Poisoning is an important and prevalent concern, occurring owing to many drugs, chemicals or natural poisons. Prompt diagnosis and treatment optimize outcomes. Initial management involves concurrently assessing the history of exposure, performing a clinical examination and resuscitation when required. The integration of symptoms and clinical signs, and possibly investigations and/or the response to an antidote, can enable the identification of a potential toxidrome. Toxidromes are important in the assessment and management of patients with poisoning. Each toxidrome may be caused by a particular group of poisons, so diagnosis of a toxidrome may indicate what a patient was exposed to, guiding further clinical assessment and management. Identifying a toxidrome can be especially informative when a history cannot be obtained, for example in patients who are drowsy or extremely agitated. Additionally, a toxidrome may help to confirm the accuracy of the history of exposure, when this is available, facilitating further assessment and management. Classic poisoning-related toxidromes include the opioid, sympathomimetic, serotonergic, antimuscarinic, muscarinic and nicotinic toxidromes. Other toxidromes that are common and require careful clinical consideration include bradycardia with hypotension, 'knockdown', mushroom poisoning, neuroleptic malignant and uncoupling of oxidative phosphorylation syndromes. Multiple toxidromes can occur together following exposure to certain single xenobiotics or to multiple xenobiotics, which can complicate clinical decision-making. Future directions include refining diagnostic tools including bedside and/or laboratory investigations to complement clinical assessments, improving access to region-specific toxidrome data, and developing targeted therapies to enhance outcomes and address current gaps in care.
Varicella zoster virus (VZV) is an exclusively human alphaherpesvirus that infects >90% of the global population. Primary infection typically causes varicella (chickenpox), after which VZV establishes lifelong latency in ganglionic neurons along the entire neuroaxis. Virus reactivation, typically triggered by age-associated immune dysfunction or immune suppressive conditions, produces herpes zoster (shingles) that can be complicated by post-herpetic neuralgia. In limited instances, VZV reactivation (and rarely primary infection) also produces multisystem disease including vasculopathy, cranial neuropathies, myelopathy and cardiovascular or gastrointestinal complications; these complications can occur without, or temporally dissociated from, rash. Diagnosis of varicella or herpes zoster relies on clinical presentation of a disseminated or dermatomal-distribution rash, respectively; diagnosis of VZV infection (owing to replicating virus) is more challenging when cases are atypical and/or occur without rash. Prevention strategies include administration of live attenuated varicella vaccine and recombinant zoster vaccine. VZV infection is treated with antiviral drugs including oral valacyclovir (drug of choice), famciclovir, acyclovir or amenamevir; for severe or disseminated disease, intravenous acyclovir or foscarnet (when other drugs fail) are used. Critical challenges remain in recognizing and diagnosing atypical presentations, developing novel therapeutics, establishing the causal role of VZV in vascular and neurodegenerative disease, and achieving broader vaccine implementation worldwide.
Cancer pain is a persistent and multifaceted global health problem that profoundly impairs quality of life, function and prognosis. Cancer pain occurs across all cancer types and stages, including in long-term survivors, with prevalence and severity influenced by tumour location, treatment modality, metastatic burden, sex, age and comorbidities. Mechanistically, cancer pain is not a single entity but arises from diverse processes including peripheral nociception, central sensitization and maladaptive neuroplasticity. Growing evidence highlights a key contribution of non-neuronal cells, such as immune cells, Schwann cells and central glia, in regulating cancer-related nociceptive signalling. Sex differences and effects of sex hormones further modulate pain perception, susceptibility to treatment-related toxicities and response to analgesic therapies. Comprehensive assessment integrates quantitative sensory testing with psychosocial screening to capture biological and psychosocial determinants of pain. Effective management requires individualized, multimodal strategies combining non-opioid and opioid analgesics, adjuvant agents and emerging targeted therapies with non-pharmacological approaches such as interventional and neuromodulatory procedures, psychological therapies and palliative care. Improving patient-reported outcomes remains central, particularly in cancer survivors with chronic pain. Precision medicine approaches, including mechanistic phenotyping and biomarker-driven and pharmacogenomic strategies, hold promise for tailoring cancer pain management to individual clinical, psychosocial and molecular profiles, ultimately enhancing treatment efficacy and long-term outcomes.
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of antimicrobial-resistant infection worldwide. The spectrum of diseases caused by MRSA range from uncomplicated skin and soft-tissue infections to life-threatening invasive infections such as bacteraemia, pneumonia, osteomyelitis and endocarditis. MRSA commonly colonizes the skin and mucosal surfaces as an asymptomatic commensal but can transition to an invasive pathogen when host barriers are disrupted or immune defences are compromised. The shift from commensal to pathogen is facilitated by a broad repertoire of virulence factors that promote adhesion, immune evasion, tissue invasion and persistence within host tissues. Despite the development of several new antibiotics with activity against MRSA, clinical outcomes during invasive infections are poor, with many patients experiencing persistent or recurrent infection. Strategies to prevent MRSA infection include infection control measures, screening and targeted decolonization approaches; however, the effectiveness of these interventions varies and often depends on local MRSA prevalence and epidemiological context. Understanding the epidemiology, pathogenesis and clinical management of MRSA remains essential to guide effective prevention and treatment strategies.
Influenza A and B viruses are considerable public health threats. Annual seasonal epidemics are driven by antigenic drift and cause an estimated 3-5 million severe cases and 290,000-650,000 deaths annually. The clinical presentation of seasonal influenza is typically an abrupt, uncomplicated acute respiratory illness with full recovery; however, it can lead to severe, life-threatening complications in individuals at high risk. Antigenic shift caused by reassortment of a seasonal influenza A virus with avian and/or swine influenza A viruses has led to unpredictable pandemics. The successful cross-species transmission of influenza A viruses requires key viral adaptations, including changes in receptor specificity and compatibility with host factors such as ANP32A. Host defence involves a layered innate response, which is antagonized by proteins, such as non-structural protein 1, and a robust adaptive immunity comprising cytotoxic CD8+ T cells targeting conserved internal proteins and B cells producing neutralizing antibodies. Diagnosis primarily depends on highly sensitive PCR-based methods and multiplexed rapid antigen tests. Prevention involves annually updated seasonal vaccines (including inactivated, live attenuated and protein-based vaccines), while treatment relies on early use of neuraminidase and polymerase acidic protein inhibitors. Research priorities include the development of improved vaccines and a better understanding of influenza virus transmission from animals to humans.
