Young Adult

Omalizumab for the Treatment of Multiple Food Allergies

Alex Haga — Fri, 05 Apr 2024 01:11:55 +0000

Date Added:

April 4, 2024

Journal/Publication:

New England Journal of Medicine

Publication Date:

February 25, 2024

Issue:

Volume:

390

Pages:

889-899

URL:

Omalizumab for the Treatment of Multiple Food Allergies

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa2312382

PMID (1):

38407394

An apparently effective (and probably very expensive) treatment for children with food allergies. James W. Mold, MD, MPH

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BACKGROUND
Food allergies are common and are associated with substantial morbidity; the only approved treatment is oral immunotherapy for peanut allergy.
METHODS
In this trial, we assessed whether omalizumab, a monoclonal anti-IgE antibody, would be effective and safe as monotherapy in patients with multiple food allergies. Persons 1 to 55 years of age who were allergic to peanuts and at least two other trial-specified foods (cashew, milk, egg, walnut, wheat, and hazelnut) were screened. Inclusion required a reaction to a food challenge of 100 mg or less of peanut protein and 300 mg or less of the two other foods. Participants were randomly assigned, in a 2:1 ratio, to receive omalizumab or placebo administered subcutaneously (with the dose based on weight and IgE levels) every 2 to 4 weeks for 16 to 20 weeks, after which the challenges were repeated. The primary end point was ingestion of peanut protein in a single dose of 600 mg or more without dose-limiting symptoms. The three key secondary end points were the consumption of cashew, of milk, and of egg in single doses of at least 1000 mg each without dose-limiting symptoms. The first 60 participants (59 of whom were children or adolescents) who completed this first stage were enrolled in a 24-week open-label extension.

RESULTS
Of the 462 persons who were screened, 180 underwent randomization. The analysis population consisted of the 177 children and adolescents (1 to 17 years of age). A total of 79 of the 118 participants (67%) receiving omalizumab met the primary end-point criteria, as compared with 4 of the 59 participants (7%) receiving placebo (P<0.001). Results for the key secondary end points were consistent with those of the primary end point (cashew, 41% vs. 3%; milk, 66% vs. 10%; egg, 67% vs. 0%; P<0.001 for all comparisons). Safety end points did not differ between the groups, aside from more injection-site reactions in the omalizumab group.
CONCLUSIONS
In persons as young as 1 year of age with multiple food allergies, omalizumab treatment for 16 weeks was superior to placebo in increasing the reaction threshold for peanut and other common food allergens. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT03881696.)

Author/s:

Wood RA, Togias A, Sicherer SH, Shreffler WG, Kim EH, Jones SM

Recommended Adult Immunization Schedule, United States, 2022

Saige Blanchard — Mon, 28 Feb 2022 06:00:00 +0000

Date Added:

February 28, 2022

Journal/Publication:

Annals of Internal Medicine

Publisher:

American College of Physicians

Publication Date:

February 18, 2022

URL:

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

https://doi.org/10.7326/M22-0036

Keywords

MeSH

Immunization Schedule

Advisory Committees

This is a summary of the 2022 CDC adult immunization recommendations. James W. Mold, MD, MPH

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In November 2021, the Advisory Committee on Immunization Practices (ACIP) voted to approve the Recommended Adult Immunization Schedule for Ages 19 Years or Older, United States, 2022. The 2022 adult immunization schedule, available at www.cdc.gov/vaccines/schedules/hcp/imz/adult.html, summarizes ACIP recommendations in the cover page, tables, notes, and appendix (Figure). The appendix lists the contraindications and precautions for all routinely recommended vaccines on the adult immunization schedule (Figure). The full ACIP recommendations for each vaccine are available at www.cdc.gov/vaccines/hcp/acip-recs/index.html. The 2022 schedule has also been approved by the director of the Centers for Disease Control and Prevention (CDC) and by the American College of Physicians (www.acponline.org), the American Academy of Family Physicians (www.aafp.org), the American College of Obstetricians and Gynecologists (www.acog.org), the American College of Nurse-Midwives (www.midwife.org), the American Academy of Physician Associates (www.aapa.org), and the Society for Healthcare Epidemiology of America (www.shea-online.org).

Author/s:

N., Wodi, A. P., Bernstein, H., Ault, K. A.

Extended follow-up of local steroid injection for carpal tunnel syndrome: A randomized clinical trial

Bethie Seay — Tue, 26 Oct 2021 05:00:00 +0000

Date Added:

October 26, 2021

Journal/Publication:

JAMA

Publication Date:

October 22, 2021

Issue:

Volume:

Pages:

e2130753

Type:

Clinical Research Results

DOI (1):

10.1001/jamanetworkopen.2021.30753

MeSH

carpal tunnel syndrome

double-blind method

Shoulder

Kaplan-Meier Estimate

Anti-Inflammatory Agents

Carpal tunnel injections with methylprednisolone appear to reduce or delay surgery but symptoms are no different at 5 years than with a placebo injection.

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Importance Local steroid injection is commonly used in treating patients with idiopathic carpal tunnel syndrome, but evidence regarding long-term efficacy is lacking.

Objective To assess the long-term treatment effects of local steroid injection for carpal tunnel syndrome.

Design, Setting, and Participants This exploratory 5-year extended follow-up of a double-blind, placebo-controlled randomized clinical trial was conducted from November 2008 to March 2012 at a university hospital orthopedic department. Participants included patients aged 22 to 69 years with primary idiopathic carpal tunnel syndrome and no prior treatment with local steroid injections. Data were analyzed from May 2018 to August 2018.

Interventions Patients were randomized to injection of 80 mg methylprednisolone, 40 mg methylprednisolone, or saline.

Main Outcomes and Measures The coprimary outcomes were the symptom severity score and rate of subsequent carpal tunnel release surgery on the study hand at 5 years. Secondary outcomes were time from injection to surgical treatment, SF-36 bodily pain score, and score on the 11-item disabilities of the arm, shoulder, and hand scale.

Results A total of 111 participants (mean [SD] age at follow-up, 52.9 [11.6] years; 81 [73.0%] women and 30 [27.0%] men) were randomized, with 37 in the 80 mg methylprednisolone group, 37 in the 40 mg methylprednisolone group, and 37 in the saline placebo group. Complete 5-year follow-up data were obtained from all 111 participants with no dropouts (100% follow-up). At baseline, mean (SD) symptom severity scores were 2.93 (0.85) in the 80 mg methylprednisolone group, 3.13 (0.70) in the 40 mg methylprednisolone group, and 3.18 (0.75) in the placebo group, and at the 5-year follow up, mean (SD) symptom severity scores were 1.51 (0.66) in the 80 mg methylprednisolone group, 1.59 (0.63) in the 40 mg methylprednisolone group, and 1.67 (0.74) in the placebo group. Compared with placebo, there was no significant difference in mean change in symptom severity score from baseline to 5 years for the 80 mg methylprednisolone group (0.14 [95%CI, −0.17 to 0.45]) or the 40 mg methylprednisolone group (0.12 [95%CI, −0.19 to 0.43]). After injection, subsequent surgical treatment on the study hand was performed in 31 participants (83.8%) in the 80 mg methylprednisolone group, 34 participants (91.9%) in the 40 mg methylprednisolone group, and 36 participants (97.3%) in the placebo group; the number of participants who underwent surgical treatment between the 1-year and 5-year follow-ups was 4 participants (10.8%) in the 80 mg methylprednisolone group, 4 participants (10.8%) in the 40 mg methylprednisolone group, and 2 participants (5.4%) in the placebo group. All surgical procedures were conducted while participants and investigators were blinded to type of injection received. The mean (SD) time from injection to surgery was 180 (121) days in the 80 mg methylprednisolone group, 185 (125) days in the 40 mg methylprednisolone group, and 121 (88) days in the placebo group. Kaplan-Meier survival curves showed statistically significant difference in time to surgical treatment (log-rank test: 80 mg methylprednisolone vs placebo, P = .002 ; 40 mg methylprednisolone vs placebo, P = .02; methylprednisolone 80 mg vs 40 mg, P = .37).

Conclusions and Relevance These findings suggest that in idiopathic carpal tunnel syndrome, local methylprednisolone injection resulted in statistically significant reduction in surgery rates and delay in need for surgery.

Trial Registration ClinicalTrials.gov Identifiers: NCT00806871 and NCT02652390

Author/s:

Hofer, M., Ranstam, J., Atroshi, I.

Incidence, co-occurrence, and evolution of long-COVID features: A 6-month retrospective cohort study of 273,618 survivors of COVID-19

Bethie Seay — Tue, 05 Oct 2021 05:00:00 +0000

Date Added:

October 5, 2021

Journal/Publication:

PLOS Medicine

Publication Date:

September 28, 2021

Issue:

Volume:

Type:

Clinical Research Results

DOI (1):

10.1371/journal.pmed.1003773

An assessment of the epidemiology and characteristics of long COVID syndrome from nearly 275,000 linked electronic records.

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Background
Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim of this study is to address these issues.

Methods and findings
We conducted a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/breathlessness, fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression). Their co-occurrence network was also analyzed. Comparison with a propensity score–matched cohort of patients diagnosed with influenza during the same time period was achieved using Kaplan–Meier analysis and the Cox proportional hazard model. The incidence of atopic dermatitis was used as a negative control.

Among COVID-19 survivors (mean [SD] age: 46.3 [19.8], 55.6% female), 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza (with an overall excess incidence of 16.60% and hazard ratios between 1.44 and 2.04, all p < 0.001), co-occurred more commonly, and formed a more interconnected network. Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity. Besides the limitations inherent to EHR data, limitations of this study include that (i) the findings do not generalize to patients who have had COVID-19 but were not diagnosed, nor to patients who do not seek or receive medical attention when experiencing symptoms of long-COVID; (ii) the findings say nothing about the persistence of the clinical features; and (iii) the difference between cohorts might be affected by one cohort seeking or receiving more medical attention for their symptoms.

Conclusions
Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.

Author summary
Why was this study done?
Long-COVID has been described in recent studies. But we do not know the risk of developing features of this condition and how it is affected by factors such as age, sex, or severity of infection.
We do not know if the risk of having features of long-COVID is more likely after Coronavirus Disease 2019 (COVID-19) than after influenza.
We do not know about the extent to which different features of long-COVID co-occur.
What did the researchers do and find?
This research used data from electronic health records of 273,618 patients diagnosed with COVID-19 and estimated the risk of having long-COVID features in the 6 months after a diagnosis of COVID-19. It compared the risk of long-COVID features in different groups within the population and also compared the risk to that after influenza.
The research found that over 1 in 3 patients had one or more features of long-COVID recorded between 3 and 6 months after a diagnosis of COVID-19. This was significantly higher than after influenza.
For 2 in 5 of the patients who had long-COVID features in the 3- to 6-month period, they had no record of any such feature in the previous 3 months.
The risk of long-COVID features was higher in patients who had more severe COVID-19 illness, and slightly higher among females and young adults. White and non-white patients were equally affected.
What do these findings mean?
Knowing the risk of long-COVID features helps in planning the relevant healthcare service provision.
The fact that the risk is higher after COVID-19 than after influenza suggests that their origin might, in part, directly involve infection with SARS-CoV-2 and is not just a general consequence of viral infection. This might help in developing effective treatments against long-COVID.
The findings in the subgroups, and the fact that the majority of patients who have features of long-COVID in the 3- to 6-month period already had symptoms in the first 3 months, may help in identifying those at greatest risk.

Author/s:

Taquet, M., Dercon, Q., Luciano, S., Geddes, J. R., Husain, M., Harrison, P. J.

Trajectories of Opioid Use Following First Opioid Prescription in Opioid-Naive Youths and Young Adults

Devin Evans — Thu, 29 Apr 2021 05:00:00 +0000

Date Added:

May 19, 2021

Journal/Publication:

Journal of the American Medical Association Network Open

Publication Date:

April 1, 2021

Issue:

Volume:

URL:

Trajectories of Opioid Use Following First Opioid Prescription in Opioid-Naive Youths and Young Adults

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2021.4552

Keywords

PMID (1):

33885777

MeSH

opioid-related disorders

prescriptions

Very interesting study showing two distinct patterns of opioid use behaviors among adolescents after being given a first opioid prescription for pain. Predictors of subsequent misuse were identified. James W. Mold, MD, MPH

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Importance: Although prescription opioids are the most common way adolescents and young adults initiate opioid use, many studies examine population-level risks following the first opioid prescription. There is currently a lack of understanding regarding how patterns of opioid prescribing following the first opioid exposure may be associated with long-term risks.

Objective: To identify distinct patterns of opioid prescribing following the first prescription using group-based trajectory modeling and examine the patient-, clinician-, and prescription-level factors that may be associated with trajectory membership during the first year.

Design, setting, and participants: This cohort study examined Pennsylvania Medicaid enrollees' claims data from 2010 through 2016. Participants were aged 10 to 21 years at time of first opioid prescription. Data analysis was performed in March 2020.

Main outcomes and measures: This study used group-based trajectory modeling and defined trajectory status by opioid fill.

Results: Among the 189 477 youths who received an initial opioid prescription, 107 562 were female (56.8%), 81 915 were non-Latinx White (59.6%), and the median age was 16.9 (interquartile range [IQR], 14.6-18.8) years. During the subsequent year, 47 477 (25.1%) received at least one additional prescription. Among the models considered, the 2-group trajectory model had the best fit. Of those in the high-risk trajectory, 65.3% (n = 901) filled opioid prescriptions at month 12, in contrast to 13.1% (n = 6031) in the low-risk trajectory. Median age among the high-risk trajectory was 19.0 years (IQR, 17.1-20.0 years) compared with the low-risk trajectory (17.8 years [IQR, 15.8-19.4 years]). The high-risk trajectory received more potent prescriptions compared with the low-risk trajectory (median dosage of the index month for high-risk trajectory group: 10.0 MME/d [IQR, 5.0-21.2 MME/d] vs the low-risk trajectory group: 4.7 MME/d [IQR, 2.5-7.8 MME/d]; P < .001). The trajectories showed persistent differences with more youths in the high-risk trajectory going on to receive a diagnosis of opioid use disorder (30.0%; n = 412) compared with the low-risk group (10.1%; n = 4638) (P < .001).

Conclusions and relevance: This study's results identified 2 trajectories associated with elevated risk for persistent opioid receipt within 12 months following first opioid prescription. The high-risk trajectory was characterized by older age at time of first prescription, and longer and more potent first prescriptions. These findings suggest even short and low-dose opioid prescriptions can be associated with risks of persistent use for youths.

Author/s:

Wilson, J.D., Zbebe, K.Z., Kraemer, K., Liebschutz, J., Merlin, J., Miller, E., D., Donohue, J.

Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 2020

Brian Desmarais — Wed, 29 Jul 2020 15:21:15 +0000

Date Added:

July 29, 2020

Publisher:

Centers for Disease Control and Prevention

Publication Date:

July 24, 2020

URL:

Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network — United States, March–June 2020

Type:

Clinical Research Results

Format:

Article

DOI (1):

http://dx.doi.org/10.15585/mmwr.mm6930e1

MeSH

COVID-19

public health

outpatients

severe acute respiratory syndrome coronavirus 2

Severe Acute Respiratory Syndrome

Public Health Practice

Telephone

Surveys and Questionnaires

Young Adult

Adults

It often takes a long time to recover from COVID-19. James W. Mold, MD, MPH

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Summary

What is already known about this topic?

Relatively little is known about the clinical course of COVID-19 and return to baseline health for persons with milder, outpatient illness.

What is added by this report?

In a multistate telephone survey of symptomatic adults who had a positive outpatient test result for SARS-CoV-2 infection, 35% had not returned to their usual state of health when interviewed 2–3 weeks after testing. Among persons aged 18–34 years with no chronic medical conditions, one in five had not returned to their usual state of health.

What are the implications for public health practice?

COVID-19 can result in prolonged illness, even among young adults without underlying chronic medical conditions. Effective public health messaging targeting these groups is warranted.

Author/s:

Tenforde, M.W., Kim, S.S., Lindsell, C.J., Rose, E.B.

Handgun Ownership and Suicide in California

Brian Desmarais — Thu, 04 Jun 2020 19:59:09 +0000

Date Added:

June 4, 2020

Journal/Publication:

New England Journal of Medicine

Publication Date:

June 4, 2020

Volume:

382

Pages:

2220-2229

URL:

Handgun Ownership and Suicide in California

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMsa1916744

Keywords

MeSH

Proportional Hazards Models

Ethnic Groups

I know it isn’t always easy to inquire about gun ownership in Oklahoma. However, if the goal is to prevent premature death, you should certainly ask patients who are depressed. James W. Mold, MD, MPH

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BACKGROUND

Research has consistently identified firearm availability as a risk factor for suicide. However, existing studies are relatively small in scale, estimates vary widely, and no study appears to have tracked risks from commencement of firearm ownership.

METHODS

We identified handgun acquisitions and deaths in a cohort of 26.3 million male and female residents of California, 21 years old or older, who had not previously acquired handguns. Cohort members were followed for up to 12 years 2 months (from October 18, 2004, to December 31, 2016). We used survival analysis to estimate the relationship between handgun ownership and both all-cause mortality and suicide (by firearm and by other methods) among men and women. The analysis allowed the baseline hazard to vary according to neighborhood and was adjusted for age, race and ethnic group, and ownership of long guns (i.e., rifles or shotguns).

RESULTS

A total of 676,425 cohort members acquired one or more handguns, and 1,457,981 died; 17,894 died by suicide, of which 6691 were suicides by firearm. Rates of suicide by any method were higher among handgun owners, with an adjusted hazard ratio of 3.34 for all male owners as compared with male nonowners (95% confidence interval [CI], 3.13 to 3.56) and 7.16 for female owners as compared with female nonowners (95% CI, 6.22 to 8.24). These rates were driven by much higher rates of suicide by firearm among both male and female handgun owners, with a hazard ratio of 7.82 for men (95% CI, 7.26 to 8.43) and 35.15 for women (95% CI, 29.56 to 41.79). Handgun owners did not have higher rates of suicide by other methods or higher all-cause mortality. The risk of suicide by firearm among handgun owners peaked immediately after the first acquisition, but 52% of all suicides by firearm among handgun owners occurred more than 1 year after acquisition.

CONCLUSIONS

Handgun ownership is associated with a greatly elevated and enduring risk of suicide by firearm. (Funded by the Fund for a Safer Future and others.)

Author/s:

Studdert, D.M., Zhang, Y., Swanson, S.A., Prince, L., Rodden J.A., Holsinger, E.E., Wintemute, G.J., Miller, M., Spittal, M.J.

Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis

Brian Desmarais — Wed, 03 Jun 2020 14:42:13 +0000

Date Added:

June 3, 2020

Journal/Publication:

New England Journal of Medicine

Publication Date:

May 14, 2020

Issue:

Volume:

382

Pages:

1906-1915

URL:

Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1915254

MeSH

Lactobacillus crispatus

Vaginosis, Bacterial

Societies, Medical

Administration, Intravaginal

risk factors

random allocation

Intention to Treat Analysis

follow-up studies

double-blind method

Confidence Intervals

anti-bacterial agents

incidence

Odds Ratio

RPR Commentary: This RCT suggest that intravaginal Lactin V (a probiotic) delayed recurrence of bacterial vaginosis in women following treatment with metronidazole. James W. Mold, MD, MPH

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Abstract

Background: Bacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence suggests the need for new treatments to prevent recurrent bacterial vaginosis.

Methods: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial to evaluate the ability of Lactobacillus crispatus CTV-05 (Lactin-V) to prevent the recurrence of bacterial vaginosis. Women 18 to 45 years of age who had received a diagnosis of bacterial vaginosis and who had completed a course of vaginal metronidazole gel as part of the eligibility requirements were randomly assigned, in a 2:1 ratio, to receive vaginally administered Lactin-V or placebo for 11 weeks; follow-up occurred through week 24. The primary outcome was the percentage of women who had a recurrence of bacterial vaginosis by week 12.

Results: A total of 228 women underwent randomization: 152 to the Lactin-V group and 76 to the placebo group; of these participants, 88% in the Lactin-V group and 84% in the placebo group could be evaluated for the primary outcome. In the intention-to-treat population, recurrence of bacterial vaginosis by week 12 occurred in 46 participants (30%) in the Lactin-V group and in 34 participants (45%) in the placebo group (risk ratio after multiple imputation for missing responses, 0.66; 95% confidence interval [CI], 0.44 to 0.87; P = 0.01). The risk ratio for recurrence by week 24 (also calculated with multiple imputation for missing responses) was 0.73 (95% CI, 0.54 to 0.92). At the 12-week visit, L. crispatus CTV-05 was detected in 79% of participants in the Lactin-V group. The percentage of participants who had at least one adverse event related to Lactin-V or placebo by week 24 did not differ significantly between the groups. The percentage of participants with local or systemic adverse events was similar in the two groups.

Conclusions: The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02766023.).

Author/s:

Cohen, C.R., Wierzbicki, C.R., French, A.L., Morris, S., Newmann, S., Reno, H., Green, L., Miller, S., Powell, J., Parks, T., Hemmerling, S.

Hepatitis C Virus Infection in Adolescents and Adults: Screening

Brian Desmarais — Tue, 03 Mar 2020 14:44:41 +0000

Date Added:

March 3, 2020

Publisher:

U.S. Preventive Services Task Force

Publication Date:

March 1, 2020

URL:

Hepatitis C Virus Infection in Adolescents and Adults: Screening

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Web Page

MeSH

The USPSTF is now recommending that you screen all adults between age 18 and 79 for hepatitis C. James W. Mold, MD, MPH

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Osteoporosis Screening in Younger Postmenopausal Women

Brian Desmarais — Sat, 11 Jan 2020 20:19:49 +0000

Date Added:

January 11, 2020

Journal/Publication:

Journal of the American Medical Association

Publication Date:

January 9, 2020

URL:

Osteoporosis Screening in Younger Postmenopausal Women

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

doi:10.1001/jama.2019.18343

Keywords

MeSH

osteoporotic fractures

This is a nice review of when to consider screening for osteoporosis in postmenopausal women younger than 65. James W. Mold, MD, MPH

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Osteoporotic fractures, especially hip fractures, are associated with mobility limitations, chronic disability, loss of independence, and reduced quality of life.

Several randomized trials have demonstrated the benefit of drug treatment in reducing clinical fractures among postmenopausal women with existing vertebral fractures or bone mineral density (BMD) T-scores of −2.5 or lower and among adults aged 50 years and older with recent hip fracture.

Thus, osteoporosis in the clinical setting should be diagnosed in patients with a history of hip or clinical vertebral fracture not due to excessive trauma, those with existing radiographic vertebral fractures, and those with a BMD T-score of −2.5 or lower at the hip (femoral neck or total hip) or lumbar spine. In the absence of a history of hip or vertebral fracture, osteoporosis screening is aimed at identifying individuals with a BMD T-score of −2.5 or lower because those individuals may be candidates for osteoporosis pharmacotherapy. The BMD T-score quantifies the difference (expressed in standard deviations) between a patient’s BMD and the average BMD of young adult white women (reference group).

Author/s:

Crandall, C.J., Ensrud, Kristine E.

Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents

Tracy Ashby — Mon, 03 Dec 2018 06:00:00 +0000

Date Added:

October 30, 2019

Journal/Publication:

The New England Journal of Medicine

Publisher:

Massachusetts Medical Society

Publication Date:

September 6, 2018

Issue:

Volume:

379

Pages:

913-923

URL:

Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1056/NEJMoa1716197

Keywords

baloxavir marboxil

oseltamivir

influenza

PMID (1):

30184455

MeSH

adolescent

Adult

Antiviral Agents/administration & dosage

Antiviral Agents/adverse effects

Antiviral Agents/therapeutic use

child

double-blind method

Endonucleases/antagonists & inhibitors

Intention to Treat Analysis

Kaplan-Meier Estimate

male

Middle Aged

oseltamivir/therapeutic use

Oxazines/administration & dosage

Oxazines/adverse effects

Pyridines/administration & dosage

Pyridines/adverse effects

Thiepins/admistration & dosage

Thiepins/adverse effects

Triazines/administration & dosage

Triazines/adverse effects

viral load

Virus Replication/drug effects

Young Adult

These RCTs of the new anti-viral agent, baloxavir marboxil (Zofluza), found that, when given within 48 hours of onset of symptoms, it relieves symptoms one day sooner than placebo (same as Tamiflu). Viral shedding is reduced more effectively though. Resistance appears to develop quickly. The single-dose treatment costs about $150. James W. Mold, MD, MPH

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BACKGROUND:

Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.

METHODS:

We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.

RESULTS:

In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.

CONCLUSIONS:

Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).

Author/s:

Hayden, Frederick G., Sugaya, Norio, Hirotsu, Nobuo, Lee, Nelson, de Jong, Menno D., Hurt, Aeron C., Ishida, Tadashi, Sekino, Hisakuni, Yamada, Kota, Portsmouth, Simon, Kawaguchi, Keiko, Shishido, Takao, Arai, Masatsugu, Tsuchiya, Kenji, Uehara, Takeki, Watanabe, Akira, Baloxavir Marboxil Investigators Group