‘Three strikes and rethink,’ an unspoken mantra in healthcare, was legally established on 23rd September 2025, thanks to ‘Jess’s rule,’ the patient safety initiative launched to improve diagnostic practices in primary care across England. The initiative was named after Jessica Brady, a 27-year-old woman who tragically passed away in December 2020 after more than 20 fruitless general practitioner (GP) consultations and a delayed, terminal stage 4 adenocarcinoma of the colon. Advocated by Andrea Brady (Jess’s mother) in conjunction with the Royal College of General Practitioners (RCGP) and National Health Services England, the rule mandates GP practices to rethink diagnoses and consider further investigations should patients fail to improve or further deteriorate after three consultations.

In several studies assessing the diagnostic time in primary care, young patients and Black, Asian, and Minority ethnic (BAME) group patients consistently had longer intervals between first presentation and diagnosis, compared to their Caucasian counterparts. It is hoped that the new initiative can tackle such diagnostic disparities in the UK and prevent late presentations of disease.

Jess’s rule, like Martha’s rule (the right of the patient or family to advocate for escalation of treatment, if visibly deteriorating), is a key addition to a list of patient safety initiatives within the UK, which promote patient autonomy and place an emphasis on extending safe and effective healthcare to all. It is important to remember that age does not preclude the development of serious disease, and unexplained symptoms should not be ignored.

SAHIL SHAH, England

ORCID iD: 0009-0006-5328-335X

Many children (n=24) have died in Madhya Pradesh in October 2025 because they ingested possibly contaminated cough syrup. The fatalities have been traced to the consumption of Coldrif cough syrup, reportedly manufactured by Sresan Pharmaceuticals, based in Kanchipuram district, Tamil Nadu.

Several children in Khandwa and Shivpuri districts presented with acute renal failure after taking the syrup. Preliminary findings from the state health department and the Central Drugs Standard Control Organization (CDSCO) indicated that samples of Coldrif may have contained diethylene glycol (DEG) or ethylene glycol, toxic industrial solvents sometimes used improperly as adulterants in glycerine-based formulations. Both compounds can cause multi-organ failure, particularly acute kidney injury, when ingested.

Following the deaths, the Madhya Pradesh government ordered an immediate recall of the product and suspended the company’s manufacturing licence. The Drugs Controller General of India (DCGI) has initiated an independent investigation, while joint inspection teams comprising officials from CDSCO and the state drug control department have sealed the production premises. Samples from multiple batches have been sent to the Central Drugs Laboratory, Kolkata, for confirmatory testing.

The distribution of the product was largely confined to Madhya Pradesh, but neighbouring states have been alerted as a precaution. The state’s health minister has directed that all paediatric cough syrup samples in pharmacies be tested and that medical officers ensure prompt clinical management of children who may have consumed the syrup.

The tragedy has revived national concerns over pharmaceutical quality control and the enforcement capacity of state drug regulators. Several incidents of diethylene glycol contamination linked to Indian-manufactured cough syrups have been reported in recent years, notably in Jammu (2020), The Gambia (2022), and Uzbekistan (2022), each drawing international scrutiny of manufacturing oversight and raw material testing. Experts have reiterated that small-scale producers remain particularly vulnerable to lapses in supply-chain quality assurance and inadequate analytical verification. Public health specialists have called for systemic reform in post-market surveillance, regular third-party audits, and stricter vendor verification for excipients used in paediatric formulations.

As of now, toxicological confirmation of the contaminant in Coldrif remains pending. Post-mortem and laboratory analyses are expected to establish causality. Beyond the immediate legal and regulatory consequences, the case underscores persistent gaps in quality assurance and pharmacovigilance mechanisms within the domestic pharmaceutical sector.

NISCHAL P.M., Mysuru, Karnataka

ORCID iD: 0000-0003-3491-5500

Elevated concentrations of lead and uranium have been detected in the blood and hair of children, as well as in groundwater samples from Bathinda, Rupnagar, and Chandigarh (Punjab and Haryana). The findings emerged from a pilot study jointly conducted and published by Panjab University’s Geo-Environmental Research Laboratory, Chandigarh, and the Baba Farid Centre for Health Research and Action, Faridkot, on 28 September 2025.

The study analysed 149 blood samples, 137 hair samples, and 37 groundwater samples collected from children aged 5 to 15 years and their surrounding environments. The analysis showed that 39 of 149 children (26.2%) had blood lead levels exceeding the WHO safe limit (3.5 μg/dl). In Bathinda, 22 of 68 children (32.6%) recorded levels above the threshold, with some readings crossing 10 μg/dl and the highest at 16.5 μg/dl. In Rupnagar, 12 of 62 children (19.3%) showed elevated levels (average 6.4 μg/dl), while in Chandigarh, 5 of 19 children (26.3%) exceeded the limit (average 6.3 μg/dl).

Hair analysis indicated wider exposure. Of 137 hair samples tested, 54 (39%) contained lead concentrations above the WHO permissible limit of 2 μg/g. In Chandigarh, 15 of 19 children (79%) had elevated values, with concentrations up to 21.4 μg/g. In Rupnagar, 24 of 61 samples (39%) exceeded the limit (maximum 22.9 μg/g), while in Bathinda, 15 of 57 samples (26%) showed raised levels, including extreme readings reaching 218.7 μg/g.

Groundwater testing revealed uranium contamination in all 19 samples from Bathinda, each exceeding both the WHO and the Bureau of Indian Standards (BIS) permissible limits. In Rupnagar, 1 of 13 samples breached WHO guidelines, and 5 showed additional arsenic contamination. None of the 5 samples tested from Chandigarh crossed the thresholds. The results point to major regional variation, with Bathinda emerging as the most affected area. The Punjab State Human Rights Commission and the Chandigarh Human Rights Commission have now directed the respective administrations to conduct comprehensive surveys on heavy metal contamination, establish toxicology units in major government hospitals, ensure the availability of chelation therapy, and verify the functionality of reverse-osmosis filtration systems in schools and anganwadis.

Environmental and industrial regulators have been asked to identify potential sources of contamination, including emissions from thermal power plants, cement factories, and industrial effluents in the affected districts. The commissions have also emphasized that administrative or financial constraints cannot justify delays in remedial measures.

Lead and uranium exposure pose serious long-term health risks, particularly for children. Chronic exposure can result in neurodevelopmental impairment, learning deficits, renal dysfunction, and irreversible cognitive damage. Experts have recommended periodic biomonitoring, stricter environmental surveillance, and improved regulation of water and industrial waste disposal to prevent further exposure.

NISCHAL P.M., Mysuru, Karnataka

ORCID iD: 0000-0003-3491-5500

For the past year, Kerala has been witnessing a surge in cases of amoebic encephalitis (‘brain fever’). From May 2024 till mid-October 2025, there have been 129 reported cases of amoebic encephalitis with 29 casualties, including a sharp rise in the number of cases in the current year. The causative agents are Acanthamoeba and Naegleria fowleri. Following the Nipah virus outbreak in late 2023, the Ministry of Health, Kerala, made it mandatory for all cases of amoebic encephalitis to be reported from 2024 onwards.

The reported cases are dispersed, rather than concentrated, with multiple districts affected. Cases from Thiruvananthapuram alone were 36 (the highest in the state). People from all age groups, from a 3-month-old child to a 92-year-old man, have been affected. While the global mortality rate is over 90% for amoebic encephalitis, by virtue of early detection and diagnosis, Kerala has reduced it to a mere 26%. This change has been brought about by the quick establishment of detection centres in microbiology laboratories of medical colleges across the state.

Naegleria fowleri infects humans primarily through exposure to contaminated freshwater. Acanthamoeba, on the other hand, may invade through skin abrasions, apart from water sources. A recent report of an affected labourer in Kerala with no major exposure to water bodies suggests alternate routes of transmission besides contaminated water.

Most of the patients experienced mild symptoms, sometimes not even a fever. A small subset showed the characteristic neurological symptoms such as stiff neck, increased sensitivity to light, confusion, severe headache, seizures and even coma. There is no definite treatment for this disease as of now.

Kerala’s response has been impressive. In November 2024, the Government of Kerala issued the revised ‘One Health-based Multi-Pronged Action Plan,’ which aimed to optimize and strengthen preventive and control measures against the disease. The State public health laboratory in early 2025 developed molecular diagnostic tests to detect free-living amoebae. Presumptive diagnosis by analysis of cerebrospinal fluid samples is largely being done by Government medical colleges in Thiruvananthapuram and Kozhikode. Chlorination of public water sources is being done, and residents are being issued advisories to avoid bathing in unsafe ponds. Households are being advised to clean their residential tanks and pools. The drug miltefosine is being used for the treatment of primary amoebic encephalitis. Ascertaining the cause behind this abrupt increase in the number of cases is essential. Scientists warn that climate change might be one of the reasons behind this menace, as the amoeba prefers warmer waters to reside.

DEBJYOTI MANDAL, Kolkata, West Bengal

ORCID iD: 0009-0001-1100-7166

On 8th October 2025, the WHO released new guidelines recommending, for the first time, nutritional support for household contacts of tuberculosis (TB) patients in food-insecure settings. This important policy shift, detailed in the WHO consolidated guidelines on tuberculosis: Module 6: Tuberculosis and comorbidities, 2nd edition, was directly influenced by findings from a landmark study from India. The new guidelines now advocate for a comprehensive ‘household-centred response,’ urging member states to integrate nutritional assessment and food assistance into standard TB care.

The primary evidence behind this change is the ‘Reduction by activation of tuberculosis by improvement of nutritional status’ (RATIONS) trial. This field-based, cluster-randomized trial in Jharkhand, a state in eastern India, demonstrated that providing nutritional support to the household contacts of pulmonary TB patients reduced the incidence of all forms of TB by 39% (adjusted hazard ratio [aHR] of 0.59) and infectious pulmonary TB by 48% (aHR 0.51). The study was published in The Lancet (Bhargava A, Bhargava M, Meher A, Benedetti A, Velayutham B, Teja GS, et al. Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India [RATIONS]: A field-based, open-label, cluster-randomised, controlled trial. Lancet 2023;402:627–40).

Key recommendations of the policy include: (i) nutritional assessment and counselling for all TB patients and their household contacts; (ii) provision of nutritional interventions (like food baskets) to TB patients with undernutrition; and (iii) provision of food assistance to prevent TB in household contacts in food-insecure settings.

Dr Anurag Bhargava, the RATIONS trial’s principal investigator, emailed this writer and explained that ‘unlike logistically challenging TB-specific interventions (like preventive treatment) or an effective vaccine (which is currently lacking), addressing undernutrition is a broad public health intervention with multiple other benefits for health, growth, development, and protection from other diseases.’ Dr Bhargava continued, ‘Members of a household with a patient with TB are at high risk of developing TB because of close contact as well as recent infection from a patient with active infectious TB, as well as the shared environment of risk factors like poverty and undernutrition. Consider the implications of contact of an undernourished family member with a patient with drug-resistant TB. The current recommendations for nutritional assessment, counselling and nutritional support of household members for the duration of the patient’s treatment, based on the current evidence, are likely to be an effective and cost-effective intervention …’ He added, ‘Tuberculosis is a biosocial problem that requires biosocial solutions… The RATIONS trial has shown that nutritional support can improve TB treatment outcomes and complement other interventions for TB prevention.

AKHIL R NAIR, Pune, Maharashtra

ORCID iD: 0000-0003-2560-5279

The Impact of Research and Innovation Scale (IRIS) was proposed by the Indian Council of Medical Research (ICMR) as a scale to measure the impact of research projects funded by the organization in biomedical, public health, and allied areas. To date, tools like h-index or i10-index, Almetric attention score, and translational research impact scale (TRIS) have been used for evaluation of research impact, but thus far, an ideal tool has proven elusive.

ICMR-IRIS aims to convert all domains of research impact to a single measure using a new metric, the publication-equivalent (PE). A publication in an indexed, peer-reviewed journal reporting results or methods of primary research, or a systematic review and meta-analysis, is considered 1 PE. A research publication that has resulted in a change of clinical guidelines or public health programmes is assigned an additional 10 PEs (i.e. it is equivalent to 10 research papers). Similarly, a national or international granted patent is assigned 5 PEs, and that of a commercial device being used at scale is 20 PEs. A research publication in a journal with an impact factor >10, one that has received >100 citations, is assigned an additional score of 2 PE. In ICMR-IRIS, translational research involving research studies evaluating health technologies developed by industry or others is awarded 3 PE. ICMR-IRIS is being used for the evaluation of the research impact of ICMR intramural and extramural research grants programmes; 5 of the 8 indicators of ICMR-IRIS have also been used to assess the research impact of each of the ICMR research institutes.

The scope of ICMR-IRIS extends beyond citations. Further, standardization using PE is expected to facilitate comparison of research impact across research in biomedical, public health, and allied areas. However, it has also been felt that this method of assessment may discourage researchers in pursuit of career progress from pursuing non-PE fetching forms of publication like case reports, editorials, opinion pieces, perspectives, narrative reviews; such an attitude could ultimately be non-beneficial to the spirit of medical research in the context of public good.

ALLADI MOHAN, Tirupati, Andhra Pradesh

ORCID iD: 0000-0002-3214-9884

The Nobel Prize for Physiology or Medicine in 2025 was awarded to Mary E. Brunkow, (Princeton University, Institute of Systems Biology, Seattle, USA), Fred Ramsdell (University of California; Sonoma Biotherapeutics, San Francisco, USA), and Shimon Sakaguchi (Kyoto University; Immunology Frontier Research Center, Osaka University, Japan), for their seminal research work leading to the discovery of regulatory T cells contributing to peripheral immune tolerance that prevents the immune system from attacking our own body. This remarkable contribution has found its application in the treatment of cancers, the management of autoimmune diseases, and in preventing rejection of transplanted organs, etc. The story of this discovery is a reminder that the culture of science lies in sharing and liaising across geographical boundaries.

T cells identify any invading pathogen, trigger an immune attack, and eliminate the pathogen. The T-cell receptors that recognise the body’s own proteins or endogenous antigens trigger an immune response, leading to tissue destruction as in autoimmune disorders. It was known by the 1980s that maturation processing of T-cells in the thymus of a neonate eliminated the T-cells that carried receptors against endogenous proteins, termed central tolerance. However, some T-cells escape this selection process and pose the threat of autoimmunity.

Shimon Sakaguchi, then working at the Aichi Cancer Research Centre, Nagoya, Japan, conducted experiments on mice whose thymus had been removed and used injections of isolated CD4 T cells in such mice to understand the post-thymus regulatory mechanisms that keep the T-cells against self under check. After more than a decade of work, he reported a new kind of T cell in 1995 in J Immunol (Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155: 1151–64.), that served the role of keeping the autoimmune T cells quiescent, and named them regulatory T cells. These cells had both CD25 and CD4 antigens on their surface. However, more proof was needed to accept this theory.

The proof came from an unexpected source that had its beginning in the 1940s. As a part of the Manhattan Project for the development of the atom bomb, researchers were studying the effects of radiation on mice in a laboratory at Oak Ridge, Tennessee. In this experiment, some male mice were born with scaly, flaky skin, enlarged spleen and lymph nodes and lived only for a few weeks. They were named the scurfy strain, and the mutation resulting in massive immune destruction in them was found to have an X-linked inheritance pattern.

Several decades later, in the 1990s, Mary Brunkow and Fred Ramsdell, who worked at a biotech company, Celltech Chiroscience in Bothell, Washington, USA, that developed pharmaceuticals for autoimmune diseases, started studying the scurfy mouse model. They were able to identify the mutant FOXP3 gene in these mice, and reported it in Nature Genetics in 2001 (Brunkow ME, Jeffery EW, Hjerrild KA, Paeper B, Clark LB, Yasayko SA, Wilkinson JE, Galas D, Ziegler SF, Ramsdell F. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse. Nat Genet 2001;27:68–73). This remarkable step further led to the understanding and proof by Sakaguchi and other researchers that the FOXP3 gene controls the regulatory T cells. The combined work opened the doors for a promising use of regulatory T cells in therapeutics.

Meanwhile, the IgNobel prizes were awarded again. Instituted in 1991 by the magazine Annals of Improbable Research, for research that makes you ‘laugh, then think,’ the 35th Annual IgNobel awards ceremony was held at Boston University, Boston, USA, on 18th September 2025.

The award winners related to human medicine included Julie Menella and Gary Beauchamp in Paediatrics for their research, which showed that if lactating mothers eat garlic, the breast milk smells stronger and results in babies being attached longer and drinking more milk (Mennella JA, Beauchamp GK. The effects of repeated exposure to garlic-flavoured milk on the nursling’s behaviour. Pediatr Res 1993;34:805–8; and the late Dr William Bean in literature, for his 35 year-long study on growth of fingernails (Bean WB. Nail growth. Thirty-five years of observation. Arch Intern Med 1980;140:73–6); and to Rotem and Daniel Naftalovich along with Daniel Greenway for investigating whether eating Teflon can lead to satiety without increasing the calorie intake (Naftalovich R, Naftalovich D, Greenway FL. Polytetrafluoroethylene ingestion as a way to increase food volume and hence satiety without increasing calorie content. J Diabetes Sci Technol 2016;10:971–6).

The ceremony also featured a 24/7 talk, in which Dr Trisha Pasricha, a gastroenterologist at Harvard Medical School, Boston, USA, spoke for 24 seconds and then summed up her talk in 7 words, on the topic of smartphone usage and haemorrhoid formation (Ramprasad C, Wu C, Chang J, Rangan V, Iturrino J, Ballou S, et al. Smartphone use on the toilet and the risk of haemorrhoids. PLoS One 2025;20:e0329983).

JYOTI NATH MODI, Bhopal, Madhya Pradesh

ORCID iD: 0000-0002-0626-1637