A Dutch cost-effectiveness analysis of fremanezumab versus best supportive care in patients with chronic migraine and inadequate response to prior preventive therapy.

BACKGROUND: Chronic migraine (CM) is the most severe and burdensome subtype of migraine. Fremanezumab is a monoclonal antibody that targets the calcitonin gene-related peptide pathway as a migraine preventive therapy. This study aimed to conduct a cost-effectiveness analysis of fremanezumab from a societal perspective in the Netherlands, using a Markov cohort simulation model. METHODS: The base-case cost-effectiveness analysis adhered to the Netherlands Authority guidelines. Fremanezumab was compared with best supportive care (BSC; acute migraine treatment only) in patients with CM and an inadequate response to topiramate or valproate and onabotulinumtoxinA (Dutch patient group [DPG]). A supportive analysis was conducted in the broader group of CM patients with prior inadequate response to 2-4 different classes of migraine preventive treatments. One-way sensitivity, probabilistic sensitivity, and scenario analyses were conducted. RESULTS: Over a lifetime horizon, fremanezumab is cost saving compared with BSC in the DPG (saving of €2514 per patient) and led to an increase of 1.45 quality-adjusted life-years (QALYs). In the broader supportive analysis, fremanezumab was cost effective compared with BSC, with an incremental cost-effectiveness ratio of €2547/QALY gained. Fremanezumab remained cost effective in all sensitivity and scenario analyses. CONCLUSION: In comparison to BSC, fremanezumab is cost saving in the DPG and cost effective in the broader population.

Real-world Impact of Fremanezumab on Migraine-Related Health Care Resource Utilization in Patients with Comorbidities, Acute Medication Overuse, and/or Unsatisfactory Prior Migraine Preventive Response.

INTRODUCTION: Fremanezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, is indicated for preventive treatment of migraine in adults. Real-world evidence assessing the effect of fremanezumab on migraine-related medication use, health care resource utilization (HCRU), and costs in patient populations with comorbidities, acute medication overuse (AMO), and/or unsatisfactory prior migraine preventive response (UPMPR) is needed. METHODS: Data for this US, retrospective claims analysis were obtained from the Merative® MarketScan® Commercial and supplemental databases. Eligible adults with migraine initiated fremanezumab between 1 September 2018 and 30 June 2019 (date of earliest fremanezumab claim is the index date), had ≥ 12 months of continuous enrollment prior to initiation (preindex period) and ≥ 6 months of data following initiation (postindex period; variable follow-up after 6 months), and had certain preindex migraine comorbidities (depression, anxiety, and cardiovascular disease), potential AMO, or UPMPR. Changes in migraine-related concomitant acute and preventive medication use, HCRU, and costs were assessed pre- versus postindex. RESULTS: In total, 3193 patients met the eligibility criteria. From pre- to postindex, mean (SD) per patient per month (PPPM) number of migraine-related acute medication and preventive medication claims (excluding fremanezumab), respectively, decreased from 0.97 (0.90) to 0.86 (0.87) (P < 0.001) and 0.94 (0.74) to 0.81 (0.75) (P < 0.001). Migraine-related outpatient and neurologist office visits, emergency department visits, and other outpatient services PPPM decreased pre- versus postindex (P < 0.001 for all), resulting in a reduction in mean (SD) total health care costs PPPM from US$541 (US$858) to US$490 (US$974) (P = 0.003). Patients showed high adherence and persistence rates, with mean (SD) proportion of days covered of 0.71 (0.29), medication possession ratio of 0.74 (0.31), and persistence duration of 160.3 (33.2) days 6 months postindex. CONCLUSIONS: Patients with certain migraine comorbidities, potential AMO, and/or UPMPR in a real-world setting had reduced migraine-related medication use, HCRU, and costs following initiation of fremanezumab. Graphical abstract available for this article.

Testing cancer patients for HIV: Just do it

@#Who do we test for HIV? In a perfect world, the answer to this question is, “Everyone.” The United States Centers for Disease Control and Prevention (CDC) recommends that anyone between the age of 13 to 64 years old should have at least one HIV test as part of routine healthcare. 1 In addition, they recommend that anyone who comes into contact with the healthcare system be tested, along with all pregnant women. The main justification for these recommendations is that 40% of new HIV infections in the United States are transmitted by people who do not know their HIV status, which is about 10% of their people living with HIV (PLHIV).

Stigma kills

@#Stigma due to an HIV diagnosis is a well-known phenomenon and is a major barrier to accessing care.1 Over the last forty years, HIV has been transformed from a fatal disease to a manageable one, thanks to the remarkable success of antiretroviral (ARV) medication.2 When people living with HIV (PLHIV) start ARV treatment early, their life expectancy is almost completely restored. Moreover, a suppressed viral load means that PLHIV are no longer able to infect other people.3 They can have children naturally without risk to their seronegative partner or their child. PLHIV nowadays are more likely to die with HIV, not of HIV. While a cure remains elusive, the successful global rollout of ARVs means that there is no good reason for a PLHIV to die of AIDS and its complications due to lack of access to proper treatment. The Philippine AIDS Law Republic Act 8504 and its successor, Republic Act 11116 explicitly states that the State should “ensure access to HIV and AIDS-related services by eliminating the climate of stigma and discrimination that surrounds the country’s HIV and AIDS situation, and the people directly and indirectly affected by it.” Unfortunately, despite this admonition, stigma remains a significant cause of delayed HIV testing and of not seeking treatment in our country. In this issue of the journal, Dr. De Los Santos and her colleagues examine the effect of healthcare facility stigma on PLHIV accessing care in the Philippines.4 They report that 81% of their Filipino PLHIV respondents experienced stigma, which is an unacceptably high number. They identify which facilities are more likely to be correlated with stigma and make suggestions on how to address this problem. This study is very timely and comes at a time when the Department of Health is shifting first line antiretrovirals to dolutegravir-based regimens.5 Dolutegravir-based treatment is associated with fewer side effects than efavirenz-based regimens and is much more durable against resistance.6 With an HIV transmitted-drug resistance rate of 11.7%, it is imperative that PLHIV are started on more durable regimens which they are less likely to discontinue.7 Properly addressing stigma means that more people will access care. Better regimens will ensure that people stay in care. This will go a long way towards minimizing the impact of HIV and AIDS on Filipino PLHIV. Stigma among PLHIV is a complicated subject matter. Aside from the stigma associated with diagnosis, there is also stigma associated with the mode of acquisition of the disease. The most-at-risk populations are highly stigmatized. Men who have sex with men, people who inject drugs, and female sex workers experience additional stigma on top of the stigma from an HIV diagnosis.8 Aside from societal stigma, PLHIV are also prone to self-stigma.9 This phenomenon occurs when PLHIV believe they no longer deserve to live since they contracted the disease from deviant or sinful behavior. High rates of depression are found among these self-stigma sufferers. This significantly impacts the entire HIV healthcare cascade, starting from early diagnosis, to accessing treatment, and staying in care. The finding that Public Rural Health Units are the most stigmatizing healthcare facilities is very concerning since these are usually the only facilities available to PLHIV in far-flung areas. This needs to be addressed with better sensitivity training as well as concrete guidelines on avoiding stigma. It is very troubling that facilities that are supposed to cater to vulnerable populations inadvertently make it difficult for them to access care.10 Unfortunately, even facilities in urban areas are not immune to discrimination and stigmatizing behavior. I recall the experience of one of my early PLHIV patients who developed and eventually succumbed to a disseminated fungal infection.11 He told me that he had tried getting tested several years earlier but he had a traumatic experience in the government health facility that he accessed. He made a wrong turn and entered a different clinic in that hospital and when he asked for an HIV test, people recoiled from him in horror. Because of that terrible experience, he put off getting his HIV test for years until he started developing the fungal infection that eventually killed him. Had he been started on proper treatment earlier, he could have been saved. For me, it wasn’t just the fungus that killed him but it was the delay in diagnosis and care as a direct result of stigma. Addressing HIV-related stigma in our country entails a whole-of-society and a whole-of-nation approach. Mental health services to address self-stigma and depression should be standard of care not just among confirmed PLHIV but among the most-at-risk populations. Proactive education of all members of society, especially healthcare workers in facilities that diagnose and care for PLHIV is essential for ensuring sustained linkage to care. Ensuring that the majority of the PLHIV population are properly diagnosed, enrolled in treatment hubs, and have suppressed viral loads will ultimately lead to fewer transmissions and less AIDS-related deaths.

HIV-1 Subtype Shift in the Philippines is Associated With High Transmitted Drug Resistance, High Viral Loads, and Fast Immunologic Decline.

OBJECTIVES: The Philippines has one of the fastest growing HIV epidemics in the world. A subtype shift from B to CRF01_AE may have contributed to the increase in cases. We undertook a genotyping and transmitted drug resistance (TDR) study to determine if the dominant subtype has any advantages in resistance and transmission. METHODS: Filipinos who were treatment-naive who were living with HIV were recruited from two large government treatment hubs from March 2016 to August 2018. HIV-1 viral load, CD4 count, genotyping, and TDR testing were performed. Demographic and clinical data were collected and compared across subtypes. RESULTS: A total of 298 Filipinos living with HIV were recruited. Median CD4 count was 143 cells/µl and HIV viral load was 2,345,431 copies/ml. Sanger-based sequencing showed 230/298 (77.2%) had subtype CRF01_AE, 41 (13.8%) subtype B, and the rest had other subtypes or recombinants. Overall TDR was 11.7%. TDR was associated with lower viral loads and no previous HIV testing. CRF01_AE had a higher likelihood of a viral load >100,000 copies/ml and having a baseline CD4 count <50 cells/mm3. CONCLUSION: TDR in the Philippines is high at 11.7%. CRF01_AE was observed to have a higher baseline viral load and lower CD4 counts compared with other cocirculating subtypes. Further research needs to confirm this observation because it suggests that CRF01_AE may have a survival advantage that led to replacement of subtype B as the dominant subtype. Drug resistance testing is recommended in the Philippines when initiating NNRTI-based antiretroviral therapy but may not be necessary for INSTI-based regimens.

Real-world effectiveness after initiating fremanezumab treatment in US patients with episodic and chronic migraine or difficult-to-treat migraine.

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (mAb; IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for the preventive treatment of migraine in adults. The efficacy and safety of fremanezumab for migraine prevention have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world effectiveness data are needed to complement clinical trial data. This study assessed the effectiveness of fremanezumab across different subgroups of adult patients with episodic migraine (EM), chronic migraine (CM), or difficult-to-treat (DTT) migraine in real-world clinical settings. METHODS: This retrospective, panel-based online chart review used electronic case report forms. Patient inclusion criteria were a physician diagnosis of EM or CM; age ≥ 18 years at the time of first fremanezumab initiation; ≥ 1 dose of fremanezumab treatment; ≥ 1 follow-up visit since first initiation; and ≥ 2 measurements of monthly migraine days (MMD; with 1 within a month before or at first initiation and ≥ 1 after first initiation). Changes in MMD and monthly headache days were assessed during the follow-up period. These endpoints were evaluated in subgroups of patients by migraine type (EM/CM) and in subgroups with DTT migraine (diagnosis of medication overuse [MO], major depressive disorder [MDD], generalized anxiety disorder [GAD], or prior exposure to a different CGRP pathway-targeted mAb [CGRP mAb]). RESULTS: Data were collected from 421 clinicians and 1003 patients. Mean (percent) reductions from baseline in MMD at Month 6 were - 7.7 (77.0%) in EM patients, - 10.1 (68.7%) in CM patients, - 10.8 (80.6%) in the MO subgroup, - 9.9 (68.3%) in the MDD subgroup, - 9.5 (66.4%) in the GAD subgroup, and - 9.0 (68.7%) in the prior CGRP mAb exposure subgroup. Improvements in MDD or GAD severity were reported by 45.5% and 45.8% of patients with comorbid MDD or GAD, respectively. CONCLUSIONS: In this real-world study, fremanezumab demonstrated effectiveness for migraine regardless of migraine type or the presence of factors contributing to DTT migraine (MO, GAD, MDD, or prior exposure to a different CGRP mAb).

A real-world study of acute and preventive medication use, adherence, and persistence in patients prescribed fremanezumab in the United States.

BACKGROUND: Following approval of fremanezumab for the prevention of migraine in adults, health care decision makers are interested in understanding real-world clinical characteristics and treatment patterns among patients initiating fremanezumab therapy. METHODS: Data were obtained for this retrospective (pre-post) study from the Veradigm Health Insights database. The study period was January 1, 2014, to June 30, 2019. Patients were included if they were aged ≥ 18 years; had ≥ 1 migraine diagnosis during the study period; and had a medication record for fremanezumab on or after diagnosis during the identification period (September 1, 2018-December 31, 2018). Treatment patterns, including adherence, persistence, and utilization of acute and preventive migraine medication prescriptions, were evaluated. RESULTS: Of 987 patients initiating fremanezumab during the study period, 738 (74.8%) were adherent to fremanezumab by proportion of days covered (PDC; ≥ 80%) and 780 (79.0%) were adherent by medication possession ratio (MPR; ≥ 80%). A total of 746 (75.6%) patients were persistent for ≥ 6 months. Quarterly fremanezumab (n = 186) was associated with higher rates of adherence versus monthly fremanezumab (n = 801) by PDC (quarterly, 91.3%; monthly, 84.9%; P < 0.001) and MPR (quarterly, 92.2%; monthly, 87.9%; P = 0.006) and higher persistence at ≥ 6 months (quarterly, 82.8%; monthly, 73.9%; P = 0.011). After fremanezumab initiation, patients who were persistent for ≥ 6 months experienced significant reductions from baseline in the mean monthly number of acute and preventive migraine medication prescriptions (P < 0.001). Subgroup analyses in patients with comorbid depression and anxiety showed meaningful real-world benefits based on significant reductions in the number of patients who were prescribed antidepressants (baseline, 68.6%; follow-up, 56.4%; P = 0.0025) and anxiolytic medications (baseline, 55.0%; follow-up, 47.2%; P = 0.037), respectively. In a subgroup of patients with comorbid hypertension at baseline, fremanezumab treatment resulted in nonsignificant reductions in blood pressure. CONCLUSIONS: Overall, adherence and persistence to fremanezumab in this real-world study was high in patients with migraine, with higher rates observed for quarterly fremanezumab. Patients who were persistent for ≥ 6 months experienced significant reductions in acute and preventive migraine medication use, while a subgroup of migraine patients with comorbid depression and anxiety at baseline showed significant reductions in antidepressant and anxiolytic medication use.

Real-world effectiveness of fremanezumab in migraine patients initiating treatment in the United States: results from a retrospective chart study.

BACKGROUND: The efficacy and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP) and is approved for the preventive treatment of migraine in adults, have been demonstrated in randomized, double-blind, placebo-controlled trials. Real-world data can further support those clinical trial data and demonstrate the full clinical benefits of fremanezumab. This chart review assessed the effectiveness of fremanezumab for improving clinical outcomes in adult patients with migraine treated according to real-world clinical practice. METHODS: This retrospective, panel-based, online physician chart review study used electronic case report forms with US physicians. Patient inclusion criteria were a physician diagnosis of migraine, fremanezumab treatment initiation at ≥ 18 years of age after US Food and Drug Administration approval, ≥ 1 dose of fremanezumab treatment, and ≥ 2 assessments of monthly migraine days (MMD; 1 within 30 days before treatment initiation and ≥ 1 after initiation). Changes from baseline in MMD, monthly headache days (MHD), and Migraine Disability Assessment (MIDAS) and 6-item Headache Impact Test (HIT-6) scores were assessed over 6 months. These endpoints were evaluated in the overall population and subgroups divided by dosing schedule and number of prior migraine preventive treatment failures. RESULTS: This study included data from 421 clinicians and 1003 patients. Mean age at fremanezumab initiation was 39.7 years, and most patients were female (75.8%). In the overall population, mean baseline MMD and MHD were 12.7 and 14.0, respectively. Mean (percent) reductions from baseline in MMD and MHD, respectively, were - 4.6 (36.2%) and - 4.7 (33.6%) at Month 1, - 6.7 (52.8%) and - 6.8 (48.6%) at Month 3, and - 9.2 (72.4%) and - 9.8 (70.0%) at Month 6. Mean (percent) reductions from baseline in MIDAS and HIT-6 scores also increased over the 6-month study period, from - 6.2 (21.6%) and - 8.4 (14.0%) at Month 1 to - 18.1 (63.1%) and - 16.2 (27.0%) at Month 6, respectively. Improvements in these outcomes over 6 months were observed across all evaluated subgroups. CONCLUSIONS: This real-world study demonstrated effectiveness of fremanezumab treatment for up to 6 months, irrespective of dosing regimen or number of prior migraine preventive treatment failures, reflecting ongoing, clinically meaningful improvements in patient outcomes.

Real-world patient characteristics, treatment patterns and costs in relapsing multiple sclerosis patients treated with glatiramer acetate, dimethyl fumarate or teriflunomide in Germany.

Aim: To evaluate adherence, healthcare resource utilization (HRU) and costs for glatiramer acetate (GA; injectable), dimethyl fumarate (oral) and teriflunomide (oral) in relapsing multiple sclerosis. Patients & methods: Retrospective analyses of a claims database. Results: Teriflunomide patients were older with more co-morbidities and fewer relapses versus GA and dimethyl fumarate. GA patients were mostly disease-modifying therapies (DMTs)-treatment naive. Treatment adherence was 61-70%. All DMTs reduced HRU versus pre-index. Costs were comparable across cohorts. High adherence reduced hospitalizations and several costs versus low adherers. Conclusion: Adherence rates were high and comparable with all DMTs. Similar (and high) reductions in HRU and costs occurred with all DMTs. High adherence improved economic outcomes versus low adherence. Thus, investing in adherence improvement is beneficial to improve outcomes in relapsing multiple sclerosis.

Drugs used for relapsing multiple sclerosis (RMS) include, among others, glatiramer acetate (injection), dimethyl fumarate (tablet) and teriflunomide (tablet). We compared treatment adherence (based on drug claims), healthcare use and costs for these drugs. Treatment adherence and healthcare use was similar for these three drugs. The need to be in hospital was lower with these drugs compared with not using them. No differences in treatment costs were seen between these drugs. Adherence reduced the need for hospital stays and lowered some costs compared with patients who were classified as adherent. RMS patients should be encouraged to take their RMS medication as prescribed. Improving treatment adherence will have a positive effect on RMS, and a good impact on healthcare use and costs.

Vacuum pressure combined with osmosonication as an innovative pre-drying technique for Ghanaian ginger: Evidence from the metabolome and quality characteristics of the dried product.

We assessed the impact of selected pretreatment techniques, thus, vacuum-assisted osmotic dehydration (VOD), vacuum-assisted sonication (VSON) and vacuum-assisted osmosonication (VOS) on the metabolomes and quality characteristics of infrared-dried ginger slices. We found marked metabolome differences between the pretreated ginger samples, evidenced by differential amounts of 6-gingerol and 6-shogaol, total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activities. We also found distinct differences in the drying kinetics and sensory characteristics of the pretreated samples. Generally, VOS pretreatment gave the best outcomes. The VOS-pretreated samples contained the highest contents of the marker compounds, TPC, TFC and gave the best antioxidant activity. The VOS-pretreated samples also recorded the shortest drying time and exhibited the best sensory attributes. Overall, the general order observed was, VOS > VSON > VOD > control for all quality parameters examined. VOS pretreatment of ginger before drying therefore holds a great potential for large-scale industrial application.

Comment on: Gao B, Lu Q, Wan R, Wang Z, Yang Y, Chen Z, Wang Z. "Monthly versus quarterly fremanezumab for the prevention of migraine: a systemic review and meta-analysis from randomized controlled trials". Naunyn Schmiedebergs Arch Pharmacol. 2021 Apr;394(4):819-828. Epublished November 2020.

Recently, Gao et al. published an article titled "Monthly versus quarterly fremanezumab for the prevention of migraine: a systemic review and meta-analysis from randomized controlled trials" which concluded that monthly administration of fremanezumab led to significant reduction in monthly migraine days (MMD) when compared to quarterly fremanezumab. We have noted a critical flaw in Gao et al. meta-analysis wherein the authors have mistakenly utilized standard error values in place of standard deviation values in performing their pooled analyses. This error directly impacts the study results and conclusions. In this brief communication, we present revised analysis using correct methods. Using the correct SD values, our pooled analysis showed no significant difference in mean change from baseline in MMD between the two fremanezumab dosing regimens (P = 0.17). Furthermore, in the corrected subgroup analyses by type of migraine, there were no significant differences in mean change from baseline in MMD between monthly fremanezumab and quarterly fremanezumab (chronic migraine, P = 0.50; episodic migraine, P = 0.69). Overall, results from our corrected meta-analyses show that there is no significant difference in migraine prevention efficacy between monthly and quarterly fremanezumab dosing.

Assessment of rituximab-abbs, a biosimilar, and rituximab outcomes in patients with CLL or NHL: A real-world UK study.

BACKGROUND: Rituximab (chimeric anti-CD20 monoclonal antibody) treatment is approved for chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Rituximab-abbs (first biosimilar approved in 2017) is expected to significantly reduce healthcare economic burden due to lower acquisition costs. This non-interventional, non-comparative study assessed real-world effectiveness and tolerability of rituximab-abbs and rituximab in treatment-naive patients with CLL or NHL. MATERIALS AND METHODS: Via an online physician survey, 46 UK-registered hematologists and oncologists retrospectively reported on randomly selected patients aged ≥18 years with CLL or NHL with rituximab-abbs or rituximab as first-line immunotherapy. Overall, 201 patient charts were examined across 4 cohorts: rituximab-abbs in CLL, rituximab-abbs in NHL, rituximab in CLL, rituximab in NHL. RESULTS: Demographic profiles across cohorts were similar. Most patients (94 %-100 %) received combination therapy (rituximab-abbs or rituximab mainly with chemotherapy). For both treatments, overall response rate (94 %-98 %) and 1-year overall survival (98 %-100 %) were very high for patients with CLL or NHL. Most common serious adverse events were neutropenia, fatigue, anemia and infusion reactions. The majority of patients (54 %-66 %) did not experience a grade ≥3 adverse event. Healthcare resource utilization was similarly high across cohorts, driven by diagnostic testing, oncologist office visits, and day-case hospital admissions; many patients required supportive medical therapies. Mean annual savings of ∼£1000/patient driven by acquisition costs occurred with rituximab-abbs versus rituximab, administration costs were similar. CONCLUSION: Rituximab-abbs and rituximab demonstrated similar effectiveness and tolerability in treating CLL and NHL in routine UK clinical practice and demonstrate the utility of the biosimilar as a cost-saving alternative treatment.

Clinical Outcomes and Health-Care Resource Use Associated With Reslizumab Treatment in Adults With Severe Eosinophilic Asthma in Real-World Practice.

BACKGROUND: Reslizumab, an anti-IL-5 monoclonal antibody, is indicated as add-on maintenance treatment for adults with severe eosinophilic asthma. RESEARCH QUESTION: What are the real-world outcomes associated with reslizumab use in patients with severe eosinophilic asthma in a US clinical practice? STUDY DESIGN AND METHODS: In this retrospective study, patient-level data from adults treated with reslizumab were obtained from center- and panel-based medical chart reviews. Eligible patients had available medical records and treatment history for ≥ 6 months before initiation of reslizumab treatment (index date) to ≥ 7 months after reslizumab initiation. The primary outcome was response to reslizumab treatment, based on clinical expert predefined definitions of response. Other outcomes included clinical asthma exacerbations (CAEs), use of maintenance oral corticosteroids (OCS), FEV1 percent predicted, Asthma Control Test (ACT) score, and health-care resource use (HRU). RESULTS: Medical charts were obtained for 215 patients. Most patients (58.6%) showed an excellent response, 16.3% showed a clinically meaningful response, 21.9% showed a partial response, and 3.3% were nonresponders or treatment failures. A significant reduction was observed in the proportion of patients experiencing a CAE in a 6-month period (from 86.0% to 40.5%; P < .001) and in the mean number of CAEs per patient (2.84 [SD, 2.41] vs 0.94 [SD, 1.86]) after reslizumab initiation. Improvements were observed in FEV1 percent predicted (65.1% [SD, 20.5%] vs 73.1% [SD, 23.1%]; P < .001) and in ACT scores (13.8 [SD, 4.2] vs 18.6 [SD, 4.0]; P < .001) before to after reslizumab initiation. Among patients using maintenance OCS at baseline, more than half discontinued use of these by approximately 10 months after reslizumab initiation. Significant reductions in asthma-related HRU were observed after reslizumab initiation. INTERPRETATION: In clinical practice, reslizumab may have been initiated in response to heavy symptom burden and CAEs. Reslizumab was associated with improved clinical and patient-reported outcomes and significant reductions in asthma-related HRU.

Intracranial Mass Lesions in Human Immunodeficiency Virus Patients in the Philippines: A Retrospective Cohort Study.

BACKGROUND: Central nervous system involvement is commonly seen in patients with human immunodeficiency virus (HIV) infection, with up to 2%-10% of patients presenting with intracranial mass lesions. The management of these lesions depends largely on their etiology and their relative frequency in the local population. METHODS: We performed a retrospective chart review of patients with HIV and evidence of intracranial mass lesions on cranial magnetic resonance imaging or computed tomography from 2007 to 2018. Demographic data, clinical features, etiology, surgical management, and outcomes were collected. RESULTS: The prevalence of intracranial mass lesions in our cohort was 2.2% (45/2032). Patients were predominantly male (98%), with a mean age at diagnosis of 28 years. The most common clinical manifestations were headache (75%), focal weakness (49%), and seizures (32%). The most common diagnoses were toxoplasmic encephalitis (51%) and tuberculosis (24%). Biopsy or excision was performed in 10% of cases, leading to a definitive diagnosis in 60% of these cases. A favorable outcome was observed in 58% of all patients at 46 months median follow-up, with adequate disease-specific treatment. CONCLUSIONS: The prevalence of intracranial mass lesions in Filipino patients with HIV is 2.2%. The most common etiology was toxoplasmic encephalitis followed by tuberculosis. These findings are substantially different from other findings reported in the literature and should be considered in formulating guidelines for the Filipino population.

High rates of tenofovir failure in a CRF01_AE-predominant HIV epidemic in the Philippines.

BACKGROUND: The Philippines has the fastest growing HIV epidemic in the Asia-Pacific. This increase was accompanied by a shift in the predominant HIV subtype from B to CRF01_AE. Increasing evidence points to a difference in treatment responses between subtypes. We examined treatment failure and acquired drug resistance (ADR) in people living with HIV (PLHIVs) after one year on antiretrovirals (ARVs). METHODS: PLHIV maintained on ARVs for one year were recruited. Treatment failure was defined as a viral load of ≥1000 copies/mL. Sanger sequencing for genotyping and drug resistance mutation (DRM) detection was performed on patients failing treatment. RESULTS: 513 PLHIV were enrolled. The most common antiretroviral regimens were TDF+3TC + EFV (269) and AZT+3TC + EFV (155). 53 (10.3%) subjects failed treatment. Among these, 48 (90.6%) had DRMs, 84.9% were subtype CRF01_AE. Tenofovir-based regimens performed worse than zidovudine-based regimens (OR 3.28, 95% CI 1.58-7.52 p < 0.001). Higher rates of NRTI, NNRTI, K65R tenofovir resistance, and multi-class resistance were found compared to those reported in literature. CONCLUSIONS: HIV treatment failure at one year of treatment in the Philippines is 10.3%. We found unusually high tenofovir and multiclass resistance, and optimal ARV regimens may need to be reevaluated for CRF01_AE-predominant epidemics.

Long-term cost and utility consequences of short-term clinically important deterioration in patients with chronic obstructive pulmonary disease: results from the TORCH study.

Purpose: Clinically important deterioration (CID) in chronic obstructive pulmonary disease (COPD) is a novel composite endpoint that assesses disease stability. The association between short-term CID and future economic and quality of life (QoL) outcomes has not been previously assessed. This analysis considers 3-year data from the TOwards a Revolution in COPD Health (TORCH) study, to examine this question. Patients and methods: This post hoc analysis of TORCH (NCT00268216) compared costs and utilities at 3 years among patients without CID (CID-) and with CID (CID+) at 24 weeks. A positive CID status was defined as either: a deterioration in forced expiratory volume in 1 second (FEV1) of ≥100 mL from baseline; or a ≥4-unit increase from baseline in St George's Respiratory Questionnaire (SGRQ) total score; or the incidence of a moderate/severe exacerbation. Patients from all treatment arms were included. Utility change was based on the EQ-5D utility index. Costs were based on healthcare resource utilization from 24 weeks to end of follow-up combined with unit costs for the UK (2016 GBP), and reported as per patient per year (PPPY). Adjusted estimates were generated controlling for baseline characteristics, treatment assignment, and number of CID criteria met. Results: Overall, 3,769 patients completed the study and were included in the analysis (stable CID- patients, n=1,832; unstable CID+ patients, n=1,937). At the end of follow-up, CID- patients had higher mean (95% confidence interval [CI]) utility scores than CID+ patients (0.752 [0.738, 0.765] vs 0.697 [0.685, 0.71]; difference +0.054; P<0.001), and lower costs PPPY (£538 vs £916; difference: £378 [95% CI: £244, £521]; P<0.001). The cost differential was primarily driven by the difference in general hospital ward days (P=0.003). Conclusion: This study demonstrated that achieving early stability in COPD by preventing short-term CID is associated with better preservation of future QoL alongside reduced healthcare service costs.

Benefits and risks of prolonged cotrimoxazole prophylaxis among people living with HIV in immune reconstitution phase: A retrospective cohort study

@#<p style="text-align: justify;"><strong>OBJECTIVES:</strong> To determine the effect of prolonged cotrimoxazole prophylaxis (CP) in reducing hospitalization and opportunistic infection rates among people living with HIV (PLHIV) with CD4 count >200 cells/mm3.<br /> <strong>METHODS:</strong>  We retrospectively reviewed 349 medical charts of PLHIV with CD4 count (or T-cell count) of >200 cells/mm3 enrolled in an HIV treatment hub in Manila, Philippines, from January 2004 to July 2016. Demographic, clinical characteristics and outcomes were extracted. Descriptive statistics were generated. Chi-square test for two proportions was done to compare the difference in outcomes between the CP and non-CP groups.<br /> <strong>RESULTS:</strong>  Of the 349 patients, majority (96.6%) were male with a mean age of 28 years (SD 6.4) and mean CD4 count of 373 cells/mm3 (SD 148). CP was continued in 103 patients (29.5%) with mean duration of 1.7 (SD 1.9) years. The prolonged CP group had more events of adverse drug reactions (p<0.001), specifically minor cutaneous reactions (p<0.001) and immunologic failures (p<0.001), compared to the non-CP group. There were no statistically significant differences in the frequency of hospitalization, PJP (Pneumocystis jirovecii pneumonia), non-PJP, other respiratory illnesses, diarrhea, toxoplasmosis, tuberculosis, stage 3/4 events and mortality, between the prolonged CP and non-CP groups.<br /> <strong>CONCLUSION:</strong> We did not observe any additional benefit in giving prolonged CP among PLHIV with CD4 count >200 cells/mm3. More adverse effects were also seen in the CP group.</p>

Systematic review of association between critical errors in inhalation and health outcomes in asthma and COPD.

Inhaled medications are the cornerstone of treatment and management of asthma and COPD. However, inhaler device errors are common among patients and have been linked with reduced symptom control, an increased risk of exacerbations, and increased healthcare utilisation. These observations have prompted GINA (Global INitiative for Asthma) and GOLD (Global initiative for chronic Obstructive Lung Disease) to recommend regular assessment of inhaler technique in a bid to improve therapeutic outcomes. To better define the relationship between device errors and health outcomes (clinical outcomes, quality of life, and healthcare utilisation) in asthma and COPD, we conducted a systematic review of the literature, with a particular focus on the methods used to assess the relationship between device errors and outcomes. Sixteen studies were identified (12 in patients with asthma, one in patients with COPD, and three in both asthma and COPD) with varying study designs, endpoints, and patient populations. Most of the studies reported that inhalation errors were associated with worse disease outcomes in patients with asthma or COPD. Patients who had a reduction in errors over time had improved outcomes. These findings suggest that time invested by healthcare professionals is vital to improving inhalation technique in asthma and COPD patients to improve health outcomes.

The Response of Rhodotorula mucilaginosa to Patulin Based on Lysine Crotonylation.

Patulin (PAT) is a mycotoxin produced by some Penicillium, Aspergillus, and Byssochlamys species. Rhodotorula mucilaginosa is able to degrade PAT in vivo as well as in vitro, up till date, the process and molecular mechanism(s) involved patulin degradation still remains unknown. Protein lysine crotonylation (Kcr) plays an important role in regulating chromatin dynamics, gene expression, and metabolic pathways in mammals and eukaryotes. Investigation of the Kcr changes accompanying degradation of patulin in R. mucilaginosa were observed to investigate the mechanisms of patulin inhibition. Tandem mass tag (TMT) labeling and Kcro affinity enrichment, followed by high-resolution LC-MS/MS analysis, were used to perform quantitative lysine crotonylome analysis on R. mucilaginosa. Consequently, 1691 lysine crotonylation sites in 629 protein groups were identified, among which we quantified 1457 sites in 562 proteins. Among the quantified proteins, 79 and 46 crotonylated proteins were up-regulated and down-regulated, respectively. The differentially up expressed modified proteins were mainly involved in tricarboxylic acid cycle and gluconeogenic pathway. The differentially down expressed Kcr proteins were mainly classified to ribosome and carbohydrate transport and metabolism. Bioinformatic analyses were performed to annotate the quantifiable lysine crotonylated targets. Moreover, interaction networks and high confidence domain architectures of crotonylated proteins were investigated with the aid of bioinformatic tools, and these results showed that there was an increase in the number of yeasts with crotonylated proteins. The results also provided information on the various roles of crotonylation, which are involved in PAT degradation.