Expert Consensus Report Research Articles

Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions—Part III

IntroductionIn 2016 the International Society for the Study of Women’s Sexual Health (ISSWSH) published an expert consensus report on new nomenclature that addressed the need for comprehensive, evidence-based criteria for new diagnoses in desire, arousal, and orgasm, with the definition on arousal focusing exclusively on female genital arousal disorder (FGAD). AimA new expert panel solely focused on mechanisms of arousal disorders convened to revise the nomenclature to include female cognitive arousal disorder (FCAD) and FGAD. MethodsThe ISSWSH co-chairs identified experts on arousal disorders in women. The 10 participants included clinicians, researchers, and educators, representing a diverse, multidisciplinary group. Pre-meeting preparation included evidence-based literature review as the basis of presentations panelists made at the meeting on the current knowledge in cognitive arousal. Consensus was reached using a modified Delphi method. Writing assignments were made as a basis of manuscript development. Main Outcome MeasuresThe new definition of FCAD is characterized by distressing difficulty or inability to attain or maintain adequate mental excitement associated with sexual activity, as manifested by problems with feeling engaged and mentally turned on or sexually aroused for a minimum of 6 months. ResultsFemale sexual arousal disorder encompasses both FGAD (revised definition) and FCAD (new definition). Recommendations regarding diagnosis include a clinical interview to assess for FCAD using targeted questions. Patient-reported outcomes that contain questions to assess FCAD are described, including limitations for differentiating between cognitive arousal, genital arousal, and sexual desire. Laboratory measures of cognitive and genital arousal are discussed, including the relationships between genital and cognitive arousal patterns. Biopsychosocial risk factors for FCAD and FGAD, as well as exclusionary conditions, are presented. Clinical ImplicationsThe revision of the ISSWSH nomenclature regarding the criteria for the 2 arousal categories, FCAD and FGAD, and the recommended diagnostic strategies offers a framework for management of women with arousal disorders. Strengths & LimitationsThis nomenclature allows for basic science and clinical research in subtypes of arousal in order to develop better diagnostic and treatment options for use by clinicians, scientists, and regulatory agencies. There are limited validated measures of cognitive arousal, including the Female Sexual Function Index, the most commonly used measure, which does not effectively distinguish between cognitive excitement, genital sensations, and event-related desire. ConclusionFuture directions include the refinement of FCAD and FGAD and development and validation of patient-reported outcomes that distinguish between the cognitive processes and genital responses to enhance clinical care and research in this area.Parish SJ, Meston CM, Althof SE, et al. Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions—Part III. J Sex Med 2019;16:452–462.

Reporting criteria for clinical experts consensus of Chinese medicine

Due to its own characteristics and research status, traditional Chinese medicine research often faces the reality of "insufficient evidence" or "very low quality" when making clinical practice guidelines. Therefore, in many cases, clinical decision-making of traditional Chinese medicine should rely mainly on expert consensus to achieve. A clear and detailed list of expert consensus report specifications will provide a good reporting tool for Chinese clinical expert consensus makers, which is very important for promoting the quality of consensus production and the promotion and application of consensus results. The author consulted the internationally published authoritative expert consensus, summarized the main points of the reports, combined with the formulation process of the clinical experts consensus of Chinese medicine, and the demonstration of clinical experts and methodologists, and then formulated the list of items for clinical expert consensus reports adapt to the field of Chinese medicine. This article introduces the entire list of items and elaborates on the key parts. It is expected to provide reference for the standardization of future clinical expert consensus reports.

F16. Standardizing neonatal EEG report based on expert consensus report

Introduction Continuous EEG monitoring provides valuable diagnostic and prognostic information for critically ill neonates that are at high risk of adverse neurological sequelae. The EEG of a developing brain is unique. The parameters used to monitor brain electrophysiological functions in neonates are different from fully mature brains. The EEG report should contain all these essential parameters. Consensus guidelines were published in 2013(1) to standardize the neonatal EEG reports for neurophysiologist, bedside physicians, and clinical researchers. In this study, we compared our neonatal EEG reports to consensus guidelines and attempted to modify it to include all clinically relevant information. Methods We retrospectively reviewed EEG reports of ten (10) neonates that underwent EEG monitoring at Duke Neonatal ICU from March 2017 to June 2017. We compared these reports to consensus guideline published in 2013. We then created a new standardized neonatal EEG report. It included all of the parameters suggested in the guidelines such as characteristics of background activity, awake and sleep state, normal graphoelements, EEG transient patterns and seizure burden. The updated EEG template was implemented in July 2017. We conducted another chart review from September 2017 to November 2017 for ten (10) more EEG reports. We compared the results of both chart reviews. Results From the consensus statement, we identified 20 parameters that were deemed essential for a neonatal EEG report The first chart review from March 2017 to June 2017 of ten patient suggested that majority of reports were inadequate or missing critical information. Out of 20 parameters, only three were regularly documented. After three months of implementing the updated EEG report, the quality of documentation improved. Out of 20 parameters, 18 were consistently documented (100%). One parameter was documented 80% of the time, and only one parameter was reported 20% of the time. Conclusion Our chart review suggested documentation for neonatal EEG reports was lagging behind what was recommended in the consensus report. We made a template in the electronic health record to include all of the important parameters suggested by ACNS guidelines. On a follow-up chart review we noted a marked improvement in our documentation of neonatal EEGs. The standardize EEG reports for neonates will improve patient care, caregiver communication, and future clinical research.The neonatal EEG template made can be used in other institutions to achieve similar results.

Nutritional support and parenteral nutrition in the oncological patient: an expert group consensus report

Malnutrition is a frequent medical problem of cancer patients that negatively impacts their quality of life. To analyze and respond to different issues related to the nutritional management of cancer patients in the clinical setting. A multidisciplinary group of experts in Medical Oncology, Pharmacy, and Nutrition developed a list of topics related to the nutritional status of cancer patients, which were grouped into three blocks: Nutritional support; Parenteral nutrition (PN); and Home PN (HPN) in cancer patients. A literature search, which included articles published in Spanish, English, and French until February 2017, was carried out. The document was organized as a questionnaire with those questions that, according to the panel's criteria, could generate greater controversy or doubt. Of the 18 questions addressed, 9 focused on nutritional support: 5 were related to PN and 4 about HPN. Among the different recommendations, the panel emphasized that in the cancer patient, PN is indicated mainly when it is not possible to use the digestive tract and/or oral feeding and/or enteral nutrition is not sufficient or possible. Additionally, the objective of the HPN is to improve or maintain the nutritional status of a patient at home. This document seeks to lay down a set of recommendations and to identify key issues that may be useful for the nutritional management of cancer Patients.

Allergic respiratory disease (ARD), setting forth the basics: proposals of an expert consensus report

BackgroundThe variability of symptoms observed in patients with respiratory allergy often hampers classification based on the criteria proposed in guidelines on rhinitis and asthma.ObjectivesWe assessed specific aspects of allergic respiratory disease (ARD) that are not explicitly addressed in the guidelines in order to issue specific recommendations and thus optimize clinical practice.MethodsUsing the Delphi technique, 40 Spanish allergists were surveyed to reach consensus on 71 items related to ARD.ResultsConsensus was achieved for 95.7% of the items. These included the following: the clinical manifestations of ARD are heterogeneous and individual airborne allergens can be related to specific clinical profiles; the optimal approach in patients with ARD is based on the global assessment of rhinoconjunctivitis and asthma; aeroallergens are largely responsible for the clinical features and severity of the disease; and clinical expression is associated with the period of environmental exposure to the allergen. Pharmacological treatment of ARD is often based on the intensity of symptoms recorded during previous allergen exposures and cannot always be administered following a step-up approach, as recommended in clinical practice guidelines. Allergen immunotherapy (AIT) is the only option for overall treatment of respiratory symptoms using an etiological approach. AIT can modify the prognosis of ARD and should therefore be considered a valuable first-line treatment.ConclusionsThe present study highlights gaps in current asthma and rhinitis guidelines and addresses specific aspects of ARD, such as global assessment of both asthma and rhinitis or the specific role of variable allergen exposure in the clinical expression of the disease.

Optimizing the Use of Linaclotide in Patients with Constipation-Predominant Irritable Bowel Syndrome: An Expert Consensus Report.

IntroductionIrritable bowel syndrome (IBS) is a functional bowel disorder characterized by chronic or recurrent abdominal pain in association with defecation or a change in bowel habits. A predominant disorder of bowel habits, IBS is classified into three main subtypes: constipation-predominant IBS (IBS-C), diarrhea-predominant IBS (IBS-D) and IBS alternating between constipation and diarrhea (IBS-M). Linaclotide is a first-in-class, oral, once-daily guanylate cyclase-C receptor agonist (GC-CA) that is licensed for the symptomatic treatment of moderate-to-severe IBS-C in adults. This review aims to facilitate and optimize clinical practices, establishing common guidelines to monitor patients with IBS-C that are treated with linaclotide.MethodsA group of experts in functional digestive disorders was convened to review the efficacy and safety of linaclotide and to develop an updated consensus report for the treatment of patients with IBS-C. A search was performed for English, French and Spanish language articles in PubMed. On the basis of the articles identified, an initial document was drafted addressing different issues frequently raised by general practitioners and GI specialists that are related to the prescription, efficacy and safety of linaclotide. This document was then reviewed and modified by the expert panel until a final text was agreed upon and validated.ResultsBased on the evidence, the panel addressed the following recommendations: (1) Linaclotide is indicated for the treatment of moderate to severe IBS-C in adults; (2) it is recommended that patients take linaclotide continuously and not sporadically; (3) patients should be warned about the risk of diarrhea and given choices concerning how to deal with this possible side effect; (4) the absence of tachyphylaxis or potential risks implies that linaclotide treatment can be maintained for long periods of time.ConclusionsThis document seeks to lay down a set of recommendations and to identify key issues that may be useful for the clinical management of IBS-C patients treated with linaclotide.

Clinical significance of molecular subtypes of breast cancer in patients aged over 60 years

Objective To retrospectively analyze the distribution percentage points of molecular subtypes of breast cancer and investigate its guiding significance in the prognosis and personalized therapy in patients with breast cancer aged over 60 years. Methods A retrospective analysis of all patients with invasive breast cancer aged over 60 years from January 2009 to June 2014 in Breast Center of Beijing Hospital was performed.Based on the immunohistochemical methods recommended in the St.Gallen International Expert Consensus Report 2013, the molecular subtypes of breast cancer in these patients were identified.All patients were followed up every 6 months after operation until December 2014.Clinical pathological characteristics and prognosis indexes in different molecular subtypes of breast cancer were evaluated. Results Totally 770 patients aged over 60 years with invasive breast cancer met the criterion.The luminal A, luminal B, human epidermal growth factor receptor 2(HER2)over-expression, triple- negative subtypes accounted for 29.1%(224 cases), 47.5%(366 cases), 6.5%(50 cases)and 16.9%(130 cases)of patients, respectively.The luminal A subtype of breast cancer had larger tumor size, more lymph node metastasis and more late TNM stage as compared with other subtypes(all P<0.01). Univariate and multivariate analysis showed that aged ≥80 years and the triple- negative molecular subtype were the independent poor prognostic factors for breast cancer(both P<0.05). The luminal A subtype of breast cancer had relatively good prognosis, while the triple- negative subtype had relatively poor prognosis. Conclusions Molecular subtypes have a significant prognostic effect on breast cancer in patients aged over 60 years, which suggests molecular subtype can be considered as a reference indicator in personalized therapy.Patients aged over 80 years has poor prognosis due to less rational treatment.The reasonable and target treatment based on the molecular subtype of breast cancer should be provided for patients aged over 80 years in clinical medicine. Key words: Breast neoplasms; Molecular subtype; Prognosis

Clinicopathological features of Luminal B-like breast cancer

To explored the clinicopathological features of Luminal B-like breast cancer and analyze the value of St. Gallen consensus in its treatment. The patients with invasive breast cancer treated at our hospital between January 2010 and December 2012 were recruited and divided into five subtypes according to the criteria of St. Gallen International Expert Consensus report 2013. And their TNM stages, pathological characteristics and Ki-67 status were analyzed for Luminal B-like subtype. The Luminal B-like subtype was found in 390 patients (52.8%), human epidermalgrowth factor receptor 2(HER-2) positive in 89 patients (22.8%) and negative in 301 patients (77.2%).Only 7.3% required chemotherapy based upon the result of gene detection. Only those patients for whom the need of chemotherapy is to be determined shall really benefit from gene detection.

Telomerase reverse transcriptase promoter mutation is an early somatic genetic alteration in the transformation of premalignant nodules in hepatocellular carcinoma on cirrhosis.

Genetic determinants of the early steps of carcinogenesis on cirrhosis are still poorly understood. We aimed to evaluate the occurrence of telomerase reverse transcriptase (TERT) promoter mutations in the transformation of cirrhotic nodules into hepatocellular carcinoma (HCC). We analyzed a series of 268 liver samples, including 96 nodules developed in 58 patients with cirrhosis and 114 additional cirrhosis. All samples were screened for TERT promoter mutations, and in 31 nodules, for 10 genes recurrently mutated in HCC. Immunohistochemistry (IHC) analyses were performed for glypican 3, glutamine synthase, and heat shock protein 70. Six liver pathologists reviewed all the samples. Among The 96 nodules, 88 were firmly diagnosed as low-grade dysplastic nodules (LGDNs; 32 cases), high-grade dysplastic nodules (HGDNs; 16 cases), early HCC (eHCC; 23 cases), or small and progressed HCC in 17 cases. The agreement between the initial diagnosis from pathological report and the final expert consensus report was moderate for the diagnosis of benign versus malignant nodules (weighted kappa = 0.530). TERT promoter mutations were highly related to the step-wise hepatocarcinogenesis because mutations were identified in 6% of LGDNs, 19% of HGDNs, 61% of eHCCs, and 42% of small and progressed HCC. TERT promoter mutation is the most frequent molecular alteration in eHCC given that the IHC criteria for diagnosis of malignancy were found in only 39% of the cases. TERT promoter mutation was also the earliest genetic alteration because mutations in 10 other genes were only identified in 28% of the small and progressed HCC. Frequency of TERT promoter mutations rapidly increases during the different steps of the transformation of premalignant lesions into HCC on cirrhosis. Consequently, somatic TERT promoter mutation is a new biomarker predictive of transformation of premalignant lesions into HCC.

Study on clinicopathological classification and clinical and pathological characteristics in breast cancer

To explored the relationship of clinicopathological classification and clinical and pathological characteristics of breast cancer and analyze the value in treatment. The patients with invasive breast carcinoma had been treated between January 2011 and December 2012. The breast cancer have been divided into luminal A, luminal B, HER2-positive and triple-negative subtypes according to criteria of St. Gallen International Expert Consensus report 2011. The Mann-Whitney test and Kruskal-Wallis test were used to analyze the relationships between four subtypes and TNM staging, histopathological grading. The 530 cases of invasive breast cancer patients were included in this study. The luminal A was 94 cases (17.7%), the luminal B was of 285 cases (53.8%), the HER2-positive was 59 cases (11.1%), and the triple-negative subtype was 92 cases (17.4%). In luminal B subtype, the HER2-positive was 56 (19.6%) and negative was 229 (80.4%). Most of luminal B was later in grade (71.7% of cases were more than II grade) and stage (66.7% were more than stage II). Clinical pathological classification is important in the individualized treatments of breast cancer, and the Luminal types (A+B) are more than 71.5% of all breast cancer patients, and they should be paid more attention to the endocrine therapy; Luminal B type accounted for 53.8% of all breast cancer and it needs further study to improve the precision of the diagnosis and treatment.

Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information.

BACKGROUNDThe St. Gallen International Expert Consensus of 2011 proposes a new classification system for breast cancer based on its division into five subgroups. The criteria to identify these subtypes were recently refined at the 2013 Conference. In this respect, the authors of this paper have conducted a retrospective analysis of breast cancer subtypes, related to Ki-67 and involvement of the axillary lymph nodes (ALNs). The analysis was performed only in the cases of invasive breast cancer in the pT2 stages. The research and results of the paper have shown that investigating the value of these parameters could be of great benefit in future treatment strategies of invasive breast cancer.METHODSA retrospective analysis of breast cancer subtypes, tumor nodal metastatic staging, and histopathological grading of 108 cases has been performed according to the methods recommended and provided by the St. Gallen International Expert Consensus Report, 2011. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 of 108 tumor samples were all investigated by immunohistochemistry according to the methods used to classify breast cancer subtypes as proposed in the St. Gallen Consensus Report, 2011. Invasive breast cancers (n = 108) were immunohistochemically classified as follows: 28 (25.92%) as Luminal A, 51 (47.22%) as Luminal B (HER2 negative), 21 (19.44%) as Luminal B-like (HER2 negative), 2 (1.85%) as HER2 positive, and 6 (5.55%) as being a triple-negative subtype.RESULTSThe conclusion was made that when Ki-67 was found to be higher, patients also showed a higher involvement in their ALNs. The chi-square test shows the difference to be significant (chi-square = 4.757; P = 0.029). Luminal B subtypes had the highest percentage (54.9%) of involvement of lymph nodes when compared to the other four subtypes. The Luminal B subtype had a higher percentage (51.4%) of involvement of lymph nodes than did Luminal A (10.7%). The chi-square test also shows the difference to be significant (P < 0.05).CONCLUSIONA combination of the Ki-67 index, HER negative tumors, PR negativity, and a low value that can be used to segregate ER positive pT2 tumors into prognostically significantly different clinical outcomes may be utilized clinically to guide patient management in accordance with these tumor characteristics.

Clinicopathological classification and individualized treatment of breast cancer

Background The clinicopathological classification was proposed in the St. Gallen Consensus Report 2011. We conducted a retrospective analysis of breast cancer subtypes, tumor-nodal-metastatic (TNM) staging, and histopathological grade to investigate the value of these parameters in the treatment strategies of invasive breast cancer. Methods A retrospective analysis of breast cancer subtypes, TNM staging, and histopathological grading of 213 cases has been performed by the methods recommended in the St. Gallen International Expert Consensus Report 2011. The estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2), and Ki-67 of 213 tumor samples have been investigated by immunohistochemistry according to methods for classifying breast cancer subtypes proposed in the St. Gallen Consensus Report 2011. Results The luminal A subtype was found in 53 patients (24.9%), the luminal B subtype was found in 112 patients (52.6%), the HER2-positive subtype was found in 22 patients (10.3%), and the triple-negative subtype was found in 26 patients (12%). Histopathological grade and TNM staging differed significantly among the four subtypes of breast cancer (P &lt;0.001). Conclusion It is important to consider TNM staging and histopathological grading in the treatment strategies of breast cancer based on the current clinicopathological classification methods.

Managing incidentally diagnosed isolated factor VII deficiency perioperatively: a brief expert consensus report

While isolated factor VII (FVII) deficiency is being more frequently diagnosed owing to improved preoperative screening procedures, there is no specific guideline for perioperative management of such patients. To complicate the issue, FVII activity levels seem to correlate less well with the risk of hemorrhage than the patient’s past and family bleeding history do. We have devised expert consensus recommendations for managing such patients perioperatively, taking into consideration the personal and family bleeding history, the FVII activity level and the inherent bleeding risk of the procedure itself. We hope that clinicians will find this a useful tool in the decision-making process, thereby limiting the use of recombinant factor VIIa to those who need it most, and preventing possible thrombotic complications in those without a strong indication for its use.

Expert consensus report on remote monitoring of implantable devices: the Dutch experience

The annual absolute number of cardiovascular implantable devices (CIEDs) is steadily increasing and is expected to rise even further, mostly due to the ageing demographic changes. [1] Consequently this will have a major impact on the post-implantation follow-up of monitor device function and patient condition both in terms of time and personnel. In a recent survey in 14 European countries remote monitoring (RM) was used in about 85% of all centres and the responding centres estimated that this percentage will increase to 93% by 2015. [2] In the same survey, guidelines and/or recommendations for the use of RM available from national scientific societies were reported to be totally absent in 93%. This lack of structural guidelines and/or recommendations will undoubtedly lead to a wide heterogeneity among centres using RM for the optimal care of patients after implantation. In addition responsibility related to remote follow-up is not clearly defined and leaves the device specialist and allied professionals in doubt with respect to the legal issues of RM. In 2009 the Netherlands Heart Rhythm Association (NHRA) took the initiative to develop a consensus document for RM in order to make a more uniform approach for RM and remote follow-up of the device patient. Close to 60 individuals have contributed to this expert consensus report. All aspects related to RM were divided into subgroups focussing on well-defined issues. The following subgroups were defined: Description of remote CIED monitoring Indications, benefits and limitations of remote CIED monitoring Patient perception of remote CIED monitoring Contribution of manufacturer to remote CIED monitoring Costs and reimbursement of remote CIED monitoring Preliminary recommendations for remote CIED monitoring For each subgroup a working group was formed. For each working group a chairperson was appointed and 5 to 8 members were carefully selected based on personal experience and individual expertise in the field. During half-day sessions working groups focussed on their specific subject which resulted in a concept document which was subsequently distributed by the chairperson for additional review. All sessions were also attended by the first three authors of the final expert consensus documents (CdC, JE and NvH) for process surveillance without interference with the contents. Finally the concept consensus report was reviewed during half-day sessions with all chairpersons. Despite the fact that RM was introduced more than 10 years ago, guidelines are available in only 5% of European countries, although RM is already widely implemented in medical practice. [2] A uniform approach to patients with CIED permitting RM is essential for a safe and optimal treatment. Clear and standardised information to the patient is also needed for optimal transmissions. In the CONNECT trial up to 45% of all alerts were not transmitted simply because the setup of the system was inappropriate.[3] In the Dutch expert consensus document a brochure is presented with patient instructions and education emphasising the responsibilities of the patient with respect to RM. [4] In addition a minimal set of parameters and alerts has been defined which may impose early medical treatment and prevent appropriate and inappropriate shocks. [5] Furthermore the introduction of RM into a device clinic needs a tailored organisation with structured appointments on scheduled or unscheduled visits, reason and type of device reprogramming etc. Of interest, the present expert consensus document has made a clear statement that RM can and will not be capable to be used as a 24/7 emergency system. The Heart Rhythm Society/European Heart Rhythm Association expert consensus document on monitoring of CIEDs was published in 2008 and lacks a clear statement on 24/7 surveillance, which fuelled concern with respect to legal issues for alerts. Finally, reimbursement will be a key issue for a wide implementation of RM. For private insurance companies and national health services the major challenge is in demonstrating improved health care with no rise in health rise costs. [6] In 82% of the countries in Europe there is no reimbursement structure despite the fact that preliminary studies demonstrated the cost effectiveness of RM and a high patient acceptance and satisfaction. [7] More prospective studies are needed with health economic costs as one of the primary endpoints before RM will be standard of care for all patients after device implantation. [8, 9]

Recommendations for the treatment of Crohnʼs disease with tumor necrosis factor antagonists: An expert consensus report

Symptom relief is the traditional treatment goal in Crohn's disease (CD). New goals including mucosal healing and bowel preservation are now achievable with tumor necrosis factor (TNF) antagonists. Infliximab and adalimumab are approved as second-line treatments for severe, active CD. Certolizumab pegol is approved only in the U.S. and Switzerland as second-line treatment for moderate-to-severe, active CD. Data from trials of infliximab suggest that high-risk patients and patients with active inflammation (CRP elevation and/or ileocolonic ulcers) may benefit from earlier use of this drug. A Delphi survey was used to obtain consensus on issues surrounding bowel preservation and use of TNF antagonists. At the time of this survey, infliximab was the only TNF antagonist approved for the treatment of CD in Europe, Canada, and Australia. An expert panel of 12 gastroenterologists with substantial clinical experience using infliximab in clinical practice and trials in these areas participated. The experts agreed that bowel preservation and mucosal healing are relevant and achievable goals, and form a rationale for using TNF antagonists in CD patients. Control of inflammation and induction of mucosal healing were considered essential for bowel preservation. Consensus areas: 1) mucosal healing is predictive of improved long-term disease course and increases the likelihood of steroid-free remission; 2) infliximab induces sustained mucosal healing, promotes bowel preservation, and reduces hospitalizations and surgeries; 3) benefits of infliximab in relation to mucosal healing, bowel preservation, and clinical remission increase when therapy is initiated earlier. Treatment with TNF antagonists helps preserve the bowel in CD patients.

Panel Endorses Some PPI-Antiplatelet Therapy

Panel Endorses Some PPI-Antiplatelet Therapy

Standards for Clinical Trials in Sexual Dysfunction in Women: Research Designs and Outcomes Assessment

Clinical trial design in female sexual dysfunction (FSD) is an evolving science, with some areas of controversy. To develop an evidence-based, expert consensus-report on design of FSD clinical research. Literature review including the Food and Drug Administration (FDA) clinical trial guidelines with critique by six experts from three countries, modified after public presentation and debate. Expert opinion and recommendations were based on grading of evidence based literature, internal committee dialogue, open presentation, and debate. Design of clinical research for regulatory approval is driven by FDA guidelines. Diagnostic and Statistical Manual-IV definitions and consideration of comorbidity of sexual disorders may complicate patient selection and outcomes. Measures for study end points include satisfying sexual events utilizing a daily diary, sexual distress, and patient-reported outcomes measures of the construct under study. Currently, trial duration is recommended to be 6 months for efficacy trials to allow for modification of behavioral adaptations to changes in desire. Important issues include safety assessments, generalizability, having a representative study population, stratification by reproductive status, partner assessment, contextual and interpersonal factors, symptom duration and severity, management of placebo response, and drug dosing. Statistical analysis should include assessment of change from baseline to end point between study drug and placebo, determination of statistically significant change vs. clinically meaningful effects, linear mapping of all measures of the same construct, and determination of responders and remitters. Future trials should include clear population definitions, direct and indirect measures of the specific FSD construct, and procedures to allow generalizability of diagnosis and treatment to the target population.

Targeted drugs in metastatic colorectal cancer with special emphasis on guidelines for the use of bevacizumab and cetuximab: An Acta Oncologica expert report

From having been a ‘single-drug not very interesting cancer type’ from a medical treatment perspective, treatment of colorectal cancer (CRC) has during the past five years become a more complex issue of the appropriate use of several cytotoxic drugs sometimes integrated with advanced metastatic surgery with curative intent. The new drugs have provided significant benefit to the patients, so far mostly in the metastatic setting but also in adjuvant treatment. The significant progress in molecular and tumour biology has produced a great number of new ‘targeted’ drugs that are now in various stages of clinical development. Two of these drugs, the monoclonal antibodies bevacizumab (Avastin™) and cetuximab (Erbitux™), directed against VEGF and EGFR, respectively, have recently been approved within the EU for use in metastatic CRC. This Nordic Expert Consensus Report summarizes the current status of chemotherapy in metastatic CRC, overviews the clinical status of targeted drugs in CRC and, finally, provides guidelines for the routine clinical use of bevacizumab and cetuximab based on the most recently available clinical data.

Preventive Therapy for Asthmatic Children Under Florida Medicaid: Changes During the 1990s

Background: In response to the increasing prevalence and severity of asthma in this country, the National Institutes of Health in 1991 published an expert consensus report Guidelines for the Diagnosis and Management of Asthma. An important aspect of the report included the recommendation that children with moderate asthma may benefit from daily treatment with anti‐inflammatory drugs such as inhaled corticosteroids and cromolyn. Objectives: The objective of this article is to examine changes in prescribing of daily anti‐inflammatory drugs for children covered by Florida Medicaid during two 2‐year periods, the first just after publication of the Guidelines and the second 7 years later; and to estimate adherence to treatment by children who received one of them. Design: The study groups for each of the two 2‐year periods included only children 2 to 18 years old who had medical or institutional claims to Medicaid for asthma and who were continuously covered during the period. From outpatient claims files, a record was assembled for each child containing the number of prescriptions in each category of asthma drugs during each interval. For each child who had received a prescription for any daily preventative drug, the number of such prescriptions and the time after the first were used to calculate availability of medication. Results: The proportion of children receiving at least one prescription for a preventive drug rose from 26.9 per cent of children in 1990–1992 to 52.6 per cent in 1997–1998. African‐American children were less likely to receive a preventive in the earlier period, but the difference narrowed by 1997. Assuming that one refill provided a month's supply of drug, the percentage of children who had enough drug dispensed to treat for more than half of the time following the initial prescription rose from 6.1 to 11.2 per cent. For children with the highest use of β‐agonist (11 or more prescriptions over 2 years), the percentage rose from 25.3 to 35.8; in those with 5 or more courses of a systemic steroid, the proportion rose from 36.6 to 40.2. During the second interval, adherence to use of oral montelukast was no better than to inhaled daily medications. Conclusion: In the 7 years after the publication of the NIH Guidelines, asthmatic children covered by Florida Medicaid had an approximate doubling in the proportion who received a prescription for a daily anti‐inflammatory drug. However, during both intervals the adherence to treatment once prescribed remained low even among those with the severest asthma. Effective strategies to improve adherence will be needed before these drugs can realize their potential.