Probability Of Treatment Success Research Articles

Post-Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High-Flux Hemodialysis.

Patients with end-stage renal disease (ESRD) requiring intermittent hemodialysis (IHD) are at increased risk of infection, which represents a leading cause of mortality in this population. The use of additional vascular access devices such as peripherally inserted central catheters to treat such infections should be minimized in patients with ESRD requiring IHD in order to mitigate complications such as infection and thrombosis and to maintain venous patency for hemodialysis access. Intravenous antimicrobial dosing following IHD has the advantages of avoiding additional access devices and providing convenience for patients and providers. Vancomycin, cefazolin, and aminoglycosides have historically been regarded as the primary intravenous antimicrobials administered with IHD given their relatively low cost, convenient dosing, and longevity of clinical use. Despite this, a growing body of literature is evaluating the use of an expanded list of antimicrobials that may be employed using post-dialysis dosing for patients requiring IHD; however, the available data are largely limited to pharmacokinetic studies and small cohorts of infected patients or uninfected subjects. Post-dialytic dosing of intravenous antimicrobials may be considered on a patient-by-patient basis after careful consideration of clinical, microbiological, and logistical factors that may influence the probability of treatment success. This document reviews and evaluates currently available information on the post-dialytic administration of an expanded list of intravenous antimicrobials in the setting of thrice-weekly, high-flux IHD.

Optimal trough concentration of teicoplanin for the treatment of methicillin-resistant Staphylococcus aureus infection: A systematic review and meta-analysis.

It has been recommended that the trough concentration (Cmin ) of teicoplanin should be maintained at ≥20μg/ml for difficult-to-treat complicated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Conversely, Cmin of teicoplanin of at least 10μg/ml is required for non-complicated MRSA infections. Considering the low incidence of nephrotoxicity for teicoplanin, Cmin =15-30μg/ml has been suggested for most MRSA infections. Thus, we assessed the clinical efficacy and adverse effects of teicoplanin at this target Cmin . We searched electronic databases (PubMed, Cochrane Central Register of Controlled Trials and Ichushi-Web) to identify eligible studies. Studies were included if they provided the incidence of treatment success, mortality in patients with MRSA infection, and/or hepatotoxicity and nephrotoxicity according to the Cmin range. Four trials assessing clinical success (n=299) and three studies assessing adverse effects (n=546) were included. Cmin =15-30μg/ml significantly increased the probability of treatment success compared with Cmin <15μg/ml (odds ratio [OR]=2.68, 95% confidence interval [CI]=1.14-6.32, p=0.02). The all-cause mortality rate did not differ between the groups (OR=0.46, 95% CI=0.13-1.61, p=0.22). Cmin =15-30μg/ml did not increase the risks of nephrotoxicity (OR=0.91, 95% CI=0.49-1.69, p=0.76) or hepatotoxicity (OR=0.67, 95% CI=0.18-2.44, p=0.54). Teicoplanin therapy using a Cmin target of 15-30μg/ml is likely to be associated with better clinical responses than Cmin <15μg/ml without increasing the risk of adverse effects.

ROLE OF DAY 4 AND DAY 7 Β-HCG AS AN EARLY PREDICTOR OF SUCCESS AFTER METHOTREXATE THERAPY FOR TUBAL ECTOPIC PREGNANCIES

Background: Tubal ectopic pregnancy is potentially life-threatening with an estimated incidence of 1% to 2% of all pregnancies with the wide availability of transvaginal ultrasound and quantitative serum beta human chorionic gonadotropin (β-hCG) assay; ectopic pregnancies can be diagnosed early, leading to successful management without resort to surgery. Objective: Evaluation of β-hCG levels between days 4 and 7 as a predictor of methotrexate therapy success for ectopic pregnancy. Patients and Methods: 50 cases, diagnosed of ectopic pregnancy, This study was carried out on Al-Hussein Hospital during July 2018 and August 2019 All cases were subjected to full history taking, complete clinical examination, ultrasongraphy and Laboratory investigations as Complete blood count, Liver profile (ALT and AST), Serum creatinine, and Serum β-hCG levels on day1, 4, and7 after methotrexate therapy. Results: The mean age was 28 ± 5 years, ranging between 20 and 40 years. The average gestational age was 5 weeks, while the average parity was 1. Of 50 cases, 36 patients (72%) succeeded and 14 failed. The ROC curve for the hCG index identified an hCG index value of 0.192 (19% decrease of hCG value between day 1 and day 4) as the best predictor for ectopic pregnancy treated successfully with a single dose of methotrexate. Sensitivity for the test was 80% and accuracy was 75%. Conclusion: Early serum β-hCG decline is associated with a very high probability of treatment success. However, given that we found an 80% success rate, not 100%, we suggest it is prudent to continue the serial monitoring of serum β-hCG until the complete resolution of the ectopic pregnancy.

Enasidenib, an Oral Therapy in Mutant IDH2 Relapsed/Refractory Acute Myeloid Leukemia: A Real-Life Single Center Experience

Background: The treatment for relapsed or refractory acute myeloid leukemia (R/R AML) has minimal chances and a low impact on improving survival. One of the most important goal is to treat unfit patients who are often intolerant to intensive chemotherapy and are not eligible for allogeneic stem cell transplantation. Most patients with AML, including nearly all patients older than 60 years, present multiple, sequentially acquired, somatic mutations. Isocitrate dehydrogenase 2 (IDH2) mutations are present in approximately 8-19% of cases (Buege MJ, Cancers 2018). IDH2 mutations occur early in the leukemogenesis and accumulate an oncogenic product (R-2-hydroxyglutarate) that arrests the histone demethylation pathway, thereby stopping haematopoietic differentiation (Rakheja D, Hum Pathol. 2012). Enasidenib (ENA) is a selective, powerful oral inhibitor of the oncogenic activity of the IDH2 mutant enzyme, that decreases R-2-hydroxyglutarate levels in vitro and in vivo. Interestingly, phase I/II trials showed an overall response rate (ORR) of 40.3% in R/R disease, with 19.3% of complete remission (CR) and with 6.8 % of CR with incomplete haematological recovery (CRi). Moreover, the reported median overall survival was 9.3 months, with 19.7 months (mo) for patients who achieved CR (Stein E, Blood 2017). Aims: To study retrospectively the efficacy and safety of ENA, as single agent, in improving overall survival (OS) and progression-free survival (PFS) in IDH2 mutated R/R AML patients (pts), unfit for intensive chemotherapy. Furthermore, to compare outcomes with a cohort of patients with R/R AML IDH2 wild-type (wt). Methods: Since 2018 we have retrospectively collected and analyzed data of unfit IDH2 mutated R/R AML patients, treated with ENA, thanks to the expanded access program of this drug. The dose was 100 mg/day for all pts. PFS and OS were estimated using the Kaplan-Meier product limit method. Therefore, we considered, as historical comparison, a sample of 28 pts with R/R IDH2 wt AML, treated with the best available therapy at our Institution in the same time frame and matched for clinical features. OS and PFS were compared using the log-rank test. Results: Nine IDH2 mutated pts were considered for analysis: 4 (44%) cases were de novo AML, while 5 (56%) were secondary (1 myelodysplasia and 4 myeloproliferative neoplasms). Median age at relapse was 71 years (range 47-79). Median number of previous therapies was 2 (range 1-3). All pts completed at least one cycle of ENA with a median number of 5 cycles (range 1-16). Median OS from AML diagnosis and from the beginning of ENA was 28 mo (range 3-65), and 15 mo (range 1-27) respectively; median PFS was 13 mo (range 1-14). Among the 28 patients of the control group, with a median age at relapse of 74 years (range 65-86) we recorded a median OS of 14 mo (range 7-62) and an OS from the last relapse of 2 mo (range 0,5-26). The ENA pts group showed a significantly better OS than the control population (p = 0,0419) (Figure 1). The most prominent toxicities were hyperbilirubinemia in 2 pts (22,2%) and IDH-differentiation syndrome (IDH-DS) in 3 (33,3%); though the drug was generally well tolerated. Therefore, patients were treated as outpatients in most cases. Conclusions: In the era of precision medicine, molecular target therapy is the most promising strategy to increase the probability of treatment success with limited side effects. Our experience confirms the efficacy of the IDH2 inhibitor ENA to treat unfit patients with R/R AML in the real life, showing significantly better outcome in terms of survival for the pts treated with target therapy, compared to pts treated with standard therapy. Disclosures Veronese: Janssen Cilag:Honoraria;Bayer:Honoraria;Novartis:Other: Travel Expenses;AstraZeneca:Other: Travel Expenses.

Information Technology for Decision-making Support for Personalized Parameter Selection in Retinal Laser Treatment and Photocoagulation Outcome Prognostication

We propose a new information technology for mapping macular photocoagulation patterns in the laser treatment of diabetic retinopathy and evaluating the treatment strategy efficacy. The technology relies on processing optical coherence tomography (OCT) data, fundus image segmentation, mapping photocoagulation plans, and development of prognostic indicators of the laser photocoagulation treatment outcome. Analysis of the OCT data enables a pathological area to be extracted and then refined based on retinal image segmentation results, allowing a photocoagulation treatment region to be outlined. A photocoagulation plan mapped for the region of interest (ROI) is then analyzed to identify the treatment success probability based on prognostic indicators. The technology developed will offer the retina specialist a preliminary photocoagulation plan, as well as allowing the assessment of the diabetic retinopathy treatment efficacy to be carried out.

Changes in treatment for multidrug-resistant tuberculosis according to national income.

The aim of this study was to analyse temporal changes in treatments for and outcomes of multidrug-resistant (MDR)/rifampin-resistant (RR)-tuberculosis (TB) in the context of national economic status.We analysed data collected by the Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB Treatment on MDR/RR-TB patients from 37 countries. The data were stratified by three national income levels (low-/lower-middle, upper-middle and high) and grouped by time of treatment initiation (2001-2003, 2004-2006, 2007-2009, 2010-2012 and 2013-2015). Temporal trends over the study period were analysed. The probability of treatment success in different income groups over time was calculated using generalised linear mixed models with random effects.In total, 9036 patients were included in the analysis. Over the study period, use of group A drugs (levofloxacin/moxifloxacin, bedaquiline and linezolid) recommended by the World Health Organization increased and treatment outcomes improved in all income groups. Between 2001-2003 and 2013-2015, treatment success rates increased from 60% to 78% in low-/lower-middle-income countries, from 40% to 67% in upper-middle-income countries, and from 73% to 81% in high-income countries. In earlier years, the probability of treatment success in upper-middle-income countries was lower than that in low-/lower-middle-income countries, but no difference was observed after 2010. However, high-income countries had persistently higher probability of treatment success compared to upper-middle income countries.Improved treatment outcomes and greater uptake of group A drugs were observed over time for patients with MDR/RR-TB at all income levels. However, treatment outcomes are still unsatisfactory, especially in upper-middle-income countries.

Outcome-Based Pricing for New Pharmaceuticals via Rebates

The price of new brand-name prescription drugs has been rising fast in the United States. For example, the Amgen cholesterol drug Repatha had an initial list price of $14,523 per year. Patients, even with insurance coverage, must pay out of pocket a significant portion of this price. The treatment might not be successful, and this possibility reduces risk-sensitive patients’ incentives to purchase the drug. The high price together with the chance of negative treatment outcomes may lead payers to deny coverage for the drug. Outcome-based pricing has been proposed as a way to reallocate the risks and improve both payer resource allocation and patient access to drugs. According to an outcome-based rebate contract between Amgen and Harvard Pilgrim Healthcare, if a patient on Repatha suffers a heart attack or a stroke, both patient and insurer are refunded the cost of the drug. We use a stylized model to analyze the effect of outcome-based pricing via rebates. Our model captures the interaction between heterogenous, price-sensitive, risk-sensitive patients who decide whether to purchase the drug; a payer deciding whether to provide coverage for the drug; and a price-setting pharmaceutical firm seeking to maximize expected profits. We find that, in many cases, a pharmaceutical firm and payer cannot simultaneously benefit from outcome-based pricing, and who will benefit is determined by the probability of treatment success. Outcome-based pricing thus appears unlikely to solve the issues of high drug prices and high payer expenditures. However, supplementing outcome-based pricing with a transfer payment from firm to payer can make payer and firm (but not necessarily the patients) better off than under uniform pricing when the drug has a low chance of success. This paper was accepted by Stefan Scholtes, healthcare management.

Salvage Hyperthermic Gemcitabine and Docetaxel Combination Chemotherapy After BCG Failure in Non-Muscle Invasive Bladder Cancer Patients

BACKGROUND: Bacillus Calmette-Guerin (BCG) is the recommended therapy for high and intermediate risk non-muscle invasive bladder cancer (NMIBC), but treatment failure is common. While a radical cystectomy is recommended after BCG failure, some patients desire bladder preservation and others are poor surgical candidates. Salvage chemotherapy treatments may be offered to this subgroup of patients. OBJECTIVE: To assess if combination, hyperthermic Gemcitabine and Docetaxel chemotherapy (GEM/DOCE) is a safe and effective salvage option for treating NMIBC. METHODS: Sixty patients who received our GEM/DOCE protocol between 2007–2017 were identified (51 BCG failures, 9 BCG naïve). This study measured overall treatment success, defined as no recurrence, progression, cystectomy, nor death due to bladder cancer. Kaplan-Meier curves were used to ascertain probability of treatment success. The log-rank test was used to identify factors associated with treatment success. RESULTS: Sixty patients received treatment with a median follow-up of 14.9 months. All patients completed the induction course with no significant adverse effects. Overall treatment success was 83% at first surveillance, 69% at 1 year, and 55% at 2 years in the entire cohort, and 90% at first surveillance, 74% at 1 year, and 56% at 2 years in the BCG-failure patients. All-cause and bladder-cancer-specific survival were both 97.9% at 1 year, 85.9% and 94.6% respectively at 2 years. Three patients underwent cystectomy at a median of 10.2 months, two of these were secondary to recurrences. Three patients had progression of their disease. CONCLUSIONS: Hyperthermic GEM/DOCE seems to be a well-tolerated salvage regimen that demonstrates a reasonable efficacy and warrants further investigation.

INFLUENCE OF GENOTYPIC VARIABILITY OF M. TUBERCULOSIS ON THE COURSE OF TUBERCULOSIS WITH MULTIPLE DRUG RESISTANCE

Tuberculosis is infectious and socially dependent disease, being now one of the most pressing issues in practical health care. As well the usual types of tuberculosis infection, chemoresistant tuberculosis is spreading rapidly in the world. The WHO estimates that about 500,000 people on the planet are infected with M. tuberculosis, which is resistant to standard anti−tuberculosis drugs. The probability of successful treatment decreases with emergence of new genotypes of M. tuberculosis with total resistance. In the modern epidemiology of tuberculosis, it is important to identify genotypes on certain signs, allowing to address issues such as their origin, identification of the infection source, possible routes and factors of transmission, as well as to reveal cases and spread of resistance to anti−tuberculosis drugs. To evaluate the therapy efficiency of multidrug−resistant tuberculosis patients with revealed genotypic variability during treatment, 10 patients with chemoresistant pulmonary tuberculosis having M. tuberculosis genotypic variability were treated. In these patients, the clinical, laboratory and radiological dynamics of disease in intensive phase of treatment were studied. Analysis of treatment results for patients with chemoresistant tuberculosis with genotypic variability of M. tuberculosis was evaluated by the intoxication syndrome dynamics of, the timing of closure of the decay cavities and cessation of bacterial excretion. The study found that the genotypic variability of M. tuberculosis is characterized by the change of less virulent genotypes of M. tuberculosis to more virulent. Signs of intoxication have been shown to change from less virulent M. tuberculosis genotypes to M. tuberculosis Beijing genotypes. Genotypic variability of mycobacteria in hospital suggests that hospitalization in tuberculosis facilities is a risk of exogenous tuberculosis superinfection. Studying the influence of genotypic variability of M. tuberculosis on the course of multidrug−resistant tuberculosis requires more extensive research, being a very relevant and promising area in phthisiology. Key words: Mycobacterium tuberculosis, genotypic variability, VNTR−genotyping, treatment.

Development and Validation of a Machine Learning Individualized Treatment Rule in First-Episode Schizophrenia

Little guidance exists to date on how to select antipsychotic medications for patients with first-episode schizophrenia. To develop a preliminary individualized treatment rule (ITR) for patients with first-episode schizophrenia. This prognostic study obtained data from Taiwan's National Health Insurance Research Database on patients with prescribed antipsychotic medications, ambulatory claims, or discharge diagnoses of a schizophrenic disorder between January 1, 2005, and December 31, 2011. An ITR was developed by applying a targeted minimum loss-based ensemble machine learning method to predict treatment success from baseline clinical and demographic data in a 70% training sample. The model was validated in the remaining 30% of the sample. The probability of treatment success was estimated for each medication for each patient under the model. The analysis was conducted between July 16, 2018, and July 15, 2019. Fifteen different antipsychotic medications. Treatment success was defined as not switching medication and not being hospitalized for 12 months. Among the 32 277 patients in the analysis, the mean (SD) age was 36.7 (14.3) years, and 15 752 (48.8%) were male. In the validation sample, the treatment success rate (SE) was 51.7% (1.0%) under the ITR and was 44.5% (0.5%) in the observed population (Z = 7.1; P < .001). The estimated treatment success if all patients were given a prescription for 1 medication was significantly lower for each of the 13 medications than under the ITR (Z = 4.2-16.8; all P < .001). Aripiprazole (3088 [31.9%]) and amisulpride (2920 [30.2%]) were the medications most often recommended by the ITR. Only 1054 patients (10.9%) received ITR-recommended medications. Observed treatment success, although lower than the success under the ITR, was nonetheless significantly higher than if medications had been randomized (44.5% [SE, 0.55%] vs 41.3% [SE, 0.4%]; Z = 6.9; P < .001), although only marginally higher than if medications had been randomized in their observed population proportions (44.5% [SE, 0.5%] vs 43.5% [SE, 0.4%]; Z = 2.2; P = .03]). These results suggest that an ITR may be associatded with an increase in the treatment success rate among patients with first-episode schizophrenia, but experimental evaluation is needed to confirm this possibility. If confirmed, model refinement that investigates biomarkers, clinical observations, and patient reports as additional predictors in iterative pragmatic trials would be needed before clinical implementation.

An evaluation of predictors for success of two-duct ligation for drooling in neurodisabilities

BackgroundDrooling is dependent on various clinical variables. However, while drooling proves refractory to two-duct ligation in 40% of patients, predictors for treatment success are sparse and to date there is little evidence why some respond well while others are non-responders. We aim to find predictors for treatment success and study the effectiveness of two-duct ligation for drooling in neurodisabilities.MethodsFifty-four patients with moderate to severe drooling who had undergone two-duct ligation were screened for inclusion. Four patients were excluded due to missing or unreliable primary outcomes. The average age at the time of surgery was 12 years. Predictors were evaluated for treatment success which was defined as ≥ 50% visual analog scale for severity of drooling and/or drooling quotient reduction from baseline. Treatment effect was measured after 8 and 32 weeks compared to baseline.ResultsAge (more mature), adequate posture (no anteflexion), and normal speech are predictors for treatment success. Compared to baseline, drooling quotient was significantly lower at 8 (difference 18.6%, 95% confidence interval 12.3–24.9%) and 32 weeks (difference 10.1%, 95% confidence interval 3.9–16.4%). Compared to baseline, visual analog scale was significantly lower at 8 (difference 45.0, 95% confidence interval 37.0–52.9) and 32 weeks (difference 32.9, 95% confidence interval 25.0–40.7).ConclusionsAge, adequate posture, and a normal speech are predictors for treatment success, are easily determined pre-operatively, and help the clinician providing patient-specific probability of treatment success. There is a significant subjective and objective decrease of drooling after two-duct ligation.

Therapeutic Drug Monitoring Can Improve Linezolid Dosing Regimens in Current Clinical Practice: A Review of Linezolid Pharmacokinetics and Pharmacodynamics.

Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and neuropathy, which are more prevalent with higher exposures and longer treatment durations. Although linezolid is traditionally administered at a standard 600 mg dose every 12 hours, the resulting exposure can vary greatly between patients and can lead to treatment failure or toxicity. The efficacy and toxicity of linezolid are determined by the exposure achieved in the patient; numerous clinical and population pharmacokinetics (popPK) studies have identified threshold measurements for both parameters. Several special populations with an increased need for linezolid dose adjustments have also been identified. Therapeutic Drug Monitoring (TDM) is a clinical strategy that assesses the response of an individual patient and helps adjust the dosing regimen to maximize efficacy while minimizing toxicity. Adaptive feedback control and model-informed precision dosing are additional strategies that use Bayesian algorithms and PK models to predict patient-specific drug exposure. TDM is a very useful tool for patient populations with sparse clinical data or known alterations in pharmacokinetics, including children, patients with renal insufficiency or those receiving renal replacement therapy, and patients taking co-medications known to interact with linezolid. As part of the clinical workflow, clinicians can use TDM with the thresholds summarized from the current literature to improve linezolid dosing for patients and maximize the probability of treatment success.

Effect of Age and Body Mass Index on Surgical Treatment Outcomes in Patients with Carpal Tunnel Syndrome.

To investigate the effect of age, diabetes mellitus, and body mass index (BMI) on the outcomes of carpal tunnel syndrome (CTS) surgery in patients with moderate CTS according to neurophysiological classification. Postsurgical outcomes were evaluated via a nerve conduction study (NCS) six to nine months after the surgery. Patients were divided into two groups according to neurophysiological classification based on the findings of postsurgical NCS: patients with mild CTS (partial recovery) or normal NCS (complete recovery) were classified as surgical success, and patients with moderate to more severe CTS were defined as surgical failure. Forty-seven patients who underwent surgery for moderate CTS were included in the study. The mean age of the patients with surgical success (47.3 ± 10.9 years) was significantly lower than that of patients with surgical failure (54.3 ± 12.6 years; p=0.048). The mean BMI of the patients with surgical success (31.3 ± 4.03 kg/m2) was significantly lower than that of patients with surgical failure (36.75 ± 5.5 kg/m2; p < 0.001). Multivariate logistic regression analysis demonstrated that higher BMI (p=0.003) and older age (p=0.031) were independent prognostic factors for surgical failure. In addition, there was a statistically significant and strong correlation between postoperative CTS severity and BMI (rho=0.606, p < 0.001). Advanced age and high BMI negatively affect the success of surgical treatment in patients with CTS. Ensuring weight loss before surgery in CTS patients who have high BMI may increase the probability of treatment success.

The Influence of Angioarchitectural Features on the Success of Endovascular Embolization of Cranial Dural Arteriovenous Fistulas with Onyx.

Endovascular embolization can be an effective treatment for cranial dural arteriovenous fistulas. However, a considerable number of dural arteriovenous fistulas still cannot be treated sufficiently. The purpose of this study was to report our single-center experience of endovascular embolization of dural arteriovenous fistulas with Onyx, including the investigation of the influence of angioarchitectural features on the treatment success. Clinical data, angioarchitectural features, complications, treatment success (defined as complete symptom remission for low-grade dural arteriovenous fistulas and complete occlusion for high-grade dural arteriovenous fistulas), and occlusion rates were assessed. The influence of various angioarchitectural features (including location, pattern of venous drainage, and quantity and origin of feeding arteries) was investigated using multivariable backward logistic regression. One hundred four patients with 110 dural arteriovenous fistulas were treated in 132 treatment procedures. Treatment success and complete occlusion rates were 81.8% and 90.9%, respectively. After a mean follow-up of 23.6 months, 95.5% of the patients showed complete symptom remission or symptom relief. The overall complication rate was 8.3% (4.5% asymptomatic, 2.3% transient, and 1.5% permanent complications). Logistic regression showed that ≥10 feeding arteries (P = .041) and involvement of the ascending pharyngeal artery (P = .039) significantly lowered the probability of treatment success. Treatment success tended to be lower for low-grade dural arteriovenous fistulas, Cognard type I dural arteriovenous fistulas, and dural arteriovenous fistulas with involvement of dural branches of the internal carotid artery, however without reaching statistical significance in the multivariable model. The presence of multiple feeding arteries and involvement of the pharyngeal artery negatively influence the treatment success of endovascular embolization of cranial dural arteriovenous fistulas with Onyx.

Outcome-Based Pricing for New Pharmaceuticals via Rebates

The price of new brand-name prescription drugs has been rising fast in the US. For example, the Amgen cholesterol drug Repatha had an initial list price of $14,523 per year. Patients, even with insurance coverage, must pay out-of-pocket a significant portion of this price. The treatment might not be successful, and this possibility reduces risk-sensitive patients' incentives to purchase the drug. The high price together with the chance of negative treatment outcomes may lead payers to deny coverage for the drug. Outcome-based pricing has been proposed as a way to re-allocate the risks and improve both payer resource allocation and patient access to drugs. According to an outcome-based rebate contract between Amgen and Harvard Pilgrim Health Care, if a patient on Repatha suffers a heart attack or a stroke, both patient and insurer are refunded the cost of the drug. We use a stylized model to analyze the effect of outcome-based pricing via rebates. Our model captures the interaction between heterogenous, price-sensitive, risk-sensitive patients who decide whether to purchase the drug; a payer deciding whether to provide coverage for the drug; and a price-setting pharmaceutical firm seeking to maximize expected profits. We find that in many cases, a pharmaceutical firm and payer cannot simultaneously benefit from outcome-based pricing, and who will benefit is determined by the probability of treatment success. Outcome-based pricing thus appears unlikely to solve the issues of high drug prices and high payer expenditures. However, supplementing outcome-based pricing with a transfer payment from firm to payer can make payer and firm (but not necessarily the patients) better off than under uniform pricing when the drug has a low chance of success.

Treatment of Isoniazid-Resistant Pulmonary Tuberculosis.

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only first-line drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB.

Evaluation of adding the community reinforcement approach to motivational enhancement therapy for adults aged 60years and older with DSM-5 alcohol use disorder: a randomized controlled trial.

To examine whether adding the Community Reinforcement Approach for Seniors (CRA-S) to Motivational Enhancement Therapy (MET) increases the probability of treatment success in people aged ≥60years with alcohol use disorder (AUD). A single blind multi-centre multi-national randomized (1:1) controlled trial. Out-patient settings (municipal alcohol treatment clinics in Denmark, specialized addiction care facilities in Germany and a primary care clinic in the United States). Between January 2014 and May 2016, 693 patients aged 60+ years and fulfilling DSM-5 criteria for AUD participated in comparing MET (n=351) and MET + CRA-S (n=342). MET (comparator) included four manualized sessions aimed at increasing motivation to change and establishing a change plan. CRA-S (intervention) consisted of up to eight further optional, manualized sessions aimed at helping patients to implement their change plan. CRA-S included a specially designed module on coping with age and age-related problems. The primary outcome was either total alcohol abstinence or an expected blood alcohol concentration of ≤0.05% during the 30days preceding the 26weeks follow-up (defined as success) or blood alcohol concentration of >0.05% during the follow-up period (defined as failure). This was assessed by self-report using the Form 90 instrument. The main analysis involved complete cases. The follow-up rate at 26weeks was 76.2% (76.9% in the MET group and 76.0% in the MET+CRA-S group). The success rate in the MET group was 48.9% [95% confidence interval (CI)=42.9-54.9%] versus 52.3% (95%CI=46.2-58.3%) in the MET+CRA-S group. The odds of success in the two conditions did not differ (odds ratio=1.22. 95% CI=0.86-1.75, P=0.26, Bayes factor=0.10). Sensitivity analyses involving alternative approaches to missing values did not change the results. In older adults with an alcohol use disorder diagnosis, adding the 'community reinforcement approach for seniors' intervention to brief out-patient motivational enhancement therapy treatment did not improve drinking outcome.

CN103 - Radiation dose variables related to the causes of skin toxicities in women with breast cancer: A study proposal

BackgroundDermatologic toxicities related to radiotherapy treatments affect substantially the patient’s quality of life. It is well stated that the causes are closely related to the radiotherapy treatment technique and to the individual genetic variation factors. More specifically, the received by each skin point is suggested as one of the most important among those causes. But there are still no studies proving this correlation as the skin radiation dose is only assessed within a 15% uncertainty using the current feasible procedures in a common department. On the contrary, we would expect a good correlation, even more, stating a skin-toxicities predicting method by assessing the skin dose using a feasible 5% uncertainty procedure. MethodsProspective transversal study of breast cancer patients receiving normofractionated external radiation therapy, without bolus compensator. This study uses a non-invasive innovative method to obtain accurate skin radiation doses based in a Software as a Service and radiochromic films.The prescribed dose, the dose report from the Treatment Planning System as well as its class and version, the irradiated volume and measured skin dose and extension by means of this innovative method at fractions 1, 2, 3, 15, 25 and end of treatment will be collected and correlated to acute skin toxicities of the patients. This will be performed using the Radiation Therapy Group gradation during the nurse visit ongoing- and post-treatment till 90 days since its ending. ResultsThis study will state a skin radiation dose – toxicity relationship for breast cancer patients as a result of a Pearson correlation coefficient analysis for each pair of variables. ConclusionsThe most common action in a nurse care plan is to treat signs and symptoms of the dermatologic toxicities but its causes are excluded, mainly due to a lack of knowledge. This study tries to formally state the skin radiation dose – toxicities relationship and, furthermore, the theoretical bases to determine and predict the skin radiation toxicities grade for each treatment. Even more, this will become a useful tool to improve the treatment success probability as well as empowering nursing for designing more accurate patient-specific radiotherapy care plans. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Phenotypic isoniazid resistance and associated mutations in pediatric tuberculosis

Background and objectivesTuberculosis (TB) remains one of the most challenging global health problems as resistance to first-line antimycobacterial drugs continues to rise in many countries worldwide. Isoniazid-resistant TB without MDR-TB poses a serious threat to the management and control of TB across the world. The aim of this study was to investigate the extent of katG315 and inhA-15 mutations in Mycobacterium tuberculosis strains isolated from pediatric TB patients from a tertiary care hospital. Material and methodsA total of 51 pulmonary and extra pulmonary specimens were collected from clinically suspected pediatric TB cases, who were microbiologically confirmed. Resistance to INH was detected by 1% proportion method. katG315 and inhA-15 genes were amplified by PCR and detection of mutations in katG315 and inhA-15 genes was done by sequencing. ResultA sample size of only 51 could be achieved due to short duration of the study. 36/51 (70.6%) culture isolates were obtained and put for drug susceptibility test, 5(13.89%) were resistant for isoniazid. M. tuberculosis DNA was found in fifty samples. Mutations in either katG315 or inhA-15 genes were found in 7/50 (14%) samples. Six of seven (85.7%) had mutation in katG315 gene and 1/7 (14.2%) had mutation in inhA-15 gene. ConclusionINH resistance not only reduces the probability of treatment success, but may also facilitate the spread of MDR-TB and reduce the effectiveness of INH preventive therapy (IPT) therefore quantification of the magnitude of INH resistant TB and variation in frequency of isoniazid resistance associated mutations is important.

AAOS Systematic Literature Review: Summary on the Management of Surgical Site Infections.

The purpose of this systematic review is to improve outcomes for the care of surgical site infections by presenting the current best evidence on important diagnostic and care issues. The findings led to ten recommendations and five consensus statements that address diagnosis and treatment of orthopaedic surgical site infections. There is strong evidence to supports anemia, obesity, HIV/AIDS, depression, dementia, immunosuppressive medications, duration of hospital stay, history of alcohol abuse, and history of congestive heart failure as factors that increased the risk of infection, some of which are modifiable before surgical intervention. Diagnostically, synovial fluid and tissue cultures were found to be strong "rule-in" tests for the diagnosis of infection, but negative synovial fluid and tissue cultures do not reliably exclude infection. C-reactive protein was found to be a strong rule-in and rule-out marker for patients with suspected surgical site infections. Therapeutically, only for patients with retained implants, antimicrobial protocols of 8 weeks of duration were found to be associated with outcomes that are not inferior to outcomes from protocols of 3- to 6-month duration. Also only for patients with retained implants, rifampin, used as a second antimicrobial, increases the probability of treatment success for staphylococcal infections. The surgical site infection work group identified a lack of high-level outcomes data, highlighting the need for high-quality clinical trials in the treatment of surgical site infections.