Carbon Chemist

Tag: Placebo

  • Monoclonal antibody Prasinezumab shows promise in slowing rapid Parkinson’s progression

    Monoclonal antibody Prasinezumab shows promise in slowing rapid Parkinson’s progression

    [ad_1]

    In a recent study published in the journal Nature Medicine, a large, international team of researchers conducted an exploratory analysis to evaluate whether the monoclonal antibody prasinezumab, which had previously been observed to be effective in slowing the progression of motor-associated signs of Parkinson’s disease, did indeed show benefits in subgroups of Parkinson’s disease patients with faster progression of motor degeneration.

    Study: Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease. Image Credit: Naeblys / ShutterstockStudy: Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease. Image Credit: Naeblys / Shutterstock

    Background

    A hallmark of Parkinson’s disease is the aggregation of α-synuclein, which is thought to propagate between neurons and contribute to the pathogenesis of Parkinson’s disease. One of the first therapeutic options to target the aggregated α-synuclein was the monoclonal antibody prasinezumab, which was investigated in phase II clinical trials among patients with early-stage Parkinson’s disease who were part of the PASADENA study.

    The primary endpoint of the phase II trials of the PASADENA study was the Movement Disorder Society Unified Parkinson’s Disease Rating Scale or MDS-UPDRS score. Although the monoclonal antibody was not found to be effective along all the parameters of the MDS-UPDRS, compared to individuals treated with placebo, those who received prasinezumab showed slower progression of motor-associated degeneration. Furthermore, the team also believed that the MDS-UPDRS subscales are unlikely to show changes over short observation periods such as a year.

    About the study

    In the present study, the team examined the impact of prasinezumab on slowing motor degeneration progression in subgroups of Parkinson’s patients who had the rapidly progressing form of the disease. Given that MDS-UPDRS subscales might not show short-term changes associated with treatment, observing subgroups with the rapidly progressing form of Parkinson’s disease could help in improving the signal-to-noise ratio and reveal potential effects of the monoclonal antibody treatment.

    The PASADENA study consisted of three treatments — placebo, 1,500 mg prasinezumab, and 4,500 mg prasinezumab. The patients were randomly assigned to the three groups after being stratified by age (above or below 60), sex, and monoamine oxidase B inhibitor use. Patients using other symptomatic Parkinson’s disease medications, such as dopamine agonists or levodopa at baseline, were excluded. In cases where the use of these medications was considered imperative, the MDS-UPDRS scores were calculated before the initiation of treatment.

    The present study examined the impact of prasinezumab among patients who were on stable doses of monoamine oxidase B inhibitors at baseline and who exhibited other indicators of faster disease progression. The analyses of the six primary prespecified subpopulations included in phases I and II of the PASADENA study only included the results of four subpopulations.

    The subpopulations were based on the use of monoamine oxidase B inhibitors, stage 2 or Hoehn and Yahr stage versus stage 1 Parkinson’s disease, those with and without REM or rapid eye movement sleep behavior disorder, and those with diffuse malignant phenotype versus nondiffuse malignant phenotype.

    The analysis was also stratified along six exploratory subpopulations based on age, sex, duration of disease, age at diagnosis, and motor subphenotypes such as tremor dominant versus akinetic rigid or postural instability gait dysfunction. Furthermore, since previous studies reported no dose response, the two treatment groups consisting of 1,500 mg and 4,500 mg prasinezumab were pooled for the analysis.

    Results

    The findings suggested that prasinezumab was more effective in slowing the progression of motor signs in Parkinson’s disease patients with the rapidly progressing form of the disease. The subpopulation analyses revealed that patients with diffuse malignant phenotypes, or those who were using monoamine oxidase B inhibitors at baseline, which are indicators of rapid disease progression, showed slower signs of motor-associated degeneration compared to the patients with phenotypes that did not indicate rapid progression of Parkinson’s disease.

    The MDS-UPDRS part III score, which corresponds to clinician-rated motor signs, showed a slower increase or worsening of degeneration in the patients treated with prasinezumab than in those treated with a placebo. Parts I and II of the MDS-UPDRS score correspond to patient-reported motor and nonmotor signs, respectively.

    The researchers believe that since the data indicated a faster progression along MDS-UPDRS part III compared to parts I and II, part III or clinician-rated motor signs might precede parts I and II changes. These findings also indicate that more extended observation periods are required to assess the potential effect of treatments such as prasinezumab accurately.

    Conclusions

    Overall, the results suggested that the monoclonal antibody prasinezumab could potentially be used to slow the progression of motor-associated degeneration in patients with the rapidly progressing form of Parkinson’s disease. Furthermore, more extended observation periods are required to observe the impact of prasinezumab treatment in patients with the slowly progressing form of the disease. Moreover, additional randomized clinical trials need to validate these findings further.

    Journal reference:

    • Pagano, G., Taylor, K. I., Cabrera, A., Simuni, T., Marek, K., Postuma, R. B., Pavese, N., Stocchi, F., Brockmann, K., Svoboda, H., Trundell, D., Monnet, A., Doody, R., Fontoura, P., Kerchner, G. A., Brundin, P., Nikolcheva, T., Bonni, A., PASADENA Investigators, & Prasinezumab Study Group. (2024). Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson’s disease. Nature Medicine. DOI: 10.1038/s4159102402886y, https://www.nature.com/articles/s41591-024-02886-y

    [ad_2]

    Source link

  • Phase 2 trial reveals Lixisenatide may reduce motor disability in Parkinson’s patients

    Phase 2 trial reveals Lixisenatide may reduce motor disability in Parkinson’s patients

    [ad_1]

    A recent study published in the New England Journal of Medicine conducted a trial of lixisenatide to assess its effects in early Parkinson’s disease.

    Study: Trial of Lixisenatide in Early Parkinson’s Disease. Image Credit: create jobs 51/Shutterstock.comStudy: Trial of Lixisenatide in Early Parkinson’s Disease. Image Credit: create jobs 51/Shutterstock.com

    Background

    Current treatments for Parkinson’s disease are primarily based on dopaminergic replacement therapy and have not convincingly demonstrated effects on disease progression. Further, epidemiological studies have observed increased Parkinson’s disease risk in individuals with type 2 diabetes.

    Moreover, some studies have shown a lower prevalence of Parkinson’s disease among diabetes patients treated with dipeptidyl peptidase-4 inhibitors or glucagon-like peptide (GLP)-1 receptor agonists compared to recipients of other medications.

    Lixisenatide is a GLP-1 receptor agonist used to treat type 2 diabetes. Its neuroprotective actions have been demonstrated in animal models of Parkinson’s disease and Alzheimer’s disease.

    About the study

    In the present study, researchers evaluated the disease-modifying effect of lixisenatide in individuals with early Parkinson’s disease. This phase 2, double-blind, randomized, multicenter, placebo-controlled trial was performed in France.

    People aged 40–75 diagnosed with Parkinson’s disease within the past three years were recruited. Eligible subjects were treated with a stable, optimized dopaminergic medication regimen for at least a month before starting trial agents.

    Participants were randomized to receive lixisenatide or placebo in addition to their standard treatment for Parkinson’s disease.

    The trial agent was initially administered at 10 μg/day for 14 days and 20 μg/day for the remainder of 12 months. Subjects continued their existing medication for Parkinson’s disease for the first six months at least.

    Clinical assessments were performed at baseline, six-month, and 12-month visits. Subjects were evaluated in an on-medication state based on scores on the Parkinson’s Disease Questionnaire summary index, Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson’s Disease Rating Scale (UPDRS) parts I–IV, and Montreal Cognitive Assessment.

    Besides, subjects were assessed in an off-medication state after a two-month washout period at 14 months.

    Fasting blood glucose and insulin levels were measured. Vital signs and adverse events were recorded at visits. The primary efficacy endpoint was the MDS-UPDRS part III scores change from baseline to 12 months.

    Secondary efficacy endpoints were the change in scores on MDS-UPDRS part III at six months, change in scores on MDS-UPDRS parts I, II, and IV at six and 12 months, and change in total MDS-UPDRS score at 12 months. Efficacy was assessed using Student’s t-test.

    Linear regression analyses investigated the potential effects of baseline levels of fasting blood glucose and insulin on the primary endpoint.

    Findings

    The study enrolled 156 subjects; seventy-eight were assigned to receive lixisenatide, and the remainder were assigned to the placebo group. In the lixisenatide arm, 28 subjects were switched back to the 10 μg/day dose due to side effects at the 20 μg/day dose.

    Further, dose reduction was required for three placebo recipients. Adherence to the trial agent was over 92% at all visits.

    Participants’ baseline clinical and demographic characteristics were similar between groups. In both groups, the average time from diagnosis was 1.4 years.

    The average baseline MDS-UPDRS motor score was 14.8 in lixisenatide subjects and 15.5 in placebo recipients. At 12 months, these scores were 14.9 and 18.8 in the lixisenatide and placebo groups, respectively.

    Lixisenatide recipients improved their score by 0.04 points from baseline, while placebo subjects had worsened it by 3.04 points. At 14 months, these scores were 17.7 and 20.7 in the lixisenatide and placebo groups, respectively.

    Results for secondary/exploratory measures were similar between groups at six and 12 months. No associations were observed between fasting blood glucose and insulin levels at baseline and MDS-UPDRS part III score at 12 months.

    Most participants had at least one adverse event. Gastrointestinal side effects were more prevalent with lixisenatide.

    The two groups had a similar incidence of serious adverse events. One serious adverse event, syncope in placebo recipients and pancreatitis in the lixisenatide group was deemed treatment-related.

    Conclusions

    In sum, this phase 2 trial showed that lixisenatide, administered in an on-medication state, had a three-point improvement on a motor disability scale over 12 months compared to baseline.

    This difference was driven by an increase in scores in placebo recipients. Further, a three-point between-group difference in the motor score was observed after the two-month washout period, favoring active treatment.

    Notably, the trial involved subjects with early disease; as such, it has to be investigated whether drug effects persist at other stages of the disease.

    Moreover, secondary endpoints did not definitively support primary endpoint results; therefore, longer washout periods may be necessary to test if the drug has long-lasting effects.

    Journal reference:

    • Meissner WG, Remy P, Giordana C, et al. (2024) Trial of Lixisenatide in Early Parkinson’s Disease. N Engl J Med,. doi: 10.1056/NEJMoa2312323.

    [ad_2]

    Source link

  • Studies link extract to reduced cognitive aging

    Studies link extract to reduced cognitive aging

    [ad_1]

    The researchers of a recent study published in Nutrients examined whether consuming wild blueberry extracts (WBE) may improve cognitive performance in an acute period, including recognized times of impaired functioning.

    Study: Wild Blueberry Extract Intervention in Healthy Older Adults: A Multi-Study, Randomised, Controlled Investigation of Acute Cognitive and Cardiovascular Effects. Image Credit: Kolpakova Svetlana/Shutterstock.comStudy: Wild Blueberry Extract Intervention in Healthy Older Adults: A Multi-Study, Randomised, Controlled Investigation of Acute Cognitive and Cardiovascular Effects. Image Credit: Kolpakova Svetlana/Shutterstock.com

    Background

    Flavonoid-rich foods like berries can enhance cognitive function and happiness across the lifespan, especially in healthy and cognitively impaired individuals.

    Studies have shown that blueberry therapy can improve vascular function and slow cognitive decay in older individuals.

    However, additional studies are needed to establish whether additional stabilizing agents can produce high bioactivity and advantages with a modest product dosage and whether blueberry intake can improve cognitive and cardiovascular health among healthy older adult individuals.

    About the study

    In the present randomized, double-blinded, placebo-controlled cross-over trial, researchers examined the effectiveness of wild blueberry extracts in sustaining episodic memory and executive function and cardiovascular consequences among healthy older individuals (ROAB trial).

    They aimed to duplicate cognitive decline reduction during an expected post-prandial drop while also enhancing cardiovascular outcomes after acute supplementation with 222mg of wild blueberry extract (BEAT trial).

    In the ROAB trial, 28 subjects received WBE doses of 111.0 mg, 222.0 mg, 444.0 mg, and 888.0 mg, or a placebo (inert artificially colored maltodextrin 300 mg, once daily, 3-hard capsule regimen) during five weeks, followed by a one-week washout.

    The researchers evaluated outcomes at baseline, two hours, four hours, and six hours following the intervention, with the intervention happening immediately after study initiation.

    In the BEAT experiment, the team administered 222 mg of wild blueberry extracts or a placebo (one-week washout) to 45 subjects and evaluated outcomes at baseline and six hours, corresponding to a post-prandial drop in cognitive function, with the intervention occurring immediately after baseline.

    The 222 mg WBE intervention coincided with known maxima in serum blueberry polyphenols two hours after dosage, corresponding to an expected reduction in post-prandial performance.

    Study participants were healthy older individuals recruited via the University of Reading Psychology Department’s Older Adult Panel, the University of the Third Age, local community noticeboards, and other activity organizations in Reading, United Kingdom, and the surrounding region.

    Study participants were aged 68 to 75 years without a prior history of diabetes, metabolic diseases, substance addiction, or neurological or mental illnesses.

    The study excluded smokers, vegetarians, individuals with a body mass index (BMI) ≥30, those allergic to WBE, and those who consume more than two alcoholic beverages each day.

    They also excluded individuals who used alternative drugs to boost cognitive function and memory the month before the study began and those who had participated in other studies in the preceding 30 days or cognitive trials in the previous six months.

    The researchers used Folin-Ciocalteu tests to determine total phenolic content and liquid chromatography to quantify anthocyanins.

    They used the Mini-Mental State Examination (MMSE), the National Adult Reading Test (NART), the Frequency of Forgetting (FoF) scale, Ravens Progressive Matrices (RPM), Rey’s Auditory Verbal Learning task (RAVLT), the Corsi Blocks task, the Task Switch task (TST), and the Trail Making tasks A and B (TMT-A and B) to assess cognitive function.

    Mood was measured using the Positive and Negative Affect Scale (PANAS). They produced composite scores consistent with the Alzheimer’s Disease Composite Score (ADCOMS) and the Z-scores of Attention, Verbal Fluency, and Episodic Memory for Nondemented Older Adults Composite (ZAVEN) scores. They used linear mixed modeling (LMM) for analysis.

    Results and discussion

    The study showed that wild blueberry extract, specifically 222 mg, caused a significant decrease in executive function at the 4-hour timepoint compared to placebo.

    However, 222 mg of wild blueberry extract significantly decreased diastolic and systolic blood pressures compared to a placebo. WBE 222 mg had a quicker EF reaction time during the projected post-lunch decrease.

    The ROAB experiment discovered that WBE 111 mg therapy resulted in lower executive performance after 4 hours compared to the placebo. WBE 888 mg produced quicker response speeds, although sessions were a strong predictor of CRT accuracy.

    WBE 222 mg was associated with reduced systolic and diastolic blood pressures compared to placebo, with the highest values occurring during the six hours.

    Flavonoids may have comparable biological processes in acute and chronic states, such as boosting cerebral blood flow (CBF) via better endothelial function and nitric oxide generation.

    Flavanoids enhance nitric oxide (NO)-mediated vasodilation, which improves cerebral blood flow and cognitive performance by enhancing metabolic substrate supply. Flavonoid eating may also help to lower blood pressure.

    Based on the study findings, wild blueberry extracts may have cardiovascular benefits and minimize cognitive decline in healthy older individuals when paired with a post-prandial dip.

    Acute WBE supplementation enhanced response speeds while decreasing cognitive performance on executive function tests. Post-lunch testing may improve the circadian decrease in cognition ability.

    Low dosages of WBE (222 mg, 444 mg, and 111 mg) enhanced episodic memory and executive function. Further study is required to determine the efficacy of wild blueberry extracts in those with minor cognitive deficits and to align cognitive test schedules.

    [ad_2]

    Source link

  • Insights from a controlled trial

    Insights from a controlled trial

    [ad_1]

    In a recent study published in the journal Translational Psychiatry, researchers from New Zealand conducted a phase I trial to assess the effect of micro-dosing of lysergic acid diethylamide (LSD) on the sleep and activity patterns of 80 healthy male adults.

    They found that compared to controls, participants who microdosed on LSD slept longer the next night, with no reduction in sleep observed on dosing days.

    Study: LSD increases sleep duration the night after microdosing. Image Credit: Olena Yakobchuk/Shutterstock.comStudy: LSD increases sleep duration the night after microdosing. Image Credit: Olena Yakobchuk/Shutterstock.com

    Background

    Micro-dosing, the practice of self-administering psychedelic drugs below hallucinogenic thresholds, is believed to enhance mood, creativity, and productivity. While its effects on neurophysiological function are documented, its impact on sleep behavior remains unexplored.

    Previous studies on macrodoses of psychedelics like ayahuasca and psilocybin suggest alterations in rapid eye movement (REM) sleep but do not affect total sleep time. Animal studies similarly show increased wakefulness and reduced REM and non-REM durations with serotonergic psychedelics.

    A 1966 study objectively measured sleep in association with micro-dosing and showed that low doses of LSD significantly increased REM duration and interrupted slow-wave sleep. Still, the timing of drug administration differed from modern micro-dosing practices.

    Subjective reports on sleep quality from micro-dosing studies indicate mixed effects, with some reporting improvements and others experiencing difficulties, such as insomnia. While some individuals cite improved sleep quality as a motivation for micro-dosing, others report challenges, suggesting a bidirectional impact on sleep.

    Given the current shortage of evidence in the field, in the present phase I trial, researchers assessed the effect of LSD micro-dosing on sleep duration using commercially available watches.

    About the study

    The present study employed a double-blind parallel-group design, randomizing healthy male volunteers into LSD (n = 40) and placebo (n = 40) groups. Participants self-administered ten µg LSD base or placebo every three days for six weeks.

    Five participants did not complete the trial protocol, and three were administered an extra dose due to scheduling issues.

    Key inclusion criteria were males aged 25–60 years. On the other hand, exclusion criteria included specific medical conditions, psychiatric disorders, substance use, and prior psychedelic microdosing.

    Four visits were conducted: screening, baseline, first dosing (day 1), and follow-up (day 42). Screening involved urine drug and breathalyzer tests. Participants were given Fitbit Charge 3/4 devices to wear throughout the trial, syncing sleep and activity data via the Fitbit app.

    Dosing occurred before 11 am on dosing days. Compliance was ensured by video recording dose administration.

    The analysis included 3231 nights of data, with an average of 40.39 nights per participant. The study processed Fitbit sleep data focusing on sleep states: “REM,” “deep,” “light,” and “awake.”

    Statistical analysis involved the use of linear mixed-effects modeling without imputation for missing data, and Bonferroni correction.

    Results and discussion

    The analysis revealed a significant increase in REM sleep (p = 0.0037), time asleep (p = 0.0026), and total sleep (p = 0.0027) on the night after microdosing with LSD compared to placebo.

    These differences amounted to an additional 8.13 minutes of REM sleep, 21.1 minutes asleep, and 24.3 minutes of total sleep. While deep sleep approached significance (p = 0.043), no changes in sleep stage proportions reached significance.

    Participants in the LSD group went to bed significantly earlier (around 25.17 minutes, p =0.005) on the night after microdosing, but no significant change was observed in wake-up time. Additionally, there were no effects across time regarding the modification in sleep time on the night after microdosing.

    No significant changes were observed in physical activity patterns between the LSD and placebo groups. Additionally, no noticeable interaction effects were observed in metrics such as calories, distance, steps, or activity states (sedentary, light activity, moderate activity, very active).

    Participants in the LSD group reported marginally increased tiredness on the day after dosing, with ten sleep-related adverse events reported compared to four in the placebo group.

    In qualitative interviews, participants noted varied effects on energy levels with micro-dosing but did not explicitly mention needing extra sleep or earlier bedtimes.

    Overall, the study is strengthened by the use of wearable devices that enabled the collection of a large amount of naturalistic sleep data while being minimally intrusive compared to traditional sleep laboratory settings.

    However, the study’s limitations include the exclusive focus on healthy male participants, potential lack of generalizability to females and individuals with mental health conditions, and reliance on wearable devices, which may lack access to important clinical sleep metrics.

    Conclusion

    In conclusion, the study’s findings highlight the significant increase in total sleep observed with LSD microdosing. The findings support the integration of wearable devices for sleep monitoring in the ongoing phase II trials of LSD micro-dosing for major depressive disorder.

    Additionally, they emphasize the need for “off” days between micro-dosing sessions to facilitate adequate recovery, offering valuable insights for future research and clinical practice in psychedelic-assisted therapy.

    [ad_2]

    Source link

  • Study shows potential for universal flu vaccine with broad antibody response

    Study shows potential for universal flu vaccine with broad antibody response

    [ad_1]

    A recent study published in the journal Nature Communications observed antibody breadth and effector functions as important immune correlates that can be used to develop universal influenza vaccines. This vaccine could be effective against all influenza virus strains, even those having pandemic potential.

    Study: Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children. Image Credit: Africa Studio / ShutterstockStudy: Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children. Image Credit: Africa Studio / Shutterstock

    Background

    Children are particularly vulnerable to influenza viruses that cause seasonal epidemics and sporadic pandemics. Seasonal influenza epidemics not only lead to an upsurge in hospital admissions but also increase mortality rates in older adults with comorbidities. Many studies have shown that seasonal influenza vaccines provide limited protection against influenza viruses that have the potential to cause a pandemic. However, the 2009 H1N1 pandemic (pH1N1) revealed the effectiveness of seasonal vaccines in protecting children and older adults from the infection. This protection could be due to cross-reactive antibody responses. 

    Compared to children, adults possess additional immune correlates, such as T-cell responses and non-neutralizing antibody functions. This is the reason why children require higher concentrations of HAI antibodies for an equivalent amount of immune protection from the infection. To design a next-generation vaccine, it is important to identify immune correlates of protection. In the context of pH1N1 infection, HA-stem-specific antibodies play a crucial role in providing protection, which is mediated by the Fc Receptor (FcR) function. 

    Some antibodies that can cross-react between pandemic, seasonal, and avian influenza viruses could reduce the severity of influenza virus infection. In this context, serum antibodies, particularly IgG, can facilitate effector functions, such as directing immune cells to kill infected cells, engulfing infected cells via antibody-dependent phagocytosis (ADCP), and promoting antibody-dependent cellular cytotoxicity (ADCC). These functions are mediated by Fc gamma receptors (FcγR) 3a and FcγR2a.

    Mechanistically, FcγR 3a and FcγR2a employ macrophages and natural killer (NK) cells to remove viruses-infected cells. Cross-reaction of ADCC antibodies has been associated with targeting conserved antigenic sites of influenza virus hemagglutinin (HA), the Nucleoprotein (NP), and Matrix 1 (M1).

    About the Study

    The current study identified several gaps in research regarding antibody effector functions. For instance, few studies have assessed the vaccine-induced ADCC changes, longitudinal durability of vaccine-induced antibody FcR binding and isotype changes, and the alterations in HA-specific antibody responses with vaccination and infection. The currently performed randomized placebo control trial (RCT) investigated the influenza-specific antibody breadth and function of seasonal (S1) H1N1 vaccination and pH1N1 infection.

    The antibody features, particularly HAI titer, from seasonal vaccination that could have helped in reducing or delaying contraction of pH1N1 were assessed using selected archived samples. These samples were collected from NCT00792051, a randomized placebo-controlled trial and its follow-up study that used school children between 6 and 17 years old. 

    A subset of children who received any influenza vaccination in Year 1 (V1) or not (placebo-V0) was selected for secondary analyses, which helped determine the effectiveness of vaccination against pH1N1 infection.

    Study Findings

    The current study indicated that non-neutralizing antibodies are highly cross-reactive between different influenza strains and subtypes, which could play an important role in reducing the incidence and severity of infection.

    Detecting antibody functions other than HAI is vital to developing next-generation vaccines. This study identified the serological correlates that play an important role in protecting children from pandemic infection. In 2009, when schools were closed for two months, H1N1 transmission was low. However, soon after schools reopened in September 2009, more than 50% of the students were infected within a few months. A very low community uptake of the monovalent pH1N1 vaccine has been documented.

    The half-life of different antibody subclasses alters significantly. The current study observed that seasonal vaccination enhances Fc effector functions of pH1N1 specific NP, HA, and neuraminidase (NA) antibodies. However, their function was short-term as it waned off within one year of vaccination. A greater antibody decline was observed in unvaccinated children.

    Seasonal vaccination did not boost FcR effector functions to other seasonal-specific antibody responses. Unvaccinated, uninfected children also exhibited increased FcR-mediated effector functions of pandemic-specific NA, HA, and NP antibodies. These children displayed a higher antibody level of NK cell function. pH1 antibodies against H3-HA responses were associated with cross-reactive avian H5-specific IgG, FcγR2a, and FcγR3a responses. This finding implies that cross-reactive responses are less focused and are not trained by seasonal virus exposure of other groups. 

    Considering the experimental results, vaccination and prior infection are not associated with the lack of infection in unvaccinated, uninfected children or susceptibility of V1S1 children. More research is required to understand the host factors leading to these outcomes.

    Results also indicated that group 2 H3 HA-specific IgG3 antibodies are negative predictors of infection. However, seasonal H1 and pH1-IgG3 antibodies before infection were positively associated and, therefore, protected against infection.

    Conclusions

    This study shows how universal influenza vaccines, effective against seasonal to pandemic viruses, can be developed. Antibody breadth and FcR effector functions are two important immune correlates that could be exploited to develop this vaccine.

    Journal reference:

    • Jia, J. Z. et al. (2024) Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children. Nature Communications. 15(1), 1-15. DOI: 10.1038/s41467-024-47590-0, https://www.nature.com/articles/s41467-024-47590-0

    [ad_2]

    Source link

  • Esketamine after childbirth cuts risk of postnatal depression by three-quarters

    Esketamine after childbirth cuts risk of postnatal depression by three-quarters

    [ad_1]

    In a recent study published in the British Medical Journal, researchers investigated whether low-dose esketamine delivered after labor improves post-delivery depression in women with prenatal depression.

    Study: Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. Image Credit: christinarosepix / ShutterstockStudy: Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. Image Credit: christinarosepix / Shutterstock

    Background

    Perinatal depression is common among women, particularly in low-income nations, and has negative consequences for both the mother and her child. Mothers with depression frequently feel anxiety, weaker connections, and lower attachment. Their kids are more likely to experience behavioral and emotional issues, as well as long-term psychological and developmental disorders. Poor physical health, a lack of social support, a low socioeconomic level, insufficient education, and a history of violent exposure are all risk factors for prenatal depression.

    Prenatal depression is a primary predictor of postnatal depression, and pharmacological therapies are occasionally required. Esketamine, a rapid-onset antidepressant, offers potential advantages for treatment-resistant depression, but its effect on women with perinatal depression is unknown. Previous studies have mainly focused on cesarean births, omitting moms who are depressed or at high risk of developing depression after delivery.

    About the study

    In the present randomized, placebo-controlled, double-blinded, controlled trial, researchers evaluated whether low-dose esketamine administered immediately after birth lowers depression in moms suffering from prenatal depression for 42 days.

    The researchers conducted the trial at five hospitals across China between June 19, 2020, and August 3, 2022. They included pregnant women aged 18 years and above with mild, moderate, or severe prenatal depression [defined as Edinburgh postnatal depression scale (EPDS] scores equal to or above 10) hospitalized for delivery. They excluded women with pre-pregnancy mood disorders, severe pregnancy complications, physical status III or higher, or contraindications to ketamine or esketamine use, such as severe cardiovascular disease, refractory hypertension, or hyperthyroidism. Exclusion criteria included American Society of Anesthesiologists (ASA) physical status III or higher.

    The researchers randomized the individuals in a 1:1 ratio to the esketamine group (0.20 mg per kg body weight) or placebo group, with drugs administered intravenously during the initial 40 minutes post-delivery while clipping the birth cord. The primary research outcomes were major depressive events after 42 days of delivery, identified using mini-international neuropsychiatric interviews.

    Secondary study outcomes included EPDS scores on days one and 42 after childbirth and the Hamilton Depression Rating Scale (HDRS) score 42 days after delivery. The researchers monitored adverse occurrences until 24 hours after delivery. They used logistic regression to determine the relative risk (RR) values. They used imputed missing primary outcome data in post-hoc sensitivity analyses.

    The researchers measured anxiety using the Zung self-rating anxiety scale, social assistance using the social support rating scale, marital satisfaction using the ENRICH (evaluation and nurturing relationship issues, communication, and happiness) scale, and agitation-sedation using the Richmond agitation-sedation scale. Maternal data included epidural analgesia acceptance, delivery style, fluid infusion, and blood loss, as well as the use of additional analgesics and sedatives. Bodyweight, sex, Apgar scores at one and five minutes after delivery, and initial destination were all recorded.

    Results

    The researchers screened 14,243 women and randomly assigned 364 to the study groups. The average participation age was 32 years. After 42 days, 12 (6.7%) esketamine recipients and 46 (25%) placebo recipients experienced a severe depressive episode (RR 0.3). After accounting for missing data, 14 (7.7%) of esketamine recipients and 46 (25%) of placebo recipients experienced severe depressive episodes (RR 0.3). The protocol analysis yielded comparable results.

    Esketamine-treated women had lower EPDS scores on day 7 and day 42 (median difference, -3). Individuals receiving esketamine also had reduced HDRS scores 42 days after delivery (mean difference, -4). Neuropsychiatric adverse event occurrence (including dizziness, diplopia, and hallucinations) was higher among individuals receiving esketamine (45%, n=82) compared to those receiving placebo 22% (n=40); however, the symptoms lasted <24 hours, with none requiring pharmacological therapy.

    Esketamine-treated women had lower EPDS scores on day seven and 42 (median difference, -3). Individuals receiving esketamine also had reduced HDRS scores 42 days after delivery (mean difference, -4). Neuropsychiatric adverse event occurrence (including dizziness, diplopia, and hallucinations) was higher among individuals receiving esketamine (45%, n=82) compared to those receiving placebo 22% (n=40); however, the symptoms lasted <24 hours, with none requiring pharmacological therapy.

    Overall, the study found that a single modest dosage of 0.2 mg/kg of esketamine administered soon after childbirth reduces major depressive events among women with prenatal depressive symptoms by almost three-quarters at 42 days postpartum. Esketamine increased the frequency of neuropsychiatric symptoms, but they were brief and lasted <24 hours, requiring no medication. The antidepressant effect of low-dose esketamine appears to continue longer in women with prenatal depression than in the overall population with depression. Further analysis is required to establish whether the reaction continues after 42 days.

    Journal reference:

    • Shuo Wang et al., Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial, BMJ 2024;385:e078218, DOI: 10.1136/bmj-2023-078218, https://www.bmj.com/content/385/bmj-2023-078218

    [ad_2]

    Source link

  • Cannabis compound d-limonene reduces anxiety-inducing effects of THC

    Cannabis compound d-limonene reduces anxiety-inducing effects of THC

    [ad_1]

    A Johns Hopkins Medicine-led research team has added to evidence that a chemical found naturally in cannabis (also known as marijuana) can -; in the right amounts -; lessen the anxiety-inducing effects of tetrahydrocannabinol (THC), the primary psychoactive sister chemical found in cannabis. The finding has the potential to advance the medicinal use of THC, and reduce the risks of its recreational use in some people.

    The substance, called d-limonene, is one of the most abundant terpenes, or essential oils, in the cannabis plant, and has shown promise in rodent studies in reducing anxiety behaviors. However, there has been little research on d-limonene or other terpenes in humans. As a group, terpenes are responsible for the taste, aroma and color of plants.

    In a recent study, first published online April 1 in the Journal of Drug and Alcohol Dependence, investigators tested the effects of vaporized d-limonene alone and mixed with THC to examine the anxiety-reducing effects in humans. They found the addition of d-limonene significantly reduced overall ratings of feeling “anxious/nervous” and “paranoid” compared with rating the effect of THC alone.

    As cannabis legalization becomes more prevalent, its use for both medicinal and non-medicinal purposes is expanding rapidly. In recent years, selective breeding of cannabis plants has resulted in strains that contain upwards of 20% – 30% THC, compared with an average of 12% a decade ago. This may make it more difficult for users to be consistent with the amount of THC they consume on a given occasion.

    THC interacts with receptors in the brain to produce feelings of relaxation and euphoria. However, researchers say that when a user is exposed to higher-than-usual doses of THC, the drug can also trigger anxiety, fear and panic.

    People use cannabis to help reduce anxiety, depression and post-traumatic stress disorder, but since THC levels vary widely, if a person overshoots their tolerance of THC, cannabis can induce anxiety rather than relieve it. Our study demonstrates that d-limonene can modulate the effects of THC in a meaningful way and make THC more tolerable to people using it for both therapeutic and non-therapeutic purposes.”


    Ryan Vandrey, Ph.D., study senior author, professor of psychiatry and behavioral sciences, Johns Hopkins University School of Medicine

    In the study, 20 healthy adults with a median age of 26 participated in up to 10 outpatient sessions, during which they inhaled vaporized d-limonene alone, vaporized THC alone, vaporized THC and d-limonene together, or vaporized distilled water (as a placebo).

    The study was double-blinded, meaning neither the researchers nor participants knew who was receiving which mixture. Twenty participants completed nine test sessions, while 12 participants also took part in an optional tenth session of THC combined with a triple-dose (15 milligrams) of d-limonene to test the extreme extent of the essential oil’s dose response curve. This was conducted after appropriate safety data were obtained from the lower doses (1 milligram and 5 milligrams).

    In all participants, the researchers measured subjective drug effects, subjective ratings of mood, vital signs (heart rate and blood pressure) and cognitive performance (measures of memory, psychomotor ability and attention) at baseline, and then an additional nine times after initial exposure over the course of each of the six-hour test sessions. They also collected blood and urine samples from each subject before, during and after each six-hour session to test for THC and d-limonene levels.

    The research team concluded that combining d-limonene with THC significantly reduced subjective indicators/reports of THC-induced anxiety in participants. These reductions were greater as the dose of d-limonene was increased.

    Additionally, they saw no interference with THC’s subjective, cognitive or physiological effects when co-administered with d-limonene, as well as no effects from d-limonene alone that differed from the placebo test.

    “This study is a first step in uncovering how we can mitigate risks of THC when used in medicine, and also is targeted at making cannabis safer for the general, non-therapeutic consumer,” says study lead author Tory Spindle, Ph.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

    The researchers plan to continue experimenting with other terpenes alone and in combination with THC to see how they interact with each other, as well as replicate the d-limonene study in larger and more diverse clinical populations. They also plan to test alternative methods of administration, such as oral ingestion.

    Along with Vandrey and Spindle, members of the study team from Johns Hopkins Medicine are George Bigelow, Lauren Pollak and C. Austin Zamarippa. Other team members are Ethan Russo at CReDO Science, and Uwe Christians, Jost Klawitter, Cristina Sempio, Touraj Shokati, Bridget Tompson and Alexandra Ward at the University of Colorado Anschutz Medical Campus. 

    Spindle has served as a consultant for Canopy Health Innovations Inc. and has received research funding from Cultivate Biologics. Vandrey has served as a consultant or received honoraria from Mira1a Therapeutics Inc., Jazz Pharmaceuticals, Charlotte’s Web, Syqe Medical Ltd. and WebMD. Russo is the founder and CEO of CReDo Science and a scientific adviser to True Terpenes.

    A patent application (PCT/US2022/014296) has been submitted by The Johns Hopkins University on behalf of Vandrey, Spindle and Russo for the use of d-limonene to reduce THC-induced anxiety, based on the data presented in this study (after the trial concluded and data were analyzed).

    Source:

    Journal reference:

    Spindle, T. R., et al. (2024). Vaporized D-Limonene Selectively Mitigates the Acute Anxiogenic Effects of Δ9-Tetrahydrocannabinol in Healthy Adults Who Intermittently Use Cannabis. Drug and Alcohol Dependence. doi.org/10.1016/j.drugalcdep.2024.111267.

    [ad_2]

    Source link

  • Low dose esketamine injection after childbirth reduces postpartum depression

    Low dose esketamine injection after childbirth reduces postpartum depression

    [ad_1]

    A single low dose injection of esketamine given immediately after childbirth reduces major depressive episodes in individuals with depressive symptoms during pregnancy (prenatal depression), finds a clinical trial published by The BMJ today.

    The results suggest that low dose esketamine should be considered in new mothers with prenatal depressive symptoms.

    Depression is common during pregnancy and shortly after giving birth and can have several adverse effects on new mothers and their infants.

    Esketamine is made from a drug called ketamine. It’s used as an anesthetic and to treat depression, yet the effect for mothers with perinatal depression is unclear.

    To examine this further, researchers based in China and the USA wanted to find out if a single low dose injection of esketamine given just after childbirth might reduce subsequent depression in mothers with pre-existing prenatal depression.

    Their findings are based on 361 mothers (average age 32 years) enrolled from five Chinese hospitals from June 2020 to August 2022 with no medical history of depression and no diagnosis of depression in pregnancy, but who had scores on a scale consistent with mild prenatal depression and were preparing for childbirth. 

    None of the participants had severe pregnancy complications, or any condition that meant they couldn’t be given esketamine.

    Information on factors including age, weight (BMI), education level, family income and existing health conditions was recorded at the start of the trial and participants were randomly assigned to either esketamine or placebo intravenously infused over 40 minutes after childbirth.

    Participants were interviewed 18 to 30 hours after giving birth and again at 7 and 42 days. 

    Major depressive episode was diagnosed with the Mini-International Neuropsychiatric Interview at 42 days. Depression was also assessed using the Edinburgh depression score at 7 and 42 days, and the Hamilton Depression Rating Scale score at 42 days. No participant took antidepressants or received psychotherapy during the follow-up period.

    At 42 days after giving birth, 12 of 180 (6.7%) of mothers given esketamine experienced a major depressive episode compared with 46 of 181 (25.4%) of those given placebo (a relative risk reduction of about three-quarters). 

    As expected, mothers given esketamine had lower Edinburgh depression scores at 7 and 42 days, and a lower Hamilton depression score at 42 days.

    Based on these figures, the researchers estimate that, for every five mothers given esketamine, one major depressive episode would be prevented.

    More neuropsychiatric adverse events such as dizziness and diplopia (double vision) occurred with esketamine (45% v 22%). However, symptoms lasted less than a day and none needed drug treatment. 

    The researchers acknowledge that excluding mothers with pre-pregnancy mood disorders may have affected the validity of their results, and the short follow-up period may have led to under-reporting of neuropsychiatric symptoms and other adverse events.

    What’s more, most participants had only mild prenatal depressive symptoms, so it’s unclear whether esketamine is equally effective in those with more severe depressive symptoms.

    Nevertheless, they conclude that for mothers with prenatal depressive symptoms, a single low dose of esketamine given shortly after childbirth decreases major depressive episodes at 42 days postpartum by about three quarters. 

    These results are generally consistent with previous work investigating the effects of low dose ketamine or esketamine on postpartum depression, mainly in mothers after cesarean delivery, and, importantly, the researchers say their trial “extends existing understanding by targeting women with pre-existing prenatal depression, who were therefore at high risk of postnatal depression.”

    As such, they conclude that low dose esketamine should be considered in mothers with symptoms of prenatal depression.

    Source:

    Journal reference:

    Wang, S., et al. (2024). Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. BMJ. doi.org/10.1136/bmj-2023-078218.

    [ad_2]

    Source link

  • A game-changer in preventing heart failure and sudden cardiac deaths

    A game-changer in preventing heart failure and sudden cardiac deaths

    [ad_1]

    In a trial-level meta-analysis published in the journal Circulation, researchers assessed the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2i) on major adverse cardiovascular events (MACE) across three patient populations: diabetes at high risk for atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or chronic kidney disease (CKD). They found that SGLT2i reduced the rate of MACE by 9% with a consistent effect across all patient populations and key subgroups, primarily driven by a reduction in cardiovascular (CV) death, particularly HF and sudden cardiac death.

    Study: Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis. Image Credit: Lightspring / ShutterstockStudy: Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis. Image Credit: Lightspring / Shutterstock

    Background

    SGLT2i have been extensively studied in large, randomized, placebo-controlled trials involving diverse populations of patients, including those with type 2 diabetes mellitus (T2DM) and ASCVD, HF, and CKD. While SGLT2i was primarily developed for diabetes, the trials have consistently shown these drugs to reduce HF and kidney-related issues, regardless of diabetes status. However, their impact on MACE remains unclear, with variations observed among trial results. Prior meta-analyses failed to assess the effects on MACE components definitively. Uncertainty persists, particularly in subgroups without ASCVD or diabetes and those with advanced chronic kidney disease stages. Therefore, using data from all significant placebo-controlled trials, researchers in the present study performed a collaborative meta-analysis to explore SGLT2i’s effects on MACE risk and its components and death subtypes across relevant patient subgroups.

    About the study

    The researchers conducted a collaborative trial-level meta-analysis within the SGLT2i Meta-Analysis Cardio-Renal Trialists Consortium (SMART-C). A systematic literature search was conducted, and the included studies were phase 3 placebo-controlled, double-blind, randomized trials with ≥ 1,000 participants in every arm and median follow-up of six months and above. Combination SGLT1/2 inhibitors studies were excluded.

    The study included 11 randomized trials comparing SGLT2i to placebo, with 78,607 participants in total. Among them, 54.2%, 26.4%, and 19.5% of individuals participated in trials focused on diabetes at high ASCVD risk, established HF, or CKD, respectively. The mean age of participants was between 62 and 72 years. While 34.4% of them were females, 74.5% of them were white. At baseline, about 79.7% of the patients had diabetes, 36% had HF, and 37.2% had eGFR (short for estimated glomerular filtration rate)  less than 60 mL/min/1.73 m². Established ASCVD was present in 58.9%, and 28.5% had prior MI.

    The median follow-up duration ranged between 2.4 – 4.2 years, 1.3 – 2.2 years, and 2.0 – 2.6 years for trials focused on diabetes at high ASCVD risk, HF, and CKD, respectively. The primary outcome was the composite of 3-point MACE, including cardiovascular death, myocardial infarction (MI), and all types of stroke. The analysis also assessed the individual components of MI and stroke, including fatal and non-fatal events. Additionally, all-cause mortality (ACM) and death subtypes such as fatal MI, fatal stroke, HF death, sudden cardiac death, as well as other CV and non-CV deaths were examined. The analysis treated each outcome as a time-to-event event, and the effect estimates from each trial were derived from intention-to-treat analysis.

    Trial effect estimates were meta-analyzed within primary patient groups using fixed-effects models and then combined as random effects for overall estimates. Sensitivity analysis was conducted using fixed effects. Heterogeneity was assessed using the Cochrane Q statistic and Higgins and Thompson’s I2.

    Results and discussion

    About 10.1% of participants experienced MACE, with 5.3% experiencing CV death, 3.6% experiencing MI, and 2.8% experiencing a stroke. SGLT2i was found to reduce the rate of MACE by 9% overall, with consistent effects across trial populations. The most evident effect was observed on CV death, with reductions in HF death and sudden cardiac death driving the reduction in CV death. There was no significant effect on MI or stroke overall. SGLT2i were also found to reduce ACM, with the most significant effects observed in CKD trials.

    Patients with established ASCVD were found to have higher MACE incidence rates across all trial types. SGLT2i consistently reduced the risk of MACE and CV death regardless of established ASCVD status at baseline. Similarly, the effects remained consistent across subgroups stratified by diabetes status, prior HF, kidney function, and baseline eGFR. Stratification by albuminuria suggested a potential benefit primarily among those with ≥30 mg/g albuminuria. Across all the Kidney Disease Improving Global Outcomes (KDIGO) risk groups, the benefits for MACE and CV death were found to be consistent.

    The study is limited by fewer trials in each drug in each disease state and variations in eligibility criteria, follow-up duration, and subgroup definitions across studies. These restrictions restrict robust comparisons within the SGLT2i class and lower the generalizability of findings to broader patient populations.

    Conclusion

    In conclusion, SGLT2i consistently lowers the risk of MACE across diverse patient populations, regardless of baseline ASCVD, diabetes, or kidney function. This benefit predominantly comes from reduced cardiovascular death, notably HF and sudden cardiac death, with no significant impact on MI or stroke overall. These findings suggest the potential utility of SGLT2i across the spectrum of cardiovascular-kidney-metabolic disease, aiding in therapeutic decision-making.

    [ad_2]

    Source link

  • Nirmatrelvir fails to shorten COVID-19 symptoms in latest trial

    Nirmatrelvir fails to shorten COVID-19 symptoms in latest trial

    [ad_1]

    In a recent study published in The New England Journal of Medicine, researchers evaluate the efficacy of nirmatrelvir in combination with ritonavir against the coronavirus disease 2019 (COVID-19).

    Study: Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19. Image Credit: Alexsey t17 / Shutterstock.com

    A brief history of COVID-19 patient care

    Since its emergence at the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, has infected almost 700 million individuals and claimed over seven million lives worldwide. COVID-19 is associated with a wide range of pathologies in different populations, with the very young and elderly at the most significant risk of mortality and morbidity.

    Rapid global medical research and vaccination programs have significantly reduced the burden of COVID-19 by attenuating SARS-CoV-2 transmission. Currently, COVID-19 patients are treated symptomatically through general antiviral interventions; however, an extensive search for a COVID-19-specific cure is still in the clinical trials phase.

    Nirmatrelvir is an orally administered antiviral agent that inhibits the SARS-CoV-2 main protease (Mpro), which is critical for viral replication. Nirmatrelvir is administered with the pharmacokinetic enhancer ritonavir to inhibit metabolism by CYP3A4.”

    One of the most promising antiviral therapies currently in clinical trials is the combination of nirmatrelvir and ritonavir. In unvaccinated adults, phase II and III clinical trials have produced promising results by reducing COVID-19 mortality risk by over 80%. Nevertheless, the anti-COVID-19 benefits of this intervention in vaccinated individuals remain unverified.

    About the study

    In the current study, researchers evaluate the efficacy and side effects of nirmatrelvir-ritonavir in non-hospitalized patients of various ages, ethnicities, and infection severity.

    Data were obtained from the Evaluation of Protease Inhibition for Covid-19 in Standard-Risk Patients (EPIC-SR) trial, which is a randomized, double-blind, and placebo-controlled trial involving adult participants 18 years of age and older with laboratory reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19. Individuals were enrolled in the study between August 2021 and July 2022 if their symptoms initially appeared in the five days prior to study enrollment.

    Study participants were randomly assigned to receive either the nirmatrelvir-ritonavir intervention, which comprised 300 mg of nirmatrelvir and 100 mg of ritonavir, or placebo. The dosage was fixed once every 12 hours for five days, thus leading to a final total of 10 doses.

    For statistical analyses, randomization was stratified across vaccination status, geographic region, and COVID-19 symptom onset. Data collection included participants’ sociodemographic, anthropometric, and medical records.

    Digital diaries were also used to record daily intervention use, COVID-19 symptom severity on a four-point scale, and associated side effects. Efficacy measurements were conducted through day 34.

    Sustained alleviation was considered to have occurred on the first of four consecutive days during which all symptoms that had been scored as moderate or severe and as mild or absent at baseline were scored as mild or absent and as absent, respectively.”

    Study findings and relevance

    Of the 1,296 participants initially enrolled in the study, 1,288 individuals, 654 of whom received nirmatrelvir-ritonavir and 634 placebo, provided completed data and were included in the statistical analyses. The study cohort primarily comprised women and individuals of the White ethnicity at 54% and 78.5%, respectively.

    About 57% of the study cohort were vaccinated, with smoking as the most commonly severe COVID-19 risk factor reported among 13.3% of the study participants. Study intervention compliance was high across both cohorts at 94.8% and 96.5% for nirmatrelvir-ritonavir and placebo, respectively.

    Efficacy evaluations revealed no statistically different outcomes between nirmatrelvir-ritonavir and placebo treatment cohorts. While the safety evaluation found no statistically significant differences between the side effects reported across trial groups, dysgeusia, diarrhea, and nausea were often reported by those who received nirmatrelvir-ritonavir during the study.

    Conclusions

    The study findings suggest that nirmatrelvir-ritonavir may not be as effective as suspected in alleviating adverse viral SARS-CoV-2 outcomes, especially in symptomatic, non-hospitalized, vaccinated, or unvaccinated adults. Given the known and study-reported side effects, nirmatrelvir-ritonavir cannot yet be established as a safe and beneficial treatment for severe COVID-19 outpatients, irrespective of prior vaccination status.

    Nirmatrelvir–ritonavir was not associated with a significantly shorter time to sustained alleviation of COVID-19 symptoms than placebo, and the usefulness of nirmatrelvir–ritonavir in patients who are not at high risk for severe COVID-19 has not been established.”

    Journal reference:

    • Hammond, J., Fountaine, R. J., Yunis, C., et al. (2024). Nirmatrelvir for Vaccinated or Unvaccinated Adult Outpatients with Covid-19. The New England Journal of Medicine 390(13); 1186-1195. doi:10.1056/nejmoa2309003

    [ad_2]

    Source link