Developments in mechanical thrombectomy devices for the treatment of acute ischemic stroke

Several recent prospective randomized controlled trials of endovascular stroke therapy using latest generation thrombectomy devices, so called stent-retrievers, have shown significantly improved clinical outcome compared to the standard treatment with intra-venous thrombolysis using r-tPA alone. Despite some differences in inclusion criteria between these studies, all required non-invasive vessel imaging to proof occlusion of a major brain supplying vessel. Furthermore, in most studies additional imaging techniques were used to exclude patients with already established large cerebral infarction or unfavorable collateral or penumbral status. Patients with small infarct volume, severe neurological deficits and in whom thrombectomy can be initiated within the first 6 hours after symptom onset seem to benefit the most. Therefore, mechanical thrombectomy using stent-retrievers in addition to intra-venous thrombolysis is recommended for the treatment of acute ischemic stroke with proven major vessel occlusion in the anterior circulation.

Open radical cystectomy: still the gold standard for muscle invasive bladder cancer

INTRODUCTION Muscle invasive bladder cancer is an unforgiving disease, and if untreated, it leads to death within 2 years of the diagnosis in >85 % of the patients. Long-term oncologic efficacy remains the ultimate standard that all procedures have to be measured by. In the past decades, open radical cystectomy (RC), extended pelvic lymph node dissection (PLND), and urinary diversion have been established as the gold standard. In the last few years, however, growing attention has been set on robotic-assisted radical cystectomy (RARC). RESULTS Even in the very long term, open RC has good oncological results and if an ileal neobladder is performed excellent functional results. Follow-up of patients after open RC exceeds more than a decade which is unsurpassed by any other technique. Its outcomes have been proven to be durable and cost-effective. Least perioperative complications as well as best oncological and functional results can be achieved if open RC and urinary diversion were performed in a high-volume hospital by high-volume surgeons and an experienced team. CONCLUSIONS Despite upcoming new technologies such as RARC, open RC following extended (PLND) remains the gold standard treatment for high-grade muscle invasive bladder cancer.

Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment-Resistant Schizophrenia: A Network Meta-analysis.

Importance In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. Objective To integrate all the randomized evidence from the available antipsychotics used for treatment-resistant schizophrenia by performing a network meta-analysis. Data Sources MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. Study Selection At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. Data Extraction and Synthesis At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. Main Outcomes and Measures The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. Results Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. Conclusions and Relevance Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence.

Treatment of optic neuritis with erythropoietin (TONE): a randomised, double-blind, placebo-controlled trial-study protocol.

INTRODUCTION Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. METHODS AND ANALYSIS Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33 000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. ETHICS AND DISSEMINATION TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. TRIAL REGISTRATION NUMBER NCT01962571.

Near infra-red-activatable nanocarriers for selective cancer diagnosis and treatment

Standard treatment strategies for cancer patients include surgery, radiation therapy, and chemotherapy. Although these strategies have been proven effective, they also have associated limitations. An attractive and innovative approach that can be used alone or in combination with the above modalities is based on the systemic or topical administration of a nanomaterial-based photoactive compound. Interaction with light in the near infrared (NIR) region results in either emission of fluorescence, which can be used for photodetection, or absorption of light which results in phototherapy. Nanomaterials have the advantage of providing multi-functional and unique properties in a single device that cannot be readily acquired with conventional small molecular weight compounds. ^ In this study, three different novel nanocarrier systems were designed and evaluated in mediating photodetection and phototherapy in the NIR. The first compound synthesized was a dual-labeled magnetic resonance/optical imaging agent for sentinel lymph node mapping and biopsy. This dual-labeled agent combines the high resolution of magnetic resonance imaging with the highly sensitive detection of optical imaging. The second imaging agent was an activatable optical imaging agent used to monitor cathepsin B activity in vivo and to probe the degradation of poly(L-glutamic acid). This polymeric nanocarrier offers highly sensitive technique for the detection of enzymatic activity, with is not yet possible with small molecular weight compounds. The third agent was a C225-conjugated hollow nanoshell that is targeted to epidermal growth factor receptors. This targeting agent has been demonstrated to mediate photothermal therapy both in vitro and in vivo. ^ These nanocarrier systems are an invaluable tool for the detection of cancer and many other diseases. With improved targeted delivery of these agents, the ability to diagnose diseases will become more sensitive and more specific. Finally, when designed properly, these agents would allow concurrent diagnosis and treatment of patients of various diseases. ^

A systematic review of the evidence for use of herbal medicine for the treatment of acute diarrhea

Background. Acute diarrhea (AD) is an important cause of morbidity and mortality among both children and adults. An ideal antidiarrheal treatment should be safe, effective, compatible with Oral Rehydration Solution, and inexpensive. Herbal medicines, if effective, should fit these criteria as well or better than standard treatment. ^ Objective. The objective of the present study was to assess the effectiveness of plant preparations in patients with AD in reports of randomized and non-randomized controlled trials. ^ Aims. The aims of the present study were to identify effective antidiarrheal herbs and to identify potential antidiarrheal herbs for future studies of efficacy through well designed clinical trials in human populations. ^ Methods. Nineteen published studies of herbal management of AD were examined to identify effective plant preparations. Ten plant preparations including Berberine (Berberis aristata), tormentil root ( Potentialla tormentilla), baohauhau (from the baobaosan plant), carob (Ceratonia siliqua), pectin (Malus domestica), wood creosote (Creosote bush), guava (Psidium guajava L.), belladonna (Atropa belladonna), white bean (Phaseolis vulgaris), and wheat (Triticum aestivum) were identified. ^ Results. Qualitative data analysis of nineteen clinical trials indicated berberine’s potentially valuable antisecretory effects against diarrhea caused by Vibrio cholerae and enterotoxigenic Escherichia coli. Tormentil root showed significant efficacy against rotavirus-induced diarrhea; carob exhibited antidiarrheal properties not only by acting to detoxify and constipate but by providing a rich source of calories; guava and belladonna are antispasmodics and have been shown to relieve the symptoms of AD. Finally, white bean and wheat yielded favorable clinical and dietary outcomes in children with diarrhea. ^ Conclusion. The present study is the first to review the evidence for use of herbal compounds for treatment of AD. Future randomized controlled trials are needed to evaluate their efficacy and safety.^

Assessing the patterns of colorectal cancer treatment, adherence to treatment guidelines and survival in Texas

Colorectal cancer (CRC) is the third leading cancer in both incidence and mortality in Texas. This study investigated the adherence of CRC treatment to standard treatment guidelines and the association between standard treatment and CRC survival in Texas. The author used Texas Cancer Registry (TCR) and Medicare linked data to study the CRC treatment patterns and factors associated with standard treatment in patients who were more than 65 years old and were diagnosed in 2001 through 2007. We also determined whether adherence to standard treatment affect patients' survival. Multiple logistic regression and Cox regression analysis were used to analyze our data. Both regression models are adjusted for demographic characteristics and tumor characteristics. We found that for the 3977 regional colon cancer patients 80 years old or younger, 60.2% of them received chemotherapy, in adherence to the recommended treatment guidelines. People with younger age, female gender, higher education and lower comorbidity score are more likely adherent to this surgery guideline. Patients' adherence to chemotherapy in this cohort have better survival compared to those who are not (HR: 0.76, 95% CI: 0.68-0.84). For the 12709 colon cancer patients treated with surgery, 49.3% have more than 12 lymph nodes removed, in adherence to the treatment guidelines. People with younger age, female gender, higher education, regional stage, lager tumor size and lower comorbidity score are more likely to adherent to this surgery guideline. Patients with more than 12 lymph nodes removed in this cohort have better survival (HR: 0.86, 95% CI: 0.82-0.91). For the 1211 regional rectal cancer patients 80 years old or younger, 63.2% of them were adherent to radiation treatment. People with smaller tumor size and lower comorbidity score are more likely to adherent to this radiation guideline. There is no significant survival difference between radiation adherent patients and non-adherent patients (HR: 1.03, 95% CI: 0.82-1.29). For the 1122 regional rectal cancer patients 80 years old or younger who were treated with surgery, 76.0% of them received postoperative chemotherapy, in adherence to the treatment guidelines. People with younger age and smaller comorbidity score are related with higher adherence rate. Patients adherent with adjuvant chemotherapy in this cohort have better survival than those were not adherent (HR: 0.60, 95% CI: 0.45-0.79).^

Can Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography Be Used As a Useful Method to Evaluate the Treatment Response to Neoadjuvant Therapy Combined With Sorafenib and Anti-VEGF in Children Diagnosed With Metastatical Bone Sarcoma?

Background: The prognosis is still poor for patients with a metastatic bone tumor and new treatment approaches (anti-VEGF and tyrosine kinase inhibitors vs) are therefore needed. Objectives: The aim of our study was to evaluate how the primary and metastatic lesions of our patients with a bone tumor were affected by these treatments and to determine the importance of the 18F-FDG PET method. Patients and Methods: Twenty metastatic bone tumor cases were included. Sorafenib and anti-VEGF were added to the standard treatment in cases with widespread metastatic disease at diagnosis or after neoadjuvant chemotherapy showing less than 90% tumor necrosis in the surgical sample. Positron emission tomography (PET) imaging was performed at diagnosis, the preoperative period following neoadjuvant chemotherapy, during postoperative follow-up, and when treatment was discontinued. Results: The primary treatment region median SUVmax level decreased from 7.35 to 2.5 in the living patients (n = 16) while there was no significant decrease in the patients who succumbed to the disease (P < 0.001). Comparison of the pre- and post-treatment metastasis region median SUVmax levels in patients with metastatic involvement showed a decrease from 2.1 to 0 in the surviving patients but only from 4.8 to 3.2 in the deceased patients (P < 0.01). Survival results indicated that 28.6% of the patients receiving classical treatment only died while all the patients receiving additional sorafenib and anti-VEGF survived. Conclusions: 18F-PET may be a useful technique before and during the follow-up of neoadjuvant treatment in pediatric metastatic bone tumor patients. The addition of sorafenib and anti-VEGF to classical treatment has a favorable contribution to the response and therefore the survival duration.

Is it necessary to re-fuse a non-union of a hallux metatarsophalangeal joint arthrodesis?

BACKGROUND: The standard treatment for a non-union of the hallux metatarsophalangeal joint fusion has been to revise the fusion. Revision fusion is technically more demanding, often involving bone grafting, more substantial fixation and prolonged period of immobilization postoperatively. We present data to suggest that removal of hardware and debridement alone is an alternative treatment option. ---------- MATERIALS AND METHODS: A case note review identified patients with a symptomatic non-union after hallux metatarsophalangeal joint (MTPJ) fusion. It is our practice to offer these patients revision fusion or removal of hardware and debridement. For the seven patients that chose hardware removal and were left with a pseudarthrosis, a matched control group was selected from patients who had had successful fusions. Three outcome scores were used. Hallux valgus and dorsiflexion angles were recorded.---------- RESULTS: One hundred thirty-nine hallux MTPJ arthrodeses were carried out. Fourteen non-unions were identified. The rate of non-union in males and following previous hallux MTPJ surgery was 19% and 24%, respectively. In females undergoing a primary MTPJ fusion, the rate was 2.4%. Twelve non-union patients were reviewed at 27 months (mean). Eleven patients had elected to undergo removal of hardware and debridement. Four patients with pseudarthrosis were unhappy with the results and proceeded to either revision fusion or MTPJ replacement. Seven non-union patients, who had removal of hardware alone, had outcome scores marginally worse compared to those with successful fusions.---------- CONCLUSION: Removal of hardware alone is a reasonable option to offer as a relatively minor procedure following a failed arthrodesis of the first MTPJ. This must be accepted on the proviso that in this study four out of 11 (36%) patients proceeded to a revision first MTPJ fusion or first MTPJ replacement. We also found that the rate of non-union in primary first MTPJ fusion was significantly higher in males and those patients who had undergone previous surgery.

Bariatric surgery or medicine for type 2 diabetes?

Diet and medical treatment are the standard treatment for type 2 diabetes. In obese subjects with type 2 diabetes, bariatric surgery is effective in resolving diabetes. Two clinical trials comparing bariatric surgery to medical treatment were evaluated. Both the Surgical Treatment And Medications Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial (laparoscopic Roux-En Y gastric bypass and sleeve gastrectomy) and the DIet and medical therapy versus BAriatric SurgerY in type 2 diabetes (DIBASY) trial (laparoscopic gastric bypass and biliopancreatic-diversion) showed that surgery was more effective than medical care in resolving or managing type 2 diabetes. Larger studies, or a compilation of studies, are needed to determine whether one of these procedures is better, or if they are all similarly effective, and this should also be weighed against the risk of the operations.

A randomized controlled pilot study comparing aqueous cream with a beeswax and herbal oil cream in the provision of relief from postburn pruritis

Postburn itch is reported to affect up to 87% of the burn population. Although treatments for postburn itch are multimodal, they remain consistently ineffective. However, recent anecdotal evidence from several outpatients at a tertiary referral hospital suggests that a cream combining beeswax and several herbal oils may be effective in the minimization of postburn itch. The aim of this study was to test the efficacy of beeswax and herbal oil cream against the standard treatment of aqueous cream in the provision of relief from the symptoms of postburn itch. A randomized controlled trial compared two groups using a visual analog scale, frequency of cream application, itch recurrence after cream application, use of antipruritic medications, and sleep disturbance to determine the effect of itch severity and duration. Fifty-two participants were enrolled in the study (84% male) with a mean age of 35 years (SD = 16) and mean burn TBSA of 7.2% (SD = 7.7). Study results found that the beeswax and herbal oil cream reduce itch after application more frequently than aqueous cream (P = .001). In addition, when managed with beeswax and herbal oil cream, participants found that their itch recurred later (P ≤ .001) and their use of antipruritic medications was lower (P = .023). Findings of this study suggest beeswax and herbal oil cream to be more effective in the minimization of postburn itch than aqueous cream. Given this, a larger study examining the efficacy of beeswax and herbal oil cream appears warranted.

Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: Results from two phase I studies

Purpose: PTK787/ZK 222584 (PTK/ZK), an orally active inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, inhibits VEGF-mediated angiogenesis. The pharmacodynamic effects of PTK/ZK were evaluated by assessing changes in contrast-enhancement parameters of metastatic liver lesions using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced colorectal cancer treated in two ongoing, dose-escalating phase I studies. Patients and Methods: Twenty-six patients had DCE-MRI performed at baseline, day 2, and at the end of each 28-day cycle. Doses of oral PTK/ZK ranged from 50 to 2000 mg once daily. Tumor permeability and vascularity were assessed by calculating the bidirectional transfer constant (Ki). The percentage of baseline Ki (% of baseline Ki) at each time point was compared with pharmacokinetic and clinical end points. Results: A significant negative correlation exists between the % of baseline Ki and increase in PTK/ZK oral dose and plasma levels (P = .01 for oral dose; P = .0001 for area under the plasma concentration curve at day 2). Patients with a best response of stable disease had a significantly greater reduction in Ki at both day 2 and at the end of cycle 1 compared with progressors (mean difference in % of baseline Ki, 47%, P = .004%; and 51%, P = .006; respectively). The difference in % of baseline Ki remained statistically significant after adjusting for baseline WHO performance status. Conclusion: These findings should help to define a biologically active dose of PTK/ZK. These results suggest that DCE-MRI may be a useful biomarker for defining the pharmacological response and dose of angiogenesis inhibitiors, such as PTK/ZK, for further clinical development. © 2003 by American Society of Clinical Oncology.

What do most Americans think of cost-effectiveness research in health care?

My impression is that explicit data on the cost-effectiveness of different health care services are not valued highly by US policy makers. An example is a recent decision to approve ipilimumab for the treatment of metastatic melanoma. The extra health benefit over standard treatment is 2.1 months in previously untreated patients and the cost is $120,000 for 4 doses. This is poor value for money. Had $120,000 been allocated to an intensive lifestyle modification programme for diabetes risk (Diabet Med. 2004 Nov;21(11):1229-36) then 67 years of life or 800 months could have been returned. A massive increase in health benefits for the same costs.

What are the barriers of quality survivorship care for haematology cancer patients? Qualitative insights from cancer nurses

Purpose: Many haematological cancer survivors report long-term physiological and psychosocial effects beyond treatment completion. These survivors continue to experience impaired quality of life (QoL) as a result of their disease and aggressive treatment. As key members of the multidisciplinary team, the purpose of this study is to examine the insights of cancer nurses to inform future developments in survivorship care provision. Methods: Open text qualitative responses from two prospective Australian cross-sectional surveys of nurses (n=136) caring for patients with haematological cancer. Data were analysed thematically, using an inductive approach to identify themes. Results: This study has identified a number of issues that nurses perceive as barriers to quality survivorship care provision. Two main themes were identified; the first relating to the challenges nurses face in providing care (‘care challenges’), and the second relating to the challenges of providing survivorship care within contemporary health care systems (‘system challenges’). Conclusions: Cancer nurses perceive the nature of haematological cancer and its treatment, and of the health care system itself, as barriers to the provision of quality survivorship care. Care challenges such as the lack of a standard treatment path and the relapsing or remitting nature of haematological cancers may be somewhat intractable, but system challenges relating to clearly defining and delineating professional responsibilities and exchanging information with other clinicians are not. Implications for Cancer Survivors: Addressing the issues identified will facilitate cancer nurses’ provision of survivorship care, and help address haematological survivors’ needs with regard to the physical and psychosocial consequences of their cancer and treatment.

Combined pharmacotherapy and psychological therapies for post traumatic stress disorder (PTSD)

BACKGROUND PTSD is an anxiety disorder related to exposure to a severe psychological trauma. Symptoms include re-experiencing the event, avoidance and arousal as well as distress and impairment resulting from these symptoms.Guidelines suggest a combination of both psychological therapy and pharmacotherapy may enhance treatment response, especially in those with more severe PTSD or in those who have not responded to either intervention alone. OBJECTIVES To assess whether the combination of psychological therapy and pharmacotherapy provides a more efficacious treatment for PTSD than either of these interventions delivered separately. SEARCH STRATEGY Searches were conducted on the trial registers kept by the CCDAN group (CCDANCTR-Studies and CCDANCTR-References) to June 2010. The reference sections of included studies and several conference abstracts were also scanned. SELECTION CRITERIA Patients of any age or gender, with chronic or recent onset PTSD arising from any type of event relevant to the diagnostic criteria were included. A combination of any psychological therapy and pharmacotherapy was included and compared to wait list, placebo, standard treatment or either intervention alone. The primary outcome was change in total PTSD symptom severity. Other outcomes included changes in functioning, depression and anxiety symptoms, suicide attempts, substance use, withdrawal and cost. DATA COLLECTION AND ANALYSIS Two or three review authors independently selected trials, assessed their 'risk of bias' and extracted trial and outcome data. We used a fixed-effect model for meta-analysis. The relative risk was used to summarise dichotomous outcomes and the mean difference and standardised mean difference were used to summarise continuous measures. MAIN RESULTS Four trials were eligible for inclusion, one of these trials (n =24) was on children and adolescents. All used an SSRI and prolonged exposure or a cognitive behavioural intervention. Two trials compared combination treatment with pharmacological treatment and two compared combination treatment with psychological treatment. Only two trials reported a total PTSD symptom score and these data could not be combined. There was no strong evidence to show if there were differences between the group receiving combined interventions compared to the group receiving psychological therapy (mean difference 2.44, 95% CI -2.87, 7.35 one study, n=65) or pharmacotherapy (mean difference -4.70, 95% CI -10.84 to 1.44; one study, n = 25). Trialists reported no significant differences between combination and single intervention groups in the other two studies. There were very little data reported for other outcomes, and in no case were significant differences reported. AUTHORS' CONCLUSIONS There is not enough evidence available to support or refute the effectiveness of combined psychological therapy and pharmacotherapy compared to either of these interventions alone. Further large randomised controlled trials are urgently required.