Congenital myopathies are a heterogeneous group of rare, inherited muscle diseases that typically announce themselves in infancy or childhood through progressive muscle weakness. The genetic defects behind these conditions disrupt the fundamental machinery of the muscle fiber, affecting structures such as the contractile apparatus itself, the systems that handle calcium within muscle cells, and the mitochondria that supply the energy muscle contraction demands. The resulting weakness can compromise the ability to walk, to rise from the floor, and to use the arms and hands for everyday tasks, and in the most severe cases it extends to the respiratory muscles, threatening breathing itself. Because the underlying genetic faults cannot currently be repaired, clinical care has been confined to symptom management: physical therapy, orthopedic interventions, respiratory support, and vigilance against complications. There has been no drug that meaningfully changes what these children can do with their bodies day to day.

The new study, led by researchers at the University of Gothenburg together with clinicians at the Queen Silvia Children’s Hospital, set out to test whether salbutamol, known in some countries as albuterol, could change that picture. Salbutamol is a beta-2 adrenergic agonist, a molecule that stimulates beta-2 receptors and has been inhaled by asthma patients for decades because it rapidly relaxes the smooth muscle of the airways. But when the same compound is taken orally rather than inhaled, it reaches the bloodstream in concentrations that allow it to act on skeletal muscle as well. Beta-2 receptors on muscle fibers participate in signaling pathways that influence protein turnover, and experimental work has shown that beta-2 agonists can stimulate the synthesis of muscle protein, tilting the balance between muscle building and muscle breakdown toward growth. This anabolic side effect is precisely why the drug attracted the attention of neuromuscular researchers interested in conditions defined by weakness rather than by airway disease.

The trial, known as COMPIS, enrolled 18 individuals aged 6 to 16, every one of whom had a congenital myopathy confirmed by genetic testing. The design was a randomized, open-label, blinded-endpoint crossover study, a format well suited to rare diseases where patient numbers are inevitably small. Half the participants began with 24 weeks of oral salbutamol added to their usual care, while the other half continued with usual care alone; after that period, the groups switched. Because each child served as their own control, the comparison between treatment and no treatment could be made within the same individual, reducing the noise that genetic heterogeneity and differing disease severity would otherwise introduce. Assessors scoring the outcomes remained blinded to which treatment period the measurements came from, protecting the results from observer bias even though participants and clinicians necessarily knew what drug was being taken.

The primary outcome was motor function measured with the MFM-32, a standardized rating scale developed specifically for neuromuscular diseases that evaluates what patients can actually do, from standing and transferring to handling objects. After the salbutamol periods, motor function scores were on average 3.61 points higher than after the standard-care periods. In the world of neuromuscular medicine, where meaningful change on such scales is often measured in single digits over years, a difference of that magnitude achieved in half a year is regarded as a clear and clinically relevant improvement. Muscle strength told the same story. Grip strength in the dominant hand increased by the equivalent of roughly 1.5 kilograms during salbutamol treatment compared with standard care alone, and although increases in other tested muscle groups did not reach statistical significance, the direction of change was consistently favorable.

Perhaps the most striking results came from the functional tests performed by the eleven participants who were able to walk. In the six-minute walk test, a standard measure of endurance and mobility in neuromuscular research, the children covered an average of 435 meters before the trial. During salbutamol treatment, that distance rose to 473 meters, an additional 38 meters of walking that represents real, visible gains in stamina for children whose energy reserves are severely limited. For context, children of similar age with typical muscle function walk about 600 meters in six minutes, so the drug moved these patients meaningfully closer to normal performance. The researchers also timed how quickly the ambulatory children could rise from the floor to a standing position, a classic test of proximal muscle power. Before treatment, the task took an average of 8.29 seconds; with salbutamol, it took 6.39 seconds. A child with normal strength completes the same movement in one to two seconds, which illustrates both how impaired these children were and how much ground the medication helped them recover.

The benefits extended beyond the limbs. Forced vital capacity, the volume of air a person can exhale after taking the deepest possible breath, was on average approximately 0.2 liters higher during salbutamol treatment than during standard care. In congenital myopathies, weakening of the respiratory muscles is one of the most feared aspects of the disease, driving recurrent chest infections, sleep-disordered breathing, and eventually the need for ventilatory support. A measurable improvement in respiratory muscle performance, even a modest one, therefore carries potential importance well beyond the numbers themselves. The treatment was well tolerated throughout the study, and no serious side effects were reported, an encouraging safety profile for a drug whose tolerability in children is already extensively characterized from decades of asthma use.

For the families involved, the significance of the trial is captured less by rating scales than by daily life. Eva Michael, a doctoral student in pediatric neurology at the University of Gothenburg and a specialist physician at the Queen Silvia Children’s Hospital, described the change she observed in the children’s everyday functioning. Simply the fact that they had more energy, she noted, that they could manage a full day at school followed by activities and homework without becoming completely exhausted and bursting into tears, is very important for these children. That framing underscores a point that clinical trials in rare diseases often struggle to convey: for a child who cannot sustain a normal day, an incremental gain in endurance can translate into participation in school, friendships, and family life that would otherwise be out of reach.

The researchers themselves are careful about what the study can and cannot establish. With 18 participants at a single center in Sweden, the trial is small, and congenital myopathies encompass many distinct genetic subtypes that may respond differently to a beta-2 agonist. The open-label design, with blinded endpoint assessment, cannot fully exclude expectation effects on the part of participants and families. Michael and her colleagues emphasize that the findings need to be confirmed in larger international studies involving longer treatment periods and follow-up before any change to clinical practice. Even so, the results suggest that oral salbutamol could potentially become a symptom-relieving treatment option for children and adolescents with congenital myopathies in the future, pending the development of other drugs that might address the diseases more fundamentally.

If those larger trials succeed, the implications would extend well beyond this single rare disease community. Salbutamol is cheap, globally available, and already approved for pediatric use, meaning that a positive confirmation could translate into treatment access far faster than a newly developed molecule ever could. The trial also adds to a growing body of evidence that repurposing established drugs can open doors in neuromuscular medicine, where the small patient populations of individual genetic disorders rarely justify the cost of developing therapies from scratch. For now, the COMPIS results stand as a carefully controlled demonstration that a familiar asthma inhaler medication, taken by mouth, can give children with congenital myopathies something they have never had before: a medicine that measurably strengthens the muscles they rely on to stand, to walk, and simply to get through their day.

Subject of Research: Oral salbutamol treatment for motor function and muscle strength in children with congenital myopathies

Article Title: Asthma medication improved motor skills and strength in children with muscle disease

Article References: Asthma medication improved motor skills and strength in children with muscle disease. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: salbutamol, congenital myopathies, neuromuscular disease, randomized crossover trial, muscle strength, motor function, pediatric neurology, six-minute walk test, forced vital capacity, drug repurposing, University of Gothenburg, EClinicalMedicine

The review, published in eClinicalMedicine by Maria Vedechkina, Prerna Banati, and Valentina Baltag, systematically mapped instruments used to measure adolescent digital technology use across 533 studies published between 2014 and 2025. Conducted under PRISMA-ScR guidelines with a protocol registered on the Open Science Framework, the team searched PubMed, Web of Science, and Scopus using a strategy that combined population terms such as adolescent, teen, and youth with device and media terms and measurement keywords. After removing 711 duplicates from 1,600 records and screening 583 full texts, the authors retained 533 studies spanning more than 20 countries, predominantly in East Asia, North America, and Europe.

The timing matters. Only 120 of the included studies appeared before 2020; the rest were published in the last five years, reflecting the surge of research interest that followed the COVID-19 pandemic, when remote learning and online socialisation deepened adolescents’ reliance on digital platforms. Governments and bodies such as the World Health Organization are increasingly pressed to issue guidance on balancing the risks and benefits of digital engagement, and young people themselves have voiced concerns about technology-facilitated gender-based violence, misinformation, and weak digital safeguards. But sound policy, the authors argue, requires sound measurement first—and that is precisely what is missing.

From the 533 studies, the team identified 135 validated instruments, most of them brief self-report questionnaires of between 4 and 51 items. Just over half of the studies, about 59 percent, used at least one validated instrument, while the remaining 41 percent relied on study-specific, ad hoc questions—often a single item asking how many hours per day an adolescent spends on social media. Strikingly, only two alternative assessment methods were found: passive data collection via a mobile app. Despite the availability of device logs, screen-time tracking, and ecological momentary assessment, the field remains almost entirely dependent on teenagers remembering and honestly reporting their own behaviour, a method known to suffer from recall error and social desirability bias.

What the instruments measure is as revealing as how they measure it. Applying a logic-model framework that distinguishes inputs, processes, outputs, outcomes, and impacts, the reviewers found that duration (79 instruments) and frequency (70) dominated, followed by addiction (47) and problematic use (43). Over two-thirds of the identified tools were explicitly designed to detect pathological or addictive use, borrowing clinical criteria such as withdrawal, tolerance, dependence, and loss of control. Familiar names include the Internet Addiction Test, the Smartphone Addiction Scale, and the Bergen Social Media Addiction Scale. By contrast, fewer than 2 percent of instruments assessed positive dimensions of digital technology use, such as enjoyment, peer bonding, creativity, or skill-building.

The consequences of this risk-heavy orientation are profound. When nearly every tool is built to find dysfunction, the resulting evidence base paints a distorted picture of adolescent digital life—one heavy on deficiency and light on the nuanced middle ground where most use likely falls. Motivations for engagement, such as emotion regulation, identity exploration, or social support, were captured by only about ten instruments. Contextual factors fared worse: parenting practices and family media rules appeared in just four tools, while peer influence and school context were strikingly absent. By overlooking the social and motivational environment, the authors warn, existing measures risk conflating elevated use with harmful use.

Developmental appropriateness emerged as another critical weakness. The reviewers classified most instruments as age-insensitive: they had not been developed or validated specifically for adolescents aged 10 to 19, contained no developmentally specific content such as schoolwork impairment or parental mediation, and lacked age-referenced norms. Only about 12 percent, including the Social Media Disorder Scale, were built and validated specifically for adolescents. Widely used tools such as the Internet Addiction Test were adapted from adult versions with minimal modification, and few incorporated adolescent input during formative work. Generic wording like neglecting responsibilities does little to reflect the realities of teenage life, where peer dynamics, school demands, and family supervision shape how technology is used.

Cross-cultural applicability is similarly thin. Although many instruments have been translated—Chinese, Korean, Spanish, and French were the most common languages—genuine cross-cultural adaptation and validation were rare. Most studies reported translation without content modification or validation across cultural groups, and socioeconomic factors such as device access, digital norms, and urban-rural differences were seldom considered. Roughly 35 percent of the included studies presented data from low- and middle-income countries, but Africa and Latin America were notably underrepresented. The upshot is that instruments are applied globally while remaining tailored to none of the diverse sociocultural settings in which adolescents actually live.

Psychometric quality varied widely. Using an adapted version of the COSMIN guidelines, the team appraised content validity, construct validity, internal consistency, and test-retest reliability. Internal consistency was commonly reported and generally satisfactory, but validity metrics were inconsistent, often limited to exploratory factor analysis or simple correlations. Independent validation studies were scarce, and interpretability and responsiveness were rarely assessed. Only 19 instruments, about 14 percent, earned a strong overall rating, typically through multiple validations and transparent reporting; 14 instruments, about 10 percent, were rated poor, often due to unclear methodology or validation conducted solely by the original developers. The majority, 76 percent, fell in the moderate category.

Perhaps the most fundamental problem is conceptual fragmentation. Definitions of screen time, problematic use, and high usage varied enormously across studies. Some tools defined use as general screen time, others focused on specific platforms, and still others required a clinical threshold on a behavioural scale; some classified adolescents as problematic users based purely on daily hours. Without agreed core constructs or standardised metrics, studies measuring different phenomena under the same label cannot be meaningfully compared or synthesised, stalling cumulative knowledge. The pace of technological change compounds the issue: instruments developed in 2015 contain no questions about TikTok, AI companions, or live-streaming, and almost none captured the commercial dimensions of digital life, such as the ubiquitous targeted advertising of food and beverages to minors.

The review, which forms part of the WHO’s broader effort to inform global policy on adolescent digital health, closes with targeted recommendations. The authors call for holistic instruments co-designed with young people that capture positive, normative, and qualitative dimensions of use, including digital literacy, creativity, and social connection. They urge consensus on core constructs and standardised definitions to enable cross-study comparison, rigorous validation across demographic and cultural groups, and multi-method approaches that combine self-report with passive device logging, wearable sensors, and ecological momentary assessment to reduce recall bias. They also caution researchers against clinging to legacy measures for the sake of comparability at the expense of relevance. Emerging tools such as the Cyber Virtues Scale, the EHealth Literacy Scale, and the Digital Media Use Effects Scales for Adolescents suggest the field may be beginning to broaden, but progress since a 2021 review flagged the same gaps has been minimal. Better measurement, the authors conclude, is not an end in itself but the means to understanding—and ultimately improving—adolescent development in the digital age.

Subject of Research: Measurement instruments for adolescent digital technology use

Article Title: Systematized scoping review of instruments for measuring adolescent digital technology use

Article References: Vedechkina, M., Banati, P., & Baltag, V. (2026). Systematized scoping review of instruments for measuring adolescent digital technology use. eClinicalMedicine, 101, Article 104247. https://doi.org/10.1016/j.eclinm.2026.104247

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104247

Keywords: adolescent health, digital technology use, screen time, measurement instruments, scoping review, psychometrics, internet addiction, WHO, cross-cultural validation, self-report bias, digital wellbeing, eClinicalMedicine

The research, published in eClinicalMedicine and based on data from the St. Jude Lifetime Cohort Study, found that adult survivors of childhood cancer living in the most vulnerable neighborhoods face roughly double the risk of accumulating chronic health conditions compared with survivors living in the least vulnerable communities. Vulnerability, in this context, is not a vague notion of disadvantage. The researchers measured it through concrete community-level indicators, including low per-capita income, poor walkability, limited access to nearby healthcare facilities, fewer healthy food options, and the socioeconomic and demographic composition of the area. The study is among the first to track how these environmental conditions interact with clinical outcomes over time in a survivor population followed with repeated assessments.

Scientists had already established that individual socioeconomic characteristics, such as a survivor’s own income, education, and insurance status, influence long-term health after childhood cancer. What remained unclear was whether the surrounding social and physical environment exerted an independent effect. To answer that question, the St. Jude team compared neighborhood vulnerability indicators against longitudinal clinical data from survivors enrolled in the St. Jude LIFE cohort, which has been monitoring participants since 2007 with periodic comprehensive health evaluations. This repeated-measure design allowed the investigators to observe not just a snapshot of disease but the progression of multimorbidity, the accumulation of multiple chronic conditions, across years of follow-up.

The headline finding, that neighborhood vulnerability doubles the overall chronic disease burden, is striking on its own. But when the researchers disaggregated the data by specific disease categories rather than total burden, the associations became even more dramatic, and arguably more actionable. Survivors in neighborhoods with poor walkability showed a fivefold increased risk of metabolic disease and a tenfold increased risk of heart attack. These effect sizes, the authors note, provide first-of-its-kind information that can help researchers prioritize which community barriers deserve the closest scrutiny in future intervention studies, a critical consideration given that neighborhood-level interventions demand substantial time, money, and coordinated effort.

The study also revealed that environmental and individual risk factors do not operate in isolation; they compound one another. Survivors who relied on public insurance and simultaneously lived in one of the most vulnerable neighborhoods faced a sevenfold increased risk of muscle and cardiac problems. This intersectional pattern underscores a central challenge in survivorship research: disentangling how personal circumstances, treatment history, and community context jointly shape health trajectories. The authors caution that identifying the most effective ways to support patients and reduce their chronic disease risk will require further study, precisely because these relationships are so intertwined.

For corresponding author I-Chan Huang, PhD, of the St. Jude Department of Epidemiology & Cancer Control, the findings represent both a warning and an opportunity. The team found that neighborhood conditions likely play a significant role in how survivors’ health outcomes evolve over time, which means researchers now have the beginning of what they need to design effective, accessible, and affordable support and interventions to overcome environmental barriers and improve survivors’ health trajectories. In other words, the same data that expose a problem also sketch a roadmap for addressing it.

Co-author Melissa Hudson, MD, of the St. Jude Department of Oncology, placed the findings in the context of decades of progress in pediatric oncology. Over the past several decades, she explained, substantial efforts to improve outcomes for children with cancer have concentrated on limiting the intensity of therapies most strongly linked to chronic health problems, a strategy that has successfully reduced late effects for newly treated patients. But for the large and growing population of survivors treated in earlier eras, and even for those on modern protocols, the new results serve as a reminder that survivorship care must also consider factors such as access to nutritious food, safe venues for physical activity, and reliable primary medical care, particularly for those living in disadvantaged neighborhoods.

The practical implications extend well beyond Memphis, where the cohort is centered. As the population of childhood cancer survivors continues to expand, health systems and policymakers face mounting questions about how to deliver long-term care that accounts for where patients actually live. A survivor who wants to exercise to reduce cardiovascular risk cannot easily do so without safe sidewalks or parks. A survivor counseled to eat a heart-healthy diet may live in a neighborhood where fresh produce is scarce or unaffordable. A survivor urged to attend regular surveillance screenings may face a lengthy journey to the nearest clinic. The study’s findings suggest that these environmental realities are not peripheral concerns but measurable determinants of whether survivors develop the very conditions survivorship programs aim to prevent.

Huang emphasized that the modifiability of neighborhood factors is what makes the research promising. Treatment history remains the most significant determinant of a survivor’s chronic disease risk, and the therapies a patient received decades ago cannot be changed. But access to everyday resources in the surrounding community can be, and the study’s authors argue that community-level supports can begin to be changed and tested today. That framing shifts the conversation from fatalism to intervention: rather than viewing a survivor’s risk as fixed at the end of treatment, clinicians and researchers can evaluate the environments patients return to and design supports, from improved food access to better-connected primary care, that address modifiable barriers.

The research was conducted by a team led by first author Jaesung Choi, PhD, alongside Huang and colleagues at St. Jude, with additional contributions from Wake Forest University School of Medicine and Washington University in St. Louis. It was supported by grants from the National Cancer Institute and by the American Lebanese Syrian Associated Charities, the fundraising and awareness organization of St. Jude. As follow-up studies test which community-level interventions deliver the greatest benefit, the message for the survivorship community is already clear: the zip code a survivor returns home to may matter nearly as much as the treatment chart in the medical record, and addressing neighborhood vulnerability could become an essential component of long-term cancer care.

Subject of Research: The association between neighborhood-level social and environmental vulnerability and the longitudinal progression of chronic disease among adult survivors of childhood cancer.

Article Title: Neighborhood conditions linked to childhood cancer survivors’ long-term health

Article References: Neighborhood conditions linked to childhood cancer survivors’ long-term health. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: childhood cancer survivors, neighborhood vulnerability, chronic health conditions, St. Jude Lifetime Cohort Study, health disparities, multimorbidity, walkability, food access, healthcare access, survivorship care, eClinicalMedicine, social determinants of health

The technical distinction at the heart of the argument is deceptively simple. Relative risk reduction describes the proportional decrease in event risk between two groups, calculated as one minus the risk ratio, expressed as a percentage. Absolute risk reduction, by contrast, is the raw difference in cumulative event rates between the control and treatment groups at a specified time point. The number needed to treat is simply the inverse of that absolute reduction: it tells you how many patients must be treated, over that same period, to prevent one additional event. For time-to-event outcomes, the authors stress that these absolute measures should be estimated from cumulative event probabilities using appropriate survival methods, not by crudely subtracting annualized incidence rates. A hazard ratio of 0.79, for example, indicates an estimated 21 percent lower hazard assuming the proportional hazards interpretation holds, and is emphatically not the same thing as a 21 percent reduction in cumulative risk.

The consequences of conflating these measures are vividly illustrated by the PIONEER-6 trial of oral semaglutide. A physician reviewing the study sees a hazard ratio of 0.79 for major adverse cardiovascular events and may reasonably conclude that semaglutide offers a substantial cardiovascular benefit. Yet the trial actually reported such events in 3.8 percent of patients on the drug versus 4.8 percent on placebo over a median follow-up of 15.9 months, an absolute difference of roughly one percentage point and a number needed to treat of approximately 100 over that period. The distinction is not a statistical nicety. It directly shapes how clinicians, patients, guideline committees, and policymakers weigh therapeutic benefit, and it can mean the difference between an enthusiastic endorsement and a measured one.

The problem extends far beyond cardiology. In oncology, the CLEOPATRA trial showed that adding pertuzumab to trastuzumab and docetaxel improved overall survival in HER2-positive metastatic breast cancer with a hazard ratio of 0.68; in an eight-year landmark analysis, overall survival was 37 percent versus 23 percent, an absolute gap of roughly 14 percentage points. In neurology, the AFFIRM trial of natalizumab in relapsing multiple sclerosis reported a 68 percent reduction in annualized relapse rate, while the proportion of patients remaining relapse-free at two years was 67 percent versus 41 percent, an absolute difference of 26 percentage points. Across therapeutic areas, relative and absolute measures tell complementary but strikingly different stories, and the discrepancy is pervasive.

The authors assembled a comparison of seven major cardiorenal outcome trials to show how widely absolute benefit varies even when relative effects look similar. In CREDENCE, canagliflozin produced a hazard ratio of 0.80 for major adverse cardiovascular events, with events in 9.9 percent of treated patients versus 12.2 percent on placebo over a mean follow-up of 2.62 years, a crude absolute difference of 2.3 percentage points; the trial’s own survival-based estimate at 2.5 years was an absolute risk reduction of 2.5 percentage points, corresponding to a number needed to treat of 40. In HARMONY Outcomes, albiglutide yielded a hazard ratio of 0.78, with events in 7.1 percent versus 9.0 percent over 1.6 years, an absolute difference of 1.9 percentage points and a number needed to treat of roughly 53. Viewed through hazard ratios alone, these agents appear broadly comparable; the absolute measures reveal differences in benefit that are strongly driven by baseline event risk and follow-up duration rather than by any intrinsic superiority of one molecule over another.

The kidney field illustrates a further layer of complexity. Canagliflozin in CREDENCE and empagliflozin in EMPA-KIDNEY showed broadly similar relative effects on renal outcomes, with hazard ratios of 0.70 and 0.72 respectively, yet the composite endpoints differed importantly between the trials. CREDENCE used a composite of doubling of serum creatinine, end-stage kidney disease, and renal or cardiovascular death, whereas EMPA-KIDNEY included kidney disease progression defined by a sustained 40 percent or greater decline in estimated glomerular filtration rate, end-stage kidney disease, sustained filtration below 10 milliliters per minute per 1.73 square meters, or renal death, together with cardiovascular death. DAPA-CKD used yet another composite built around a 50 percent or greater sustained decline in filtration rate. These differing definitions, eligibility criteria, baseline risk profiles, and follow-up durations all influence absolute event rates, and EMPA-KIDNEY enrolled a broader and overall lower-risk population. Apparent differences in absolute benefit across these trials therefore cannot be read as evidence of differential drug efficacy.

The stakes are rising because the volume of cardiovascular and kidney outcome trials involving GLP-1 receptor agonists and SGLT2 inhibitors has expanded rapidly, and these therapies are increasingly prescribed across cardiology, nephrology, endocrinology, and primary care. As treatment indications broaden, clinicians need measures that communicate not merely whether a therapy works but how much benefit an individual patient can realistically expect. Absolute measures are often already partially available in journals that report event rates alongside hazard ratios, from which attentive readers can estimate absolute effects themselves, but explicit reporting would make the calculations immediately accessible and reduce the risk of misinterpretation. Methodological evidence indicates that numbers needed to treat derived from differences in incidence rates can be biased, whereas estimates built on cumulative event probabilities from survival analysis are more appropriate.

One domain where absolute effects prove especially valuable is in weighing efficacy against safety. Relative risks alone are insufficient for balancing events caused by treatment against events prevented. The ASCEND trial, which tested aspirin against placebo in patients with type 2 diabetes, is an instructive example: the absolute reduction in serious vascular events was 1.1 percentage points, while the absolute increase in major bleeding was 0.9 percentage points. Placed side by side, those figures make the delicate balance between benefit and harm immediately apparent in a way that any pair of relative percentages never could. The recently published SOUL trial of oral semaglutide reinforces the point about method as well: over a median follow-up of 49.5 months, major adverse cardiovascular events occurred in 12.0 percent of treated patients versus 13.8 percent on placebo, a crude absolute difference of 1.8 percentage points, while the prespecified survival-based estimate at three years was an absolute risk reduction of 2.0 percentage points and a number needed to treat of 50. The corresponding annualized incidence rates, 3.1 and 3.7 events per 100 person-years, form an incidence rate difference that should never be converted directly into a conventional number needed to treat by taking its reciprocal.

The authors are careful to acknowledge that their argument cuts both ways. Relative measures have genuine and distinct advantages: where there is no strong evidence of effect modification, relative risk reductions are generally more generalizable beyond the trial population, because absolute event rates vary substantially with baseline risk, secular trends, geography, and selection criteria. For an individual patient, the most appropriate estimate of absolute benefit comes from applying an applicable relative treatment effect to that patient’s own baseline risk over a specified time horizon, rather than simply importing the trial’s figure. Moderate to large relative reductions in the 20 to 39 percent range represent substantial treatment effects even in lower-risk populations and can have major consequences for population-level disease burden. The proposal, then, is not that absolute measures should supplant relative ones, but that they should travel together.

There are also inherent limits to the number needed to treat itself. It is inherently time-specific, so a figure calculated over one year is not equivalent to one calculated over five, because treatment effects and baseline event rates change over time. Cardiorenal trials typically run for two to five years, yet in practice these therapies are used far longer, and longer treatment may yield greater cumulative benefit, though this cannot be assumed to accrue linearly given changing hazards, competing risks, adherence, and discontinuation. Trial populations are highly selected and may differ substantially from routine clinical practice. The proposed solution is straightforward: journals should routinely require absolute risk reduction, number needed to treat, and baseline event rates alongside relative measures, with the time horizon and estimation method clearly stated, ideally at standardized time points such as one, three, and five years. Guidelines and regulators should follow suit. Transparent communication of treatment effects, the authors conclude, is essential if clinicians and patients are to make genuinely informed decisions.

Subject of Research: Reporting of absolute risk reduction and number needed to treat in cardiorenal outcome trials

Article Title: Relative risk reduction is not enough: why cardiorenal trials should routinely report absolute risk reduction and number needed to treat

Article References: Zaitoon, H., Abdul-Ghani, M., & DeFronzo, R. A. (2026). Relative risk reduction is not enough: why cardiorenal trials should routinely report absolute risk reduction and number needed to treat. eClinicalMedicine, 101, Article 104258. https://doi.org/10.1016/j.eclinm.2026.104258

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104258

Keywords: absolute risk reduction, number needed to treat, hazard ratio, cardiorenal outcome trials, SGLT2 inhibitors, GLP-1 receptor agonists, semaglutide, chronic kidney disease, major adverse cardiovascular events, clinical trial reporting, eClinicalMedicine, evidence-based medicine

The EMBORES trial, a phase 2 study conducted at six French hepatobiliary centres and published in eClinicalMedicine, tested whether a temporary embolization using powdered absorbable gelatin sponge could induce enough growth of the future liver remnant to permit major hepatectomy. Between May 2018 and May 2021, the investigators enrolled 34 patients with primary or secondary liver malignancies who required preoperative portal vein embolization before resection of three or more liver segments. Two patients were excluded from the efficacy analysis, one because of consent withdrawal and one because of technical difficulty in catheterizing the portal branches, leaving 32 patients who underwent the temporary procedure and could be evaluated with CT volumetry.

The technique itself is elegantly simple in concept. Interventional radiologists dissolved powdered absorbable gelatin, marketed as Curaspon, in a mixture of 80 percent iodixanol contrast agent and 20 percent saline, producing a homogeneous, radiopaque suspension that could be seen fluoroscopically as it was injected. The mixture was selectively delivered into the portal vein branches supplying the diseased liver until complete angiographic occlusion was achieved, while flow to the future liver remnant was carefully preserved. Roughly four grams of gelatin powder were typically needed for a right portal vein embolization, and the amount was tailored to each patient’s portal anatomy. No coils or permanent agents were used at any point.

The results were striking. After a mean follow-up interval of 30 days, CT scans showed that the portal veins had completely recanalized in 17 of 32 patients, or 53 percent, and partially recanalized in another nine, or 28 percent. In other words, in more than four out of five patients, blood flow through the embolized vessels had returned. Yet the liver had grown anyway. Mean future liver remnant volume rose from 580 millilitres before the procedure to 690 millilitres afterwards, corresponding to a mean hypertrophy ratio of 9.5 percent, with a median kinetic growth rate of 1.94 percent per week. The comparison with the historical benchmark of 13 percent hypertrophy after conventional permanent embolization yielded a p value of 0.059, just short of conventional statistical significance but well within the range of what the trial was powered to detect.

This recanalization paradox is the scientific heart of the study. Conventional wisdom holds that sustained portal occlusion is necessary to drive compensatory hypertrophy, on the logic that the deprived liver tissue must remain starved of portal blood for the growth signal to persist. The EMBORES findings, consistent with earlier experimental work in nonhuman primates and swine by the same French group, suggest instead that a transient period of portal deprivation is enough to switch on the regenerative programme, which then continues even after blood flow is restored. The authors note that the kinetics of recanalization, rather than its mere occurrence, may be the critical variable, since experimental models showed progressive restoration of portal flow during the first two weeks after embolization while regeneration continued unabated.

Safety data were reassuring. Intra-procedural complications occurred in six patients, or about 19 percent, and consisted mainly of abdominal pain, nausea, or transient fever. No patient developed liver failure or sepsis after embolization. A single clinically significant complication, a 3.1 percent rate, involved one patient with bilobar colorectal metastases and a history of multiple prior liver procedures who developed portal vein thrombosis extending to the contralateral branch and the superior mesenteric vein; the persistent thrombosis and inadequate hypertrophy ultimately precluded surgery, and the patient was shifted to palliative chemotherapy. For context, major complications after conventional permanent portal vein embolization are reported in roughly 2 to 5 percent of patients, and some of those complications stem precisely from the irreversibility of the occlusion.

Surgery followed in 23 of the 32 patients, a resection rate of 71.8 percent that matches figures reported after conventional embolization. Hepatectomy took place a median of 50 days after embolization, with a mean operative time of 357 minutes and median blood loss of 600 millilitres. Notably, adhesions around the portal pedicle were absent or filmy in 74 percent of operated patients, a finding the authors interpret as evidence that temporary occlusion provokes far less inflammation than permanent agents, which have been associated in prior reports with dense inflammatory scarring that complicates dissection. Ninety-day morbidity affected 11 of the 23 surgical patients, including two cases of post-hepatectomy liver failure defined by the 50-50 criterion of prothrombin time below 50 percent and bilirubin above 50 micromoles per litre. There were no deaths within 90 days.

Not every patient responded equally well. Five patients, or 15.6 percent, required a second embolization using conventional permanent materials because their livers did not grow enough, and four of those five ultimately underwent surgery without developing liver failure. More importantly, the hypertrophic response was significantly blunted in cirrhotic patients, whose mean hypertrophy ratio of 5.7 percent fell statistically short of the 13 percent reference value, whereas non-cirrhotic patients achieved 10.7 percent with no significant difference from the benchmark. This is consistent with the well-documented impairment of regenerative capacity in cirrhotic livers, and the authors caution that the absorbable gelatin approach should be used carefully in this population until more evidence accumulates.

The study has honest limitations that temper enthusiasm. Recruitment fell short of the planned 44 evaluable patients because of funding constraints, reducing statistical power, and the trial lacked a control group receiving conventional permanent embolization, so no direct comparison was possible. Recanalization was assessed at a single time point roughly one month after the procedure, leaving the precise timing and kinetics of vessel reopening unknown. Functional liver reserve was not measured, an omission highlighted by the two cases of post-hepatectomy liver failure, one of which occurred in a patient whose liver had grown briskly. The authors argue that future trials should combine volumetry with functional imaging such as technetium-99m mebrofenin hepatobiliary scintigraphy with SPECT/CT.

Even with those caveats, the conceptual implications are considerable. A reversible method of modulating portal inflow could reshape preoperative liver conditioning, particularly for patients who need only a modest increase in remnant volume, and could preserve therapeutic options for those whose disease progression ultimately rules out resection. It might even find applications beyond surgery, wherever transient portal deprivation could be useful without committing the patient to permanent vascular change. The investigators are careful to frame EMBORES as hypothesis-generating rather than practice-changing, and properly so: adequately powered comparative trials against permanent embolization are the necessary next step. But the core message is already provocative. The liver, it appears, does not need the door locked shut to be told to grow; a brief, dissolvable signal may be enough to set the regenerative machinery in motion.

Subject of Research: Temporary portal vein embolization with absorbable gelatin sponge to induce future liver remnant hypertrophy before major hepatectomy

Article Title: Efficacy and safety of temporary selective portal vein embolization before major hepatectomy (EMBORES): a phase 2 trial

Article References: Tranchart, H., Maitre, S., Girard, E., Ghelfi, J., Gelli, M., Tselikas, L., Barat, M., Fuks, D., Sarran, A., Benoist, S., Meyrignac, O., Sepulveda, A., Ronot, M., Pou, M., Chirica, M., Dagher, I., Sengel, C., Brouquet, A., Gayet, B., … Debry, J.-B. (2026). Efficacy and safety of temporary selective portal vein embolization before major hepatectomy (EMBORES): a phase 2 trial. eClinicalMedicine, 101, Article 104262. https://doi.org/10.1016/j.eclinm.2026.104262

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104262

Keywords: portal vein embolization, liver regeneration, hepatectomy, absorbable gelatin sponge, future liver remnant, EMBORES trial, phase 2 study, liver surgery, interventional radiology, post-hepatectomy liver failure, cirrhosis, eClinicalMedicine

The implications reach well beyond the obesity clinic. Systolic blood pressure, the force blood exerts against artery walls when the heart contracts, is among the most powerful modifiable predictors of heart attack, stroke and premature death. For decades, clinicians have observed that losing weight lowers blood pressure, but the evidence base was built largely on lifestyle interventions that produced modest, hard-to-sustain reductions. The 2003 meta-analysis by Neter and colleagues, drawing on 25 trials and fewer than 5,000 participants, estimated that each kilogram lost yielded roughly 1 mmHg of systolic improvement. The new analysis updates that relationship for an era in which a single weekly injection can strip away 10 to 20 percent of body weight, approaching the results of bariatric surgery.

The researchers, led by Massimo Nardone and Marcel Muskiet, systematically searched MEDLINE, Embase and Cochrane databases through December 2025, screening more than 2,000 records to identify eligible trials. To qualify, studies had to be phase 3, randomized and placebo-controlled, enrolling adults with a body mass index of at least 30, or at least 27 with a weight-related comorbidity such as hypertension or sleep apnea. Crucially, the trials had to be designed for obesity treatment rather than glucose control, ensuring the analysis captured the drugs as they are actually deployed in weight management. The final dataset spanned liraglutide, semaglutide, tirzepatide, CagriSema, orforglipron, mazdutide and ecnoglutide, with median treatment duration of 68 weeks.

The pooled results were unambiguous. Across all trials, active treatment produced a placebo-adjusted weight loss of 10.1 percent and a systolic blood-pressure reduction of 4.9 mmHg. Heterogeneity between trials was substantial, but the meta-regression showed that most of it traced back to a single variable: how much weight participants actually lost. Trials in which patients shed less than 5 percent of body weight saw systolic pressure fall by only 3.1 mmHg, while those achieving 10 to 15 percent weight loss recorded drops of 5.4 mmHg. Most dramatic were trials exceeding 15 percent weight loss, where systolic pressure fell by an average of 8.1 mmHg, a figure that approaches the lower end of what standard antihypertensive monotherapy achieves.

That benchmark matters. A 2025 meta-analysis of more than 484 double-blind, placebo-controlled trials of conventional blood-pressure drugs, including ACE inhibitors, beta-blockers, calcium-channel blockers and diuretics, found an average systolic reduction of 8.7 mmHg. By that yardstick, the most powerful of the new obesity agents are delivering cardiovascular benefits of a comparable order of magnitude through weight loss alone. The authors calculated that matching the full effect of a standard antihypertensive drug would require roughly 23 percent weight loss, a target within sight of next-generation therapies such as retatrutide, which is currently in phase 3 testing.

Not every drug behaved identically, however. Tirzepatide, which engages both the GLP-1 and GIP receptors, produced the largest blood-pressure reduction at 7.1 mmHg alongside 14.9 percent weight loss, while mazdutide achieved 6.4 mmHg. CagriSema, the amylin-GLP-1 combination that produced nearly 14 percent weight loss, yielded a comparatively smaller 5.5 mmHg reduction, and phase 2 studies of cagrilintide alone showed meaningful weight loss without significant blood-pressure benefit. These discrepancies hint that receptor-specific biology, involving pathways such as GIP, glucagon and amylin signalling, may modulate the hemodynamic effects of these drugs in ways that are not yet understood, sometimes amplifying and sometimes potentially blunting the benefits of weight reduction.

Diabetes status also shaped the response. Trials enrolling participants without type 2 diabetes recorded greater weight loss, 11.1 percent versus 6.6 percent, and larger blood-pressure reductions, 5.4 versus 3.5 mmHg, than those enrolling people with diabetes. Yet the direction of effect was consistent in both groups, and baseline blood pressure itself did not materially modify the response, countering earlier suggestions of a floor effect at lower starting pressures. The authors note that patients with diabetes often take medications and have metabolic profiles that blunt weight loss, which likely explains much of the difference.

Intriguingly, the true cardiovascular impact of these drugs may be even larger than the headline numbers suggest. Several trials reported that participants on active treatment reduced or stopped their background antihypertensive medications during follow-up, which would narrow the measured gap between drug and placebo. A participant-level analysis of three STEP trials of semaglutide found twice the rate of antihypertensive de-escalation compared with controls, and mediation analyses suggested that nearly 89 percent of the observed systolic reduction was mediated by weight loss. In the REDEFINE-1 trial of CagriSema, roughly 40 percent of participants on blood-pressure medication either reduced or discontinued it. The measured 4.9 mmHg average may therefore understate the drugs’ intrinsic effect.

Mechanistically, the findings reinforce that shrinking adipose tissue is the dominant driver of blood-pressure improvement, acting through improved insulin sensitivity, reduced sympathetic nervous system activation, enhanced sodium excretion by the kidneys and favourable effects on vascular function. But they do not rule out weight-independent actions. GLP-1 receptors are expressed in the kidney and vasculature, and mechanistic studies have documented direct GLP-1-mediated natriuresis, improved endothelial function and reduced arterial stiffness. The example of albiglutide, which conferred cardiovascular benefit despite minimal weight loss and little blood-pressure reduction, is a reminder that the cardiovascular pharmacology of this class is not reducible to the bathroom scale alone.

The study has limitations the authors acknowledge. The analysis operated at the trial level rather than the individual level, leaving it vulnerable to ecological bias and unable to adjust for patient-specific confounders. Blood pressure was not a primary endpoint in any of the included trials, and measurements came predominantly from office visits rather than ambulatory monitoring. Thirty-six of the 37 trials were judged at low risk of bias, and sensitivity analyses excluding the one high-risk trial left the core relationship essentially unchanged. Even so, the authors caution that the association describes treatment effects across studies, not a causal chain within any individual patient. What the analysis does establish, with unusual precision, is that in the era of potent obesity pharmacotherapy, weight loss has re-emerged as a first-order lever for blood-pressure control, one that international guidelines now formally endorse and that clinicians treating the roughly half of hypertensive adults who also live with obesity can no longer afford to treat as an afterthought.

Subject of Research: The relationship between weight loss and blood pressure reduction with GLP-1 receptor agonists and multi-hormone receptor modulators in adults with overweight or obesity

Article Title: Weight loss and blood pressure lowering with GLP-1 receptor agonists and multi-hormone receptor modulators in overweight and obesity: a systematic review and meta-regression of phase 3 clinical trials

Article References: Nardone, M., Kugathasan, L., Daunt, L., Parikh, E. J., River Zhang, H.-Y., Pasricha, S. V., Orchanian-Cheff, A., Cherney, D. Z., Odutayo, A., & Muskiet, M. H. (2026). Weight loss and blood pressure lowering with GLP-1 receptor agonists and multi-hormone receptor modulators in overweight and obesity: a systematic review and meta-regression of phase 3 clinical trials. eClinicalMedicine, 101, Article 104251. https://doi.org/10.1016/j.eclinm.2026.104251

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104251

Keywords: obesity, hypertension, GLP-1 receptor agonists, multi-hormone receptor modulators, semaglutide, tirzepatide, weight loss, systolic blood pressure, meta-analysis, cardiovascular risk, pharmacotherapy, eClinicalMedicine

The study, led by Melanie Sloan of the University of Cambridge together with colleagues including David D’Cruz and Arvind Kaul, surveyed 6,607 adults with confirmed autoimmune or inflammatory rheumatic diseases between December 2024 and March 2025. The overwhelming majority of respondents, 91.2 percent, were female, a proportion that mirrors the epidemiology of autoimmunity itself: women account for roughly 70 to 80 percent of autoimmune disease cases worldwide, a skew attributed to a combination of sex hormones, X-chromosome-linked genetic factors, and aberrant immune responses. Participants were recruited through social media, patient charities, and community groups across the United Kingdom, North America, Europe, Africa, Asia, and Oceania, with the survey translated into five languages and targeted efforts made to reach under-served populations.

The headline numbers are striking. Among men, the most frequently reported interval from first symptoms to diagnosis was less than three months, whereas among women it was one to two years. Nearly half of male respondents, 49.7 percent, said they were diagnosed within a year of symptom onset, compared with just 39.7 percent of women. At the other end of the spectrum, 31.8 percent of women reported waiting four years or longer for a diagnosis, against 25.5 percent of men. The consultation burden told a similar story: 26.2 percent of women reported seeing a clinician eleven or more times before their autoimmune disease was identified, compared with 18.4 percent of men. Bayesian ordinal regression models, which estimate the probability of falling into each delay category while quantifying uncertainty, confirmed that these differences were not statistical noise.

The most provocative findings concern the kinds of wrong turns patients report along the way. Significantly more women than men said their autoimmune symptoms had been misattributed to a mental health condition, 43.3 percent versus 32.7 percent, or to psychosomatic causes, meaning physical symptoms attributed to psychological factors, at 33.9 percent versus 21.5 percent. After adjusting for age, disease group, continent, and household financial situation, female sex remained associated with roughly 46 percent higher odds of reporting a mental health misdiagnosis and 74 percent higher odds of reporting a psychosomatic one. Notably, there was no significant sex difference in the proportion reporting misdiagnosis with an alternative physical disease, suggesting that the disparity is specific to psychiatric and psychosomatic attribution rather than a general diagnostic disadvantage.

The researchers were careful to frame these as perceived misdiagnoses, reflecting the patient’s side of the clinical encounter. In some cases, an early diagnosis of anxiety or depression may represent a reasonable differential diagnosis during a phase when the disease has not yet declared itself, or a genuine co-existing condition. Yet the sheer scale of the reported figures, with high rates of perceived misdiagnosis in both sexes, points to something systemic. Many autoimmune diseases begin with non-specific, relapsing-remitting symptoms such as fatigue, low mood, poor sleep, and diffuse pain, which are common in the general population and can plausibly be explained by psychological or hormonal causes. Without definitive biomarkers, clinicians face genuine diagnostic uncertainty, and the temptation to reach for a psychological explanation can be strong, particularly early in the disease course.

The variation across diseases was itself revealing. Autoimmune encephalitis and undifferentiated connective tissue disease, or UCTD, showed the highest reported rates of both mental health and psychosomatic misdiagnoses, exceeding 50 percent, while polymyalgia rheumatica, type 1 diabetes, and rheumatoid arthritis showed the lowest, below 25 percent. The pattern is consistent with a simple principle: diseases with clearer biomarkers or externally visible manifestations are harder to misattribute to the mind. Autoimmune encephalitis, which can present with florid psychiatric symptoms, and UCTD, which by definition lacks a definitive signature, sit at the opposite extreme. Misdiagnosis with another physical disease was most common in inflammatory bowel disease and vasculitis, both above 57 percent, and lowest in type 1 diabetes.

Why should women bear the brunt of these diagnostic difficulties? The authors point to a convergence of biological and systemic factors. On the biological side, hormonal fluctuations and the overlap between menopausal symptoms, such as musculoskeletal pain, fatigue, mood disturbance, and sleep disruption, and the early features of many autoimmune diseases can complicate assessment. On the systemic side, historical biases in medicine have long positioned women as less credible, more emotional reporters of their own symptoms, a stereotype documented across chronic pain and medically unexplained symptom research. Women’s health has also historically received less research funding, and pre-clinical research has disproportionately relied on male models. The authors raise a modern twist: artificial intelligence diagnostic tools trained on sex-biased data, and digital patient twins that under-represent women and minoritised ethnicities, risk perpetuating these disparities into the algorithmic era.

The consequences of delayed and misattributed diagnosis are not merely academic. Prolonged untreated inflammation increases the risk of irreversible organ damage in many autoimmune diseases and is associated with greater morbidity, reduced quality of life, and premature mortality. Previous work by the same team documented lasting psychological fallout from psychiatric and psychosomatic misdiagnoses, including eroded trust in clinicians and reluctance to report new symptoms or seek care, effects that can themselves compound diagnostic delay. There is also a subtler risk of diagnostic overshadowing, in which a pre-existing label such as anxiety leads clinicians to interpret subsequent physical symptoms through a psychological lens. The study found that lower household financial status was independently associated with higher odds of both mental health and psychosomatic misdiagnosis, adding socioeconomic inequity to the picture.

The study has limitations the authors acknowledge candidly. Most participants were from the United Kingdom and of white ethnic background, the survey may have attracted people with particularly negative experiences, and retrospective self-report is subject to recall bias. The researchers could not distinguish biological sex from gender-related factors, and some diseases had too few male participants for robust comparison. Yet recall bias is unlikely to differ systematically by sex, lending weight to the observed disparities. The patient-reported approach also captures elements of the diagnostic journey, such as symptom onset and interim explanations, that medical records routinely miss; studies relying solely on records may underestimate both the duration and the complexity of diagnostic pathways.

The authors argue that the findings should reshape clinical practice. Autoimmune disease should be considered early in patients presenting with multiple, multi-system, or medically unexplained symptoms, and sex biases in medicine should be actively examined and mitigated. Continuity of care with the same clinician, explicit validation of patients’ symptoms, clear safety-netting in primary care, and a willingness to revisit diagnostic decisions as new information emerges have all been reported as key to building trust and shortening diagnostic journeys. Policy initiatives such as Jess’ Rule, which urges general practitioners to rethink a diagnosis after three failed consultations, may help. Above all, the study makes the case that patients’ own accounts of their symptoms and their diagnostic experiences are not soft data but essential evidence, and that incorporating them into clinical assessment could spare thousands of women, and men, years of uncertainty, misattribution, and preventable harm.

Subject of Research: Sex differences in diagnostic delays and perceived misdiagnoses among patients with autoimmune diseases

Article Title: Sex and disease differences in patients’ diagnostic experiences in autoimmune diseases: an international cross-sectional study

Article References: Sloan, M., Taylor, S., Cox, B., Naidu, K. K., Modi, R., Diment, W., Tayabali, S., Piper, M., Brimicombe, J., Kaul, A., & D’Cruz, D. (2026). Sex and disease differences in patients’ diagnostic experiences in autoimmune diseases: an international cross-sectional study. eClinicalMedicine, Article 104259. https://doi.org/10.1016/j.eclinm.2026.104259

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104259

Keywords: autoimmune disease, diagnostic delay, misdiagnosis, sex differences, psychosomatic, mental health, lupus, patient-reported outcomes, healthcare inequality, primary care, eClinicalMedicine, women's health

The study is notable less for a dramatic breakthrough than for the question it chose to ask. Most stroke trials judge success through the eyes of clinicians, using scales such as the National Institutes of Health Stroke Scale or the modified Rankin Scale, which grade neurological impairment and disability. But a patient who scores well on those measures may still feel that life has fundamentally changed. Health-related quality of life, the sense of independence and wellbeing that survivors themselves report, has been largely invisible in minocycline research. The new analysis set out to change that by deploying the EuroQol five-dimension three-level questionnaire, or EQ-5D-3L, one of the most widely used patient-reported measures in medicine.

The instrument works by asking patients to rate their own health across five domains: mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each domain is scored on three levels of severity, and the resulting profile, one of 243 possible health states, is converted into a single utility score using country-specific preference weights. The score runs from 1 for full health to 0 for death, with negative values reserved for states patients consider worse than death. A companion visual analogue scale lets patients rate their overall health from 0 to 100. For this analysis, the researchers used the Chinese value set and prespecified a utility score of 0.75 or higher as a favourable health state, a threshold roughly equivalent to no more than slight disability with preserved independence.

The underlying trial enrolled adults aged 18 to 80 within 72 hours of acute ischaemic stroke onset, all with moderately severe strokes confirmed by brain imaging. Participants received an oral loading dose of 200 milligrams of minocycline or matching placebo within 30 minutes of randomisation, followed by 100 milligrams every 12 hours for four days, on top of guideline-recommended care including thrombolysis or thrombectomy when indicated. Of the 1,724 patients randomised, 1,697 had complete 90-day quality-of-life data. The groups were well matched at baseline: mean age 63.7 years, two-thirds men, median stroke severity score of 5, and nearly half with large-artery atherosclerosis as the underlying cause.

The headline result was nuanced. On the primary continuous outcome, the median EQ-5D-3L utility score at 90 days was 0.96 in the minocycline group versus 0.89 with placebo, a difference that did not reach statistical significance. Self-rated health on the visual analogue scale similarly favoured minocycline, with a median of 85 versus 80, but again without statistical significance. Yet when the researchers examined the prespecified favourable health-state threshold, a clear signal emerged: 73.4 percent of minocycline patients achieved a utility score of at least 0.75, compared with 68.9 percent on placebo, a statistically significant 7 percent relative increase. The pattern held in the per-protocol population and, after multivariable adjustment for fifteen clinical and demographic covariates, the utility score difference itself crossed the significance threshold.

The domain-level results may be the most biologically telling. Patients who received minocycline were significantly more likely to report no problems with mobility, self-care, and usual activities, with common odds ratios of 1.27, 1.26, and 1.23 respectively. After adjustment, the mobility and self-care benefits grew stronger, with adjusted odds ratios of 1.43 and 1.38. By contrast, pain or discomfort and anxiety or depression showed no meaningful differences between groups. This split between physical and emotional domains is consistent with what is known about minocycline’s mechanism. The drug dampens microglial activation, suppresses pro-inflammatory cytokine release, and modulates excitotoxic and oxidative injury, processes concentrated in the peri-infarct tissue that supports motor recovery and neural reorganisation.

Post-stroke anxiety, depression, and pain, by contrast, arise from a far more tangled web of fronto-limbic circuit changes, pre-existing psychological vulnerability, psychosocial stressors, and maladaptive plasticity unfolding over months. A five-day course of an anti-inflammatory antibiotic delivered in the hyperacute phase may simply not reach those processes. The divergence also mirrors earlier stroke cohort studies showing that functional recovery and affective outcomes often move on separate trajectories, a reminder that restoring the body does not automatically restore the mood.

The exploratory subgroup analyses added further texture. Treatment effects varied significantly across stroke aetiology: patients with stroke of undetermined aetiology showed a substantial benefit, while those with cardioembolic stroke appeared to fare slightly worse on the utility measure. The authors speculate that strokes of undetermined cause may include covert small-vessel disease or inflammatory arteriopathy, conditions in which neuroinflammatory pathways play a larger role and against which minocycline can plausibly act. Larger effect estimates also appeared in patients with hypertension and those reporting alcohol consumption, both conditions linked to heightened neuroinflammatory priming, though the interaction tests were not strong enough to draw firm conclusions.

The researchers are candid about the limitations. Quality of life was measured only at 90 days, with no baseline assessment, making it impossible to confirm that the two groups started from equivalent perceived health or to track within-patient change. The population had relatively mild strokes, and the three-level EQ-5D instrument is prone to ceiling effects, which the authors argue may explain why the continuous utility score failed to reach significance while the binary threshold did: when scores cluster near the top of the scale, even a small shift can move many patients across a clinically meaningful line. Missing data were not imputed, race and ethnicity were not collected, and the analysis, though prespecified, remains secondary to the main trial.

Even so, the study marks a turning point in how neuroprotection trials are judged. Earlier minocycline studies produced a confusing mix of promising small trials and neutral blinded ones, all measured with clinician-rated scales. By showing that the drug’s benefits, if real, concentrate in the domains patients care about most, the EMPHASIS quality-of-life analysis gives the field a new lens and a new hypothesis. The authors themselves frame the findings as exploratory and call for future trials with baseline and longitudinal assessments, more sensitive five-level instruments, inflammatory biomarkers, and diverse populations. If those trials confirm the signal, a cheap, well-tolerated antibiotic could become an accessible adjunct to reperfusion therapy in stroke units worldwide, measured not just in scan results and disability scores but in patients’ own accounts of getting their lives back.

Subject of Research: Effects of minocycline on health-related quality of life after acute ischaemic stroke

Article Title: Effects of minocycline on health-related quality of life in patients with acute ischaemic stroke in China: a prespecified secondary analysis of the EMPHASIS trial

Article References: Yang, Q., Li, Y., Wang, L., Ai, T., Lu, Y., Zhang, M., Zhou, D., Liu, C., Ren, L., Zhou, X., Pan, Y., Qu, H., Liao, X., Liu, L., Zhao, X., Wang, D., Wang, Y., Wang, Y., & Guan, L. (2026). Effects of minocycline on health-related quality of life in patients with acute ischaemic stroke in China: a prespecified secondary analysis of the EMPHASIS trial. eClinicalMedicine, 100, Article 104239. https://doi.org/10.1016/j.eclinm.2026.104239

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104239

Keywords: minocycline, acute ischaemic stroke, health-related quality of life, EQ-5D-3L, EMPHASIS trial, neuroinflammation, neuroprotection, patient-reported outcomes, stroke recovery, randomised controlled trial, microglial activation, eClinicalMedicine

The research was conducted by a team affiliated with the Lancet Oncology Commission on the Human Crisis in Cancer, an initiative launched to quantify and correct the growing imbalance between biomedical investment and the human dimensions of oncology. Using data from the 2023 global review by the International Cancer Control Partnership, the researchers screened a standardized questionnaire of 95 items and identified 20 questions relevant to five Commission domains: compassionate care models, human-centred metrics, equitable access to psychosocial and palliative services, workforce and education reform, and value-aligned governance. Those items were then mapped into six analytical themes spanning sociocultural factors, systems of care, medical education, economic protection, mental health and palliative care.

The single most striking finding concerns who gets a seat at the table. Although 93 percent of the plans reported that stakeholders were involved in their development, only 12 percent identified people living with cancer as stakeholders. Governmental, professional and institutional actors dominate cancer planning almost everywhere, meaning the very documents that set national priorities rarely reflect the priorities of the people they are meant to serve. The authors point to power imbalances, funding and time constraints, and simple lack of awareness as likely barriers, and note that World Health Organization guidance explicitly calls for engaging patient groups in national cancer control planning.

The income gradient in the data is stark. On average, human-centred themes appeared in 44 percent of plans from upper-middle and high-income countries but only 32 percent of plans from lower-middle and low-income countries. Medical education was the exception that proved the rule: 96 percent of countries with dedicated cancer plans included workforce development or provider training, with no significant difference between income groups. But the content of that training was overwhelmingly biomedical. Oncologists, pathologists and surgical specialists featured prominently, while psychosocial support training appeared in just 16 percent of plans, community health worker training in 12 percent, and patient navigator training in a mere 4 percent.

Economic protection emerged as perhaps the most neglected theme of all. Only 13 percent of plans included strategies to shield patients from catastrophic health expenditure — typically defined as spending more than 30 percent of household income on cancer-related costs — and the figure was essentially flat across income levels, with high-income countries actually among the least likely to include such provisions. Universal health coverage strategies appeared in just 26 percent of plans overall. Given that financial toxicity is a well-established driver of cancer inequity, treatment abandonment and poorer outcomes, the authors argue that this neglect represents a fundamental misalignment between policy and patient need.

Mental health provisions fared little better. While 72 percent of countries with cancer plans included strategies to support families or caregivers of patients in active treatment, only 3 percent of all plans referenced essential medicines for treating psychological distress such as anxiety, depression and delirium — the least frequently included item in the entire analysis. Post-treatment survivorship care appeared in 80 percent of high-income country plans but only 25 percent of low-income country plans, a difference that was highly statistically significant. This gap is particularly concerning given the documented burden of depression among cancer patients, which is highest on the African continent at a pooled prevalence of 35 percent, compared with 25 percent in North America, and given established links between psychological distress, quality of life, treatment adherence and survival.

Palliative care was the strongest-performing human-centred theme, appearing in an average of 65 percent of plans, with pain management strategies present in 62 percent and no significant income-based differences. Yet even here the picture is incomplete: patient navigation — the practice of guiding patients through screening, treatment, financial assistance and supportive services — was included in 42 percent of plans overall but dropped to around 11 percent in lower-income settings, precisely where late-stage presentation is most common and navigation may deliver the greatest benefit. In many African countries, up to 80 percent of patients present with locally advanced or metastatic disease at diagnosis, making supportive and navigational infrastructure not a luxury but a necessity.

The authors are careful to spell out what their analysis can and cannot show. Roughly 18 percent of WHO Member States lacked publicly available plans, and the study measured policy intent rather than implementation, funding or patient outcomes. A plan’s silence on psychosocial care does not prove the absence of services, since mental health or financial protection may be addressed through separate national health or universal coverage policies. Countries were weighted equally regardless of population, so the figures describe the proportion of countries rather than the proportion of people covered. In conflict-affected states, a plan can look comprehensive on paper while the health system it describes barely functions. Still, the consistency of the gaps across regions and income levels suggests a genuine structural blind spot rather than a documentation artifact.

The study’s conclusions align with the Commission’s broader call to rehumanize cancer care. Its recommendations include embedding scalable patient navigation — particularly financial navigation — into national plans, strengthening structural supports for caregivers, guaranteeing access to essential psychotropic medicines, reforming workforce training to include psychosocial competencies, and shifting governance toward value-aligned, equity-oriented models. The authors also propose that future iterations of the assessment instrument move beyond binary yes-or-no questions to capture whether commitments are actually costed, assigned to an agency, implemented and monitored, with equity-stratified indicators and patient-reported experience measures built in.

What makes the findings resonate beyond oncology is what they reveal about how health systems value intangible goods. Machines, drugs and screening programs are easy to cost, procure and count; compassion, dignity and psychological safety are not. The analysis suggests that unless national strategies explicitly name and resource the human dimensions of cancer care, those dimensions will continue to lose out in budget negotiations and implementation plans — and the patients who bear the heaviest burden of advanced disease, poverty and psychological distress will continue to be the least likely to receive them. The authors’ message to policymakers is blunt: a cancer strategy that plans only for the tumor, and not for the person, is an incomplete strategy.

Subject of Research: Global policy analysis of human-centred cancer care in national cancer strategy plans

Article Title: A cross-sectional global policy analysis of the human gap in 156 national cancer strategy plans

Article References: Lau, E., Shapiro, G. K., Rodin, G., Sullivan, R., Bhoo-Pathy, N., Unger-Saldaña, K., Trapani, D., Salins, N., Skelton, M., & Li, M. (2026). A cross-sectional global policy analysis of the human gap in 156 national cancer strategy plans. eClinicalMedicine, 100, Article 104244. https://doi.org/10.1016/j.eclinm.2026.104244

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104244

Keywords: national cancer control plans, human-centred care, psychosocial support, palliative care, patient navigation, health equity, financial protection, mental health, cancer policy, low-income countries, Lancet Oncology Commission, eClinicalMedicine

The research team, led by Namita Kaushik and Andreas Tietz, screened 6,983 records and identified 341 studies reporting healthcare resource utilisation or economic outcomes in dengue. Of these, 44 studies reporting hospitalisation rates and 121 studies reporting length of stay met the rigorous feasibility criteria for quantitative synthesis. The work followed PRISMA guidelines, was registered prospectively in the PROSPERO database, and applied the Downs and Black checklist to appraise study quality. Data were drawn from five biomedical databases searched via the Ovid platform, supplemented by citation searches and conference abstracts, with no restriction on country of origin.

The headline result is a pooled global hospitalisation rate of 36.7 percent (95 percent confidence interval 29.0 to 44.4) among patients with dengue irrespective of severity, derived under a random-effects model. The mean length of stay across hospitalised patients was 4.9 days (95 percent CI 4.6 to 5.2). Both outcomes showed very high statistical heterogeneity, with I-squared values approaching 100 percent, reflecting the enormous diversity of settings, designs, and populations represented in the underlying literature. To understand that variation, the authors performed meta-regression across a range of study-level covariates, including geography, outbreak status, data source, and study design.

One variable dominated all others: disease severity. Severity was significantly associated with both higher hospitalisation rates and longer stays, explaining 31.4 percent of between-study variance in hospitalisation and 11.4 percent of the variance in length of stay, with p-values below 0.0001 in both models. Subgroup analyses quantified the gradient precisely. Patients with non-severe dengue without warning signs were hospitalised at a pooled rate of 17.7 percent, rising to 36.9 percent once WHO warning signs such as persistent vomiting, abdominal pain, mucosal bleeding, raised haematocrit, or thrombocytopaenia appeared. Among patients classified as having severe dengue, the pooled hospitalisation rate reached 79.4 percent.

Length of stay followed the same severity gradient. Patients with non-severe disease averaged 4.6 days in hospital, compared with 6.5 days for severe dengue. The most dramatic figures emerged when complications were considered: patients with severe dengue or dengue haemorrhagic fever who developed complications such as shock, renal impairment, platelet-transfusion-requiring thrombocytopaenia, or sepsis stayed a mean of 15.5 days, roughly double the 7.5 days observed in severe cases without complications. Co-infections with pathogens such as SARS-CoV-2 or chikungunya virus, and comorbidities including haematologic malignancies, autoimmune disease, and obesity, each added roughly a day or more to the average stay.

Regional patterns add a further layer of complexity. Hospitalisation rates were numerically higher in Asia, at 35.1 percent, than in Latin America, at 29.3 percent, and length of stay was correspondingly longer in Asian settings, at 5.1 days versus 4.1 days in Latin America. The authors note that this Asian excess echoes the 2016 analysis by Shepard and colleagues, which reported rates of 19.3 to 24.8 percent in Asian subregions against just 3.8 percent in Latin America and the Caribbean. Possible explanations include differing admission thresholds, a higher force of infection, multiple co-circulating serotypes, and demographic differences, but the authors emphasise that the drivers remain unclear and warrant targeted investigation.

The timing of the analysis is significant. Since the last global estimates were published, the world has witnessed record-breaking dengue waves, shifts in circulating serotypes, changing patient demographics, the disruption of the COVID-19 pandemic, and improvements in surveillance and clinical preparedness. The World Health Organization reported a doubling of reported cases from around 7 million in 2023 to approximately 14 million in 2024, while modelling work published in 2025 estimated that annual apparent cases rose from 26.45 million in 1990 to 58.96 million in 2021. Against that epidemiological backdrop, a hospitalisation rate approaching 37 percent implies a demand for inpatient beds, nursing capacity, and supportive care that many endemic health systems are ill-equipped to absorb during peak transmission seasons.

Methodological sensitivity analyses strengthen the central conclusions while exposing their limits. Excluding studies with fewer than 100 participants and those with more than 50,000 yielded a pooled hospitalisation rate of 29.4 percent with narrower confidence intervals, and excluding studies whose data were collected during the pandemic produced an estimate of 25.3 percent, hinting that overwhelmed COVID-era hospitals may have temporarily suppressed dengue admissions. A single exceptionally large nationwide Brazilian cohort dominated the fixed-effects estimate, but random-effects modelling, which the authors favoured given the heterogeneity, attenuated its influence. For length of stay, no evidence of publication bias was detected by Egger’s regression, and the GRADE certainty of evidence was rated low, primarily because of the observational design of the included studies rather than inconsistency or imprecision.

The findings carry immediate practical implications. Hospitalisation is recognised as a key outcome in dengue research: an international Delphi consensus involving experts from more than 30 countries identified the need for hospitalisation as a core endpoint for patients and clinicians. The new benchmarks should therefore help clinical trialists select endpoints and calculate sample sizes, and they align with recently published WHO target product profiles that recommend dengue-related hospitalisation as a secondary efficacy outcome in non-severe disease. For policymakers, the estimates provide a foundation for cost-effectiveness analyses of vaccines, antivirals, and vector-control strategies, and for identifying the regions where preventive investment would relieve the greatest pressure on hospitals.

The authors are careful to frame the pooled figures as average trends across highly diverse settings rather than universal constants. Admission thresholds, clinical practice, healthcare-seeking behaviour, and reporting conventions differ substantially between countries, and the denominator in most studies was skewed towards patients already seeking care, which may inflate the apparent hospitalisation rate relative to all symptomatic infections. The observation that some patients with warning signs or severe disease were nonetheless not hospitalised may reflect symptom misclassification, resource constraints, or emergency department stays that were never recorded as admissions. Even so, the overall message is difficult to escape: dengue’s demand on hospital infrastructure has likely risen considerably over the past decade, and quantifying the associated direct and indirect costs, productivity losses, and caregiver burden is now an urgent priority for global health planning.

Subject of Research: Global hospitalisation rates and length of stay for dengue patients

Article Title: Global burden of dengue on healthcare systems: a meta-analysis of healthcare resource utilisation

Article References: Kaushik, N., Subramanian, S., Gedif, K., Nallagangula, T. K., Singuru, S., Panchal, S., Meyer-Andrieux, I., Gruenberger, J.-B., McBride, A., Yacoub, S., & Tietz, A. (2026). Global burden of dengue on healthcare systems: a meta-analysis of healthcare resource utilisation. eClinicalMedicine, 100, Article 104217. https://doi.org/10.1016/j.eclinm.2026.104217

Image Credits: AI Generated

DOI: 10.1016/j.eclinm.2026.104217

Keywords: dengue, hospitalisation rate, length of stay, meta-analysis, healthcare resource utilisation, systematic review, global health burden, WHO warning signs, severe dengue, Aedes mosquitoes, health systems, eClinicalMedicine