Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study.

OBJECTIVE: To define patterns of prescription and factors associated with choice of pharmacotherapy for gestational diabetes mellitus (GDM), namely metformin, glyburide and insulin, during a period of evolving professional guidelines. DESING: Cross-sectional study. SETTING: US commercial insurance beneficiaries from Market-Scan (late 2015 to 2018). STUDY DESIGN: We included women with GDM, singleton gestations, 15-51 years of age on pharmacotherapy. The exposure was pharmacy claims for metformin, glyburide and insulin. MAIN OUTCOMES: Pharmacotherapy for GDM with either oral agent, metformin or glyburide, compared with insulin as the reference, and secondarily, consequent treatment modification (addition and/or change) to metformin, glyburide or insulin. RESULTS: Among 37 762 women with GDM, we analysed data from 10 407 (28%) with pharmacotherapy, 21% with metformin (n = 2147), 48% with glyburide (n = 4984) and 31% with insulin (n = 3276). From late 2015 to 2018, metformin use increased from 17 to 29%, as did insulin use from 26 to 44%, whereas glyburide use decreased from 58 to 27%. By 2018, insulin was the most common pharmacotherapy for GDM; metformin was more likely to be prescribed by 9% compared with late 2015/16, but glyburide was less likely by 45%. Treatment modification occurred in 20% of women prescribed metformin compared with 2% with insulin and 8% with glyburide. CONCLUSIONS: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for GDM among a privately insured US population during a time of evolving professional guidelines. Further evaluation of the relative effectiveness and safety of metformin compared with insulin is needed. TWEETABLE ABSTRACT: Insulin followed by metformin has replaced glyburide as the most common pharmacotherapy for gestational diabetes mellitus in the USA.

A prospective multicenter study assessing humoral immunogenicity and safety of the mRNA SARS-CoV-2 vaccines in Greek patients with systemic autoimmune and autoinflammatory rheumatic diseases.

OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.

Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011-2017.

BACKGROUND: There is limited evidence on the modification or stopping of antiretroviral therapy (ART) regimens, including novel antiretroviral drugs. The aim of this study was to evaluate the discontinuation of first ART before and after the availability of better tolerated and less complex regimens by comparing the frequency, reasons and associations with patient characteristics. METHODS: A total of 3019 ART-naive patients registered in the HIV-TR cohort who started ART between Jan 2011 and Feb 2017 were studied. Only the first modification within the first year of treatment for each patient was included in the analyses. Reasons were classified as listed in the coded form in the web-based database. Cumulative incidences were analysed using competing risk function and factors associated with discontinuation of the ART regimen were examined using Cox proportional hazards models and Fine-Gray competing risk regression models. RESULTS: The initial ART regimen was discontinued in 351 out of 3019 eligible patients (11.6%) within the first year. The main reason for discontinuation was intolerance/toxicity (45.0%), followed by treatment simplification (9.7%), patient willingness (7.4%), poor compliance (7.1%), prevention of future toxicities (6.0%), virologic failure (5.4%), and provider preference (5.4%). Non-nucleoside reverse transcriptase inhibitor (NNRTI)-based (aHR = 4.4, [95% CI 3.0-6.4]; p < 0.0001) or protease inhibitor (PI)-based regimens (aHR = 4.3, [95% CI 3.1-6.0]; p < 0.0001) relative to integrase strand transfer inhibitor (InSTI)-based regimens were significantly associated with ART discontinuation. ART initiated at a later period (2015-Feb 2017) (aHR = 0.6, [95% CI 0.4-0.9]; p < 0.0001) was less likely to be discontinued. A lower rate of treatment discontinuation for intolerance/toxicity was observed with InSTI-based regimens (2.0%) than with NNRTI- (6.6%) and PI-based regimens (7.5%) (p < 0.001). The percentage of patients who achieved HIV RNA < 200 copies/mL within 12 months of ART initiation was 91% in the ART discontinued group vs. 94% in the continued group (p > 0.05). CONCLUSION: ART discontinuation due to intolerance/toxicity and virologic failure decreased over time. InSTI-based regimens were less likely to be discontinued than PI- and NNRTI-based ART.

Treatment modification after starting cART in people living with HIV: retrospective analysis of the German ClinSurv HIV Cohort 2005-2017.

OBJECTIVE: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving. METHODS: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan-Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data. RESULTS: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59-66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39-0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011-2017), being on a multi-tablet regimen (MTR). CONCLUSIONS: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.

High effectiveness of recommended first-line antiretroviral therapies in Germany: a nationwide, prospective cohort study.

PURPOSE: Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany. METHODS: This nationwide observational study included treatment-naïve chronically HIV-1 infected patients receiving one of the recommended first-line regimens. Patients were allocated to three arms (INSTI, NNRTI, PI) and were prospectively followed for 24 months. Delayed treatment initiation was defined by a baseline CD4 T-cell count of < 350/µl or CDC clinical stage C. RESULTS: Among a total of 434 patients enrolled, virologic failure was rare and occurred in 4.3% (6/141) in the PI arm, in 3.3% (4/122) in the NNRTI arm and in 0.6% (1/171) in the INSTI arm (p = 0.10). De novo drug resistance mutations developed in only two patients in the NNRTI arm. Nonetheless, treatment modifications were frequent (51%) and mostly performed for strategic reasons. Retention on all initial compounds at month 24 was 64%, 49%, and 22% in the INSTI, NNRTI and PI arms respectively. Delayed treatment initiation was common (47%) and more frequently observed in patients in the PI arm. It was not associated with virological failure. CONCLUSION: High efficacy and low virological failure rates were observed with recommended first-line regimens independent of delayed treatment initiation, chosen regimen and subsequent treatment modifications, demonstrating the validity of the current treatment guidelines.

Multi-state models for the analysis of time-to-treatment modification among HIV patients under highly active antiretroviral therapy in Southwest Ethiopia.

BACKGROUND: Highly active antiretroviral therapy (HAART) has shown a dramatic change in controlling the burden of HIV/AIDS. However, the new challenge of HAART is to allow long-term sustainability. Toxicities, comorbidity, pregnancy, and treatment failure, among others, would result in frequent initial HAART regimen change. The aim of this study was to evaluate the durability of first line antiretroviral therapy and to assess the causes of initial highly active antiretroviral therapeutic regimen changes among patients on HAART. METHODS: A Hospital based retrospective study was conducted from January 2007 to August 2013 at Jimma University Hospital, Southwest Ethiopia. Data on the prescribed ARV along with start date, switching date, and reason for change was collected. The primary outcome was defined as the time-to-treatment change. We adopted a multi-state survival modeling approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another. RESULT: A total of 1284 ART naive patients were included in the study. Almost half of the patients (41.2%) changed their treatment during follow up for various reasons; 442 (34.4%) changed once and 86 (6.69%) changed more than once. Toxicity was the most common reason for treatment changes accounting for 48.94% of the changes, followed by comorbidity (New TB) 14.31%. The HAART combinations that were robust to treatment changes were tenofovir (TDF) + lamivudine (3TC)+ efavirenz (EFV), tenofovir + lamivudine (3TC) + nevirapine (NVP) and zidovudine (AZT) + lamivudine (3TC) + nevirapine (NVP) with 3.6%, 4.5% and 11% treatment changes, respectively. CONCLUSION: Moving away from drugs with poor safety profiles, such as stavudine(d4T), could reduce modification rates and this would improve regimen tolerability, while preserving future treatment options.

Can Assessment of Disease Burden Prior to Changes in Initial COPD Maintenance Treatment Provide Insight into Remaining Unmet Needs? A Retrospective Database Study in UK Primary Care.

This retrospective cohort study aimed to assess treatment patterns over 24 months amongst patients with chronic obstructive pulmonary disease (COPD), initiating a new COPD maintenance treatment, and to understand clinical indicators of treatment change. Patients included in the study initiated a long-acting ß2-agonist (LABA), a long-acting muscarinic antagonist (LAMA), or a combination of LABA and an inhaled corticosteroid (ICS/LABA) between January 1, 2009, and November 30, 2013, as recorded in the United Kingdom Clinical Practice Research Datalink (UK CPRD). Treatment modifications (switching or adding maintenance treatments) over 24 months were assessed, and patient characteristics, disease burden, medication and healthcare resource use during the 30 days before treatment modification were evaluated. The cohort comprised 17,258 patients [LABA (8%), LAMA (39%) and ICS/LABA (54%)] with similar age, body mass index and dyspnoea distribution. LABA users were more likely than LAMA users to add a maintenance therapy. Distinct patterns of treatment augmentations were noted, whereby LABA users typically received dual therapy before moving to triple therapy, while LAMA users moved to triple therapy by directly adding an ICS/LABA. Exacerbation events immediately prior to treatment change were not frequently recorded; however, the need for rescue short-acting medication and assessment of dyspnoea in the 30 days prior to the treatment change suggest that dyspnoea is a remaining unmet need driving therapy change.

Determinants of Treatment Modification in Hypercholesterolemic Patients.

BACKGROUND: There is a lack of knowledge of those contemporary factors associated with modifying subtherapeutic treatments in hypercholesterolemic patients. The aim of this study was to assess determinants of treatment modification in patients not attaining their low-density lipoprotein cholesterol goals. METHODS: The CEntralized Pan-Asian survey on tHE Under-treatment of hypercholeSterolemia enrolled patients taking stable lipid-lowering medications. The study physicians then determined existing patient treatments, which were to be continued or modified when treatments failed. The patient questionnaire surveying patient attitudes and perceptions toward their hypercholesterolemia management was prospectively collected. The odds ratios (ORs) (95% confidence intervals) were calculated. RESULTS: Among the 420 patients included for analysis, 35.7% were designated for planned treatment modification. Those patients assigned to treatment modification were more likely to have a family history of premature coronary heart disease (40% vs. 19%), an indication for secondary prevention (76% vs. 61%), elevated triglyceride (60% vs. 48%) and fasting sugar (84% vs. 67%), and were less adherent to their medications (29% vs. 12%) than patients assigned to treatment continuation. Patient recognition of treatment failure [OR, 1.82 (1.13-2.94)], the lower frequency of cholesterol checkup [OR, 2.40 (1.41-4.08)], patient satisfaction with provided cholesterol information [OR, 2.30 (1.21-4.39)], and their feelings toward cholesterol management [OR, 0.25 (0.10-0.62) and 3.80 (2.28-6.32)] for confusion and no strong feeling, respectively were determinants of the treatment modification assignment. CONCLUSIONS: There was a large gap between evidence-based goals and modification of subtherapeutic treatments, particularly among patients with lower treatment satisfaction and better compliance. Our findings have emphasized the need to further reduce inertia in implementing hypercholesterolemia management.

Treatment patterns and costs for anti-TNFα biologic therapy in patients with psoriatic arthritis.

BACKGROUND: Real-world data regarding anti-tumor necrosis factor alpha (anti-TNFα) biologic therapy use in psoriatic arthritis (PsA) are limited; therefore, we described treatment patterns and costs of anti-TNFα therapy in PsA patients in the United States. METHODS: PsA patients (N = 990) aged ≥18 years who initiated anti-TNFα therapy were selected from MarketScan claims databases (10/1/2009 to 9/30/2010). Number of patients on first- (n = 881), second- (n = 72), or third- or greater (n = 37) line of anti-TNFα therapy, persistence, time-to-switch or modification, pharmacy and medical costs (measured per patient per month [PPPM]) for each line of therapy were observed during the 3-year follow-up. RESULTS: PsA patients receiving only one line of anti-TNFα therapy remained on first-line for ~17 months while those who switched to second- or third- or greater persisted on first-line for ~11 to 12 months, respectively. Time to first-line modification was longer for patients who switched to third- or greater line therapy (7 months) than those who did not switch or switched to second-line (range, ~2 to 4 months). Time-to-switch and time to first-line modification was progressively shorter with each line of therapy for patients who received third- or greater line. PPPM medical costs were higher for patients who did not switch ($322) than those who switched to second- ($167) or third- or greater ($217) line. PPPM pharmacy costs were greater for patients with third- or greater line therapy ($2539) than those who did not switch ($1985) or switched to second-line ($2045). CONCLUSION: While the majority of patients received only one line of anti-TNFα therapy, a subset of patients switched to multiple lines of therapy during the 3-year follow-up period. Persistence and therapy modifications differed between these patients and those receiving only one line. Overall medical costs were highest for patients who did not switch, and pharmacy costs increased as patients switched to each new line of therapy.

Rheumatoid arthritis treatment with TNF inhibitors and alternative procedures in case of its failure - results of the Polish survey in the context of EULAR recommendations.

INTRODUCTION: According to the European League Against Rheumatism (EULAR), rheumatoid arthritis (RA) treatment aims to achieve remission or low disease activity (LDA) within 6 months. In Poland, despite the existence of the National Health Fund Drug Program (NHF-DP), data on the effects of treatment with biological agents in patients with RA are not publicly available. Also we cannot compare registers from other countries with the Polish results because the rules of the therapeutic program in Poland impose restrictions that do not exist in other countries. For this reason, the data will not be comparable, but the results of the currently used regimen for biological treatment in Poland should be analyzed and compared with the recommendations of the European EULAR as a contribution to further discussion. OBJECTIVES: To determine the tumor necrosis factor α (TNF-α) inhibitor treatment patterns in RA patients in Poland, to evaluate the frequency and causes of treatment failure as well as post-failure recommendations, and to compare Polish clinical practice enforced by the therapeutic program with the EULAR recommendations. MATERIAL AND METHODS: The data on 895 RA patients were retrospectively collected from routine medical records. A questionnaire was completed only once for each patient. RESULTS: After 3 months of treatment with a TNF-α inhibitor, the therapeutic target was achieved in 72% of patients: 4% in remission, 8% LDA, and 60% with moderate disease activity (MDA); after 9 months, 46% had reached the target: 16% in remission, 30% with LDA. An average of 49% of patients presented with MDA or high disease activity (HDA), thus requiring treatment modification. Treatment failure was confirmed in 14% of patients and a modified therapy administered: rituximab (72%) or adalimumab (20%). The most common cause of failure was inefficacy of treatment (70%). CONCLUSIONS: In the Polish therapeutic program, despite the persistence of MDA or HDA, the treatment with TNF inhibitors rarely qualifies as ineffective and therefore is seldom modified by switching to another biologic drug. As long as the initiation of treatment and its modifications are enforced by the NHF-DP and not the recommendations of EULAR, treatment may be less effective and paradoxically cost-intensive. Therefore, it seems obvious that it is necessary to change and adapt the NHF-DP requirements to European standards.

Combination of noninvasive neurovascular imaging modalities in stroke patients: patterns of use and impact on need for digital subtraction angiography.

BACKGROUND: The diagnostic work-up of acute stroke relies on the use of proper imaging studies. We sought to determine the use of a combination of 2 noninvasive tests, namely magnetic resonance angiography (MRA) and computed tomographic angiography (CTA) in diagnosing vascular lesions and the necessity for a subsequent digital subtraction angiography (DSA) for the definitive diagnosis. METHODS: Patients admitted to 2 comprehensive stroke centers between January 2008 and July 2010 who had an equivocal initial noninvasive test were reviewed. The proportions of patients who underwent CTA and MRA in combination and those who required additional DSA for definitive diagnosis were determined. The diagnostic yield and impact on management in patients with CTA and MRA combination was compared with patients who underwent CTA and MRA followed by DSA. RESULTS: Among a total of 1063 patients (mean age ± SD 63 ± 16), 384 (36%) underwent >1 vascular imaging study. There was no difference in the rates of cardiovascular risk factors and stroke subtype between different combination groups. The agreement between CTA and MRA was high (concordance 81%). Among the 164 patients who underwent both CTA and MRA, a DSA was required for resolution/confirmation in only 27 (16%) patients. Among these 27, DSA findings changed the clinical decision-making in 22 (82%) patients (11 stenotic severities and 11 diagnoses of arteriovenous fistula, aneurysm, or dissection). CONCLUSIONS: In our experience, a combination of CTA and MRA was frequently used in patients in whom the initial noninvasive imaging was determined insufficient. The combination of findings from CTA and MRA were considered adequate in a large portion of patients resulting in a lower requirement for DSA and higher treatment impact from DSA.

Does COVID-19 pandemic impact cancer outcomes in metastatic setting? A comparative cohort study among metastatic patients treated at day care hospital.

INTRODUCTION: COVID-19 outbreak rapidly spread since early 2020 leading to the implementation of nationwide lockdowns. To cope with this sudden change, management guidelines were quickly published to adapt oncological care, with potential impact on cancer outcomes. METHODS: We conducted a retrospective comparative cohort study to assess the impact of the COVID-19 outbreak in 2020 on cancer outcomes in metastatic patients. Two cohorts of metastatic patients receiving intravenous (iv) therapy in a French oncological day care hospital were assessed: a 2020 cohort during the first French lockdown, and a 2018 historical cohort before the COVID-19 pandemic. We performed a propensity score analysis to match patients from the two cohorts. After one-year follow-up, we compared progression-free survival (PFS) and overall survival (OS) between cohorts. Adaptations of medical oncological treatments in 2020 were also analysed. RESULTS: The 376 patients of the 2020 cohort were matched with 376 of the 2018 cohort. No SARS-CoV-2 infection was observed in the 2020 cohort. The adjusted PFS was significantly shorter in 2020 compared to 2018 (HR = 1.23; 95% CI: 1.03-1.46), as well as among patients without treatment adaptation compared to matched patients of the 2018 cohort (HR = 1.33; 95% CI: 1.10-1.61). We did not observe any significant difference of PFS among the group with treatment adaptations. OS was not significantly different. CONCLUSION: Metastatic cancer patients treated during the first lockdown had a higher risk of disease progression 1 year after COVID-19 outbreak. However, oncological treatment adaptations or SARS-CoV-2 infections do not explain these results. A longer follow-up is needed to observe the impact on OS.

Long-term Azithromycin in Children With Bronchiectasis Unrelated to Cystic Fibrosis: Treatment Effects Over Time.

BACKGROUND: Following evidence from randomized controlled trials, patients with bronchiectasis unrelated to cystic fibrosis receive long-term azithromycin to reduce acute respiratory exacerbations. However, the period when azithromycin is effective and which patients are likely to most benefit remain unknown. RESEARCH QUESTIONS: (i) What is the period after its commencement when azithromycin is most effective? and (ii) Which factors may modify azithromycin effects? STUDY DESIGN AND METHODS: A secondary analysis was conducted of our previous randomized controlled trial involving 89 indigenous children with bronchiectasis unrelated to cystic fibrosis. Semi-parametric Poisson regression identified the azithromycin efficacy period. Multivariable Poisson regression identified factors that modify azithromycin effect. RESULTS: Azithromycin was associated with fewer exacerbations per child-week during weeks 4 through 96, with the most effective period observed between weeks 17 and 62. Eleven factors were associated with different azithromycin effects; four were significant at the P < .05 level. Compared with their counterparts, higher reduction in exacerbations was observed in children with nasopharyngeal carriage of bacterial pathogens (incidence rate ratio [IRR] = 0.81 [95% CI, 0.57-1.14] vs 0.29 [0.20-0.44]; P < .001); New Zealand children (IRR = 0.73 [0.51-1.03] vs 0.39 [0.28-0.55]; P = .012); and those with higher weight-for-height z scores (interaction IRR = 0.82 [0.67-0.99]; P = .044). Compared with their counterparts, lower reduction was observed in those born preterm (IRR = 0.41 [0.30-0.55] vs 0.74 [0.49-1.10]; P = .012). INTERPRETATION: Regular azithromycin is best used for at least 17 weeks and up to 62 weeks, as these periods provide maximum benefit for indigenous children with bronchiectasis unrelated to cystic fibrosis. Several factors modified azithromycin benefits; however, these traits need confirmation in larger studies before being adopted into clinical practice. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.

Impact of Therapy Management on Axitinib-Related Adverse Events in Patients With Advanced Renal Cell Carcinoma Receiving First-Line Axitinib + Checkpoint Inhibitor.

INTRODUCTION: There are limited real-world data on the effectiveness of strategies used to manage adverse events (AEs) in patients with advanced renal cell carcinoma (RCC) treated with axitinib. This retrospective chart review examined the AE profile and effect of axitinib modifications on AE resolution/improvement and treatment discontinuation. METHODS: A retrospective physician-administered chart review was conducted. Adult patients with advanced RCC treated with first-line axitinib plus checkpoint inhibitor (CPI) therapy (ie, avelumab or pembrolizumab) and who had documented frequently reported axitinib-related AEs of fatigue, diarrhea, nausea, hypertension, or palmar-plantar erythrodysesthesia were included. Physician characteristics, patient characteristics, AE characteristics, AE management strategies used, AE resolution/improvement, and treatment duration were described. The effect of strategies used to manage AEs (axitinib dose reduction or treatment interruption) on AE resolution/improvement was evaluated by logistic regression. RESULTS: Among 219 patients (median age: 62 years, 65% male), 70 (32%) were treated with axitinib + avelumab and 149 (68%) received axitinib + pembrolizumab. Axitinib modifications increased the likelihood of AE resolution/improvement compared with no modifications (adjusted odds ratio: 6.34, P < .001). In the subset of patients who discontinued treatment among those with or without axitinib modifications, mean treatment duration was 7.0 and 1.7 months, respectively. CONCLUSION: Toxicities experienced by patients with advanced RCC treated with first-line axitinib-CPI in the real world can be effectively managed by axitinib modifications, thereby prolonging treatment duration. (Clinicaltrials.gov identifier: NCT04682587).

Real-world palbociclib effectiveness in patients with metastatic breast cancer: Focus on neutropenia-related treatment modification strategies and clinical outcomes.

INTRODUCTION: In addition to clinical trials, real-world data is needed to verify the effectiveness of the CDK 4/6 inhibitor palbociclib. The primary aim was to examine real-world variation in treatment modification strategies for neutropenia and its relation to progression-free survival (PFS). The secondary aim was to assess if there is a gap between real-world and clinical trial outcomes. MATERIALS AND METHODS: In this multicenter, retrospective observational cohort study 229 patients were analyzed who started palbociclib and fulvestrant as second- or later-line therapy for HR-positive, HER2-negative metastatic breast cancer in the Santeon hospital group in the Netherlands between September 2016 and December 2019. Data were manually retrieved from patients' electronic medical records. PFS was examined using the Kaplan-Meier method to compare neutropenia-related treatment modification strategies within the first three months after neutropenia grade 3 - 4 occurred, as well as patients' eligibility to have participated in the PALOMA-3 clinical trial or not. RESULTS: Even though treatment modification strategies differed from those in PALOMA-3 (dose interruptions: 26 vs 54%, cycle delays: 54 vs 36%, and dose reductions: 39 vs 34%), these did not influence PFS. Patients who were PALOMA-3 ineligible experienced a shorter median PFS than those who were eligible (10.2 vs. 14.1 months; HR 1.52; 95% CI 1.12 - 2.07). An overall longer median PFS was found compared to PALOMA-3 (11.6 vs. 9.5 months; HR 0.70; 95% CI 0.54 - 0.90). CONCLUSION: This study suggests no impact of neutropenia-related treatment modifications on PFS and confirms inferior outcomes outside clinical trial eligibility.

Modification to Systemic Anticancer Therapy at the Start of the COVID-19 Pandemic and its Overall Impact on Survival Outcomes in Patients with Colorectal Cancer.

BACKGROUND: Since the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care has been introduced to maximize patient safety and protect staff. We aimed to identify factors influencing clinicians' decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer. PATIENTS AND METHODS: Electronic records of patients seen in a large United Kingdom tertiary cancer center was reviewed. The frequency and type of changes to systemic anticancer therapy , as well as the factors predicting clinicians' decision were assessed. RESULTS: A total of 418 patients; mean age 63 ± 12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients (OR 1.028 [95% CI 1.010-1.047]; P = .002), and in patients who had already received higher number of cycles of systemic anticancer therapy (OR 1.040 [95% CI 1.016-1.065]; P = .001). A change in treatment was less likely further out of the first national lockdown (OR 0.837 [95% CI 0.758-0.925]; P < .001). Patients on third-line treatment were most likely to have alterations to their treatment plan (69%, n=33/48). CONCLUSION: During the first wave of COVID-19 in the United Kingdom, clinicians adapted clinical practice in accordance to local and national guidance, especially amongst older patients and those on third-line treatment. Further real-world data are needed to document the important impact of changes to treatment on outcomes in patients with cancer.

Complicated Case of Multidrug-Resistant Tuberculosis with Multiple Comorbidities, Successfully Treated After Several Treatment Modifications.

A 59-year-old man with relapsed pulmonary TB developed rifampin resistance. He presented with chronic untreated hepatitis B, which developed into liver cirrhosis, type 2 diabetes with diabetic retinopathy, and osteoarthritis of right knee. His initial MDR regimen included levofloxacin, cycloserine, bedaquiline, linezolid, and high-dose isoniazid. He developed episodes of linezolid-induced myelosuppression, resulting in temporary discontinuation and dose reduction, and ultimately, substitution of linezolid. On the seventh month of treatment, he developed severe depression with visual hallucination, resulting in cycloserine dose reduction. We maintained the principle of at least 4 active drugs throughout his treatment. He was considered cured after 26 months of treatment.

Impact of 18 FDG- PET CT in the Management of Muscle Invasive Bladder Cancer.

INTRODUCTION: Guidelines do not recommend FDG-PET CT for the staging of MIBC as a standard. The objectives of the study are to assess the accuracy of the FDG-PET CT for LN staging and to determine the rate of treatment modification according to FDG-PET CT results in MIBC. PATIENTS AND METHODS: From January 2005 to December 2017, we carried out a retrospective analysis of patients with MIBC who had a FDG-PET CT for staging in two expert centres in Bordeaux, France, and analyzed its clinical value in this setting. Nodal and metastatic staging on CT scan (CT) and FDG-PET CT were done independently. RESULTS: Accuracy of LN staging from CT and FDG-PET CT at initial diagnosis was analyzed in 85 patients (including 70 patients treated with neoadjuvant chemotherapy (NAC)) and compared to pathological examination of resected LN. Sensitivity of FDG-PET CT was better than CT (80.8% versus 26.9%) but the specificity was low (54.2% vs. 83.1%). The Youden index was better for FDG-PET CT (0.35; 0.1 for CT) and FDG-PET CT appeared to be more accurate for determining LN staging of MIBC. FDG-PET CT findings enabled a treatment decision modification in 34/130 patients (26.1%): a therapeutic intensification (9.2%), including surgery not previously planned and/or modified fields of radiotherapy; or a de-escalation (16.9%), mostly avoiding surgery. CONCLUSION: FDG-PET CT was more sensitive for detection of LN involvement at initial diagnosis of MIBC than CT alone. In our study, treatment decisions were modified, according to FDG-PET CT results, in almost a quarter of patients.

Modifying a cognitive behavioral suicide prevention treatment for adults with schizophrenia spectrum disorders in community mental health.

Suicide is among the leading causes of death for adults with schizophrenia spectrum disorders. Given a paucity of evidence-based interventions tailored for psychosis, we sought to modify a promising Cognitive-Behavioral Suicide Prevention for psychosis (CBSPp) treatment for adults in US community mental health (CMH) settings using community-based participatory research methods. This article presents our modification methodology, stakeholder data and scholarly expert input, and CBSPp adaptations prior to future intervention testing. Stakeholder data (n = 25) were collected from clients, providers, and peer advocates in a CMH setting in Michigan. Findings were subsequently presented to a panel of scholarly experts in the fields of suicide and psychosis research, intervention research, and implementation science for input. Emerging themes from stakeholders include logistic, perceptual, and clinical challenges in the process of introducing this treatment in a CMH setting. Consistent with literature, buy-in and support for the delivery of a new treatment emerged as important factors in modifying and implementing CBSPp. A final modification list is presented in this paper and collaborations among stakeholders, researchers, and scholarly experts are essential to navigate psychosocial treatment innovation barriers with an overall goal of improving access, feasibility, and quality of this suicide prevention treatment.