Citations

ObjectiveTo develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA).MethodsWe conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences.ResultsThe guideline covers the use of traditional disease‐modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat‐to‐target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional.ConclusionThis RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision‐making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Objective To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA). Methods We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. Results The guideline covers the use of traditional disease‐modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat‐to‐target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. Conclusion This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision‐making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Abstract Purpose: Preclinical studies suggest that SNPs in the Fc gamma receptor (FCGR) genes influence response to rituximab, but the clinical relevance of this is uncertain. Experimental Design: We prospectively obtained specimens for genotyping in the rituximab extended schedule or re-treatment trial (RESORT) study, in which 408 previously untreated, low tumor burden follicular lymphoma (FL) patients were treated with single agent rituximab. Patients received rituximab in 4 weekly doses and responders were randomized to rituximab re-treatment (RR) upon progression versus maintenance rituximab (MR). SNP genotyping was performed in 321 consenting patients. Results: Response rates to initial therapy and response duration were correlated with the FCGR3A SNP at position 158 (rs396991) and the FCGR2A SNP at position 131 (rs1801274). The response rate to initial rituximab was 71%. No FCGR genotypes or grouping of genotypes were predictive of initial response. A total of 289 patients were randomized to RR (n = 143) or to MR (n = 146). With a median follow-up of 5.5 years, the 3-year response duration in the RR arm and the MR arm was 50% and 78%, respectively. Genotyping was available in 235 of 289 randomized patients. In patients receiving RR (n = 115) or MR (n = 120), response duration was not associated with any FCGR genotypes or genotype combinations. Conclusions: Based on this analysis of treatment-naïve, low tumor burden FL, we conclude that the FCGR3A and FCGR2A SNPs do not confer differential responsiveness to rituximab. Clin Cancer Res; 22(4); 821–6. ©2015 AACR. See related commentary by Cartron et al., p. 787

Abstract This retrospective study evaluated the frequencies of symptoms associated with autonomic dysfunction in human immunodeficiency virus (HIV)-infected patients on stable combined antiretroviral therapy. Patients infected with HIV reported higher frequencies of dysautonomia symptoms compared with HIV-negative patients, particularly in the autonomic domains related to urinary, sleep, gastroparesis, secretomotor, pupillomotor, and male sexual dysfunction.

Purpose We compared efficacy of trastuzumab versus no trastuzumab in patients with small (≤ 2 cm) human epidermal growth factor receptor 2 (HER2) –positive breast cancer treated in randomized trials. Methods A meta-analysis was conducted using data from five of the six adjuvant trastuzumab trials. Efficacy end points were disease-free survival (DFS) and overall survival (OS). Separate analyses were prospectively planned for hormone receptor (HR) –positive and HR-negative cohorts. Random effect models and Yusuf-Peto fixed effects models assessed the impact of heterogeneity on baseline hazards and treatment effects across studies. Peto-Pike cumulative incidence estimates were stratified by study and nodal status. Results Median follow-up time was 8 years. For 2,263 patients with HR-positive disease, 8-year cumulative incidence rates comparing trastuzumab versus no trastuzumab were 17.3% versus 24.3% (P < .001) for DFS and 7.8% versus 11.6% (P = .005) for OS, respectively; for 1,092 HR-positive patients with zero or one positive lymph nodes, results were 12.7% versus 19.4% (P = .005) for DFS and 5.3% versus 7.4% (P = .12) for OS, respectively. For 1,957 patients with HR-negative disease, 8-year cumulative incidence rates were 24.0% versus 33.4% (P < .001) for DFS and 12.4% versus 21.2% (P < .001) for OS, respectively; for 1,040 HR-negative patients with zero or one positive lymph nodes, results were 20.4% versus 26.3% (P = .05) for DFS and 8.2% versus 12.2% (P = .084) for OS, respectively. Conclusion Women with HER2-positive tumors ≤ 2 cm in the randomized trastuzumab trials derived substantial DFS and OS benefit from adjuvant trastuzumab. Trastuzumab-treated patients with HR-positive disease and ≤ one positive lymph node may be candidates for trials assessing less aggressive treatment approaches.

Carriers of germline mutations in DNA mismatch repair (MMR) genes are at increased risk of several cancers including colorectal and gynecologic cancers (Lynch syndrome). There is no substantial evidence that these mutations are associated with an increased risk of cervical cancer. A total of 369 families with at least one carrier of a mutation in a MMR gene (133 MLH1, 174 MSH2, 35 MSH6 and 27 PMS2) were ascertained via population cancer registries or via family cancer clinics in Australia, New Zealand, Canada, and USA. Personal and family histories of cancer were obtained from participant interviews. Modified segregation analysis was used to estimate the hazard ratio (incidence rates for carriers relative to those for the general population), and age‐specific cumulative risks of cervical cancer for carriers. A total of 65 cases of cervical cancer were reported (including 10 verified by pathology reports). The estimated incidence was 5.6 fold (95% CI: 2.3–13.8; p = 0.001) higher for carriers than for the general population with a corresponding cumulative risk to 80 years of 4.5% (95% CI: 1.9–10.7%) compared with 0.8% for the general population. The mean age at diagnosis was 43.1 years (95% CI: 40.0–46.2), 3.9 years younger than the reported USA population mean of 47.0 years (p = 0.02). Women with MMR gene mutations were found to have an increased risk of cervical cancer. Due to limited pathology verification we cannot be certain that a proportion of these cases were not lower uterine segment endometrial cancers involving the endocervix, a recognized cancer of Lynch syndrome.

Aims and ObjectivesThis paper explores patients' perspectives on infection prevention and control.BackgroundHealthcare‐associated infections are the most frequent adverse event experienced by patients. Reduction strategies have predominantly addressed front‐line clinicians' practices; patients' roles have been less explored.DesignVideo‐reflexive ethnography.MethodsFieldwork undertaken at a large metropolitan hospital in Australia involved 300 hours of ethnographic observations, including 11 hours of video footage. This paper focuses on eight occasions, where video footage was shown back to patients in one‐on‐one reflexive sessions.FindingsViewing and discussing video footage of clinical care enabled patients to become articulate about infection risks, and to identify their own roles in reducing transmission. Barriers to detailed understandings of preventative practices and their roles included lack of conversation between patients and clinicians about infection prevention and control, and being ignored or contradicted when challenging perceived suboptimal practice. It became evident that to compensate for clinicians' lack of engagement around infection control, participants had developed a range of strategies, of variable effectiveness, to protect themselves and others. Finally, the reflexive process engendered closer scrutiny and a more critical attitude to infection control that increased patients' sense of agency.ConclusionThis study found that patients actively contribute to their own safety. Their success, however, depends on the quality of patient–provider relationships and conversations. Rather than treating patients as passive recipients of infection control practices, clinicians can support and engage with patients' contributions towards achieving safer care.Relevance to clinical practiceThis study suggests that if clinicians seek to reduce infection rates, they must start to consider patients as active contributors to infection control. Clinicians can engage patients in conversations about practices and pay attention to patient feedback about infection risk. This will broaden clinicians' understandings of infection control risks and behaviours, and assist them to support appropriate patient self‐care behaviour.

Key PointsHCT recipients have increased susceptibility to herpes zoster, but live-attenuated vaccines are not appropriate for highly immunocompromised people. An adjuvanted subunit vaccine against herpes zoster elicits strong immune responses with an acceptable safety profile in adult autologous HCT recipients.

Abstract Background Trastuzumab (T) combined with chemotherapy improves survival of women with HER2-positive breast cancer. Dual therapy with T and other HER-2 targeted agents (lapatinib/pertuzumab) has demonstrated improved efficacy compared to T alone in advanced breast cancer, and is in clinical trials in early stage disease. We hypothesize that subgroups of patients with HER2-positive tumors and limited tumor burden (tumor size and no or few positive lymph nodes) have a favorable outcome and would not be candidates for dual therapy. This study will analyze the disease-free survival (DFS)and overall survival (OS) of patients with early stage breast cancer treated with chemotherapy and T in the seminal randomized studies (RCTs). Methods RCTs were identified by a Medline search from 2004-2013. Trial groups from five phase III RCTs agreed to provide data. TrialNumberEligibilityRegimenNSABP B312130T1-3; pN1, pN2a, or pN3a; M0ACx4 then Tx4 VSACx4 then THx4 then Hx40wkNCCTG N98313505T1-3; pN1-2; M0ACx4 then Tx12wk VS ACTx4 then Hx52wk VS ACx4 then Tx12wk then Hx40wkHERA5102T1-3; pN1-2; M0Any (neo)adjuvant regimen, then H q3wk x1yr VS H q3wk x 2yr VS observationFinHER232T1-4; N0-3; M0Vx3 or T*x3 then FECx3 VS Vx3 or T*x3 with Hx9wk then FECx3PACS043010(528 HER2+)T1-3; pN1-2; M0FE(100)Cx6 VSFE(100)Cx6 then Hx1yr VS T*E(75) x6 VS T*E(75) x6 then Hx1yrA, adriamycin; C, cyclophosphamide; T, paclitaxel; T*, docetaxel; H, trastuzumab; P, carboplatin; F, 5-fluorouracil; E, epirubicin; Treatment regimen also included 5 years of hormonal therapy for ER positive patients. The ER+/HER2+ and the ER-/HER2+ cohorts will be analyzed separately. Patients with tumors 3 cm or smaller (T1a, T1b, T1c and &gt;2 cm- 3cm) and 0, 1, 2 and 3 positive lymph nodes will be included. Initially a log rank test will be used to determine if the survival results are different by study. If there is no difference across studies, Kaplan-Meier survival curves with confidence intervals will be estimated. If there is a difference between studies, individual Kaplan-Meier curves will be estimated and the mean of the curves will be estimated along with confidence intervals using the adjusted standard deviation. Estimates at 3, 5 and 8 years will be presented as well as estimates of the event rates within each subpopulation defined by tumor size, number of positive lymph nodes, and ER status. Survival endpoints of DFS, and OS as defined in the original studies will be analyzed. Results and Conclusion Data from the five trials will be analyzed and an abstract provided prior to the meeting. Subgroups of patients with a very favorable outcome when treated with adjuvant chemotherapy and T will be identified. Our survival estimates might serve as benchmarks for future trials evaluating therapy reduction. Our results will complement those of the Dana Farber single arm multicenter trial in patients with “low risk” HER2-positive disease (APT trial; NCT00542451), being submitted to SABCS 2013. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S6-03.