in combination with standard medical intervention, and to establish their applicability with diverse populations. Clinical and research implications are discussed.

Distress in Pediatric Hematology-Oncology Patients Undergoing Intravenous Procedures: Evaluation of a CD-ROM Intervention

This study assessed the influence of a developmentally specific CD-ROM intervention on cognitive appraisals, fear, behavioral distress, and pain in pediatric hematology-oncology patients scheduled for intravenous (IV) procedures. Thirty children, 7 to 18 years of age, were randomly assigned either to a standard medical care group or a standard medical care plus CD-ROM intervention group. It was hypothesized that using the CD-ROM would decrease threat appraisals of the IV procedure, causing decreased fear of the IV, less behavioral distress, and less pain during the IV. It was also hypothesized that intervention-enhanced secondary appraisal would be seen in children in the CD-ROM intervention group and that they would cope more effectively with the IV procedure. Self-report and observational ratings were used to assess the following dependent variables: primary and secondary appraisal, fear, behavioral distress, and pain. Results indicated significant effects for the reduction of threat appraisals following CD-ROM intervention (p ??.05). Children in the CD-ROM intervention group used cognitive restructuring coping more effectively than did the control group (p ??.05). No significant effects were found for fear, behavioral distress, or pain.

Hyperkeratotic Rim of Gram-Negative Toe Web Infections

T HE LESIONS SHOWN ARE FROM THE PLANTAR surface of a foot of a 41-year-old white man (Figure1) and a foot of a 48-year-old white man (Figure 2). Each photograph represents a case of gram-negative toe web infection that was resistant to several courses of antibiotics, antifungal agents, and immunosuppressants, alone or in combination. With continued disease, development of a hyperkeratotic rim was noted in these 2 cases as well as in other cases seen at our institution. This hyperkeratotic rim pattern seems to be characteristic of toe web infections that are resistant to standard medical intervention. In our experience, surgical debridement of the hyperkeratotic rim and surface exudate with a standard curette with the patient under local anesthesia leads to rapid improvement (Figure 3) with routine wound care and without further medical therapy. The hyperkeratotic rim pattern may be the result of epidermal undermining of the polymicrobial infection and may serve both as a protected environment for the infecting agents and as a barrier to wound healing, blocking lateral epidermal migration. Editor’s Note: The skINsight section is a forum for the presentation of dermatologic images. The current effort is to foster the recognition of patterns in dermatologic disease processes that may enhance both diagnostic and research capabilities. The initial focus is on dermoscopic images. Theoretically, these patterns reflect the interaction of specific gene defects with local environmental factors. The exercise here is to group lesions with similar dermoscopic patterns—not pathologic criteria. The ultimate benign or malignant behavior is not the focus of this section.

Reduction of tremor severity and disability following behavioral relaxation training

The effects of behavioral relaxation training (BRT) for the treatment of moderate to severe essential tremor (ET) was evaluated with two older adults, ages 73 and 83, using a single-case design and statistical analysis. Measures included within-session clinician and self-rated tremor severity and disability in activities of daily living (ADL), EMG activity, and daily self-ratings of tremor severity and ADL disabilities. Following a brief 2–4 week baseline period BRT was conducted. Clinically significant reductions of 47–66% in within session clinical and self-rated tremor severity and daily self-ratings were obtained. Statistically significant changes in self- and clinician ratings occurred following BRT. In some cases, EMG activity also declined following intervention. Results at a seven week follow up were mixed and related to continued use of relaxation skills. While the cost ratio (medication: BRT) indicates that relaxation training is more expensive relative to standard medical intervention, cost–benefit to patients off sets the financial difference. Relaxation training may be an efficacious first step in a biobehavioral stepped care treatment model.

Treatment of malignant fluids with OK-432, a streptococcal preparation, plus interleukin-2, or tumor necrosis factor-alpha

Massive transfusion (MT) is an empiric mode of treatment advocated for uncontrolled bleeding and massive haemorrhage, aiming at optimal resuscitation and aggressive correction of coagulopathy. Conventional guidelines recommend early administration of crystalloids and colloids in conjunction with red cells, where the red cell also plays a critical haemostatic function. Plasma and platelets are only used in patients with microvascular bleeding with PT/APTT values >1.5 times the normal values and if PLT counts are below 50 × 109/L.Massive transfusion carries a significant mortality rate (40%), which increases with the number of volume expanders and blood components transfused. Controversies still exist over the optimal ratio of blood components with respect to overall clinical outcomes and collateral damage. While inadequate transfusion is believed to be associated with poor outcomes but empirical over transfusion results in unnecessary donor exposure with an increased rate of sepsis, transfusion overload and infusion of variable amounts of some biological response modifiers (BRMs), which have the potential to cause additional harm. Alternative strategies, such as early use of tranexamic acid are helpful. However in trauma settings the use of warm fresh whole blood (WFWB) instead of reconstituted components with a different ratio of stored components might be the most cost effective and safer option to improve the patient’s survival rate and minimise collateral damage. This manuscript, after a brief summary of standard medical intervention in massive transfusion focuses on the main characteristics of various substances currently available to overcome massive transfusion coagulopathy. The relative levels of some BRMs in fresh and aged blood components of the same origin are highlighted and some myths and unresolved issues related to massive transfusion practice are discussed.In brief, the coagulopathy in MT is a complex phenomenon, often complicated by chronic activation of coagulation, platelets, complement and vascular endothelial cells, where haemolysis, microvesiculation, exposure of phosphatidyl serine positive cells, altered red cells with reduced adhesive proteins and the presence of some BRM, could play a pivotal role in the coagulopathy and untoward effects. The challenges of improving the safety of massive transfusion remain as numerous and as varied as ever. The answer may reside in appropriate studies on designer whole blood, combined with new innovative tools to diagnosis a coagulopathy and an evidence based mode of therapy to establish the optimal survival benefit of patients, always taking into account the concept of harm reduction and reduction of collateral damage.