Abstract Background Reports on associations between azole antifungal medications and acute liver injury are inconsistent and have not been based on liver-related laboratory tests. We evaluated ...incidence rates of acute liver injury associated with oral azole antifungals. Methods We conducted a cohort study among Kaiser Permanente Northern California members who initiated an oral azole antifungal in an outpatient setting during 2004-2010. We determined development of: (1) liver aminotransferases >200 U/L, (2) severe acute liver injury (coagulopathy with hyperbilirubinemia), and (3) acute liver failure. We calculated incidence rates of endpoints. Cox regression was used to determine whether chronic liver disease was a risk factor for outcomes. Results Among 195,334 azole initiators (178,879 fluconazole; 14,296 ketoconazole; 1653 itraconazole; 478 voriconazole; 28 posaconazole), incidence rates (events/1000 person-years 95% confidence intervals (CIs)) of liver aminotransferases >200 U/L were similarly low with fluconazole (13.0 11.4-14.6), ketoconazole (19.3 13.8-26.3), and itraconazole (24.5 10.6-48.2). Rates were higher with voriconazole (181.9 112.6-278.0) and posaconazole (191.1 23.1-690.4), but comparable. Severe acute liver injury was uncommon with fluconazole (2.0 1.4-2.7), ketoconazole (2.9 1.1-6.3), and itraconazole (0.0 0.0-11.2), but more frequent with voriconazole (16.7 2.0-60.2) and posaconazole (93.4 2.4-520.6). One patient developed acute liver failure due to ketoconazole. Pre-existing chronic liver disease increased risks of aminotransferases >200 U/L (hazard ratio 4.68 95% CI, 3.68-5.94) and severe acute liver injury (hazard ratio 5.62 95% CI, 2.56-12.35). Conclusions Rates of acute liver injury were similarly low for fluconazole, ketoconazole, and itraconazole. Events were more common among voriconazole and posaconazole users but were comparable. Pre-existing chronic liver disease increased risk of azole-induced liver injury.
Abstract Objectives Preplanned economic analysis of a pragmatic trial using electronic-medical-record–linked interactive voice recognition (IVR) reminders for enhancing adherence to cardiovascular ...medications (i.e., statins, angiotensin-converting enzyme inhibitors ACEIs, and angiotensin receptor blockers ARBs). Methods Three groups, usual care (UC), IVR, and IVR plus educational materials (IVR+), with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on average. Costs to implement and deliver the intervention (from a payer perspective) were tracked during the trial. Medical care costs and outcomes were ascertained using electronic medical records. Results Per-patient intervention costs ranged from $9 to $17 for IVR and from $36 to $47 for IVR+. For ACEI/ARB, the incremental cost-effectiveness ratio for each percent adherence increase was about 3 times higher with IVR+ than with IVR ($6 and $16 for IVR and IVR+, respectively). For statins, the incremental cost-effectiveness ratio for each percent adherence increase was about 7 times higher with IVR+ than with IVR ($6 and $43 for IVR and IVR+, respectively). Considering potential cost offsets from reduced cardiovascular events, the probability of breakeven was the highest for UC, but the IVR-based interventions had a higher probability of breakeven for subgroups with a baseline low-density lipoprotein (LDL) level of more than 100 mg/dl and those with two or more calls. Conclusions We found that the use of an automated voice messaging system to promote adherence to ACEIs/ARBs and statins may be cost-effective, depending on a decision maker’s willingness to pay for unit increase in adherence. When considering changes in LDL level and downstream medical care offsets, UC is the optimal strategy for the general population. However, IVR-based interventions may be the optimal choice for those with elevated LDL values at baseline.
The authors undertook a qualitative study with open-ended, structured interviews to understand patient)s educational needs for patients undergoing total hip and total knee arthroplasty (THA/TKA).
...Provider interviews explored their approach with THA/TKA patients on: pain management; barriers to opioid tapering; and recommendations/changes on educational materials to support pain management and opioid reduction. Patient interviews explored their experience, understanding, beliefs surrounding opioids, and recommendations on important content. A qualitative methodologist conducted interviews and content analysis to identify key themes.
Kaiser Permanente Northwest, community setting.
A purposeful sampling method identified interviewees (surgeons, advice nurses, physical therapists, physician assistants, and patients). Patients were recent THA/TKA cases in the top third of opioid use after surgery.
N/A.
Qualitative study.
Recommendations for patient educational content included: (1) clear descriptions of how opioids work in the body, how to taper, nonopioid pain management options, and problems from overuse; (2) messaging on how long to expect to use opioids and type of pain to expect; (3) visual timeline to illustrate opioid tapering and exercise expectations; (4) emphasize that pain management is multimodal, and stress the balance between opioids for recovery versus overuse; (5) provide educational messaging multiple times prior to and after surgery.
Patients and providers agreed that clearly stated verbal and written messaging is needed beyond what has typically been done regarding opioid expectations.
Barrett's esophagus and esophageal adenocarcinoma diagnoses have increased markedly in recent decades. Recent research with patients diagnosed with Barrett's esophagus (the only known precursor for ...esophageal adenocarcinoma) and esophageal adenocarcinoma has identified several modifiable and nonmodifiable potential risk factors. Consistent risk factors for both disorders include increasing age, male sex, white non-Hispanic race/ethnicity, gastroesophageal reflux disease, lack of infection with Helicobacter pylori, smoking, abdominal obesity, and a Western diet. The authors present detailed discussions of these risk factors along with possible explanations for some apparent discrepancies and ideas for future study.
Abstract Purpose The aim of this study was to explore how learning collaboratives cultivate leadership skills that are essential for implementing patient-centered medical homes (PCMHs). Methods We ...conducted an ethnographic evaluation of a payor-incentivized PCMH implementation in Oregon safety net clinics, known as Primary Care Renewal. Analyses primarily drew on in-depth interviews with organizational leaders who were involved in the initiative. We solicited perspectives on the history, barriers, facilitators, and other noteworthy factors related to the implementation of PCMH. We reviewed and summarized transcripts and created and applied a coding dictionary to identify emergent leadership themes. We reviewed field notes from clinic site visits and observations of learning collaborative activities for additional information on the role of engaged leadership. Results Interview data suggested that organizations followed a similar, sequential process of Primary Care Renewal implementation having 2 phases—inspiration and implementation—and that leaders needed and learned different leadership skills in each phase. Leaders reported that collaborative learning opportunities were critical for developing engaged leadership skills during the inspiration phase of transformation. Facilitative and modeling aspects of engaged leadership were most important for codesigning a vision and plan for change. Adaptive leadership skills became more important during the implementation phase, when specific operational and management skills were needed to foster standardization and spread of the Primary Care Renewal initiative throughout participating clinics. Conclusions The PCMH has received much attention as a way to reorganize and potentially improve primary care. Documenting steps and stages for cultivating leaders with the vision and skills to transform their organizations into PCMHs may offer a useful roadmap to other organizations considering a similar transformation.
Abstract While the incidence rates of many cancers have decreased in past decades, the incidence of oesophageal adenocarcinoma continues to increase. The only known precursor for oesophageal ...adenocarcinoma is Barrett's oesophagus. Studies conducted have identified white race, male sex, GORD, cigarette smoking, obesity, and the absence of Helicobacter pylori status as risk factors for oesophageal adenocarcinoma. Other potential associations include dietary factors and the absence of non-steroidal anti-inflammatory drug use. Many individual studies have been limited by sample size and several meta-analyses have pooled data from studies to address this limitation. In this review we present a synthesis of these studies and summarize current knowledge of risk factors for both oesophageal adenocarcinoma and Barrett's oesophagus.
Background Patient mammogram reminders are effective but have not been fully implemented in practice to improve routine screening. The effectiveness of implementation and maintenance phases of a ...multimodal reminder program that incorporated automated calls capable of efficiently reaching large numbers of women was evaluated to improve repeat mammography screening. Design A quasi-experimental study was conducted in 2008 using electronic medical record data during three time periods: pre-reminder phase (2004), post-reminder implementation phase (2006), and post-reminder maintenance phase (January 1–July 1, 2007). Setting/participants Participants were female Kaiser Permanente Northwest HMO members aged 42 years or more who were 20 months past their last mammogram (index date) (N=35,104). The intervention program targeted women aged 50–69 years. Women aged 42–49 years (for whom clinical guidelines also recommend mammography) not targeted by the program constituted the primary comparison group (CG1). Intervention A “mammogram due soon” postcard was mailed to participants 20 months after their last mammogram, followed by up to two automated phone calls and one live call for nonresponders. Main outcome measures The outcome measure was the time until participants received a mammogram in the 10 months following the index date. Results Pre-reminder, 63.4% of targeted women completed a mammogram; this number increased to 75.4% in the post-reminder implementation phase; 80.6% completed a mammogram in the maintenance phases. After controlling for demographics and clinic visits, intervention women were 1.51 times more likely to complete a mammogram (CI=1.40, 1.62) post-reminder implementation, compared to CG1. The effect was maintained in 2007 (hazard ratio 1.81, CI=1.65, 1.99). Conclusions The study found that this multimodal reminder system could be effectively implemented and maintained in a large health system. If widely implemented, this intervention could substantially improve community mammography screening.
Background The use of postmastectomy reconstruction varies with socioeconomic status, but the etiology of these variations is not understood. We investigated whether these differences reflect ...variations in the rate or qualitative aspects of the provider’s discussion of reconstruction as an option. Study Design Data were collected through chart review and patient survey for stages I to III breast cancer patients during the National Initiative on Cancer Care Quality. Multivariable logistic regression was used to identify predictors of reconstruction and discussion of reconstruction as an option. Predictors of not receiving reconstruction despite a documented discussion were also determined. Results There were 253 of 626 patients who received reconstruction (40.4%). Younger, more educated Caucasian women who were not overweight or receiving postmastectomy radiation were more likely to receive reconstruction. Patients who were younger, more educated, and not receiving postmastectomy radiation were more likely to have a documented discussion of reconstruction. If a discussion was documented, patients who were older, Hispanic, not born in the US, and received postmastectomy radiation were less likely to receive reconstruction. The greatest predictor of reconstruction was medical record documentation of a discussion about reconstruction. Conclusions We observed disparities in the likelihood of reconstruction that were at least partially explained by differences in the likelihood that reconstruction was discussed. But there were also differences in the likelihood of reconstruction based on age, race, and radiation once discussions occurred. Efforts to increase and improve discussions about reconstruction may decrease disparities for this procedure.
Objective This retrospective study evaluated the toxicity of extended-field radiation therapy (EFRT), whole pelvis radiotherapy, and concurrent chemotherapy in patients treated with IB2-IIIB cervical ...carcinoma. Study Design Patients treated with EFRT, whole pelvis radiotherapy, and concurrent chemotherapy were analyzed for toxicity. Median prescribed dose to the whole pelvis was 45 Gy (45-50 Gy). Median prescribed dose to the paraaortic lymph nodes was 45 Gy (36-50). Thirty-five patients received cisplatin chemosensitization at a median dose of 40 mg/m2 (40-51), with a median of 5 cycles (2-6). Results Thirty-six patients were treated, 3 with positive paraaortic lymph nodes. The median follow-up interval was 32 months. Twenty-four patients (66.7%) had no evidence of disease at last follow-up. Thirteen patients (36.1%) had recurrence. Fifteen patients (41.7%) experienced acute grade 3 toxicity. Conclusion Increased toxicity in patients warrants careful patient selection.
Background Peanut oral immunotherapy is a promising approach to peanut allergy, but reactions are frequent, and some patients cannot be desensitized. The anti-IgE medication omalizumab (Xolair; ...Genentech, South San Francisco, Calif) might allow more rapid peanut updosing and decrease reactions. Objective We sought to evaluate whether omalizumab facilitated rapid peanut desensitization in highly allergic patients. Methods Thirty-seven subjects were randomized to omalizumab (n = 29) or placebo (n = 8). After 12 weeks of treatment, subjects underwent a rapid 1-day desensitization of up to 250 mg of peanut protein, followed by weekly increases up to 2000 mg. Omalizumab was then discontinued, and subjects continued on 2000 mg of peanut protein. Subjects underwent an open challenge to 4000 mg of peanut protein 12 weeks after stopping study drug. If tolerated, subjects continued on 4000 mg of peanut protein daily. Results The median peanut dose tolerated on the initial desensitization day was 250 mg for omalizumab-treated subjects versus 22.5 mg for placebo-treated subject. Subsequently, 23 (79%) of 29 subjects randomized to omalizumab tolerated 2000 mg of peanut protein 6 weeks after stopping omalizumab versus 1 (12%) of 8 receiving placebo ( P < .01). Twenty-three subjects receiving omalizumab versus 1 subject receiving placebo passed the 4000-mg food challenge. Overall reaction rates were not significantly lower in omalizumab-treated versus placebo-treated subjects (odds ratio, 0.57; P = .15), although omalizumab-treated subjects were exposed to much higher peanut doses. Conclusion Omalizumab allows subjects with peanut allergy to be rapidly desensitized over as little as 8 weeks of peanut oral immunotherapy. In the majority of subjects, this desensitization is sustained after omalizumab is discontinued. Additional studies will help clarify which patients would benefit most from this approach.
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