Prevention of serious events in adults 65 years of age or older: A comparison between high-dose and standard-dose inactivated influenza vaccines

BackgroundA recent study showed that a high-dose inactivated influenza vaccine (IIV-HD) was 24.2% more efficacious than a standard-dose inactivated influenza vaccine (IIV-SD) in preventing laboratory-confirmed symptomatic influenza in adults ≥65 years. Here we evaluate the effectiveness of IIV-HD compared to IIV-SD in preventing serious illnesses considered potential sequelae or complications of influenza infection.MethodsThe original study was a double-blind, randomized, active-controlled, multicenter trial. Participants were adults ≥65 years randomized to receive IIV-HD or IIV-SD, and followed for 6–8 months post-vaccination for the occurrence of influenza and serious adverse events (SAEs). SAEs were events: leading to death or hospitalization (or its prolongation); considered life-threatening or medically important; or resulting in disability. For the present analysis, reported SAEs were classified as possibly related to influenza by three blinded physicians and rates per 1000 participant-seasons were calculated. Relative vaccine effectiveness (rVE) was estimated as (1 − Rate Ratio) × 100.Results31,989 participants were enrolled, with 15,991 and 15,998 randomized to receive IIV-HD and IIV-SD, respectively. IIV-HD was significantly more effective than IIV-SD in preventing SAEs possibly related to influenza overall (rVE, 17.7%; 95% confidence interval [CI], 6.6–27.4%) and serious pneumonia (rVE, 39.8%; 95% CI, 19.3–55.1%). Borderline significance was observed for the efficacy of IIV-HD relative to IIV-SD for the prevention of all-cause hospitalizations (rVE, 6.9%; 95% CI, 0.5–12.8%).ConclusionsCompared to IIV-SD, IIV-HD reduced the risk of SAEs possibly related to influenza. The observed relative effectiveness against serious pneumonia is particularly noteworthy considering the burden of influenza and pneumonia in older adults.     

Relative contributions of biomarkers in Alzheimer’s disease

PurposeTo assess relationships between biomarkers for Alzheimer’s disease (AD) and their potential contributions to AD.MethodsBiomarkers and cognitive evaluations were assessed longitudinally in 179 patients with mild cognitive impairment, from the Alzheimer’s Disease Neuroimaging Initiative from 2003 to 2006, and were used to examine, at any given time, the joint contributions of hippocampal volume, whole brain volume, and brain glucose metabolism on clinical AD progression, using the Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog). Marginal structural models were applied, and an inverse-probability of treatment weight estimation was used to account for time-dependent confounding between study variables.ResultsAt any given time, population-level differences (e.g., 1-standard deviation [SD] increase) in brain glucose metabolism (?1.036; 95% confidence interval [95% CI], ?1.608, ?0.464) and hippocampal volume (–1.537; 95% CI, ?2.399, ?0.674) independently reduced mean (ADAS-Cog), whereas a 1-SD increase in whole brain volume did not (0.372; 95% CI, ?0.283, 1.027). The effects of brain glucose metabolism differed in subgroups defined by baseline covariates (e.g., age), but no subgroup effects were observed for hippocampal volume and brain volume.ConclusionsBrain glucose metabolism and hippocampal volume represent relevant biological markers in subjects at risk for AD.     

Serious adverse events of special interest following mRNA COVID-19 vaccination in randomized trials in adults

IntroductionIn 2020, prior to COVID-19 vaccine rollout, the Brighton Collaboration created a priority list, endorsed by the World Health Organization, of potential adverse events relevant to COVID-19 vaccines. We adapted the Brighton Collaboration list to evaluate serious adverse events of special interest observed in mRNA COVID-19 vaccine trials.MethodsSecondary analysis of serious adverse events reported in the placebo-controlled, phase III randomized clinical trials of Pfizer and Moderna mRNA COVID-19 vaccines in adults (NCT04368728 and NCT04470427), focusing analysis on Brighton Collaboration adverse events of special interest.ResultsPfizer and Moderna mRNA COVID-19 vaccines were associated with an excess risk of serious adverse events of special interest of 10.1 and 15.1 per 10,000 vaccinated over placebo baselines of 17.6 and 42.2 (95 % CI ?0.4 to 20.6 and ?3.6 to 33.8), respectively. Combined, the mRNA vaccines were associated with an excess risk of serious adverse events of special interest of 12.5 per 10,000 vaccinated (95 % CI 2.1 to 22.9); risk ratio 1.43 (95 % CI 1.07 to 1.92). The Pfizer trial exhibited a 36 % higher risk of serious adverse events in the vaccine group; risk difference 18.0 per 10,000 vaccinated (95 % CI 1.2 to 34.9); risk ratio 1.36 (95 % CI 1.02 to 1.83). The Moderna trial exhibited a 6 % higher risk of serious adverse events in the vaccine group: risk difference 7.1 per 10,000 (95 % CI –23.2 to 37.4); risk ratio 1.06 (95 % CI 0.84 to 1.33). Combined, there was a 16 % higher risk of serious adverse events in mRNA vaccine recipients: risk difference 13.2 (95 % CI ?3.2 to 29.6); risk ratio 1.16 (95 % CI 0.97 to 1.39).DiscussionThe excess risk of serious adverse events found in our study points to the need for formal harm-benefit analyses, particularly those that are stratified according to risk of serious COVID-19 outcomes. These analyses will require public release of participant level datasets.     

A phase 3, randomized,active-controlled study to assess the safety and tolerability of meningococcal serogroup B vaccine bivalent rLP2086 in healthy adolescents and young adults

BackgroundNeisseria meningitidis serogroup B (MnB) is an important cause of invasive meningococcal disease (IMD). A MnB vaccine (bivalent rLP2086, Trumenba^®) consisting of 2 factor H binding protein variants received accelerated approval in the United States for the prevention of IMD caused by MnB in individuals 10–25 years of age. This randomized, active-controlled, observer-blind study further assessed the safety and tolerability of bivalent rLP2086.MethodsEligible subjects ≥10 to <26 years were randomized (2:1) to receive bivalent rLP2086 at months 0, 2, and 6, or hepatitis A virus vaccine (HAV, Havrix^®) at months 0 and 6, and saline at month 2. The primary endpoints were serious adverse events (SAEs) throughout the study and medically-attended adverse events (MAEs) within 30 days after vaccination. Additional safety assessments included SAEs at other study intervals and adverse events (AEs) during the vaccination phase.ResultsOf 5712 subjects randomized, 84.6% (n = 3219) of bivalent rLP2086 recipients and 87.2% (n = 1663) of HAV/saline recipients completed the study. Throughout the study, SAEs were reported for 1.6% and 2.5% of bivalent rLP2086 and HAV/saline recipients, respectively. SAEs related to either vaccine were rare. MAEs occurred in 7.0% and 6.1% of subjects after vaccination 1; 5.5% and 6.1% after vaccination 2; and 5.3% and 5.5% after vaccination 3 in the bivalent rLP2086 and HAV/saline groups, respectively. A greater proportion of subjects reported AEs during the vaccination phase after bivalent rLP2086 compared with HAV/saline recipients; however, when reactogenicity events were excluded, the proportion between groups was similar.ConclusionThis safety study, the largest randomized, active-controlled trial evaluating a recombinant MnB vaccine, demonstrated that bivalent rLP2086 is safe and tolerable in healthy individuals ≥10 to <26 years of age.     

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized,double-blind,placebo-controlled trial

BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE).Methods4040 participants aged 6–12 weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n = 2020) or placebo (n = 2020), administered ∼4 weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14 days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14 days after the third dose. All adverse events (AEs) were collected for 30 days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385).ResultsVE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30 days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related.ConclusionsIn Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.     

The efficacy of supplementation with the novel medical food,Souvenaid, in patients with Alzheimer's disease: A systematic review and meta-analysis of randomized clinical trials

Background and rationale: Certain nutritional supplements are being marketed for the management of Alzheimer's disease (AD), but the evidence for their effectiveness is not established. The objective of this review was to evaluate the evidence from randomized clinical trial (RCTs) examining the effect of Souvenaid in patients with AD.

Methods: We conducted electronic searches in Medline, Embase, PsychINFO, CINAHL, and The Cochrane Library. The reporting quality of the included studies was determined using the Cochrane collaboration tool for assessing the risk of bias. Two reviewers independently determined eligibility, assessed the reporting quality of included studies and extracted data.

Results: Three studies with a total of 1011 participants were included. All were of good reporting quality. Meta-analyses revealed non-significant differences in cognition (ADAS-cog scores MD: 0.08, 95% CI: ?0.71 to 0.88) and function (ADCS-ADL scores MD: 0.36, 95% CI: ?0.54 to 1.25) between Souvenaid and placebo. One study showed significant increase in neuropsychological test battery composite z-score with Souvenaid compared with placebo, and another reported significant improvement in delayed verbal recall for a subgroup of patients with very mild AD. There was no significant effect on global clinical function. No serious adverse events were observed.

Conclusions: The evidence from published clinical trials does not show that supplementation with Souvenaid has beneficial effects on functional ability, behaviour, or global clinical change. Souvenaid may cause improvements in verbal recall in patients at early stages of AD. Few RCTs examining the effect of Souvenaid have been conducted, and they are all funded by same manufacturer. Future research should include using unified tools to measure cognition, function, and behaviour in AD.     

Efficacy,immunogenicity and safety of a trivalent live human-lamb reassortant rotavirus vaccine (LLR3) in healthy Chinese infants: A randomized,double-blind,placebo-controlled trial

BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy, immunogenicity and safety of a novel trivalent live human-lamb reassortant rotavirus vaccine (LLR3) against rotavirus gastroenteritis (RVGE).MethodsHealthy children aged 6–13 weeks were enrolled and randomized (1:1) to either 3 oral doses of LLR3 or placebo according to a 0, 1, 2 month schedule. The objectives were to evaluate vaccine efficacy (VE) against RVGE of any-severity, severe RVGE (sRVGE) and inpatient caused by rotavirus serotypes contained in the vaccine and not contained in the vaccine after the third dose. Immunogenicity was also assayed in a subgroup. All adverse events (AEs) were collected from 30 min after each dose for immediate reaction, even to the entire study period, including the serious AEs (SAEs) and intussusception.ResultsVE against RVGE of any-severity, sRVGE and inpatient caused by any serotype was 56.6% (95% CI: 50.7, 61.8), 70.3% (95% CI: 60.6, 77.6) and 74.0% (95% CI: 57.5, 84.1) respectively. VE against RVGE of any-severity, sRVGE caused by serotypes not contained in vaccine were 54.2% (95% CI: 47.5, 60.1) and 70.4% (95% CI: 60.4, 77.9). The rate of seroconversion and four-fold increase of rotavirus serotype G2-, G3-, and G4-specific IgA is 60.8%, 58.0%, and 60.6% in vaccine group, which was higher than 21.35%, 22.7%, and 23.1% in placebo group (p < 0.0001 for G2, G3, G4), as well as the Geometric Mean Titer (GMT). Through the entire trial, 65.91% and 67.79% of participants reported at least one AE, and 0.02% and 0.02% reported SAEs in the vaccine and placebo groups, respectively. Two intussusception cases were reported both in vaccine and placebo group.ConclusionsIn Chinese infants, LLR3 provided a substantial protection against RVGE of any-severity, sRVGE and inpatient caused by any serotype, and showed well immunogenicity and safety.     

Safety and Immunogenicity of the HPV-16/18 AS04-Adjuvanted Vaccine: A Randomized,Controlled Trial in Adolescent Girls

PurposeImmunization of girls against oncogenic human papillomavirus (HPV) types before sexual debut is important for cervical cancer prevention. This phase III blinded, randomized, controlled trial in adolescent girls assessed safety of the HPV-16/18 AS04-adjuvanted vaccine.MethodsGirls (mean age 12 years) in 12 countries received the HPV-16/18 L1 virus-like particle AS04-adjuvanted vaccine (N = 1,035) or hepatitis A virus vaccine as control (N = 1,032) at 0, 1, and 6 months. The primary objective was to compare the occurrence of serious adverse events (SAEs) between groups. HPV-16 and HPV-18 antibody titers were assessed by enzyme-linked immunosorbent assay post-vaccination.ResultsUp to study month 7, 11 girls in the HPV-16/18 vaccine group reported 14 SAEs and 13 girls in the control group reported 15 SAEs. The difference in SAE incidence between groups was .20% (95% CI, ?.78, 1.20). No SAE in the HPV-16/18 vaccine group was considered related to vaccination or led to withdrawal. The incidence of solicited local and general symptoms up to 7 days post-vaccination was moderately higher with the HPV-16/18 vaccine than with control. The incidence of unsolicited symptoms, new onset of chronic diseases, and medically significant conditions was similar between groups. All girls seroconverted for both antigens after three doses of the HPV-16/18 vaccine; geometric mean titers were 19,882.0 and 8,262.0 EU/mL for anti-HPV-16 and -18 antibodies, respectively, in initially seronegative girls.ConclusionsThe HPV-16/18 AS04-adjuvanted vaccine was generally well tolerated and immunogenic when administered to young adolescent females, the primary target of organized vaccination programs.     

Long-term antibody persistence after a booster dose of quadrivalent meningococcal ACWY-tetanus toxoid conjugate vaccine in healthy 5-year-old children

BackgroundTo provide continuing protection, available meningococcal vaccines must provide long-term persistence of circulating functional antibodies against prevalent serogroups causing invasive meningococcal disease (IMD). This study assessed antibody persistence and safety of the quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT) and the meningococcal serogroup C vaccine conjugated to Corynebacterium diphtheriae CRM₁₉₇ protein (MenC-CRM) for up to 6 years after booster dosing in children.MethodsIn the primary vaccination study, children were vaccinated at age 12 to 23 months. In the first extension study, children who completed the primary study received a booster dose 4 years later with the same primary vaccine. The current study assessed antibody persistence at 2 to 6 years postbooster against each of the 4 meningococcal serogroups using serum bactericidal assays using rabbit (rSBA) or human (hSBA) complement with antibody titer thresholds of ≥1:8 or ≥1:4, respectively, and geometric mean titers (GMTs). Safety evaluations during this period included serious adverse events (SAEs) related to vaccination and any event related to lack of vaccine efficacy.ResultsA total of 184 subjects were enrolled (MenACWY-TT = 159; MenC-CRM = 25). For MenACWY-TT, the percentages of subjects with rSBA titers ≥1:8 ranged from 96.7% to 100% across serogroups at 2 years postbooster and 71.6% to 94.0% at 6 years postbooster; rSBA GMTs decreased from Year 2 to 4 and generally remained stable thereafter. The percentages of subjects in the MenACWY-TT group with hSBA titers ≥1:4 were 70.0% to 100% across serogroups at 2 years postbooster and 58.5% to 98.5% at 6 years postbooster. No lack of efficacy, SAEs, or vaccine-related adverse events were reported.ConclusionsThe persistence of rSBA and hSBA antibodies was shown up to 6 years postbooster (10 years postprimary vaccination) with either MenACWY-TT or MenC-CRM, suggesting that this schedule may provide long-term protection against IMD. Clinicaltrials.gov: NCT01900899.     

Infant and Early Child Appetite Traits and Child Weight and Obesity Risk in Low-Income Hispanic Families

BackgroundChild appetite traits (ATs) are associated with later child weight and obesity risk. Less research has focused on ATs in low-income Hispanic children or included longitudinal associations with infant weight.ObjectiveTo determine stability of ATs during infancy and childhood and their relationship with subsequent weight and obesity risk at age 3 years among low-income Hispanic children.DesignA secondary longitudinal analysis of data from the Starting Early Program randomized controlled obesity prevention trial.Participants/settingThree hundred twenty-two low-income, Hispanic mother–child pairs enrolled between 2012 and 2014 in a public hospital in New York City.Main outcome measuresATs, including Slowness in Eating, Satiety Responsiveness, Food Responsiveness, and Enjoyment of Food were assessed using the Baby and Child Eating Behavior Questionnaires at ages 3 months, 2 years, and 3 years. Main outcome measures were child standardized weight-for-age z score (WFAz) and obesity risk (WFA≥95th percentile) at age 3 years.Statistical analyses performedAT stability was assessed using correlations and multilevel modeling. Linear and logistic regression analyses examined associations between ATs and child WFAz and obesity risk at age 3 years.ResultsThere was limited stability for all ATs measured over time. During infancy, Slowness in Eating was associated with lower 3-year WFAz (B = –0.18, 95% CI –0.33 to –0.04; P = 0.01). At age 2 years, Slowness in Eating and Satiety Responsiveness were associated with lower WFAz (B = –0.29, 95% CI –0.47 to –0.12; P < 0.01; B = –0.36, 95% CI –0.55 to –0.17; P < 0.01) and obesity risk (adjusted odds ratio 0.49, 95% CI 0.28 to 0.85; adjusted odds ratio 0.61, 95% CI 0.38 to 0.99) at 3 years. Increased Slowness in Eating and Satiety Responsiveness over time were associated with lower 3-year WFAz (B = –0.74, 95% CI –1.18 to –0.2 [Slowness in Eating]; B = –1.19, 95% CI –1.87 to –0.52 [Satiety Responsiveness], both P values = 0.001). Higher Enjoyment of Food over time was associated with higher 3-year WFAz (B = 0.62, 95% CI 0.24 to 1.01; P = 0.002).ConclusionsInfants with lower Slowness in Eating and Satiety Responsiveness may have higher levels of obesity risk and need more tailored approaches to nutrition counseling and obesity prevention.     

Psychotropic Drugs in Patients With Alzheimer's Disease: A Longitudinal Study by the Registry of Dementias of Girona (ReDeGi) in Catalonia,Spain

ObjectivesPsychotropic drugs are usually prescribed to deal with behavioral and psychological symptoms of dementia, especially when nonpharmacologic approaches are not available or have limited efficacy. Poor outcomes and serious adverse events of the drugs used must be addressed, and risk-benefit ratios need to be considered. The aim of this longitudinal study was to describe the evolution of dispensation of psychotropic drugs in patients with Alzheimer's disease (AD) and to identify the associated demographic and clinical variables.MethodsLongitudinal study using 698 cases with AD included in the Registry of Dementias of Girona in 2007 and 2008 and followed up during 3 years. Drugs were categorized according to the Anatomical Therapeutic Chemical classification. Binary logistic regression analyses were used to detect the variables associated with the use of antipsychotics, selective serotonin reuptake inhibitors (SSRIs), anxiolytics, and hypnotics.ResultsOf the patients, 51.2% consumed antipsychotics at least once during the three years of the study, whereas 73.3% and 58.2% consumed SSRIs and anxiolytics, respectively; 32.8% used hypnotics. Antipsychotic use was associated with a diagnosis of AD with delusions) [odds ratio (OR) = 5.7] and with increased behavior disorders (OR = 1.2). Patients with AD with depressed mood were more likely to be treated with SSRIs (OR = 3.1), while being a woman was associated with increased dispensation of anxiolytics (OR = 1.9) and SSRIs (OR = 2.2).ConclusionsConsumption of psychotropic drugs by the patients with AD registered in the Registry of Dementias of Girona is very high. Despite all the described adverse effects and recommendations of caution in their use, antipsychotics still are extensively used.     

Immunogenicity,duration of protection,effectiveness and safety of rubella containing vaccines: A systematic literature review and meta-analysis

BackgroundRubella containing vaccines (RCV) prevent rubella virus infection and subsequent congenital rubella syndrome (CRS). To update the evidence on immunogenicity, duration of protection, effectiveness and safety of RCV, we conducted a systematic literature review.MethodsWe searched EMBASE and SCOPUS, using keywords for rubella vaccine in combination with immunogenicity (seroconversion and seropositivity), duration of protection, efficacy/effectiveness, and safety. Original research papers involving at least one dose of RCV (at any age), published between 1-1-2010 and 17-5-2019 were included. Where appropriate, meta-analyses were performed. Quality of included studies was assessed using GRADE methodology.ResultsWe included 36 papers (32 randomized controlled trials (RCTs) and 4 observational studies) on immunogenicity (RA27/3 strain) in children and adolescent girls, 14 papers (5 RCTs and 9 observational studies) on duration of protection, one paper on vaccine effectiveness (VE) (BRDII strain), and 74 studies on safety, including three on safety in pregnancy.Meta-analysis of immunogenicity data showed 99% seroconversion (95% CI: 98–99%) after a single dose of RCV in children, independent of co-administration with other vaccines. Seroconversion after RCV1 below 9 months of age (BRDII strain, at 8 months) was 93% (95% CI: 92–95%). For duration of protection, the included studies showed a seropositivity of 88%-100% measured 1–20 years after one or two RCV doses. The single study on VE of BRDII strain, reported 100% VE after one and two doses. Among 34,332 individuals participating in the RCTs, 140 severe adverse events (SAEs) were reported as possibly related to RCV. Among the case reports on SAEs, the association with RCV was confirmed in one report (on fulminant encephalitis). Among 3,000 pregnant women who were inadvertently vaccinated, no SAEs were reported.ConclusionsOne and two doses of RCV are highly immunogenic for a long period of time, effective in preventing rubella and CRS, and safe.     

Safety of Russian-backbone seasonal trivalent,live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh

IntroductionLive-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings.Material and methodsWe conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations.ResultsThree hundred children were randomized and administered LAIV (n = 150) or placebo (n = 150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n = 13 vs. n = 16, p = 0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p = 0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events.ConclusionsIn this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted.     

The Impact of Pharmacologic and Nonpharmacologic Interventions to Improve Physical Health Outcomes in People With Dementia: A Meta-Review of Meta-Analyses of Randomized Controlled Trials

ObjectivesWe summarized and compared meta-analyses of pharmacologic and nonpharmacologic interventions targeting physical health outcomes among people with dementia.DesignThis is a systematic review and meta-analysis.Setting and ParticipantsPeople with dementia, confirmed through validated assessment measures.MethodsMajor databases were searched until October 21, 2019. Effect sizes [standardized mean difference (SMD)/Hedges g or risk ratio (RR)] were compared separately.ResultsOf 3773 search engine hits, 4 meta-analyses were included, representing 31 meta-analyzed trials and 10,054 study participants. Although meta-analyses were generally of adequate high quality, meta-analyzed studies were less so. Nutritional supplements were the only one to show a weight-increasing effect [SMD 0.53, 95% confidence interval (CI) 0.38–0.68, ie, medium effect; N = 12, n = 748]. Acetylcholinesterase inhibitors are associated with an increased risk for weight loss (RR 2.1, 95% CI 1.5‒3.0; N = 9, n = 7010). For the treatment of pain, sensory stimulation has a medium effect (SMD –0.58, 95% CI –0.99 to −0.17; N = 6, n = 199), whereas physical activity has a small effect (SMD –0.24, 95% CI –1.06 to 0.59; N = 2, n = 75). When exploring the characteristics of the psychosocial interventions, group-based interventions demonstrated a medium (SMD –0.55, 95% CI –1.02 to −0.09; N = 6, n = 157) and individual psychosocial interventions a small effect (SMD –0.27, 95% CI –1.06 to 0.53; N = 2, n = 55).Conclusions and ImplicationsDespite frequent physical comorbidities, the current evidence for pharmacologic and nonpharmacologic interventions in people with dementia to prevent and treat these conditions is still in its infancy, and larger trials targeting a wide range of physical health outcomes are urgently needed. Based on the SMDs and RRs, nutritional supplements can be recommended as an intervention to treat malnutrition. Clinicians should be careful in treating patients with acetylcholinesterase inhibitors, as it shows medium weight reducing effects. For the treatment of comorbid pain, sensory stimulation and psychosocial interventions are recommended.     

Six-month safety follow-up of an adjuvanted SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019) in adults: A phase 2/3, double-blind,randomized study

BackgroundWe evaluated the safety of SCB-2019, a protein subunit vaccine candidate containing a recombinant SARS-CoV-2 spike (S) trimer fusion protein, combined with CpG-1018/alum adjuvants.MethodsThis ongoing phase 2/3, double-blind, placebo-controlled, randomized trial is being conducted in Belgium, Brazil, Colombia, the Philippines, and South Africa in participants ≥ 12 years of age. Participants were randomly assigned to receive 2 doses of SCB-2019 or placebo administered intramuscularly 21 days apart. Here, we present the safety results of SCB-2019 over the 6-month period following 2-dose primary vaccination series in all adult participants (≥18 years of age).ResultsA total of 30,137 adult participants received at least one dose of study vaccine (n = 15,070) or placebo (n = 15,067) between 24 March 2021 and 01 December 2021. Unsolicited adverse events, medically-attended adverse events, adverse events of special interest, and serious adverse events were reported in similar frequencies in both study arms over the 6-month follow-up period. Vaccine-related SAEs were reported by 4 of 15,070 SCB-2019 recipients (hypersensitivity reactions in two participants, Bell’s palsy, and spontaneous abortion) and 2 of 15,067 placebo recipients (COVID-19, pneumonia, and acute respiratory distress syndrome in one participant and spontaneous abortion in the other one). No signs of vaccine-associated enhanced disease were observed.ConclusionsSCB-2019 administered as a 2-dose series has an acceptable safety profile. No safety concerns were identified during the 6-month follow-up after the primary vaccination.Clinical Trials Registration: NCT04672395; EudraCT: 2020–004272-17.     

The Study of Mental and Resistance Training (SMART) Study—Resistance Training and/or Cognitive Training in Mild Cognitive Impairment: A Randomized,Double-Blind,Double-Sham Controlled Trial

BackgroundMild cognitive impairment (MCI) increases dementia risk with no pharmacologic treatment available.MethodsThe Study of Mental and Resistance Training was a randomized, double-blind, double-sham controlled trial of adults with MCI. Participants were randomized to 2 supervised interventions: active or sham physical training (high intensity progressive resistance training vs seated calisthenics) plus active or sham cognitive training (computerized, multidomain cognitive training vs watching videos/quizzes), 2–3 days/week for 6 months with 18-month follow-up. Primary outcomes were global cognitive function (Alzheimer's Disease Assessment Scale-cognitive subscale; ADAS-Cog) and functional independence (Bayer Activities of Daily Living). Secondary outcomes included executive function, memory, and speed/attention tests, and cognitive domain scores.ResultsOne hundred adults with MCI [70.1 (6.7) years; 68% women] were enrolled and analyzed. Resistance training significantly improved the primary outcome ADAS-Cog; [relative effect size (95% confidence interval) −0.33 (−0.73, 0.06); P < .05] at 6 months and executive function (Wechsler Adult Intelligence Scale Matrices; P = .016) across 18 months. Normal ADAS-Cog scores occurred in 48% (24/49) after resistance training vs 27% (14/51) without resistance training [P < .03; odds ratio (95% confidence interval) 3.50 (1.18, 10.48)]. Cognitive training only attenuated decline in Memory Domain at 6 months (P < .02). Resistance training 18-month benefit was 74% higher (P = .02) for Executive Domain compared with combined training [z-score change = 0.42 (0.22, 0.63) resistance training vs 0.11 (−0.60, 0.28) combined] and 48% higher (P < .04) for Global Domain [z-score change = .0.45 (0.29, 0.61) resistance training vs 0.23 (0.10, 0.36) combined].ConclusionsResistance training significantly improved global cognitive function, with maintenance of executive and global benefits over 18 months.