A regular series on the latest clinical studies from around the world – and what they mean ‘in practice’, compiled and written by Clare GP Dr Ray O’Connor
The National Institute for Health and Care Excellence (NICE) last updated the drug treatment section of the type 2 diabetes guideline in 2015. Since then, further evidence on drug treatment from randomised trials investigating the effects of glucose-lowering drugs on cardiovascular outcomes has emerged, leading to this update.
Key changes to current practice include new recommendations for the use of sodium glucose co-transporter 2 (SGLT2) inhibitors in adults with type 2 diabetes who have chronic heart failure or established atherosclerotic cardiovascular disease, or who are at high risk of developing cardiovascular disease.
Alzheimer’s disease, the most common cause of dementia, affects an estimated 6.5 million persons aged ≥65 years in the United States. A growing body of evidence has identified potential modifiable risk factors for Alzheimer’ disease and related dementias (ADRD). These risk factors are: high blood pressure, not meeting the aerobic physical activity guideline, obesity, diabetes, depression, current cigarette smoking, hearing loss, and binge-drinking.
To assess their status, investigators from US Department of Health and Human Services/Centers for Disease Control and Prevention analysed data from the cognitive decline module that was administered to adults aged ≥45 years in 31 states and the District of Columbia (DC) in 2019.
Their findings were that adults aged ≥45 years with subjective cognitive decline (SCD) were more likely to report four or more risk factors compared with those without SCD (34.3 per cent versus 13.1 per cent). Prevalence of SCD increased from 3.9 per cent among adults with no risk factors to 25.0 per cent among those with four or more risk factors.
This is clearly shown in the graph. The implications for public health practice are that implementing evidence-based strategies that address modifiable risk factors can help achieve the goal to reduce risk for ADRD while promoting healthy aging.
- Omura JD et al. ‘Modifiable Risk Factors for Alzheimer Disease and Related Dementias Among Adults Aged ≥45 Years — United States, 2019. US Department of Health and Human Services/Centers for Disease Control and Prevention’. MMWR / May 20, 2022 / Vol. 71 / No. 20.
Abbreviation: SCD – Subjective Cognitive Decline
- Total number of risk factors was defined as the sum of any of the following risk factors reported by the respondent: high blood pressure, not meeting the aerobic physical activity guideline, obesity, diabetes, depression, current cigarette smoking, hearing loss, or binge drinking.
- SCD was defined as the self-reported experience of worsening confusion or memory loss in the previous year.
- The following US jurisdictions instituted the SCD module in 2019: Alabama, Connecticut, District of Columbia, Florida, Georgia, Indiana, Iowa, Kansas, Louisiana, Maryland, Michigan, Minnesota, Mississippi, Missouri, Nebraska, Nevada, New Mexico, New York, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Virginia, West Virginia, and Wisconsin.
Bacterial vaginosis (BV), caused by an imbalance in the vaginal microbiota, can be treated and prevented by probiotics. Pregnant women with BV can experience premature labour and spontaneous abortions. Probiotics and prebiotics promote the proliferation of beneficial microorganisms, alter the composition of the vaginal microbiota, and prevent intravaginal infections in postmenopausal women. In addition to reducing infection symptoms, pre/probiotics can also help prevent vaginal infections.
This paper was a systematic review of studies from 2010 to 2020 to determine the efficacy of pre/probiotics on the treatment of BV in pregnant and nonpregnant women.
The electronic databases Medline, Scopus, Embase, and Google Scholar were systematically searched. A total of 1,871 articles were found in the initial search, and 24 clinical trials were considered eligible. In studies comparing the effects of pre/probiotics and placebos with or without antibiotic therapy in patients with BV, significant differences in clinical outcomes were observed. Probiotics improved restitution of a balanced vaginal microbiota.
In addition, probiotics can reduce the vaginal colonization of Group B streptococci among pregnant women. In subjects treated with probiotics, BV cure rates were higher than those in subjects treated with antibiotics. There were no additional adverse events. The study concluded that pre/probiotic regimens, when used for BV treatment, are usually safe and can exhibit long-term and short-term benefits. In order to prove the benefits of pre/probiotics in BV treatment, additional high-quality research is required.
- Afifirad R et al. ‘Effects of Pro/Prebiotics Alone over Pro/Prebiotics Combined with Conventional Antibiotic Therapy to Treat Bacterial Vaginosis: A Systematic Review’. International Journal of Clinical Practice. Volume 2022, Article ID 4774783, 16 pages. https://doi.org/10.1155/2022/4774783.
Will the Covid 19 pandemic ever end we continue to ask? The battle continues. Some recent papers that are of relevance to GPs are as follows.
Covid Vaccination and Pregnancy:
Pregnant women with symptomatic Covid-19 have a higher risk of adverse outcomes than do women who are not pregnant. Although vaccination is recommended, uptake has been lower in pregnant women than among women who are not pregnant. The concern of many women regarding safety remains a barrier to maternal vaccination.
This study1 was a retrospective, observational, matched-cohort study involving pregnant women between the ages of 16 and 49 years at eight Vaccine Safety Datalink sites from December 15, 2020, through July 1, 2021. The authors matched each dose of a Food and Drug Administration–authorized Covid-19 vaccine received by a pregnant woman to an unvaccinated pregnant woman, according to study site and pregnancy start date.
Included in the pregnancy cohort were women who were subsequently found to be pregnant within 28 days after receiving the vaccine. Hence the study included women in the earliest stages of pregnancy.
The authors evaluated the incidences of 25 medically attended acute adverse events (known reactogenic adverse events and clinically serious outcomes) among the vaccinated women as compared with the unvaccinated matched controls. They identified 45,232 pregnant women who had received one or two doses of a Covid-19 vaccine immediately preceding or during pregnancy (78,026 vaccine doses). Two doses of an mRNA vaccine were received by 72.5 per cent, 12.5 per cent had received only the first dose of an mRNA vaccine, 10.9 per cent had received only the second dose of an mRNA vaccine, and 4.1 per cent had received a single dose of the Johnson & Johnson–Janssen vaccine.
Frequencies of all medically attended acute adverse events were less than one per cent. Among vaccinees, the most common events were fever (adjusted rate ratio compared with unvaccinated controls 2.85), malaise or fatigue (adjusted rate ratio, 2.24), local reactions (adjusted rate ratio, 1.89), and lymphadenopathy or lymphadenitis (adjusted rate ratio, 2.16). No serious acute adverse events that were evaluated (e.g., cerebral venous sinus thrombosis, encephalitis or myelitis, Guillain–Barré syndrome, myocarditis or pericarditis, or pulmonary embolism) occurred more frequently in vaccinated women after each dose than among matched unvaccinated controls.
The authors concluded that medically attended acute adverse events after Covid-19 vaccination immediately preceding or during pregnancy were uncommon. Covid-19 vaccines were not associated with an increased risk of the clinically serious acute adverse events that were evaluated. The present data add to the growing literature supporting the safety of Covid-19 vaccination during pregnancy.
Covid infection in infants of mothers who have been vaccinated:
Another study2 looked at the rates and severity of Covid-19 among infants of mothers who had been vaccinated against the disease, compared with those who weren’t. The results are very reassuring.
Infants younger than six months of age are at high risk for complications of Covid-19 and are not eligible for vaccination. It has been postulated that transplacental transfer of antibodies against severe SARS-CoV-2 after maternal Covid-19 vaccination may confer protection against Covid-19 in infants. This is same the logic used for vaccinating pregnant women with pertussis containing vaccines at around 28 weeks of gestation.
The authors used a case–control test-negative design to assess the effectiveness of maternal vaccination during pregnancy against hospitalization for Covid-19 among infants younger than six months of age.2
Between July 1, 2021, and March 8, 2022, they enrolled infants hospitalized for Covid-19 (case infants) and infants hospitalized without Covid-19 (control infants) at 30 hospitals in 22 States in the USA. They estimated vaccine effectiveness by comparing the odds of full maternal vaccination (two doses of mRNA vaccine) among case infants and control infants during circulation of the B.1.617.2 (delta) variant and the B.1.1.259 (omicron) variants.
A total of 537 case infants (median age, two months) and 512 control infants were studied. Sixteen per cent of the case infants and 29 per cent of the control infants had been born to mothers who had been fully vaccinated against Covid-19 during pregnancy. Among the case infants, 113 (21 per cent) received intensive care and two died from Covid-19; neither infant’s mother had been vaccinated during pregnancy.
It was found that the effectiveness of maternal vaccination against hospitalization for Covid-19 among infants was 52 per cent overall, 80 per cent during the Delta period, and 38 per cent during the Omicron period. Effectiveness was 69 per cent when maternal vaccination occurred after 20 weeks of pregnancy, and 38 per cent during the first 20 weeks of pregnancy.
The conclusion was that maternal vaccination with two doses of mRNA vaccine was associated with a reduced risk of hospitalization for Covid-19, including for critical illness, among infants younger than six months of age. It is important to point out that both of these studies were independently funded by the Centres for Disease Control (CDC).
Omicron variant infection and future immunity:
The Omicron (B.1.1.529), variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody escape. Vaccinated individuals show protection from severe disease. The authors of this study3 investigated T and B cell immunity against Omicron in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories.
Immunity against previous variants of concern was enhanced in triple vaccinated individuals, but the magnitude of immune responses against Omicron spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less effective antibody against Omicron.
Previously infection-naïve HCW who became infected during the Omicron wave showed enhanced immunity against earlier variants, but reduced immunity against Omicron itself. It seems that Omicron infection is a poor booster of immunity, and can also evade existing immunity.
Covid-19 vaccine effectiveness in children aged 5-11:
Using data from the largest health care organization in Israel, the authors identified a cohort of children five to 11 years of age who were vaccinated on or after November 23, 2021, and matched them with unvaccinated controls to estimate the vaccine effectiveness of BNT162b2 (Pfizer NioNTech) among newly vaccinated children during the Omicron wave.4 Vaccine effectiveness against documented SARS-CoV-2 infection and symptomatic Covid-19 was estimated after the first and second vaccine doses. Vaccine effectiveness was also estimated in age subgroups.
Among 136,127 eligible children who had been vaccinated during the study period, 94,728 were matched with unvaccinated controls. The estimated vaccine effectiveness against documented infection was 17 per cent at 14 to 27 days after the first dose and 51 per cent at seven to 21 days after the second dose. The estimated vaccine effectiveness against symptomatic infection was 18 per cent at 14 to 27 days after the first dose and 48 per cent at seven to 21 days after the second dose.
Findings suggest that as Omicron was becoming the dominant variant, two doses of the Pfizer NioNTech vaccine provided moderate protection against Covid-19 infection in children five to 11 years of age. The study was funded by the EU.
- DeSilva M et al. ‘Evaluation of Acute Adverse Events after Covid-19 Vaccination During Pregnancy’. NEJM 2022 (letter). (Published online June 22).
- Halasa MB et al. ‘Maternal Vaccination and Risk of Hospitalization for Covid-19 among Infants’. NEJM 2022. (Published online June 22).
- Reynolds C, Pade C, Gibbons J, et al. ‘Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure’. Science 2022 (published online June 14).
- Cohen-Stavi C et al. ‘BNT162b2 Vaccine Effectiveness against Omicron in Children 5 to 11 Years of Age’. NEJM 2022 (Published online June 29).