Effectiveness Of Available Treatments Research Articles

Effectiveness of physically ablative and pharmacological treatments for anal condyloma in HIV-infected men.

BackgroundThere is limited information on the effectiveness of available treatments for anal condyloma acuminata in HIV-1-infected men.AimTo provide data on the effectiveness of electrosurgical excision, infrared coagulation and pharmacological (imiquimod) treatments for anal condyloma acuminata (peri-anal and/or intra-anal) in HIV-1-infected men based on authors’ practice.MethodsSingle-center, retrospective descriptive analysis of HIV-1-infected men, 18 years or older treated for anal condyloma acuminata. Standard treatments were offered: electrosurgery excision, infrared coagulation and topical imiquimod. Effectiveness was evaluated by the recurrence rate at 1 year after treatment. Recurrence was defined as any anal condyloma acuminata diagnosed after 3 months of condyloma-free survival post-treatment. Anal cytology and human-papillomavirus-infection (HPV) was assessed.ResultsBetween January 2005 and May 2009, 101 men were treated for anal condyloma acuminata: 65 (64%) with electrosurgery, 27 (27%) with infrared coagulation and 9 (9%) with imiquimod. At 1 year after treatment, the cumulative recurrence rate was 8% (4/65, 95%CI: 2–15%) with electrosurgery excision, 11% (3/27, 95%CI: 4–28%) with infrared coagulation and 11% (1/9, 95%CI: 2–44%) with imiquimod treatment. No predictive factors were associated with recurrence.Anal HPV-6 or HPV-11 was detectable in 98 (97%) patients and all had high-risk HPV genotypes, and 89 (88%) patients had abnormal anal canal cytology. Limitations: this was a retrospective descriptive analysis; limited to a single center; it cannot know if the recurrence is related to new infection.ConclusionRecurrence of anal condyloma after any treatment was common. Abnormal anal cytology and high-risk HPV-infection were highly prevalent in this population, therefore at high-risk of anal cancer, and warrants careful follow-up.

Elderly psoriatic patients under biological therapies: an Italian experience.

The number of elderly patients with psoriasis is steadily increasing in the Western world; nevertheless, they are frequently excluded from biological clinical trials and described as a high-risk group for adverse events. Thus, there is lack of information concerning safety and effectiveness of available treatments for psoriasis in the elderly, particularly about new biological systemic drugs. Our aim was to describe our experience with all biological therapies currently used in the elderly (>65 years) psoriatic patients. A retrospective multicentric review of clinical records of all psoriatic patient aged 65 years or older actually receiving biological drugs (etanercept, adalimumab, infliximab, golimumab, certolizumab pegol, ustekinumab or secukinumab) was undertaken. Our study population included 266 elderly psoriatic patients actually receiving any biological therapy (adalimumab 31.2%, ustekinumab 28.9%, etanercept 20.3%, secukinumab 15%, infliximab 3%, golimumab 1% and certolizumab pegol 0.6%). The PASI score at the baseline (week 0) ranged from 4 to 54; mean ± SD, 16.5 ± 7.1, which changed after biological administration to 3.7 ± 8 at week 16, 1.6 ± 2.1 at week 28 and 1.2 ± 2.1 at week 52. Among 266 elderly psoriatic patients, 25 adverse events were reported during the observation period. The most frequent events were infections with 12 (48%) reports, followed by malignancies with four (16%) reports. To date, our study represents the widest experience on the use of biological drugs in elderly psoriatic patients. We found that all biologics for psoriasis showed a great efficacy also in elderly people, and the rate and the type of adverse effects were similar to the younger patients. In conclusion, the age alone should not limit our therapeutic options. Further observational study using multiple data sources is needed to evaluate long-term effectiveness and safety for elderly psoriatic patients.

Effect of general practice characteristics and antibiotic prescribing on Escherichia coli antibiotic non-susceptibility in the West Midlands region of England: a 4 year ecological study.

To assess the effect of general practice characteristics and antibiotic prescribing on the number of non-susceptible Escherichia coli isolated from urine specimens submitted from community settings, we undertook an ecological study of the general practice population in the West Midlands. Descriptive analysis and multilevel modelling of temporal trends in antibiotic prescribing and non-susceptibility of E. coli urine isolates to a range of antibiotics prescribed in the community over a 4 year period. Nine of the 16 antibiotic prescribing/non-susceptibility combinations demonstrated a significant statistical linear correlation with non-susceptibility either for prescribing in a quarter or for prescribing within the previous 12 months. The magnitude of the effect varied, from a 0.3% increase in the odds of non-susceptibility to ampicillin/amoxicillin (when prescribing ampicillin/amoxicillin) to a 6.3% increase in the odds of non-susceptibility to nitrofurantoin (when prescribing nitrofurantoin) for an increase of 50 DDDs per 1000 practice population within a quarter (equivalent to ∼10 courses of antibiotics). In all 16 models, single-handed general practices were shown to have a significant association with increased numbers of non-susceptible E. coli urine isolates (adjusted ORs 1.083-1.657). Increased prescribing of ampicillin/amoxicillin in winter periods was associated with increased non-susceptibility of E. coli isolated from urine specimens. Small increases in antibiotic prescribing in individual general practices reduce the number of susceptible bacteria in the practice population. To maintain the effectiveness of available treatment, antibiotic stewardship should be encouraged and supported within each practice.

Reversing resistance: different routes and common themes across pathogens.

Resistance spreads rapidly in pathogen or pest populations exposed to biocides, such as fungicides and antibiotics, and in many cases new biocides are in short supply. How can resistance be reversed in order to prolong the effectiveness of available treatments? Some key parameters affecting reversion of resistance are well known, such as the fitness cost of resistance. However, the population biological processes that actually cause resistance to persist or decline remain poorly characterized, and consequently our ability to manage reversion of resistance is limited. Where do susceptible genotypes that replace resistant lineages come from? What is the epidemiological scale of reversion? What information do we need to predict the mechanisms or likelihood of reversion? Here, we define some of the population biological processes that can drive reversion, using examples from a wide range of taxa and biocides. These processes differ primarily in the origin of revertant genotypes, but also in their sensitivity to factors such as coselection and compensatory evolution that can alter the rate of reversion, and the likelihood that resistance will re-emerge upon re-exposure to biocides. We therefore argue that discriminating among different types of reversion allows for better prediction of where resistance is most likely to persist.

Diagnostic Value of a Tablet-Based Drawing Task for Discrimination of Patients in the Early Course of Alzheimer's Disease from Healthy Individuals.

There is a considerable delay in the diagnosis of dementia, which may reduce the effectiveness of available treatments. Thus, it is of great interest to develop fast and easy to perform, non-invasive and non-expensive diagnostic measures for the early detection of cognitive impairment and dementia. Here we investigate movement kinematics between 20 patients with early dementia due to Alzheimer's disease (eDAT), 30 patients with amnestic mild cognitive impairment (aMCI), and 20 cognitively healthy control (HC) individuals while copying a three-dimensional house using a digitizing tablet. Receiver-operating characteristic (ROC) curves and logistic regression analyzes have been conducted to explore whether alterations in movement kinematics could be used to discriminate patients with aMCI and eDAT from healthy individuals. Time-in-air (i.e., transitioning from one stroke to the next without touching the surface) differed significantly between patients with aMCI, eDAT, and HCs demonstrating an excellent sensitivity and a moderate specificity to discriminate aMCI subjects from normal elderly and an excellent sensitivity and specificity to discriminate patients affected by mild Alzheimer's disease from healthy individuals. Time-on-surface (i.e., time while stylus is touching the surface) differed only between HCs and patients with eDAT but not between HCs and patients with aMCI. Furthermore, total-time (i.e., time-in-air plus time-on-surface) did not differ between patients with aMCI and early dementia due to AD. Modern digitizing devices offer the opportunity to measure a broad range of visuoconstructive abilities that may be used as a fast and easy to perform screening instrument for the early detection of cognitive impairment and dementia in primary care.

The burden of disease in patients eligible for mentalization-based treatment (MBT): quality of life and costs.

BackgroundMentalization-Based Treatment (MBT) is a promising, though expensive treatment for severely ill patients with Borderline Personality Disorder (BPD). A high burden of disease in terms of quality of life (QoL) and life years lost can be a reason to prioritize mental health interventions, and specifically for BPD patients. Moreover, when the societal costs of the illness are high, spending resources on high treatment costs would be more easily legitimized. Therefore, the purpose of this study was to calculate the burden of disease of BPD patients eligible for MBT.MethodsThe 403 patients included in this study were recruited from two mental health care institutes in the Netherlands. All patients were eligible for MBT. Burden of disease consisted of QoL, measured with the EuroQol EQ-5D-3L, and costs, calculated using the Trimbos and Institute for Medical Technology Assessment Questionnaire for Costs Associated with Psychiatric Illness.ResultsThe mean QoL index score was .48. The mean total costs in the year prior to treatment were €16,879 per patient, of which 21 % consisted of productivity costs.ConclusionsThe burden of disease in BPD patients eligible for MBT is high, which makes it more likely that society is willing to invest in treatment for these patients. However, this finding should not be interpreted as a license to unlimitedly use resources to reimburse treatment for severe BPD patients, as these findings do not provide any information on the effectiveness of MBT or other available treatment programs for BPD. The effectiveness of available treatments should be evident by studies on the effectiveness of the treatment itself and by comparing the effectiveness of these treatments to treatment as usual and to other treatment options for BPD patients.Trial registrationThe data on this paper came from two trials: NTR2175 and NTR2292.

Aetiopathological mechanisms of negative symptoms in schizophrenia

Summary Background: Negative symptoms represent core features of schizophrenia and have an unfavorable impact on the disease outcome. Unfortunately, their aetiopathology has not been elucidated yet and the effectiveness of available treatments is not satisfactory. Aims: This review aims to provide a critical overview of research findings concerning negative symptom aetiopathology, highlighting limitations and future perspectives. Results: Enduring and transient negative symptoms, as well as motivation-related and expression-related domains of negative symptoms, have different risk factors and clinical correlates, and are associated to distinct brain abnormalities. Enduring negative symptoms seem to be related to subtle, pervasive deviations in neurodevelopmental trajectories. Expression deficit, as compared with avolition, shows a stronger association with neurological soft signs, cognitive impairment and diffuse disconnectivity. Avolition/apathy is a multifaceted construct probably related to deficits of reward and action valuation and instrumental learning, subtended by cortico-striatal dysfunctions. Conclusions: Research findings support the heterogeneity of negative symptoms and are likely to pave the way for the discovery of more effective treatments.

Should Marijuana be Used for Pain Control?

Should Marijuana be Used for Pain Control?

Characterization of Helicobacter pylori HP0231 (DsbK): role in disulfide bond formation, redox homeostasis and production of Helicobacter cystein-rich protein HcpE.

Helicobacter pylori is a human gastric pathogen that colonizes ∼ 50% of the world's population. It can cause gastritis, gastric or duodenal ulcers and also gastric cancer. The numerous side effects of available treatments and the emergence of antibiotic resistant strains are severe concerns that justify further research into H. pylori's pathogenic mechanisms. H. pylori produces secreted proteins that may play a role in virulence, including the Helicobacter cysteine-rich protein HcpE (aka HP0235). We demonstrate herein that HcpE is secreted in the culture supernatant both as a soluble protein and in association with outer membrane vesicles. We show that the structure of HcpE comprises an organized array of disulfide bonds. We identify DsbK (aka HP0231) as a folding factor necessary for HcpE production and secretion in H. pylori and show that recombinant DsbK can interact with and refold unprocessed, reduced HcpE in vitro. These experiments highlight the first biologically relevant substrate for DsbK. Furthermore, we show that DsbK has disulfide bond (Dsb) forming activity on reduced lysozyme and demonstrate a DsbA-type of activity for DsbK upon expression in E. coli, despite its similarity with DsbG. Finally, we show a role of DsbK in maintaining redox homeostasis in H. pylori.

Novel drug delivery systems for releasing growth factors to the CNS: focus on Alzheimer's and Parkinson's diseases.

Alzheimer's disease (AD) and Parkinson's disease (PD) represent the most common neurodegenerative disorders and affect more than 35 million people. Due to the limited effectiveness of available treatments in halting the neurodegenerative process, new therapies, such therapies based on growth factors (GFs), have been investigated. Nevertheless, the efficacies of these new treatments depend not only on the application of neurotrophins but also on the approaches used to deliver these proteins such that they can reach the brain. This review summarises the most widely used drug delivery systems (DDSs) for releasing GFs as possible treatments for AD and PD.

OI0369 Interventions for the management of radiotherapy-induced xerostomia: a meta-analysis

The effectiveness of available treatments of radiotherapy-induced xerostomia remains unclear, because data from previous systematic reviews included participants with dry mouth due to different causes. The aim of this meta-analysis is to summarize and estimate the effectiveness of available treatment options for radiotherapy-induced xerostomia.

MRSA Infections: From Classical Treatment to Suicide Drugs

Infections caused by the methicillin-resistant Staphylococcus aureus (MRSA) are today a major burden in nosocomial disease control. The global trend shows an alarming increase of MRSA infections as well as multi-drug resistance (MDR). The problem is exacerbated by the fact that infections with community-associated (CA) MRSA strains showing increased virulence and fitness add to infections with multi-drug resistant hospital-associated (HA) MRSA. The toxicity of pathogens and limited effectiveness of available treatment have led to high mortality rates and vast expenses caused by prolonged hospitalization and usage of additional antibiotics. Recently approved drugs still have classical targets and upcoming resistance can be expected. In a new approach by targeting co-factor syntheses of bacteria, the drug target and the affected pathways are uncoupled. This novel strategy is based on the thought of a classical pro-drug which has to be metabolized before becoming toxic for the bacterium as a dysfunctional co-factor, named suicide drug. Ideally these metabolizing pathways are solely present in the bacterium and absent in the human host, such as vitamin biosyntheses. This mini-review discusses current ways of MRSA infection treatment using new approaches including suicide drugs targeting co-factor biosyntheses.

Epidemiology, Clinical Manifestations, Risk Reduction and Treatment Strategies of Jaw Osteonecrosis in Cancer Patients Exposed to Antiresorptive Agents

Osteonecrosis of the jaws (ONJ) is an adverse side event of bisphosphonates and denosumab, antiresorptive agents that effectively reduce the incidence of skeletal-related events in patients with metastatic bone cancer and multiple myeloma. Available data suggest that 0-27.5% of individuals exposed to antiresorptive agents can develop ONJ. There is increasing evidence that avoidance of surgical trauma and infection to the jawbones can minimize the risk of ONJ, but there are still a significant number of individuals who develop ONJ in the absence of these risk factors. Bone necrosis is almost irreversible and there is no definitive cure for ONJ with the exclusion, in certain cases, of surgical resection. However, most ONJ individuals are affected by advanced incurable cancer and are often managed with minimally invasive nonsurgical interventions in order to control jawbone infections and painful symptoms. This article summarizes current knowledge of ONJ epidemiology, manifestations, risk-reduction and therapeutic strategies. Further research is needed in order to determine individual predisposition to ONJ and clarify the effectiveness of available treatments.

Hapten-enhanced personalized chemoimmunotherapy by intratumoral drug delivery in advanced pancreatic cancer.

333 Background: Currently cancer therapy is not satisfied with the effectiveness of available treatment. Engaging the power of immune system of individual patient has been considered as a highly attractive way for cancer treatment. Sipuleucel-T is an autologous cellular vaccine and represents a significant milestone for cancer immunotherapy. To evaluate the clinical effective of hapten enhanced personalized chemoimmunotherapy by intratumoral delivery of a combined drugs solution called ChemoCancerVac (CCV) in the treatment of advance pancreatic cancer and further to analyze the effect of immune adjuvant. Methods: Introtumoral injection of CCV into late stages of pancreatic cancer (92 cases), which is a proprietary therapeutic regimen composed of three components for modulation of chemoimmunotherapy, i.e. an oxidant, a cytotoxic drug and a hapten. The patients (47 patients with effect analysis and 45 patients with complete survival data were randomly divided into two groups: introtumoral chemotherapy (ITCT) alone received the CCV without hapten and introtumoral chemoimmunotherapy (ITCIT) received the CCV with the hapten. Results: In the ITCT and ITCIT groups, the clinical response rates were 92.86% and 82.88%, the median survival time and 6-month survival rate were 6.45 months vs 4.98 months and 45% vs 64%, respectively. All of mentioned above were showed no statistical difference (p>0.05), whereas 1-year survival rate of the ITCT group was 5% while that of ITCiT group was 28%. The difference was significant (p<0.05). Conclusions: The hapten enhanced personerlized immunotherapy by intratumoral injection of CCV was effective in the pancreatic cancer, meanwhile, the hapten plays an important role in prolong the patient survival time which are valuable in the clinic application.

The Effectiveness of Treatments for Cocaine Dependence in Schizophrenic Patients: A Systematic Review

Objectives:To evaluate and compare the effectiveness of available treatments for cocaine dependence in schizophrenic patients. Method: We searched articles published between May 2002 and June 2012 in the following databases: Scopus, Pubmed and Web of Knowledge. The key words utilised were “schizophrenia”, "dementia praecox", "schizophrenic disorder", "cocaine related disorder", "cocaine abuse", "cocaine addiction", "cocaine dependence", “treatment”, “therapeutic”, and "drug therapy”. Selection of studies and data extraction: Original articles in English, Portuguese and Spanish were selected. Controlled, double-blind and open-label studies involving only human subjects were included in this review.Data Synthesis:We found studies on typical and atypical antipsychotics and one monoamine transporter antagonist. There were few indications of the effectiveness of atypical antipsychotic medications for the treatment of cocaine dependence in patients with schizophrenia.Conclusions:We suggest that further studies be conducted with atypical antipsychotic medicationsand greater methodological strictness, including using a placebo group in the studies, so that health professionals can determine the real effectiveness of this class of medication for the treatment of cocaine dependence in schizophrenic patients.

Uptake and use of recommendations for the diagnosis, severity scoring and management of chronic GVHD: an international survey of the EBMT–NCI Chronic GVHD Task Force

In 2005, the NIH consensus conference published a series of papers recommending methods to improve the conduct of clinical trials in chronic graft-versus-host disease (GVHD). Although the NIH recommendations were primarily aimed at strengthening research, several papers addressed issues relevant for clinical practice, particularly diagnosis, severity scoring, and ancillary and supportive care practices. We conducted an international survey to assess the uptake of these recommendations, identify barriers to greater use, and document the use and perceived effectiveness of available treatments. The response rate for the American survey of 1,387 practitioners was 21.8%, and it was 24.6% for 407 centers surveyed in Europe, Asia, Australia and Africa. Most respondents were familiar with the NIH consensus recommendations (94-96%) and used them in practice. Multiple barriers to greater use were reported. Besides lack of time (55-62%), unfamiliarity with the recommendations, scarcity of evidence supporting the impact of recommendations on outcomes, insufficient training/experience in chronic GVHD management, and inaccessibility of subspecialists were also endorsed. Systemic corticosteroids were reported to be the most effective treatment for chronic GVHD, but many others were perceived to have moderate or great success. Therapeutic management of steroid-refractory chronic GVHD was identified as the highest priority for research.

The Effectiveness of Treatments for Cocaine Dependence in Schizophrenic Patients: A Systematic Review

To evaluate and compare the effectiveness of available treatments for cocaine dependence in schizophrenic patients. We searched articles published between May 2002 and June 2012 in the following databases: Scopus, Pubmed and Web of Knowledge. The key words utilised were "schizophrenia", "dementia praecox", "schizophrenic disorder", "cocaine related disorder", "cocaine abuse", "cocaine addiction", "cocaine dependence", "treatment", "therapeutic", and "drug therapy". Original articles in English, Portuguese and Spanish were selected. Controlled, double-blind and open-label studies involving only human subjects were included in this review. We found studies on typical and atypical antipsychotics and one monoamine transporter antagonist. There were few indications of the effectiveness of atypical antipsychotic medications for the treatment of cocaine dependence in patients with schizophrenia. We suggest that further studies be conducted with atypical antipsychotic medicationsand greater methodological strictness, including using a placebo group in the studies, so that health professionals can determine the real effectiveness of this class of medication for the treatment of cocaine dependence in schizophrenic patients.

Challenges in cancer vaccine development for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common liver malignancy, representing the third and fifth leading cause of death from cancer worldwide in men and women, respectively. The main risk factor for the development of HCC is the hepatitis B and C virus (HBV and HCV) infection; non-viral causes (e.g., alcoholism and aflatoxin) are additional risk factors. HCC prognosis is generally poor because of the low effectiveness of available treatments and the overall 5-year survival rate is approximately 5-6%. In this framework, immunotherapeutic interventions, including cancer vaccines, may represent a novel and effective therapeutic tool. However, only few immunotherapy trials for HCC have been conducted so far with contrasting results, suggesting that improvements in several aspects of the immunotherapy approaches need to be implemented. In particular, identification of novel specific tumor antigens and evaluation of most advanced combinatorial strategies could result in unprecedented clinical outcomes with great beneficial effect for HCC patients. The state of the art in immunotherapy strategies for HCC and future perspectives are reported in the present review.

Queratitis fúngica: revisión actual sobre diagnóstico y tratamiento

Fungal keratitis is a characteristic infection upon tropical zones, associated with vegetal trauma. Doubt exists about the best diagnostic test and the effectiveness of available treatment. Which is the best diagnostic method for fungal keratitis? And, which is the best management? Fungal culture remains as diagnostic gold standard of fungal elements. As of treatment, natamycin and amphotericin B are the most popular drugs for fungal keratitis and they have not shown effectiveness in randomized controlled trials or systematic reviews. Voriconazole showed effectiveness and security in multiple fungal infections. It may be the drug of choice in optimal conditions, because of its better ocular penetration and wider coverage. However, its high price difficult general application. This review establishes management recommendations and the need to perform studies that address cost-effectiveness analysis of voriconazole for fungal keratitis.

2952 – Treatment effects on mood instability in adult ADHD

ADHD is a common developmental disorder with onset in childhood that persists into adulthood in two-thirds of cases. The disorder is defined by symptoms of inattention, overactivity and impulsivity; however case-control, family and twin studies all find high rates of emotional lability that strongly co-vary with the core ADHD syndrome. 80% or more of adults with ADHD report significant levels of emotional lability, often severe, and causing impairments beyond that accounted for by inattention, hyperactivity or impulsivity. Drug treatments for ADHD have all been shown to improve symptoms of emotional lability. In children, a robust effect of methylphenidate has been demonstrated on aggression, although this has not been linked directly to the control of emotional symptoms. In contrast, the adult literature has focused more on emotional dysregulation, including affective lability, temper control and emotional over-reactivity. All these symptoms have been shown to improve following treatment with methylphenidate or atomoxetine, and to the same extent as core ADHD symptoms. Characterising the nature of the emotional symptoms in ADHD more detail, we found an increase in negative emotions such as frustration, anger and irritability, as well as an increase in their moment-to-moment variability. We conclude that patients with chronic forms of emotional instability should always be screened for ADHD, due to proven effectiveness of available treatments in the subgroup of emotionally labile patients who meet clinical criteria for ADHD.