Antimicrobial use for the management of varicella in Thailand: a retrospective observational study.

OBJECTIVE: To describe the clinical characteristics of varicella patients seeking medical consultation and the use of antimicrobials for their management in Thailand in the absence of universal varicella vaccination (UVV). METHODS: A multicenter, retrospective chart review of 260 children and adults with a primary diagnosis of varicella was conducted at one private and three public hospitals in Bangkok, Thailand. Charts of varicella patients (inpatient or outpatient) were randomly selected over a 5-year period. Key outcomes included clinical complications and the use of antibiotics, antivirals, and other medications. RESULTS: Charts of 200 children (mean age 5.7 years, range 0.3-16 years) and 60 adults (mean age 27.9 years, range 18-50 years) were reviewed. Fourteen patients (including 8 children) were hospitalized. Five percent of the children and none of the adults were immunocompromised. At least 1 varicella-related complication was reported by 7.3% (7% of children, 8.3% of adults, p = .778) of all patients, including 57.1% (62.5% of children, 50% of adults) of inpatients (p < .001, compared with outpatients). Skin/soft tissue infection (47.7%) and dehydration (47.4%) were the most common complications. Antivirals (mainly oral acyclovir) were prescribed to 46.5% of patients (31.5% of children, 96.7% of adults, p < .001). Antibiotics were prescribed to 20.8% of patients (19% of children, 26.7% of adults, p = .199). Topical, oral, and intravenous antibiotics were prescribed to 12.3%, 8.5%, and 1.2% of patients, respectively. Antimicrobial prescriptions were higher among adults (p < .001) and immunocompromised patients (p = .025). Apart from antimicrobials, acetaminophen (62.3%) and oral antihistamines (51.5%) were the most prescribed. CONCLUSION: A considerable number of varicella patients, both children and adults, seeking medical consultation in Thai hospitals are prescribed antibiotics and antivirals, with one-fifth of patients being prescribed an antibiotic and almost half prescribed an antiviral. The study may be of interest to policymakers in Thailand and other Asia-Pacific countries considering UVV implementation.

Quality-adjusted time without symptoms of disease or toxicity and quality-adjusted progression-free survival with niraparib maintenance in first-line ovarian cancer in the PRIMA trial.

Background: The PRIMA phase 3 trial showed niraparib significantly prolongs median progression-free survival (PFS) versus placebo in patients with advanced ovarian cancer (OC) responsive to first-line platinum-based chemotherapy, including those who had tumors with homologous recombination deficiency (HRd). This analysis of PRIMA examined the quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) of patients on maintenance niraparib versus placebo. Methods: Patients were randomized 2:1 to receive once-daily maintenance niraparib (n = 487) or placebo (n = 246). QA-PFS was defined as the PFS of patients adjusted for their health-related quality of life (HRQoL) prior to disease progression, measured using European Quality of Life Five-Dimension (EQ-5D) questionnaire index scores from the PRIMA trial. Q-TWiST was calculated by combining data on PFS, duration of symptomatic grade ⩾2 adverse events (fatigue or asthenia, nausea, vomiting, abdominal pain, and abdominal bloating) prior to disease progression, and EQ-5D index scores. Analyses used data collected up to the last date of PFS assessment (May 17, 2019). Results: The restricted mean QA-PFS was significantly longer with niraparib versus placebo in the HRd (n = 373) and overall intention-to-treat (ITT; n = 733) populations (mean gains of 6.5 [95% confidence interval; CI, 3.9-8.9] and 4.1 [95% CI, 2.2-5.8] months, respectively). There were also significant improvements in restricted mean Q-TWiST for niraparib versus placebo (mean gains of 5.9 [95% CI, 3.5-8.6] and 3.5 [95% CI, 1.7-5.6] months, respectively) in the HRd and ITT populations. Conclusions: In patients with advanced OC, first-line niraparib maintenance was associated with significant gains in QA-PFS and Q-TWiST versus placebo. These findings demonstrate that niraparib maintenance treatment is associated with a PFS improvement and that treatment benefit is maintained even when HRQoL and/or toxicity data are combined with PFS in a single measure. Trial registration: ClinicalTrials.gov: NCT02655016; trial registration date: January 13, 2016. Plain language summary: Background: In a large clinical trial called PRIMA, patients with advanced cancer of the ovary (ovarian cancer) were given either niraparib (a type of cancer medicine) or placebo (a pill containing no medicine/active substances) after having chemotherapy (another type of cancer medicine). Taking niraparib after chemotherapy is called maintenance therapy and aims to give patients more time before their cancer returns or gets worse than if they were not given any further treatment. In the PRIMA trial, patients who took niraparib did have more time before their cancer progressed than if they took placebo. However, it is important to consider patients' quality of life, which can be made worse by cancer symptoms and/or side effects of treatment. Here, we assessed the overall benefit of niraparib for patients in PRIMA.Methods: Both the length of time before disease progression (or survival time) and quality of life were considered using two different analyses:● The first analysis was called quality-adjusted PFS (QA-PFS) and looked at how long patients survived with good quality of life.● The second analysis was called quality-adjusted time without symptoms of disease or toxicity (Q-TWiST) and looked at how long patients survived without cancer symptoms or treatment side effects.Results: The PRIMA trial included 733 patients; 487 took niraparib and 246 took placebo. Around half of the patients in both groups had a type of ovarian cancer that responds particularly well to drugs like niraparib - they are known as homologous recombination deficiency (HRd) patients.● When information on quality of life (collected from patient questionnaires) and survival was combined in the QA-PFS analysis, HRd patients who took niraparib had approximately 6.5 months longer with a good quality of life before disease progression than those who took placebo. In the overall group of patients (including HRd patients and non-HRd patients), those who took niraparib had approximately 4 months longer than with placebo.● Using the second analysis (Q-TWiST) to combine information on survival with cancer symptoms and treatment side effects, the HRd patients taking niraparib had approximately 6 months longer without cancer symptoms or treatment side effects (such as nausea or vomiting) than patients taking placebo. In the overall group of patients, those taking niraparib had approximately 3.5 months longer without these cancer symptoms/side effects than patients receiving placebo.Conclusions: These results show that the survival benefits of niraparib treatment remain when accounting for patients' quality of life. These benefits were seen not only in HRd patients who are known to respond better to niraparib, but in the overall group of patients who took niraparib.

Real-world burden of adverse events for apalutamide- or enzalutamide-treated non-metastatic castration-resistant prostate cancer patients in the United States.

BACKGROUND: Second-generation androgen receptor inhibitors (ARIs) have been associated with adverse events (AEs) such as fatigue, falls, fractures, and rash in non-metastatic castration-resistant prostate cancer (nmCRPC) patients as identified in clinical trials. The objectives of this study were to describe the incidence and management of AEs in patients receiving apalutamide and enzalutamide. METHODS: This retrospective chart review study was conducted in nmCRPC-treating sites in the United States. Patients starting apalutamide or enzalutamide between February 1, 2018 and December 31, 2018 were included and any AEs they experienced were recorded. AEs, including those considered to be of special interest as defined in the pivotal clinical trials of the second-generation ARIs, were analyzed and grouped retrospectively in this study. Detailed chart data (patient demographics, clinical characteristics, treatment history, type of AE, outcomes, and resource utilization) were then collected for a randomly selected subset among patients with ≥1 AE to characterize AEs and their management. Descriptive results were summarized. RESULTS: Forty-three sites participated in the study. A total of 699 patients were included, of whom 525 (75.1%) experienced ≥1 AE. The most common AEs were fatigue/asthenia (34.3%), hot flush (13.9%), and arthralgia (13.6%). In the subset of 250 patients randomly selected from those who experienced ≥1 AE, patients were primarily White (72.0%), the mean age was 71 years, 86.0% had an Eastern Cooperative Oncology Group score of 0-1 at nmCRPC diagnosis, and the average prostate specific antigen (PSA) value at diagnosis was 23.2 ng/mL. PSA-doubling time < 10 months was chosen as reason to initiate treatment in 40% of patients. The median duration of follow-up was 1.1 years, with 14.4% of patients progressing to metastasis by end of study period. Grade 3-4 and Grade 5 AEs occurred in 14.4 and 0.4% of patients, respectively. Actions taken to manage AEs included AE-directed treatment (38.0%), ARI discontinuation (10.4%), dose reduction (7.6%), and AE-related hospitalization (4.8%). CONCLUSIONS: This study highlights the burden of AEs among nmCRPC patients treated with apalutamide or enzalutamide, providing a relevant real-world benchmark as clinical trial evidence and the treatment landcape for nmCRPC continues to evolve.

Treatment patterns and economic burden among newly diagnosed cervical and endometrial cancer patients.

Aim: This study evaluated treatment patterns, healthcare resource use and healthcare costs among newly diagnosed US patients with cervical or endometrial cancer. Materials & methods: The authors identified patients diagnosed between 2015 and 2018, described them by line of therapy (LOT), then summarized all-cause per patient per month healthcare resource use and healthcare costs per LOT. Results: Among 1004 patients with cervical cancer and 2006 patients with endometrial cancer, 65.2 and 71.4%, respectively, received at least LOT1. Common treatment modalities in LOT1 were surgery (cervical, 58.0%; endometrial, 92.6%), radiation therapy (cervical, 49.8%; 24.7%) and systemic therapy (cervical, 53.3%; endometrial, 26.1%). Mean per patient per month costs per LOT were pre-treatment (cervical, US$17,210; endometrial, US$14,601), LOT1 (cervical, US$10,929; endometrial, US$6859), LOT2 (cervical, US$15,183; endometrial, US$10,649) and LOT3+ (cervical, US$19,681; endometrial, US$9206). Conclusion: Overall, newly diagnosed patients with cervical or endometrial cancer received guideline-recommended treatment. Outpatient visits mainly drove healthcare costs across LOTs.

Treatment patterns and economic burden among cervical and endometrial cancer patients newly initiating systemic therapy.

Aim: To evaluate treatment patterns, healthcare resource use (HCRU) and all-cause healthcare costs among patients with cervical or endometrial cancer newly initiating systemic therapy. Methods: We identified patients with cervical or endometrial cancer newly initiating systemic therapy - a claims-based proxy for advanced disease - between 2014 and 2019, described them by line of therapy (LOT), and summarized the per patient per month (PPPM) HCRU and healthcare costs per LOT. Results: Among 1229 patients with cervical cancer and 2659 patients with endometrial cancer, LOT1 therapies included systemic only (cervical, 50.1%; endometrial, 83.2%) and systemic with radiation therapy (cervical, 49.9%; endometrial, 16.8%). Mean PPPM total costs were: LOT1 (cervical, US$15,892; endometrial, US$11,363), LOT2 (US$20,193; US$14,019) and LOT3+ (US$16,576; US$14,645). Conclusions: Overall, patients received guideline-concordant care and experienced significant economic burden, which increased with LOT.

Pre-pregnancy body mass index and parent and teacher-reported behavioral outcomes among offspring in childhood.

OBJECTIVE: Pre-pregnancy obesity has been linked to childhood neurodevelopmental outcomes, including autism and attention-deficit hyperactivity disorder. The aim of our study was to examine the association between pre-pregnancy body mass index (BMI) and scores on behavioral scales according to both mother and teacher report. METHODS: We conducted a longitudinal study of 469 mother-child pairs. Information on pre-pregnancy body mass index (BMI) was collected from standardized maternal interviews conducted after delivery and assessment of childhood behavioral problems was measured at 5-12 years of age according to maternal-report using the Child Behavior Checklist (CBCL) and teacher-report using the Teacher Report Form (TRF). Using normal pre-pregnancy BMI (18.5-24.9 kg/m2) as the reference (n = 305), we calculated adjusted mean differences (MD) for t-scores on broadband and syndrome scales of behavior for children of mothers with pre-pregnancy overweight (n = 101) or obese (n = 63) BMI. We also examined associations with scores in the clinical range using risk ratios (RR) and compared results across informants. To account for loss to follow-up between the initial interview and the childhood behavioral assessment, we weighted models using stabilized inverse probability weights. RESULTS: Pre-pregnancy obesity was associated with a mean increase in child's total behavior problem t-scores according to both mother and teacher report, after adjustment for confounders and weighted for loss to follow-up (MD: 0.7, 95% CI: -2.2, 3.6 on CBCL; MD: 3.1, 95% CI: 0.5, 5.7 on TRF), indicating poorer behavioral outcomes. Comparing the magnitude of associations between mother and teacher-report, mean differences for pre-pregnancy obesity and most behavioral problem scales were larger for teacher-reported outcomes than mother-reported outcomes. Pre-pregnancy obesity was associated with increased risks of externalizing behaviors in the clinical range regardless of informant (CBCL RR: 1.6, 95% CI: 0.8, 3.2 and TRF RR: 1.7, 95% CI: 0.8, 3.5). Pre-pregnancy obesity was also associated with increased risks of internalizing behaviors according to teacher-report (TRF RR: 2.6, 95% CI:1.5, 4.6). CONCLUSIONS: Pre-pregnancy obesity, compared to pre-pregnancy normal weight, is associated with generally higher scores on both mother and teacher reported childhood behavioral assessments, indicating an increased likelihood of behavioral problems.

Phase-specific and lifetime economic burden of cervical cancer and endometrial cancer in a commercially insured United States population.

AIM: To estimate the incremental phase-specific and lifetime economic burden among newly diagnosed cervical and endometrial cancer patients vs. non-cancer controls. METHODS: Cervical and endometrial cancer patients newly diagnosed between January 2015 and June 2018 were identified in the Optum Clinformatics DataMart database. The index date was the date of the first diagnosis for cancer cases and the first claim date after 12 months of continuous enrollment for non-cancer controls. Patients were followed until death/loss of enrollment/end of data availability. Per patient per month (PPPM) costs attributable to cancer were calculated for four phases: pre-diagnosis (3 months before diagnosis), initial (6 months post-diagnosis), terminal (6 months pre-death), and continuation (remaining time between initial and terminal phases). Survival data were obtained to determine the monthly proportion of patients in each phase. Total survival adjusted monthly costs were obtained by multiplying the proportion of patients in each phase by the total cost incurred during that month. Phase-specific and lifetime incremental costs of cervical and endometrial cancer were obtained using generalized linear models. RESULTS: The analytic cohort included 1,002 cervical cancer patients and 4,005 matched non-cancer controls and 5,003 endometrial cancer patients matched with 19,999 non-cancer controls. Mean adjusted incremental PPPM lifetime costs (95% CI) for cervical cancer and endometrial cancer cases were $5,910 ($5,373-$6,446) and $3,475 ($3,259-$3,691), respectively. Incremental total PPPM phase-specific costs attributable to cervical and endometrial cancer were pre-diagnosis (cervical: $1,057; endometrial: $3,315), initial ($12,084; $8,618), continuation ($2,732; $1,147), and terminal ($2,702; $5,442). Incremental costs were significantly higher for cancer patients vs. non-cancer controls across patient lifetime and all phases of care (except terminal phase costs for cervical cancer). Outpatient costs were the major driver of costs across all post-diagnosis phases. CONCLUSION: This study highlights the cost burden associated with cervical/endometrial cancer and cost variation by phases of care.

Real-world treatment patterns and outcomes using terlipressin in 203 patients with the hepatorenal syndrome.

BACKGROUND: Hepatorenal syndrome and acute kidney injury are common complications of decompensated cirrhosis, and terlipressin is recommended as first-line vasoconstrictor therapy. However, data on its use outside of clinical trials are lacking. AIMS: To assess practice patterns and outcomes around vasoconstrictor use for hepatorenal syndrome in UK hospitals. METHODS: This was a multicentre chart review study. Data were extracted from medical records of patients diagnosed with hepatorenal syndrome and treated by vasoconstrictor drugs between January 2013 and December 2017 at 26 hospitals in the United Kingdom. The primary outcome was improvement of kidney function, defined as complete response (serum creatinine improved to ≤1.5 mg/dL), partial response (serum creatinine reduction of ≥20% but >1.5 mg/dL) and overall response (complete or partial response). Other outcomes included need for dialysis, mortality, liver transplantation and adverse events. RESULTS: Of the 225 patients included in the analysis, 203 (90%) were treated with terlipressin (median duration, 6 days; range: 2-24 days). Mean (±standard deviation) serum creatinine at vasopressor initiation was 3.25 ± 1.64 mg/dL. Terlipressin overall response rate was 73%. Overall response was higher in patients with mild acute kidney injury (baseline serum creatinine <2.25 mg/dL), compared to those with moderate (serum creatinine ≥2.25 mg/dL and <3.5 mg/dL) or severe (serum creatinine ≥3.5 mg/dL). Ninety-day survival was 86% for all patients (93% for overall responders vs 66% for treatment nonresponders, P < 0.0001). CONCLUSION: Terlipressin is the most commonly prescribed vasoconstrictor for patients with hepatorenal syndrome in the United Kingdom. Treatment with terlipressin in patients with less severe acute kidney injury (serum creatinine <2.25 mg/dL) was associated with higher treatment responses, and 90-day survival.

Real-world incidence and burden of adverse events among non-metastatic prostate cancer patients treated with secondary hormonal therapies following androgen deprivation therapy.

Aims: To describe the incidence and identify prognostic factors of central nervous system (CNS) adverse events (AEs) and any AEs (CNS, skin rash, or fracture) and evaluate the healthcare resource utilization (HCRU), direct medical costs, and therapy discontinuation associated with these AEs among non-metastatic prostate cancer (nmPC) patients who received secondary hormone therapies.Methods and results: nmPC patients who had initiated secondary hormonal therapy with enzalutamide, bicalutamide, or abiraterone ≥1 year after androgen deprivation therapy (ADT) were identified in the MarketScan database. Survival analyses were used to describe the incidence of CNS or any AEs. Annual HCRU and costs were compared across patient groups (CNS AE vs no CNS AE; any AE vs no AE) using propensity score weighted generalized linear models. Multivariate Cox proportional hazards models were used to identify AE predictors and compare risks of discontinuation.Results: The analysis included 532 patients who initiated secondary hormonal therapies, among whom 201 (38%) and 244 (46%) experienced a CNS AE and any AE, respectively. Median times to CNS AE and any AE from therapy initiation were 17.90 and 11.00 months, respectively. Predictors of any AE were any AE in the baseline period (≤6 months before starting therapy), Charlson Comorbidity Index (CCI) score (1 vs 0), surgical castration, and older age. Predictors of CNS AEs were CNS AE in the baseline period and CCI score (1 vs 0). CNS and any AEs were associated with significantly higher HCRU. CNS AEs were associated with significantly higher incremental total medical costs ($18,522). CNS AEs and any AEs significantly increased therapy discontinuation risk by 48% and 38%, respectively.Conclusions: AEs increase the economic burden and therapy discontinuation among nmPC patients receiving secondary hormonal therapies subsequent to ADTs. These patients should be carefully evaluated for AEs to reduce therapy discontinuation, HCRU, and direct medical costs.