Lancet

Tomato flu outbreak in India

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Just as we are dealing with the probable emergence of fourth wave of COVID-19, a new virus known as tomato flu, or tomato fever, has emerged in India in the state of Kerala in children younger than 5 years.

The rare viral infection is in an endemic state and is considered non-life-threatening; however, because of the dreadful experience of the COVID-19 pandemic, the vigilant management is desirable to prevent further outbreaks.

Although the tomato flu virus shows symptoms similar to those of COVID-19 (both are associated with fever, fatigue, and bodyaches initially, and some patients with COVID-19 also report rashes on the skin), the virus is not related to SARS-CoV-2. Tomato flu could be an after-effect of chikungunya or dengue fever in children rather than a viral infection.

The virus could also be a new variant of the viral hand, foot, and mouth disease, a common infectious disease targeting mostly children aged 1–5 years and immunocompromised adults, and some case studies have even shown hand, foot, and mouth disease in immunocompetent adults

Tomato flu is a self-limiting illness and no specific drug exists to treat it.

The tomato flu was first identified in the Kollam district of Kerala on May 6, 2022, and as of July 26, 2022, more than 82 children younger than 5 years with the infection have been reported by the local government hospitals.

The other affected areas of Kerala are Anchal, Aryankavu, and Neduvathur. This endemic viral illness triggered an alert to the neighbouring states of Tamil Nadu and Karnataka. Additionally, 26 children (aged 1–9 years) have been reported as having the disease in Odisha by the Regional Medical Research Centre in Bhubaneswar. To date, apart from Kerala, Tamilnadu, and Odisha, no other regions in India have been affected by the virus. However, precautionary measures are being taken by the Kerala Health Department to monitor the spread of the viral infection and prevent its spread in other parts of India.

Editorial use only Children in a slum in New Delhi, India. Photographed in 2019.

The primary symptoms observed in children with tomato flu are similar to those of chikungunya, which include high fever, rashes, and intense pain in joints.

Tomato flu gained its name on the basis of the eruption of red and painful blisters throughout the body that gradually enlarge to the size of a tomato. These blisters resemble those seen with the monkeypox virus in young individuals

Rashes also appear on the skin with tomato flu that lead to skin irritation. As with other viral infections, further symptoms include, fatigue, nausea, vomiting, diarrhoea, fever, dehydration, swelling of joints, body aches, and common influenza-like symptoms, which are similar to those manifested in dengue.

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In children with these symptoms, molecular and serological tests are done for the diagnosis of dengue, chikungunya, zika virus, varicella-zoster virus, and herpes;

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once these viral infections are ruled out, contraction of tomato virus is confirmed. Because tomato flu is similar to chikungunya and dengue as well as hand, foot, and mouth disease, treatment is also similar—ie, isolation, rest, plenty of fluids, and hot water sponge for the relief of irritation and rashes. Supportive therapy of paracetamol for fever and bodyache and other symptomatic treatments are required.

Children are at increased risk of exposure to tomato flu as viral infections are common in this age group and spread is likely to be through close contact. Young children are also prone to this infection through use of nappies, touching unclean surfaces, as well as putting things directly into the mouth. Given the similarities to hand, foot, and mouth disease, if the outbreak of tomato flu in children is not controlled and prevented, transmission might lead to serious consequences by spreading in adults as well.

Similar to other types of influenza, tomato flu is very contagious. Hence, it is mandatory to follow careful isolation of confirmed or suspected cases and other precautionary steps to prevent the outbreak of the tomato flu virus from Kerala to other parts of India. Isolation should be followed for 5–7 days from symptom onset to prevent the spread of infection to other children or adults. The best solution for prevention is the maintenance of proper hygiene and sanitisation of the surrounding necessities and environment as well as preventing the infected child from sharing toys, clothes, food, or other items with other non-infected children.

Drug repurposing and vaccination are the most efficacious and cost-effective approaches to ensure the safety of public health from viral infections, especially in children, older people, immunocompromised people, and those with underlying health issues. As yet, no antiviral drugs or vaccines are available for the treatment or prevention of tomato flu. Further follow-up and monitoring for serious outcomes and sequelae is needed to better understand the need for potential treatments.

Source: Lancet respiratory Medicine

Covariate Adjustment in Cardiovascular Randomized Controlled Trials: Its Value, Current Practice, and Need for Improvement

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Abstract

In randomized controlled trials, patient characteristics are expected to be well balanced between treatment groups; however, adjustment for characteristics that are prognostic can still be beneficial with a modest gain in statistical power. Nevertheless, previous reviews show that many trials use unadjusted analyses. In this article, we review current practice regarding covariate adjustment in cardiovascular trials among all 84 randomized controlled trials relating to cardiovascular disease published in the New England Journal of Medicine, The Lancet, and the Journal of the American Medical Association during 2019. We identify trials in which use of covariate adjustment led to a change in the trial conclusions. By using these trials as case studies, along with data from the CHARM trial and simulation studies, we demonstrate some of the potential benefits and pitfalls of covariate adjustment. We discuss some of the complexities of using covariate adjustment, including how many covariates to choose, how covariates should be modeled, how to handle missing data for baseline covariates, and how adjusted analyses are viewed by regulators. We conclude that contemporary cardiovascular trials do not make best use of covariate adjustment and that more frequent use could lead to improvements in the efficiency of future trials.

Highlights

•Too many contemporary cardiovascular trials do not use covariate adjustment in the primary analysis
•Adjustment for a limited number of prognostic covariates is simple, has few risks, and is viewed as appropriate by regulators
•Covariates used for adjustment should be prespecified before unblinding
•Adjustment for prognostic covariates can offer a meaningful gain in statistical power

Waning effectiveness of COVID-19 vaccines

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In The Lancet, Peter Nordström and colleagues

 report the effectiveness of several COVID-19 vaccines and different vaccine schedules against any documented SARS-CoV-2 infection and against severe COVID-19, for up to 9 months of follow-up. Data for 842 974 matched pairs of vaccinated and unvaccinated individuals in this retrospective cohort study were retrieved from the Swedish national registers. These registers track health outcomes for all registered individuals nationwide. Both cohorts had a median age of 52·7 years (IQR 37·0–67·5) and included mostly women (500 297 [59·3%] in each cohort) and individuals born in Sweden (703 666 [83·5%] in the vaccinated cohort vs 578 647 [68·6%] in the unvaccinated cohort). Follow-up started 14 days after the second dose for each person vaccinated with BNT162b2 (Pfizer–BioNTech), mRNA-1273 (Moderna), ChAdOx1 nCoV-19 (Oxford–AstraZeneca), or mixed ChAdOx1 nCoV-19 and an mRNA vaccine and their unvaccinated matches. Effectiveness estimates were adjusted for date of second dose, age, sex, domestic support (proxy for disability), education, place of birth, and comorbidities. The study was completed on Oct 4, 2021, before the advent of the omicron (B.1.1.529) variant.

 found that although all vaccines elicited strong protection against SARS-CoV-2 infection in the first month after the second dose (>90% for BNT162b2 and mRNA-1273, >85% for mixed ChAdOx1 nCoV-19 plus an mRNA vaccine, and around 70% for ChAdOx1 nCoV-19), this protection waned to negligible levels within 7 months for BNT162b2 and 4 months for ChAdOx1 nCoV-19. Similar, but slower waning was noted for mRNA-1273 (effectiveness of 59% [95% CI 18–79] from day 181) and for ChAdOx1 nCoV-19 plus an mRNA vaccine (66% [41–80] from day 121).

Of greatest concern is waning effectiveness against severe COVID-19, which for all vaccines combined declined to 64% (95% CI 44–77) 121 days after the second dose, despite having been stable at around 90% initially. However, it remains unclear whether this combined statistic is exacerbated by accelerated waning of the ChAdOx1 nCoV-19 vaccine. The evidence from Nordström and colleagues’ study

Suggests lower effectiveness for older individuals and for men. The latter finding seems to be unique to this study and merits replication in other countries.The importance of this study is that it had a longer follow-up period than most studies, it examined several vaccines and different schedules, and it captured a national population in its entirety. The study manifests the true meaning of real-world vaccine effectiveness and its findings are integral to our understanding of waning vaccine protection. This study also demonstrates the expanding power of biomedical research in the era of digitised health information platforms.

In the context of other evidence on COVID-19 vaccine effectiveness, Nordström and colleagues’ study

 highlights several patterns. Unlike natural immunity, which appears robust with little waning for a year following infection

 there is gradual but relatively rapid waning in vaccine immunity against infection following the second dose.

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 Vaccines differ in effectiveness and durability of protection, with mRNA-1273 showing the highest effectiveness and slowest waning, perhaps owing to its large dose.

  

 Yet, vaccine-induced immunity against severe COVID-19 is more robust than that against infection and wanes more slowly. The gradient in effectiveness, highest against the most severe forms of infection and lowest against the least symptomatic forms, might explain the faster waning reported in studies that assessed effectiveness against infection of any severity,

 answered important questions, it raised concerns, especially with the emergence of the immune-evasive omicron variant. Omicron appears to accentuate the rapid waning of vaccine protection.

 Effectiveness against this variant is also considerably lower than against earlier variants, even in the first month after a booster dose, when protection is presumed to be highest.

 Has the current generation of vaccines reached its maximum potential?

We believe that the Nordström and colleagues’ study

 and other supporting evidence constitute a wake-up call that the world’s community are insufficiently prepared for future chapters in this evolving pandemic. For vaccines to have optimal value as public health tools, the rapid waning in vaccine immunity, in contrast to natural immunity, needs to be understood in order to develop vaccines that elicit durable protection. The ecological reality of new variants and perhaps an expanding enzootic viral reservoir demonstrate the need for vaccines that are protective against a broader spectrum of potential variants.

 SARS-CoV-2 is unlikely to be eliminated soon, if ever, and as long as it continues to circulate, it remains a threat to human health, societies, and economies. It is urgent that we develop coronavirus vaccines that are more broadly protective, with durable protection against both infection and disease.

Visual Representations of Silent Atherosclerosis

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Adherence to both pharmacologic treatment and lifestyle modification were better after patients received visual reports.

Primary prevention of cardiovascular (CV) disease often fails because of poor adherence to evidence-based guidelines by both patients and clinicians. Might visual representations of patients’ existing atherosclerosis increase adherence to preventive guidelines?

Researchers randomized 3532 participants (age, >60; or age, >40 with ≥1 conventional CV risk factor) in a Swedish population-based CV prevention program to undergo carotid ultrasound examinations and to either receive or not receive a visual report of the results. Each patient’s report displayed a stylized representation of the ultrasound image and a gauge that compared vascular age with chronological age. Patients who received visual reports also received reinforcing phone calls from a nurse and copies of their reports 6 months later; their clinicians also received copies of their visual reports. Patients who did not receive visual reports received standard guideline-based preventive care.

After 1 year, mean Framingham Risk Score decreased from 12.9 to 12.2 in patients who received visual reports and increased from 12.9 to 13.3 among controls (a statistically significant between-groups difference). A similar pattern was noted for the European Systematic Coronary Risk Evaluation score. The effect of the intervention was greatest among patients with the highest baseline CV risk.

Comment

Secondary outcome data suggested that the visual reports led to improvements in both pharmacologic treatment and lifestyle modification, implicating both provider and patient behaviors. Longer-term follow-up and cost-effectiveness data will be published later. Carotid imaging is relatively inexpensive and accessible, but given the incentives for overtreatment in the U.S., widespread carotid imaging might encourage unnecessary and potentially harmful downstream procedures.

 

Source: Lancet

Vitamin D does not prevent fractures in adults : Lancet

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https://speciality.medicaldialogues.in/vitamin-d-does-not-prevent-fractures-in-adults-lancet/

Low-calorie liquid diet may help Low-calorie liquid diet

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A reversal of type 2 diabetes (T2D) may be possible with low-calorie liquid diet for up to 5 months, increased physical activity, and cognitive behavioural therapy, preliminary results of the DiRECT* trial has shown.

“This was a clinical trial driven largely by the patients’ will and the response was very positive,” said lead author Professor Michael Lean from the University of Glasgow in Scotland at the recent IDF Congress 2017. “Our findings suggest that even if you have had T2D for 6 years, putting the disease into remission is feasible.”

The open-label randomized DiRECT trial included 250 patients (age 20-65 years) in the UK who had T2D for 6 years and were not on insulin. Half of the patients were treated using normal diabetes treatment, including medications, and weight-loss counselling while the other half were withdrawn of their antidiabetic and antihypertensive drugs and given a low calorie, liquid diet (no more than 825–853 kcal/day for 3 to 5 months), followed by gradual food reintroduction (over 2–8 weeks), and a structured support programme for long-term weight-loss maintenance, including cognitive behaviour therapy and exercise. [Lancet 2017;doi: 10.1016/S0140-6736(17)33102-1]

At 1 year, diabetes remission (HbA1c <6.5 percent after 2 months off antidiabetic medications) for up to 12 months was achieved by almost half of the patients in the intervention group (68 patients, 46 percent) and six (4 percent) in the control group (odds ratio [OR], 19.7; p<0.0001). Mean body weight dropped by 10 kg in the intervention group and 1 kg in the control group (p<0.0001).

Thirty-six patients in the intervention group achieved the primary outcome of >15 kg weight loss and diabetes remission vs zero in the control group (p<0.0001).

Overall, one patient experienced biliary colic and abdominal pain but still continued in the study. Others had constipation, headache, and dizziness but still persisted, said Lean. The trial is set to continue for 2 more years.

“The diagnosis of T2D is a medical emergency that needs action. Hopefully, this is a watershed in the understanding and management of the disease,” said lead author Professor Roy Taylor from the Newcastle University, UK. “Short-duration T2D can be put into remission by primary care staff using a structured programme.”

The researchers said the study is a bit controversial and different from previous studies as it was conducted in a real-life setting, with nurses or dietitians delivering the weight-loss regimen. What is also interesting is that it appeared to be the only study to date with T2D remission as the primary outcome.

“These results are impressive and strongly support the view that T2D is tightly associated with an excessive fat mass in the body,” said Prof Matti Uusitupa from the University of Eastern Finland, Kuopio, in an accompanying editorial. “[T]he time of diabetes diagnosis is the best point to start weight reduction and lifestyle changes because the motivation of the patient is usually high …” [Lancet 2017;doi:10.1016/S0140-6736(17)33100-8]

It is easy to lose weight but difficult to maintain weight loss. The bigger challenge is how to avoid weight rebound in the long term, added Lean. The ongoing DiRECT trial will seek to determine if weight loss and remission are achievable in the long term.

The “Deadly Breast Cancer Gene” is a Myth, Lancet Study Confirms

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A powerful new Lancet study reveals that the so-called breast cancer susceptibility genes — BRCA 1 and BRCA 2 — do not, in fact, cause breast cancer. This means Angelina Jolie’s prophylactic mastectomy, for instance, was for naught. 

A new Lancet Oncology study, reported widely in the mainstream media, confirms that the so-called “breast cancer genes” (i.e. BRCA1/2) do not have the power to determine breast cancer survival outcomes, as widely believed by the medical profession.

The study, titled “Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study“, found:

“[There is] no significant difference in overall survival or distant disease-free survival between patients carrying a BRCA1 or BRCA2 mutation and patients without these mutations after a diagnosis of breast cancer.”

The BBC broke down the study’s findings in greater detail, in their online article titled, “Breast cancer survival ‘unaffected by faulty gene“:

“The study, published in The Lancet Oncology, found 12% of 2,733 women aged 18 to 40 treated for breast cancer at 127 hospitals across the UK between 2000 and 2008 had a BRCA mutation.

“The women’s medical records were tracked for up to 10 years.

“During this time, 651 of the women died from breast cancer, and those with the BRCA mutation were equally likely to have survived at the two-, five- and 10-year mark as those without the genetic mutation.

“This was not affected by the women’s body mass index or ethnicity.

“About a third of those with the BRCA mutation had a double mastectomy to remove both breasts after being diagnosed with cancer. This surgery did not appear to improve their chances of survival at the 10-year mark.”

The study has powerful implications for the future of breast screening programs and the standard of care for ‘breast cancer’ patients. So powerful is the belief that BRCA genes ’cause’ breast cancer, that millions around the world consider it fact. Celebraties like Angelina Jolie have added fuel to the fire of this dangerous myth, by electing to have her breasts removed ‘prophylactically’ due to her BRCA status and the recommendations of her physicians. I discussed questionable nature of this decision in a previous article, titled “Did Angelina Jolie Make A Mistake By Acting On The ‘Breast Cancer Gene’ Theory?”, and elaborated further on the topic in an article titled “Pinkwashing Hell: Breast Removal as a Form of ‘Prevention“.

In the excerpt below from the Discussion portion of the new Lancet Oncology paper, researchers not only failed to find a causal link between the BRCA genes and overall breast cancer survival, but noted that some BRCA mutation carriers (diagnosed with triple negative breast cancer) may actually have improved survival relative to non-mutation carriers:

“We found no clear evidence that either BRCA1 or BRCA2 germline mutations significantly affect overall survival with breast cancer after adjusting for known prognostic factors. Decisions about timing of risk-reducing surgery should take into account primary tumour prognosis and patient preference. BRCA mutation carriers presenting with triple-negative breast cancer might have an improved survival during the first few years after diagnosis compared with non-carriers, although immediate bilateral mastectomy did not account for this advantage. Finally, analysis of early outcome data from trials exploring BRCA-deficient tumour treatment in patients with triple-negative breast cancer should be interpreted with caution in view of the possible early survival advantage for BRCA mutation carriers.” 

While this finding may be surprising to those who have been led to believe that the BRCA gene ‘mutation’ status is a death sentence, we have spent the past few years debunking this  misinformation by looking at the non-industry funded evidence itself. Millions of women have already been needlessly traumatized by overdiagnosis and overtreatment of non-cancerous, indolent growths of epithelial origin such as ductal carcinoma in situ (DCIS). The “BRCA gene causes breast cancer” meme is another example of a mythical entity which has brought significant harm to women in the name of ‘saving  lives.’ It has been leveraged by private and governmental interests alike to corral populations into cancer screening programs, whose results have often run contrary to their stated objectives of preventing suffering.

New Dressing for Diabetic Foot Ulcer Healing: Lancet

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https://speciality.medicaldialogues.in/new-dressing-for-diabetic-foot-ulcer-healing-lancet/

Drug-Resistant Tuberculosis

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Executive Summary

“Practices for the management of individual patients in settings with a high tuberculosis burden are not sufficient to prevent the emergence, amplification, and spread of drug-resistant tuberculosis” is one of the key messages from The Lancet Respiratory Medicine Commission, led by Keertan Dheda from the University of Cape Town, South Africa. The Commission focuses on multidrug-resistant, extensively drug-resistant, and incurable tuberculosis, and highlights the growing burden of disease, its implications for patient management, as well as social and legal aspects. The authors also provide practical solutions for tackling emerging resistant cases—an exponentially increasing concern in high-burden countries.

Read more: http://thelancet.com/commissions/drug-resistant-tuberculosis?dgcid=twitter_social_lancet

source: the Lancet

Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study.

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Background

Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden.

Methods

We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally.

Findings

Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1–100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants.

Interpretation

Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined.

Source:Lancet