Incident HIV-Associated Wasting/Low Weight Is Associated with Nearly Doubled Mortality Risk in the Modern ART Era.

HIV-associated wasting (HIVAW) is an underappreciated AIDS-defining illness, despite highly effective antiretroviral therapy (ART). We (a) assessed the association between incident HIVAW/low weight and all-cause mortality and (b) described virologic outcomes after people with HIV (PWH) experienced HIVAW/low weight while on ART. In the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort, PWH without prior HIVAW/low weight who were active in care in 2016-2020 were followed through the first of the following censoring events: death, loss to follow-up, or study end (October 31, 2021). HIVAW/low weight was a diagnosis of wasting or low body mass index (BMI)/underweight or a BMI measurement <20 kg/m2. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-dependent HIVAW/low weight and mortality were estimated with extended Cox regression models. Over a median follow-up of 45 months (interquartile range: 27, 65), there were 4,755 (8%) cases of HIVAW/low weight and 1,354 (2%) deaths among 62,314 PWH. PWH who experienced HIVAW/low weight had a significantly higher risk of death than those who did not (HR: 1.96; 95% CI: 1.68, 2.27) after adjusting for age, race, ethnicity, and changes in viral load (VL) and Veterans Aging Cohort Study Mortality Index scores over follow-up. Among 4,572 PWH on ART at HIVAW/low weight, 68% were suppressed (VL of <200 copies/mL); subsequent virologic failure was uncommon (7%). Among viremic PWH, 70% and 60% achieved suppression and undetectability (VL of <50 copies/mL), respectively, over follow-up. HIVAW remains a challenge for some PWH. Particular attention needs to be paid to HIVAW/low weight and virologic control to restore health and potentially reduce the risk of death.

Identifying Factors Associated with Discontinuation of Infertility Treatment Prior to Achieving Pregnancy: Results of a Nationwide Survey.

The purpose of this mixed methods, cross-sectional patient survey was to characterize patient experience, to explore the frequency of and reasons for infertility treatment discontinuation and return to infertility treatments. Participants were recruited from United States patient support groups. Participants had received or were receiving ovulation induction (OI) with or without intrauterine insemination (IUI), with or without subsequent in vitro fertilization (IVF), or IVF with no other previous infertility treatment. Live birth was achieved by 62% of participants. Compared with participants treated with OI/IUI only, participants who underwent OI/IUI followed by ≥1 IVF cycle were less likely to consider discontinuing care (64% vs 77%; P = .014) or to discontinue treatment without achieving a pregnancy (40% vs 58%; P = .004). The most commonly cited reasons for treatment discontinuation were financial (62%) and psychological burden/treatment fatigue (58%). Expected versus actual time to pregnancy differed greatly. Continued desire for a child (60%) was the most frequently cited reason for continuing or resuming treatment. Expanded access to treatment, counseling and fostering realistic expectations regarding cumulative time to pregnancy may reduce treatment discontinuation.

Fine-tuning the dose of recombinant human follicle-stimulating hormone alfa to individualize treatment in ovulation induction and ovarian stimulation cycles: a real-world database analysis.

Introduction: Fine-tuning of injectable gonadotropin doses during ovulation induction (OI) or ovarian stimulation (OS) treatment cycles with the aim of using doses low enough to minimize the risk of excessive ovarian response while maintaining optimal efficacy may be facilitated by using an adjustable-dose pen injector. We examined the incidence and magnitude of individualized gonadotropin dose adjustments made during cycles of OI or OS, followed by either timed intercourse or intrauterine insemination, with or without oral medications, and assessed the relationship between patient characteristics and dosing changes using real-world evidence. Methods: This was an observational, retrospective cohort study using electronic medical records from a large US database of fertility centers. Data from patients who had undergone a first recombinant human follicle stimulating hormone alfa (r-hFSH-alfa/follitropin alfa) treated OI/OS cycle followed by timed intercourse or intrauterine insemination between 2015 and 2016 were included. Percentages of OI/OS cycles involving r-hFSH-alfa dose adjustments (in increments of ±12.5 IU or greater) with or without oral medications (clomiphene citrate or letrozole) were analyzed. Results: Of 2,832 OI/OS cycles involving r-hFSH-alfa administration, 74.6% included combination treatment with orals; 25.4% involved r-hFSH-alfa alone. As expected, the starting dose of r-hFSH-alfa was lower for cycles that used r-hFSH-alfa with orals than r-hFSH-alfa only cycles (mean [SD]: 74.2 [39.31] vs 139.3 [115.10] IU). Dose changes occurred in 13.7% of r-hFSH-alfa with orals versus 43.9% of r-hFSH-alfa only cycles. Dose adjustment magnitudes ranged from ±12.5 IU to ±450 IU. The smallest adjustment magnitudes (±12.5 IU and ±25 IU) were used frequently and more often for dose increases than for dose decreases. For r-hFSH-alfa with orals and r-hFSH-alfa only cycles, the smallest adjustments were used in 53.5% and 64.5% of cycles with dose increases and in 35.7% and 46.8% of cycles with dose decreases, respectively. Discussion: In OI/OS cycles followed by timed intercourse or intrauterine insemination, r-hFSH-alfa dose adjustments were frequent. In cycles that included orals, r-hFSH-alfa starting doses were lower and dose changes were fewer than with r-hFSH-alfa alone. Smaller dose adjustments facilitate individualized treatment with the goal of reducing the risks of multiple gestation, cycle cancellation, and ovarian hyperstimulation syndrome.

Definition, Burden, and Predictors of HIV-Associated Wasting and Low Weight in the OPERA Cohort.

We aimed to describe the prevalence, incidence, and predictors of HIV-associated wasting (HIVAW)/low weight among people with HIV (PWH) in the United States. We conducted an observational, clinical cohort analysis, utilizing prospectively collected electronic health record data obtained from the Observational Pharmaco-Epidemiology Research & Analysis (OPERA®) cohort. HIVAW/low weight included a wasting or low body-mass index (BMI)/underweight diagnosis (ICD codes and title search) or BMI <20 kg/m2. Prevalence was estimated among adult PWH in care from 2012 to 2015 and 2016 to 2020. Incidence from January 1, 2016, to October 31, 2021, was estimated using univariate Poisson regression among eligible PWH without prior HIVAW/low weight. Demographic and clinical predictors of incident HIVAW/low weight were included in multivariable logistic regression models, stratified by antiretroviral therapy (ART) experience. The period prevalence of HIVAW/low weight was 12% in both 2012-2015 and 2016-2020. Among 67,119 PWH without any prior HIVAW/low weight, 7% experienced incident HIVAW/low weight a median 64 months from HIV diagnosis. In multivariable regression models, similar predictor patterns were observed among ART-naïve and ART-experienced PWH without any prior HIVAW/low weight: lower odds of HIVAW/low weight with older age, female sex, Black race, and Hispanic ethnicity and higher odds with Medicaid. Notably, there was a dose-response relationship between increasing Veterans Aging Cohort Study Mortality Index scores and incident HIVAW/low weight in both groups. Wasting/low weight remains a challenge for PWH and may be underappreciated by providers. Advanced HIV and comorbidities significantly predict incident HIVAW/low weight. Increasing awareness of HIVAW, especially among frailer PWH, could improve the care of affected PWH.

Impact of adherence to disease modifying therapies on long-term clinical and economic outcomes in multiple sclerosis: A claims analysis of real-world data.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurodegenerative inflammatory disease that requires long-term commitment to treatment for optimal outcomes. A variety of disease-modifying therapies (DMTs) are now available that reduce relapses and delay disease progression in people with MS. However, adherence remains a significant issue, with a variety of mental, physical, and emotional factors contributing to non-adherence. In a large number of studies, non-adherence has been associated with worse clinical outcomes (relapses and disease severity), a higher economic burden, and loss of work productivity. However, many of these studies were short-term (1-2 years) or cross-sectional studies; thus, more data are needed on the long-term clinical and economic impacts of DMT non-adherence. The objective of this study was to determine the longer-term impact of adherence to DMTs on disease activity and healthcare resource utilization (HCRU) in people with MS. The study hypothesis was that non-adherence to DMTs would be associated long-term with worse clinical outcomes and a higher economic burden. METHODS: A retrospective administrative claims analysis of the US MarketScan® Commercial database (2011-2017) in individuals (18-65 years) with MS (based on International Classification of Disease coding) was conducted. Adherence was classified by proportion of days covered (PDC) ≥0.8 and non-adherence by PDC <0.8; sensitivity analyses helped further categorize as moderately (PDC ≥0.6-<0.8) or highly (PDC <0.6) non-adherent. Cohorts were matched using propensity score matching. Time to first relapse, annualized relapse rate (ARR), time to use of assistive devices (cane/walker or wheelchair), and annual HCRU (inpatient, emergency room [ER], outpatient, and MRI visits and costs) were compared between cohorts. RESULTS: 10,248 MS cases were identified; 58% met adherence criteria, and 42% met non-adherence criteria. Mean follow-up from diagnosis or first DMT claim was 5.3 years. Adherent individuals had a longer time to first relapse (hazard ratio [HR] 0.83; 95% confidence interval [CI]: 0.77-0.90; p<0.0001), a lower ARR (0.13 vs. 0.18, respectively; rate ratio [RR] 0.75 [95% CI: 0.71-0.79]; p<0.0001), and longer lag times to cane/walker use (HR 0.79 [95% CI: 0.66-0.94]; p=0.0067) and wheelchair use (HR 0.68 [95% CI: 0.55-0.83]; p=0.0002) than non-adherent individuals. Adherent individuals had fewer annual inpatient and ER visits and lower total costs than those who were non-adherent (p<0.0001). Sensitivity analyses showed that differences in disease activity and HCRU were generally more pronounced between matched adherent and highly non-adherent pairs than between matched adherent and moderately non-adherent pairs. CONCLUSION: Significant differences in MS disease activity and HCRU were observed based on adherence to DMTs. Our study underscores the negative impact of non-adherence to DMTs on long-term clinical and economic outcomes in MS.

Improving Golden Hour Care Coordination: Using Defined Roles to Improve Nurse Confidence and Care Coordination of Neonates Following Admission.

STUDY AIM: To investigate whether use of admission lanyards improves nurse confidence, care coordination, and infant health outcomes during neonatal emergency admissions. METHODS: Admission lanyards that defined team roles, tasks, and responsibilities were evaluated in a mixed-methods, historically controlled, and nonrandomized intervention study. Methods included (i) 81 pre- and postintervention surveys to explore nurse confidence, (ii) 8 postintervention semistructured interviews to elicit nurse perceptions of care coordination and nurse confidence, and (iii) a quantitative comparison of infant care coordination and health outcomes for 71 infant admissions before and 72 during the intervention. RESULTS: Nurse participants reported that using lanyards during neonatal admissions improved clarity of roles and responsibilities, communication, and task delegation, contributing to better admission flow, team leadership, accountability, and improved nurse confidence. Care coordination outcomes showed significantly improved time to stabilization for intervention infants. Radiographies for line placement were performed 14.4 minutes faster, and infants commenced intravenous nutrition 27.7 minutes faster from time of admission. Infant health outcomes remained similar between groups. CONCLUSION: Admission lanyards were associated with improved nurse confidence and care coordination during neonatal emergency admissions, significantly reducing time to stabilization for infants, shifting outcomes closer to the Golden Hour.

Comparative effectiveness of cladribine tablets versus fingolimod in the treatment of highly active multiple sclerosis: A real-world study.

BACKGROUND: Cladribine tablets and fingolimod have similar marketing authorisations in Europe for the treatment of patients with highly active relapsing multiple sclerosis (HA-RMS). In the absence of direct head-to-head studies, real-world data are important to assess the comparative effectiveness of these oral disease-modifying therapies (DMTs). The primary objective of the present study was to compare relapse rates between patients who received either cladribine tablets or fingolimod. METHODS: This multicentre retrospective study conducted in the United Kingdom and Germany assessed non-inferiority in relapse rates of cladribine tablets versus fingolimod in HA-RMS patients over a 12-month period. Eligible patients who initiated treatment with cladribine tablets or fingolimod at least 12 months prior to the screening date were sampled consecutively until the target sample size was reached. Patients were censored at discontinuation of study treatment, commencement of another DMT, death, loss to follow-up, or at 12 months post-baseline, whichever happened earliest. The primary analytic timeframe for physician-confirmed relapse outcomes was the study effectiveness period (nine months of follow-up after an initial 12 weeks of treatment). Propensity score analysis was applied based on the inverse probability of treatment weighting approach. RESULTS: The primary analytic cohort consisted of 1,095 HA-RMS patients: 610 (55.7%) receiving cladribine tablets and 485 (44.3%) receiving fingolimod. Fewer patients discontinued cladribine tablets and/or switched to another DMT compared with fingolimod (0.2% versus 3.5%, respectively). The primary endpoint, adjusted annualised relapse rate (ARR), was 0.10 (95% confidence interval [CI]: 0.07-0.14) for cladribine tablets and 0.14 (95% CI: 0.10-0.20) for fingolimod. The adjusted ARR ratio of cladribine tablets versus fingolimod was 0.68 (95% CI: 0.42-1.11). Given the entire 95% CI was less than the non-inferiority margin of 1.2, cladribine tablets was non-inferior to fingolimod. CONCLUSIONS: In this real-world retrospective cohort study, cladribine tablets demonstrated comparable effectiveness to fingolimod at one year following treatment initiation. The full treatment dosage of cladribine tablets is completed over two years and so these results may be conservative.

Outcomes and Health Care Service Use in Adults 50 Years or Older With and Without Multiple Sclerosis: A 6-Year Observational Analysis.

BACKGROUND: Multiple sclerosis (MS) typically presents in young adulthood. Recent data show the highest prevalence of MS in people aged 55 to 64 years; however, there are limited studies of this population. METHODS: Administrative US claims data from IBM-Truven MarketScan commercial and Medicare databases (2011-2017) were analyzed. People with MS 50 years or older were assigned to the aging MS cohort (n = 10,746). The matched controls were people 50 years or older without MS (n = 10,746). Multivariable models compared outcomes between groups. RESULTS: Infections were more frequent in the aging MS cohort vs matched controls (61% vs 45%; P < .0001); urinary tract, acute upper respiratory tract, and herpes zoster were the most frequent infection types. Malignancy rates were 20% for both groups (P = .8167); skin, breast, and prostate malignancies were the most frequent types. Skilled nursing facilities (aging MS cohort, 12%; matched controls, 3%; P < .0001) and MRI (aging MS cohort, 87%; matched controls, 37%; P < .0001) were used more frequently in the aging MS cohort; brain and spine were the most frequent types of MRI in the aging MS cohort. Time to first cane/walker or wheelchair use was shorter in the aging MS cohort (cane/walker use: HR, 2.1; 95% CI, 1.9-2.3; P < .0001; wheelchair use: HR, 6.9; 95% CI, 6.0-8.1; P < .0001). CONCLUSIONS: In people 50 years or older, measures typically associated with worse health primarily resulted from having MS rather than being a consequence of aging alone.

Effectiveness of recombinant human FSH: recombinant human LH combination treatment versus recombinant human FSH alone for assisted reproductive technology in women aged 35-40 years.

RESEARCH QUESTION: According to real-world data, is recombinant human FSH (r-hFSH) combined with recombinant human LH (r-hLH) or r-hFSH alone more effective for women of advanced maternal age (AMA) in terms of live birth? DESIGN: Non-interventional study comparing the effectiveness of r-hFSH and recombinant r-hLH (2:1 ratio) versus r-hFSH alone for ovarian stimulation during ART treatment in women aged 35-40 years, using real-world data from the Deutsches IVF-Register. RESULTS: Overall clinical pregnancy (29.8%, 95% CI 28.2 to 31.6 versus 27.8%, 95% CI 26.5 to 29.2) and live birth (20.3%, 95% CI 18.7 to 21.8 versus 18.0%, 95% CI 16.6 to 19.4) rates were not significantly different between the combined r-hFSH and r-hLH group and the r-hFSH alone group (P = 0.269 and P = 0.092, respectively). Treatment effect was significantly higher for combined r-hFSH and r-hLH compared with r-hFSH alone for clinical pregnancy (33.1%, 95% CI 31.0 to 35.0 versus 28.5%, 95% CI 26.6 to 30.4; P = 0.001, not adjusted for multiplicity) and live birth (22.5%, 95% CI 20.5 to 24.2 versus 19.4%, 95% CI 17.6 to 20.9; P = 0.014, not adjusted for multiplicity) in a post-hoc analysis of women with five to 14 oocytes retrieved (used as a surrogate for normal ovarian reserve), highlighting the potential benefits of combined r-hFSH and r-hLH for ovarian stimulation in women aged 35-40 years with normal ovarian reserve. CONCLUSIONS: Women of AMA with normal ovarian response benefit from treatment with combined r-hFSH and r-hLH in a 2:1 ratio versus r-hFSH alone in terms of live birth rate. The effectiveness of treatments is best assessed by RCTs; however, real-world data are valuable for examining the effectiveness of fertility treatment, especially among patient groups that are not well represented in clinical trials.

The economic burden of HIV-associated wasting in the era of modern antiretroviral therapy.

BACKGROUND: HIV-associated wasting (HIVAW) is associated with increased morbidity and mortality in people living with HIV (PWH). Evaluating health care resource utilization and cost predictors of HIVAW is important in understanding the overall economic burden of the disease. OBJECTIVE: To evaluate the economic burden and cost predictors associated with HIVAW. METHODS: This analysis of the IBM MarketScan Commercial, Medicare Supplemental, and Medicaid databases included members with a claim for HIV (using International Classification of Diseases, Ninth Revision and Tenth Revision, Clinical Modification codes) between July 2012 and September 2018, with the HIV index date defined as the first HIV diagnosis claim in the dataset. PWH were excluded if they were aged less than 18 years, had any malignancy claim, or had less than 6 months of enrollment data pre-HIV or post-HIV index date. Members were defined as having HIVAW using an algorithm of claims for weight loss-related diagnoses, appetite stimulant or nontestosterone anabolic agents, or enteral/parenteral nutrition at any time post-HIV index. Taking antiretroviral therapy (ART) was defined as having at least 1 pharmacy claim of any ART 12 months post-HIV index. Total all-cause costs were calculated as the sum of payments for hospitalizations, emergency department visits, outpatient visits, and pharmacy use. A multivariate generalized linear model with log-link and γ distribution was used to estimate the impact of HIVAW predictors of total all-cause costs. RESULTS: Among 42,587 members with HIV included in the study (64.6% male; mean age: 44 years; 67.5% insured with Medicaid; and 63.9% taking ART), the overall prevalence of HIVAW was 18.3% during the study period. HIVAW prevalence was 17.9% for those taking ART and 19.1% for those not taking ART. Prevalence by payer type was 7.5% for Commercial ± Medicare Supplemental and 23.5% for Medicaid. Members with HIVAW had more comorbidities and opportunistic infections compared with members without HIVAW. Members with HIVAW were also more than twice as likely to be hospitalized (71.1% vs 32.1%) and had 5 times the number of hospitalizations (1.0 vs 0.2) and twice the number of emergency department visits (3.0 vs 1.3) per year post-index compared with members without HIVAW (P < 0.01). HIVAW was associated with 1.3-times-higher mean annualized total all-cause costs per member (95% CI = 1.26-1.36). CONCLUSIONS: HIVAW remains prevalent despite advances in ART and is associated with additional health care resource utilization and costs. Further research is needed to better understand the relationship between HIVAW and comorbidity burden and ART utilization and payer types. DISCLOSURES: This study was sponsored by EMD Serono, Inc., Rockland, MA, USA (CrossRef Funder ID: 10.13039/100004755). Dr Siddiqui has received consulting and speaking fees from AbbVie, BioFire, Cumberland, EMD Serono, Inc., Rockland, MA, USA, and Merck. Dr Samuel, Ms Hayward, Ms Wirka, Dr Phillips, and Dr Harbour are employees of EMD Serono, Inc., Rockland, MA, USA. Drs Deering and Harshaw are employees of EPI-Q, Inc., which received payment from EMD Serono, Inc., Rockland, MA, USA, for the development and execution of this study.

HIV-associated wasting prevalence in the era of modern antiretroviral therapy.

OBJECTIVE: To understand the prevalence of HIV-associated wasting (HIVAW) in the United States. DESIGN: Medical and pharmacy claims study using IBM MarketScan Commercial, Medicare Supplemental and Medicaid Databases. METHODS: Study period: July 2012-September 2018 (first HIV diagnosis claim = HIV index date). People with HIV (PWH) were excluded if they were aged less than 18 years, had any malignancy claim or had less than 6 months of enrollment data pre or post-HIV index date. HIVAW was defined by proxy using claims for weight loss-related diagnoses, appetite stimulant/nontestosterone anabolic agents or enteral/parenteral nutrition. Prevalence was reported cumulatively, by insurance type and antiretroviral therapy (ART) pharmacy claims (defined as ≥1 pharmacy claim of any ART within 12 months post-HIV index date). Statistical analysis assessed factors potentially associated with HIVAW. RESULTS: The study population comprised 42 587 PWH (64.6% male, mean age 44 years, 67.5% on Medicaid, 63.9% on ART). Cumulative HIVAW prevalence (2012-2018) was 18.3% (n = 7804) for all PWH (17.9% on ART, 19.1% not on ART). HIVAW prevalence by payer was 7.5% for Commercial and Medicare Supplemental and 23.5% for Medicaid. The strongest associations with the likelihood of meeting the definition of HIVAW were for individuals with Medicaid and hospitalization(s) post-HIV index date; race and ART status were not associated. CONCLUSIONS: Findings suggest HIVAW remains prevalent in PWH. ART use was not found to be associated with HIVAW. HIVAW was highest among those with Medicaid coverage or any hospitalization(s). Further research is needed to better understand additional factors associated with and contributing to HIVAW.

Recombinant Human Follicle-Stimulating Hormone Alfa Dose Adjustment in US Clinical Practice: An Observational, Retrospective Analysis of a Real-World Electronic Medical Records Database.

Purpose: To determine the pattern of dose adjustment of recombinant human follicle-stimulating hormone alfa (r-hFSH-alfa) during ovarian stimulation (OS) for assisted reproductive technology (ART) in a real-world setting. Methods: This was an observational, retrospective analysis of data from an electronic de-identified medical records database including 39 clinics in the USA. Women undergoing OS for ART (initiated 2009-2016) with r-hFSH-alfa (Gonal-f® or Gonal-f RFF Redi-ject®) were included. Assessed outcomes were patients' baseline characteristics and dosing characteristics/cycle. Results: Of 33,962 ART cycles, 13,823 (40.7%) underwent dose adjustments: 23.4% with ≥1 dose increase, 25.4% with ≥1 dose decrease, and 8.1% with ≥1 increase and ≥1 decrease. Patients who received dose adjustments were younger (mean [SD] age 34.8 [4.58] years versus 35.9 [4.60] years, p<0.0001) and had lower BMI (25.1 [5.45] kg/m2 versus 25.5 [5.45] kg/m2, p<0.0001) than those who received a constant dose. The proportion of patients with non-normal ovarian reserve was 38.4% for those receiving dose adjustment versus 51.9% for those with a constant dose. The mean (SD) number of dose changes/cycle was 1.61 (0.92) for cycles with any dose adjustment, 1.72 (1.03) for cycles with ≥1 dose increase, 2.77 (1.00) for cycles with ≥1 dose increase and ≥1 decrease (n=2,755), and 1.88 (1.03) for cycles with ≥1 dose decrease. Conclusions: Dose adjustment during OS is common in clinical practice in the USA and occurred more often in younger versus older patients, those with a high versus non-normal ovarian reserve or those with ovulation disorders/polycystic ovary syndrome versus other primary diagnoses of infertility.

Comparison of electronic versus manual witnessing of procedures within the in vitro fertilization laboratory: impact on timing and efficiency.

OBJECTIVE: To evaluate the impact of an electronic witnessing system (EWS) on witnessing standard operating procedures and to assess embryologist perceptions of the EWS. DESIGN: Prospective cohort study. SETTING: Private in vitro fertilization laboratory network. PATIENTS: None. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The time difference between manual and electronic double-witnessing procedures, and embryologist perceptions of the EWS. RESULTS: From 342 witnessing times analyzed (114 EWS, 114 manual, and 114 interruptions to witnesses), the EWS reduced mean (SD) total witnessing time (in seconds) by 91.5 (23.6) for intracytoplasmic sperm injection, 62.0 (17.9) for Day 3 embryo assessment, 58.3 (18.9) for fresh embryo transfer, and 59.4 (13.3) for frozen embryo transfer. This time reduction significantly decreased the overall time required for double-witnessing by 3.1- to 5.2-fold. A survey with 50 embryologists within the laboratory network indicated that most embryologists considered the EWS to improve sample traceability (78.3%), reduce errors in labeling issues (80.4%), and reduce the risk of sample mismatch errors by minimizing disruptions (60.9%). Furthermore, 82.6% thought that visual completion of the EWS dashboard provided peace of mind when leaving work and 84.8% were more confident knowing that all procedures were completed according to the EWS. CONCLUSIONS: An EWS can improve laboratory efficiency by significantly decreasing the time required for witnessing procedures and by minimizing interruptions. The EWS was well perceived by embryologists and laboratory managers and enhanced their confidence and peace of mind with regard to witnessing compliance and safety/accuracy.

Comparative palatability of orally disintegrating tablets (ODTs) of Praziquantel (L-PZQ and Rac-PZQ) versus current PZQ tablet in African children: A randomized, single-blind, crossover study.

BACKGROUND: Praziquantel (PZQ) is currently the only recommended drug for infection and disease caused by the schistosome species that infects humans; however, the current tablet formulation is not suitable for pre-school age children mainly due to its bitterness and the large tablet size. We assessed the palatability of two new orally disintegrating tablet (ODT) formulations of PZQ. METHODOLOGY: This randomized, single-blind, crossover, swill-and-spit palatability study (NCT02315352) was carried out at a single school in Tanzania in children aged 6-11 years old, with or without schistosomiasis infection as this was not part of the assessment. Children were stratified according to age group (6-8 years or 9-11 years) and gender, then randomized to receive each formulation in a pre-specified sequence. Over 2 days, the children assessed the palatability of Levo-Praziquantel (L-PZQ) ODT 150 mg and Racemate Praziquantel (Rac-PZQ) ODT 150 mg disintegrated in the mouth without water on the first day, and L-PZQ and Rac-PZQ dispersed in water and the currently available PZQ 600 mg formulation (PZQ-Cesol) crushed and dispersed in water on the second day. The palatability of each formulation was rated using a 100 mm visual analogue scale (VAS) incorporating a 5-point hedonic scale, immediately after spitting out the test product (VASt = 0 primary outcome) and after 2-5 minutes (VASt = 2-5). PRINCIPAL FINDINGS: In total, 48 children took part in the assessment. Overall, there was no reported difference in the VASt = 0 between the two ODT formulations (p = 0.106) without water. Higher VASt = 0 and VASt = 2-5 scores were reported for L-PZQ ODT compared with Rac-PZQ ODT in older children (p = 0.046 and p = 0.026, respectively). The VASt = 0 and VASt = 2-5 were higher for both ODT formulations compared with the standard formulation (p<0.001 for both time points). No serious adverse events were reported. CONCLUSIONS/SIGNIFICANCE: The new paediatric-friendly formulations dispersed in water were both found to be more palatable than the existing standard formulation of PZQ. There may be gender and age effects on the assessment of palatability. Further research is needed for assessing efficacy and tolerability of the newly ODTs Praziquantel drug in younger children. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT02315352) and in the Pan African Clinical Trials Registry (PACTR201412000959159).

CLICK-MS and MASTER-2 Phase IV trial design: cladribine tablets in suboptimally controlled relapsing multiple sclerosis.

Cladribine tablets 10 mg (3.5 mg/kg cumulative dose over 2 years) are approved for the treatment of relapsing forms of multiple sclerosis (MS), including relapsing-remitting MS and active secondary progressive MS. However, real-world data on cladribine tablets are limited. CLICK-MS and MASTER-2 are single arm, observational, 30-month, Phase IV studies in the US evaluating the effectiveness and safety of cladribine tablets 3.5 mg/kg in patients with relapsing-remitting MS or active secondary progressive MS who had suboptimal response to prior injectable (CLICK-MS), or infusion/oral (MASTER-2) disease-modifying therapy. The primary end point is 24-month annualized relapse rate. Key secondary end points include patient-reported outcomes on quality of life measures, treatment adherence and adverse events. Studies began in 2019 and are expected to be completed in 2023. Trial registration number • CLICK-MS: NCT03933215 (ClinicalTrials.gov) Full title; CLadribine tablets: observational evaluation of effectIveness and patient-reported outcomes in suboptimally Controlled patients previously taKing injectable disease-modifying drugs for relapsing forms of Multiple Sclerosis • MASTER-2: NCT03933202 (ClinicalTrials.gov) Full title; Cladribine tablets: observational evaluation of effectiveness and patient-reported outcomes in suboptiMAlly controlled patientS previously Taking oral or infusion disEase-modifying dRugs for relapsing forms of multiple sclerosis.

Live birth rates, infertility diagnosis, and infertility treatment in women with and without multiple sclerosis: Data from an administrative claims database.

BACKGROUND: Real-world data regarding live birth rates (LBRs) and infertility in women with multiple sclerosis (MS) are lacking. This study compared LBRs, infertility diagnoses, and infertility treatments in women with and without MS. METHODS: Using a retrospective US administrative claims database, patients 18-55 years with MS were matched 1:1 to patients without MS to compare LBRs, infertility diagnoses, and infertility treatments used between cohorts. RESULTS: Overall LBRs were lower in women with MS (n=96,937) versus women without (n=96,937; 5.0% vs 7.0%; p<0.0001). A greater proportion of women with MS than without had a diagnosis of infertility (8.5% vs 8.1%; p=0.0006). Fewer women with MS than without used any infertility treatment (1.0% vs 1.2%; p=0.0002). Among women with or without MS who received infertility treatments, no significant difference was observed in LBRs with oral (32.2% vs 31.5%; p=0.8536) or injectable (44.0% vs 49.3%; p=0.2603) treatment. CONCLUSION: Women with MS had a lower LBR, received more infertility diagnoses, and were less likely to receive infertility treatment than women without MS. There was no difference in LBRs following infertility treatment. Claims-data studies provide valuable exploratory analyses that reflect interactions between patients and the healthcare system.

Creating Health Literate Consumer Resources: Insights from a Professional Development Program.

The Rauemi Atawhai (RA) Program, delivered at Counties Manukau Health by Health Literacy New Zealand (Limited), is a professional development program that aims to develop the capability in health care professionals to recognize and develop health literate, culturally competent health education resources and systems. Local evaluation of this program explored participant learning and barriers to becoming a health literate organization. We found that program participants consolidated their understanding or built a more comprehensive understanding of health literacy. Further, they gained new skills to assist them in developing future consumer resources. However, within the evaluation period, the RA Program had limited influence on the design and refinement of systems for developing, reviewing, disseminating, and evaluating consumer resources for their service, as well as approaches for engaging patients and family in design and review. Significant organizational action is needed to support these changes. Opportunities for leaders and managers to participate in capability building and discussions to create conditions (e.g., resource and authorization) for change in the environments in which staff work are needed. [HLRP: Health Literacy Research and Practice. 2020;4(3):e185-e189.].

Clinical and MRI efficacy of sc IFN ß-1a tiw in patients with relapsing MS appearing to transition to secondary progressive MS: post hoc analyses of PRISMS and SPECTRIMS.

This study evaluated efficacy of subcutaneous (sc) interferon beta-1a (IFN ß-1a) 44 µg 3 × weekly (tiw) in patients appearing to transition from relapsing-remitting multiple sclerosis (RRMS) to secondary progressive MS (SPMS). The PRISMS study included 560 patients with RRMS (EDSS 0-5.0; ≥ 2 relapses in previous 2 years), and the SPECTRIMS study included 618 patients with SPMS (EDSS 3.0-6.5 and ≥ 1-point increase in previous 2 years [≥ 0.5 point if 6.0-6.5]) randomly assigned to sc IFN ß-1a 44 or 22 µg or placebo for 2-3 years, respectively. These post hoc analyses examined five subgroups of MS patients with EDSS 4.0-6.0: PRISMS (n = 59), PRISMS/SPECTRIMS (n = 335), PRISMS/SPECTRIMS with baseline disease activity (n = 195; patients with either ≥ 1 relapse within 2 years before baseline or ≥ 1 gadolinium-enhancing lesion at baseline), PRISMS/SPECTRIMS without baseline disease activity (n = 140), and PRISMS/SPECTRIMS with disease activity during the study (n = 202). In the PRISMS and PRISMS/SPECTRIMS subgroups, sc IFN ß-1a delayed disability progression, although no significant effect was observed in PRISMS/SPECTRIMS subgroups with activity at baseline or activity during the study (regardless of baseline activity). In the PRISMS/SPECTRIMS subgroup, over year 1 (0-1) and 2 (0-2), sc IFN ß-1a 44 µg tiw significantly reduced annualized relapse rate (p ≤ 0.001), and relapse risk (p < 0.05) versus placebo. Similar results were seen for the PRISMS/SPECTRIMS with baseline disease activity subgroup. Subcutaneous IFN ß-1a reduced T2 burden of disease and active T2 lesions in the PRISMS/SPECTRIMS subgroups overall, with and without baseline activity. In conclusion, these post hoc analyses indicate that effects of sc IFN ß-1a 44 µg tiw on clinical/MRI endpoints are preserved in a patient subgroup appearing to transition between RRMS and SPMS.

Evaluation of an embryology and genetic testing patient counseling education intervention for reproductive endocrinology nurses.

OBJECTIVE: To study the impact of an educational program on the knowledge base of reproductive endocrinology nurses on embryology and genetics topics to determine both improvement in knowledge and confidence in the nurses' ability to counsel patients on such topics. DESIGN: Interventional study. SETTING: Clinics. PATIENT(S): None; subjects were reproductive endocrinology nurses. INTERVENTION(S): Preintervention knowledge self-efficacy test, educational exposure, and 2-week follow-up testing. MAIN OUTCOME MEASURE(S): Knowledge test scores, self-efficacy scores. RESULT(S): Nurses, regardless of educational attainment, demonstrated statistically significant increases in knowledge of both embryology and genetics, which was retained at least 2 weeks after the educational intervention. Furthermore, nurse self-efficacy increased after intervention, and qualitative data support the desire for increased educational opportunities. CONCLUSION(S): Nurses benefit from focused educational efforts, resulting in improved knowledge in embryology and genetics. This improved knowledge base resulted in improved nurse confidence in patient education.

Subcutaneous Interferon-ß1a Does Not Increase the Risk of Stroke in Patients with Multiple Sclerosis: Analysis of Pooled Clinical Trials and Post-Marketing Surveillance.

INTRODUCTION: Previous studies suggest that multiple sclerosis (MS) patients have a greater stroke risk than the general population but there is limited evidence of stroke risk in patients receiving disease-modifying treatment. We assessed stroke risk in MS patients treated with subcutaneous interferon-ß1a (sc IFN-ß1a) using pooled data from clinical trials and post-marketing surveillance. METHODS: Seventeen phase II-IV Merck KGaA-sponsored trials of sc IFN-ß1a were assessed to estimate the stroke incidence rate (IR) and IR ratio (IRR) per 100 patient-years (PY), and associated 95% confidence intervals (CI). The association of treatment duration with stroke was assessed through a Cox model. IR, IRR, and hazard ratio (HR) were adjusted by age, sex, presence of any comorbidity, and MS duration. Individual case safety reports were retrieved from the Global Patient Safety Database. The reporting rates of stroke were calculated and classified as medically confirmed or non-medically confirmed according to the source of each report. RESULTS: In 17 clinical trials, 4412 patients were treated with sc IFN-ß1a for a total of 10,622 PY and 1055 patients with placebo for 2005 PY. The IR/100 PY (95% CI) of stroke was 0.025 (0.004, 0.150) in sc IFN-ß1a patients and 0.051 (0.008, 0.349) in placebo patients. The IRR for sc IFN-ß1a vs placebo was 0.486 (0.238, 0.995) and the HR was 0.496 (0.235, 1.043) for time to stroke-related event for sc IFN-ß1a treatment at any dose compared with placebo. Among sc IFN-ß1a patients, the IRR in those treated for < 2 years was 0.602 (0.159, 2.277) and for ≥ 2 years 0.469 (0.196, 1.124). Analysis of the safety database showed that the overall reporting rate for stroke was 13.286/10,000 PY. CONCLUSION: Safety data from both clinical trial and post-marketing settings indicate that treatment with sc IFN-ß1a does not increase stroke risk in patients with MS. FUNDING: Merck KGaA, Darmstadt, Germany.