The Impact of Text Messaging to Promote Patient Reported Outcome Measures (PROMs) Completion in Orthopedic Practice: Findings From a Randomized Controlled Study.

It is difficult to achieve high response rates to Patient Reported Outcome Measures (PROMs) surveys collected as part of clinical care. However, they are operationally and clinically important. To understand the impact of text message reminders on response rates to PROMs collected via email as part of routine care for hip or knee replacement surgery, initial nonresponders were randomized to receive a text reminder or not at 7 and 12 days, if needed. At day 7, the overall survey response rate was 63%. Model-derived estimates for survey return after this point were 51.1% (95% confidence interval [CI], 48.0%-54.2%) in the text arm compared to 34.5% (95% CI, 31.6%-37.6%) in the no text arm. The effect of text messages on response rates did not vary by subpopulations considered nor were there differences in rates of key outcomes between the 2 groups, suggesting that it did not impact any underlying response bias. Given the relative low cost of text messages, they can be an efficient means to increase response rates.

Is the Promise of PROMs Being Realized? Implementation Experience in a Large Orthopedic Practice.

Patient-reported outcome measures (PROMs), increasingly used for research and quality measurement, are lauded for their potential to improve patient-centered care, both through aggregate reporting and when integrated into clinical practice. However, there are few published studies of the resultant use of PROMs in clinical practice. This case study describes the implementation and use of PROMS in a Midwestern multispecialty medical group orthopedic practice among patients undergoing total knee and hip surgery. Specifically, rates of PROMs use by care teams are tracked over time once made available in the electronic health record. During this time, the orthopedics department achieved a patient PROMS survey response rate of 68% at baseline, 58% 3 months post-surgery, and 55% 12 months post-surgery. However, these data were only accessed by the care teams for fewer than 1% of associated clinical encounters. This suggests that making PROMs available for care team review in the electronic health record, even when coupled with relatively high response rates from patients and departmental leadership support is not enough to encourage integration of PROMs into clinical care for patients. Additional effort is required to identify barriers to PROMs use in clinical care and to test methods to enhance use.

What Do Orthopaedists Believe is Needed for Incorporating Patient-reported Outcome Measures into Clinical Care? A Qualitative Study.

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly promoted for use in routine orthopaedic care with the expectation that if they are made available during encounters, they will be incorporated into clinical practice. We investigated an initiative in which PROMs were systematically collected and provided via the electronic health record but were infrequently used. QUESTIONS/PURPOSES: In a qualitative study, we asked: (1) Why are PROM results not being used in clinical care when they are available to surgeons? (2) What aspects of PROMs are seen as useful for clinical care? (3) How are PROMs generally perceived by surgeons and orthopaedic leaders? METHODS: A cross-sectional qualitative study was conducted in a single health system in an urban setting using semistructured interviews with a purposive sample of orthopaedic surgeons and leaders who would have substantial knowledge of and experience with the organization's PROM system, which was embedded in the electronic health record and developed for use in clinical care but was not being used. We included surgeons whose practices consisted of at least 90% patients with osteoarthritis, including surgical and nonsurgical management, and thus their patients would be completing PROMs surveys, or surgeons who were leaders in one of the three orthopaedic divisions in the health plan. The senior research manager for orthopaedics identified 14 potential participants meeting these criteria, 11 of whom agreed to study participation. Participants included nine surgeons and two orthopaedic leaders; the majority were men, with a median of 13 years of clinical practice. Study interviews were conducted by an experienced interviewer not known to participants, in private conference rooms in the healthcare setting, and a median (range) of 27 minutes (16 to 40) in length. A content analysis approach was employed for data analysis, with thematic inductive saturation reached in the analysis and attention to trustworthiness and rigor during the analytic process. RESULTS: Interviewees reported that PROM scores are not being used in patient clinical care because of logistical barriers, such as access and display issues and the time required, and perceptual barriers, such as concerns about patient understanding and the validity and reliability of measures. Surgeons preferred talking with patients about the personal outcomes patients had identified as important; most patients preferred to assess progress toward their own goals than PROMs scores for other people. Surgeons also identified changes that could facilitate PROM use and reduce barriers in clinical care, including pushing PROM scores to physicians' inboxes, developing inserts for physician notes, using easy-to-understand graphical displays, and engaging patients about PROMs earlier in the care process. Participants all agreed that PROMs in aggregate use are valuable for the organization, department, and individual surgeons, but individual patient scores are not. CONCLUSION: Despite the availability of PROMs, there are important barriers to incorporating and using PROMs in clinical care. Providing access to PROM scores without clearly understanding how and why surgeons may consider using or incorporating them into their clinical practice can result in expensive and underused systems that add little value for the clinician, patient, or organization. CLINICAL RELEVANCE: Involving front-line orthopaedic surgeons and leaders in shaping the design and structure of PROM systems is important for use in clinical care, but these interviewees seemed to see aggregate data as more valuable than individual patient scores.

Personalized outcomes for hip and knee replacement: the patients point of view.

BACKGROUND: Patient reported outcome measures (PROMs) are increasingly being incorporated into clinical and surgical care for assessing outcomes. This study examined outcomes important to patients in their decision to have hip or knee replacement surgery, their perspectives on PROMs and shared decision-making, and factors they considered important for postoperative care. METHODS: A cross-sectional study employing survey methods with a stratified random sample of adult orthopedic patients who were scheduled for or recently had hip or knee replacement surgery. RESULTS: In a representative sample of 226 respondents, patients identified personalized outcomes important to them that they wanted from their surgery including the ability to walk without pain/discomfort, pain relief, and returning to an active lifestyle. They preferred a personalized outcome (54%) that they identified, compared to a PROM score, for tracking progress in their care and thought it important that their surgeon know their personal outcomes (63%). Patients also wanted to engage in shared decision-making (79%) about their post-surgical care and identified personal factors important to their aftercare, such as living alone and caring for pets. CONCLUSIONS: Patients identified unique personalized outcomes they desired from their care and that they wanted their orthopedic surgeons to know about. Asking patients to identify their personalized outcomes could add value for both patients and surgeons in clinical care, facilitating more robust patient involvement in shared decision-making.

What Outcomes Matter to Patients After Joint or Spine Surgery?

PURPOSE: Patient-reported outcome measures (PROMs) are increasingly used in clinical care, but there have been few studies of what patients identify as the most important outcomes. METHODS: Semi-structured interviews were conducted with 65 patients undergoing hip or knee replacement, spinal discectomy/laminotomy, or a spinal fusion. Interviews focused on outcomes patients identified as important, perceived usefulness of standardized PROMs measures, and contextual situations important to their care. Data were analyzed using a directed content analysis approach. RESULTS: Patients identified desired outcomes that were unique and important to them. Their preferred outcomes focused in the areas of freedom from pain, getting back to their normal life, and returning to an active lifestyle. Patients cared more about their individual preferred outcomes, which had more meaning for them, than a standardized PROM score. Patients also identified particular contextual situations that their care team was assumed to know about but that may not have been known. CONCLUSIONS: Patients identify specific preferred outcomes from these surgical procedures that are important and meaningful to them and that frame whether they see their surgery as a success. They also identified personal factors that they assume their surgeons know about, which affect their care and recovery. These findings underscore the importance of engaging patients in discussions about their preferences and contextual factors both prior to and after surgery.

Budgetary impact from multiple perspectives of sustained antitobacco national media campaigns to reduce the harms of cigarette smoking.

BACKGROUND: High-intensity antitobacco media campaigns are a proven strategy to reduce the harms of cigarette smoking. While buy-in from multiple stakeholders is needed to launch meaningful health policy, the budgetary impact of sustained media campaigns from multiple payer perspectives is unknown. METHODS: We estimated the budgetary impact and time to breakeven from societal, all-payer, Medicare, Medicaid and private insurer perspectives of national antitobacco media campaigns in the USA. Campaigns of 1, 5 and 10 years of durations were assessed in a microsimulation model to estimate the 10 and 20-year health and budgetary impact. Simulation model inputs were obtained from literature and both pubic use and proprietary data sets. RESULTS: The microsimulation predicts that a 10-year national smoking cessation campaign would produce net savings of $10.4, $5.1, $1.4, $3.6 and $0.2 billion from the societal, all-payer, Medicare, Medicaid and private insurer perspectives, respectively. National antitobacco media campaigns of 1, 5 and 10-year durations could produce net savings for Medicaid and Medicare within 2 years, and for private insurers within 6-9 years. A 10-year campaign would reduce adult cigarette smoking prevalence by 1.2 percentage points, prevent 23 500 smoking-attributable deaths over the first 10 years. In sensitivity analysis, media campaign costs would be offset by reductions in medical care spending of smoking among all payers combined within 6 years in all tested scenarios. CONCLUSIONS: 1, 5 and 10-year antitobacco media campaigns all yield net savings within 10 years from all perspectives. Multiyear campaigns yield substantially higher savings than a 1-year campaign.

Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism.

Mitochondrial metabolism is an attractive target for cancer therapy1,2. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (TNBC)1,3. Here we show that BTB and CNC homology1 (BACH1)4, a haem-binding transcription factor that is increased in expression in tumours from patients with TNBC, targets mitochondrial metabolism. BACH1 decreases glucose utilization in the tricarboxylic acid cycle and negatively regulates transcription of electron transport chain (ETC) genes. BACH1 depletion by shRNA or degradation by hemin sensitizes cells to ETC inhibitors such as metformin5,6, suppressing growth of both cell line and patient-derived tumour xenografts. Expression of a haem-resistant BACH1 mutant in cells that express a short hairpin RNA for BACH1 rescues the BACH1 phenotype and restores metformin resistance in hemin-treated cells and tumours7. Finally, BACH1 gene expression inversely correlates with ETC gene expression in tumours from patients with breast cancer and in other tumour types, which highlights the clinical relevance of our findings. This study demonstrates that mitochondrial metabolism can be exploited by targeting BACH1 to sensitize breast cancer and potentially other tumour tissues to mitochondrial inhibitors.

Mutant GNAS drives pancreatic tumourigenesis by inducing PKA-mediated SIK suppression and reprogramming lipid metabolism.

G protein αs (GNAS) mediates receptor-stimulated cAMP signalling, which integrates diverse environmental cues with intracellular responses. GNAS is mutationally activated in multiple tumour types, although its oncogenic mechanisms remain elusive. We explored this question in pancreatic tumourigenesis where concurrent GNAS and KRAS mutations characterize pancreatic ductal adenocarcinomas (PDAs) arising from intraductal papillary mucinous neoplasms (IPMNs). By developing genetically engineered mouse models, we show that GnasR201C cooperates with KrasG12D to promote initiation of IPMN, which progress to invasive PDA following Tp53 loss. Mutant Gnas remains critical for tumour maintenance in vivo. This is driven by protein-kinase-A-mediated suppression of salt-inducible kinases (Sik1-3), associated with induction of lipid remodelling and fatty acid oxidation. Comparison of Kras-mutant pancreatic cancer cells with and without Gnas mutations reveals striking differences in the functions of this network. Thus, we uncover Gnas-driven oncogenic mechanisms, identify Siks as potent tumour suppressors, and demonstrate unanticipated metabolic heterogeneity among Kras-mutant pancreatic neoplasms.

Cancer Metabolism: Current Understanding and Therapies.

Dysregulation of cancer cell metabolism contributes to abnormal cell growth, the biological end point of cancer. We review here numerous affected oncogenes and metabolic pathways common in cancer and how they contribute to cancer pathogenesis and malignancy. This review also discusses various pharmacological manipulations that take advantage of these metabolic abnormalities and the current targeted therapies that have arisen from this research.

A Proximity Labeling Strategy Provides Insights into the Composition and Dynamics of Lipid Droplet Proteomes.

Lipid droplet (LD) functions are regulated by a complement of integral and peripheral proteins that associate with the bounding LD phospholipid monolayer. Defining the composition of the LD proteome has remained a challenge due to the presence of contaminating proteins in LD-enriched buoyant fractions. To overcome this limitation, we developed a proximity labeling strategy that exploits LD-targeted APEX2 to biotinylate LD proteins in living cells. Application of this approach to two different cell types identified the vast majority of previously validated LD proteins, excluded common contaminating proteins, and revealed new LD proteins. Moreover, quantitative analysis of LD proteome dynamics uncovered a role for endoplasmic reticulum-associated degradation in controlling the composition of the LD proteome. These data provide an important resource for future LD studies and demonstrate the utility of proximity labeling to study the regulation of LD proteomes.

Covalent Ligand Discovery against Druggable Hotspots Targeted by Anti-cancer Natural Products.

Many natural products that show therapeutic activities are often difficult to synthesize or isolate and have unknown targets, hindering their development as drugs. Identifying druggable hotspots targeted by covalently acting anti-cancer natural products can enable pharmacological interrogation of these sites with more synthetically tractable compounds. Here, we used chemoproteomic platforms to discover that the anti-cancer natural product withaferin A targets C377 on the regulatory subunit PPP2R1A of the tumor-suppressor protein phosphatase 2A (PP2A) complex leading to activation of PP2A activity, inactivation of AKT, and impaired breast cancer cell proliferation. We developed a more synthetically tractable cysteine-reactive covalent ligand, JNS 1-40, that selectively targets C377 of PPP2R1A to impair breast cancer signaling, proliferation, and in vivo tumor growth. Our study highlights the utility of using chemoproteomics to map druggable hotspots targeted by complex natural products and subsequently interrogating these sites with more synthetically tractable covalent ligands for cancer therapy.

GSTP1 Is a Driver of Triple-Negative Breast Cancer Cell Metabolism and Pathogenicity.

Breast cancers possess fundamentally altered metabolism that fuels their pathogenicity. While many metabolic drivers of breast cancers have been identified, the metabolic pathways that mediate breast cancer malignancy and poor prognosis are less well understood. Here, we used a reactivity-based chemoproteomic platform to profile metabolic enzymes that are enriched in breast cancer cell types linked to poor prognosis, including triple-negative breast cancer (TNBC) cells and breast cancer cells that have undergone an epithelial-mesenchymal transition-like state of heightened malignancy. We identified glutathione S-transferase Pi 1 (GSTP1) as a novel TNBC target that controls cancer pathogenicity by regulating glycolytic and lipid metabolism, energetics, and oncogenic signaling pathways through a protein interaction that activates glyceraldehyde-3-phosphate dehydrogenase activity. We show that genetic or pharmacological inactivation of GSTP1 impairs cell survival and tumorigenesis in TNBC cells. We put forth GSTP1 inhibitors as a novel therapeutic strategy for combatting TNBCs through impairing key cancer metabolism and signaling pathways.

Biofeedback Assisted Stress Management in Patients with Lung Cancer: A Feasibility Study.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death for men and women in the United States. NSCLC causes a variety of symptoms which result in significant distress and reduced quality of life for patients. Behavioral and other non-pharmacologic treatment interventions for NSCLC have resulted in improved quality of life, reduced emotional distress, and improved longevity. This study investigates the feasibility and effectiveness of biofeedback assisted stress management (BFSM) to reduce stress in patients with NSCLC. Because of patient dropout, this study was terminated prematurely. Despite this, evaluation of data revealed positive trends, with patients learning to reduce their stress, improve their respiration and heart rate variability, and improve coping. These trends suggest that patients with NSCLC can learn to self-regulate physiology and BFSM may be useful for them, although a less ill patient population may be desirable for future investigations.

Clearance of nasal Staphylococcus aureus colonization with triple antibiotic ointment.

BACKGROUND: The prevalence of Staphylococcus aureus colonization of healthcare workers is reported at 30%, with colonization rates for methicillin-resistant S aureus (MRSA) reported between 2.0% and 8.5% among industrialized nations. The anterior nares are the most frequent colonization site. Mupirocin is the standard of care for nasal S aureus decolonization, with decolonization rates as high as 90%. Staphyloccocal resistance to mupirocin has been described, requiring additional management strategies. In certain situations, triple antibiotic ointment (TAO) may be a suitable alternative for elimination of nasal S aureus colonization. OBSERVATIONS: Adult healthcare workers within an academic-centered hospital (n=216) were screened via nasal swab with culture for S aureus colonization. Forty-!ve subjects (20.8%) screened positive for S aureus; of these subjects, 3 (1.4%) were positive for MRSA. Of the 45 subjects with positive cultures, 30 completed 5 days of twice-daily intranasal TAO application. One week after treatment, all 30 subjects were reswabbed; 16 (53.3%) showed evidence of decolonization on repeat culture. CONCLUSIONS: The rate of S aureus colonization of healthcare workers in our study is lower than published rates in industrialized nations. Intranasal application of TAO may be a viable option for eradication of nasal colonization by methicillin-susceptible S aureus in environments where mupirocin-resistant bacterial strains become more prevalent.

Estimating prevalence, incidence, and disease-related mortality for patients with epilepsy in managed care organizations.

PURPOSE: The purpose of the present study was to apply computer algorithms to an administrative data set to identify the prevalence of epilepsy, incidence of epilepsy, and epilepsy-related mortality of patients in a managed care organization (MCO). METHODS: The study population consisted of members enrolled in Lovelace Health Plan, a component of Lovelace Health Systems, a statewide MCO headquartered in Albuquerque, New Mexico. Patient records were obtained from July 1996 to June 2001. Four logistic regression models with high sensitivity and specificity were applied to 1-, 3-, and 5-year time frames in which members were continuously enrolled in the MCO. Incidence was defined for patients who did not have an epilepsy-associated code in the 18 months before the first diagnosis entry. Mortality estimates in the population also were assessed by using a matched control group and linkage to a statewide death registry. RESULTS: The data yielded estimated prevalence rates of 7-10 per 1,000, depending on age, sex, ethnicity, and time interval. Annualized incidence was 47 per 100,000 for members continuously enrolled for 3 years and 71 per 100,000 for members continuously enrolled for 5 years. Crude mortality rates were 2-2.5 times higher for epilepsy patients identified with the algorithms than for the matched controls. Conditional logistic regression indicated that the odds of death for epilepsy patients as compared with controls ranged from 1.24 to 2.06. CONCLUSIONS: Accurate estimation of prevalence, incidence, and mortality rates for epilepsy is an essential component of disease management in MCOs. The algorithms in this project can be used to monitor trends in prevalence, incidence, and mortality to inform decisions critical to improving the health care needs and quality of life for patients with epilepsy.