Procedural anxiety and untreated procedural pain can result in adverse clinical and behavioural outcomes. Procedural comfort is defined as the intentional, multidisciplinary management of pain, anxiety and distress before, during and after medical procedures. Strategies to provide procedural comfort can be subdivided into pharmacological and non-pharmacological.Careful planning and preparation, involving both parent and child, and tailoring the procedural comfort strategies to the individual maximise the likelihood of a successful procedure while also minimising pain and distress. This includes determining the location for the procedure (bedside versus treatment room) and consideration of clustering procedures where appropriate. A calm environment should be maintained throughout, and the use of age-appropriate and positive language is key.Non-pharmacological strategies such as positions for comfort, interactive (play therapy, distraction), relaxation (guided imagery, deep breathing, massage, hypnotic communication) and sensory (vibration and cold stimulation, aromatherapy, virtual reality) should be considered for all children and may be combined with sedation if deemed necessary.The choice to sedate must always balance risks (over-sedation/paradoxical reactions) versus the benefits (increased likelihood of a successful attempt, a calmer patient and reduced patient and family distress). If a sedative is needed, the choice is made after a discussion between the medical team and the patient (if appropriate) and their family or carers.Pharmacological strategies include local anaesthetic cream and sedatives, most commonly: benzodiazepines (midazolam and temazepam), α2-adrenoceptor agonists (dexmedetomidine and clonidine) and N-methyl-D-aspartate receptor antagonists (ketamine). Factors influencing choice of drug include the formulation, route of administration, existing comorbidities, contraindications and previous experience of the patient.Local policy with regard to fasting should be adhered to and children who have been given sedatives should remain supervised by appropriately trained medical staff with accredited paediatric life support skills and be continuously monitored.

Diazepam, commonly used in freshwater fish transport and aquaculture, poses potential food safety and public health risks due to its residues and metabolites. However, current monitoring efforts primarily focus on the parent drug and its major metabolites, leaving potential toxic transformation products uncharacterized. This study reports two novel metabolites (BP-246, 5-chloro-2-(methylamino)phenyl)(phenyl)methanone, and BP-271, 6-chloro-1-methyl-4-phenylquinazolin-2(1 H)-one) in freshwater fish muscle, a matrix in which these compounds have not been previously reported, using liquid chromatography-Orbitrap high-resolution mass spectrometry (LC-Orbitrap HRMS). Using ProTox3.0 and ADMETlab3.0 for toxicity prediction revealed that BP-246 and BP-271 exhibit high blood-brain barrier permeability, neurotoxicity and ecotoxicity. A sensitive and validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous quantification of diazepam, three established metabolites (nordiazepam, oxazepam, temazepam), and the two novel compounds in fish tissue. Sample preparation involved acetonitrile ultrasonication extraction followed by solid-phase extraction (SPE) purification. Matrix-matched calibration curves demonstrated excellent linearity (R[2] > 0.999) over the range of 0.2-10 µg/kg. Method recovery ranged from 78.5% to 119.9%, with intra-day and inter-day relative standard deviations (RSDs) below 9.9% and 9.1%, respectively. Limits of detection (LOD) and quantification (LOQ) were 0.05-0.06 µg/kg and 0.15-0.20 µg/kg, respectively. The method showed robust selectivity and consistent retention times. When applied to 10 market-sourced, diazepam-positive fish samples, the method successfully revealed differential metabolite profiles, enabling rapid, high-throughput monitoring of diazepam and transformation products in commercial fish products. These findings provide a basis for comprehensive risk assessment and regulatory control of diazepam residues in the food supply chain.

This case report presents the successful use of high-dose insulin euglycemic therapy (HIET) and venous arterial extracorporeal membrane oxygenation (VA-ECMO) in managing severe toxic cardiogenic shock following poly-intoxication in an elderly patient. A 67-year-old woman, with a history of depression, previous suicide attempts and chronic renal failure, overdosed on multiple cardiovascular active agents including metoprolol (β-blocker), nifedipine (calcium channel blocker), nortriptyline (tricyclic antidepressant), venlafaxine (serotonin-noradrenaline reuptake inhibitor), and temazepam (benzodiazepine) were reported. Initial treatment with vasopressors, HIET and supportive measures stabilized her condition temporarily. Despite these interventions, the patient developed catecholamine-refractory shock with progressive multiorgan failure, requiring escalation to VA-ECMO as a bridge to recovery. VA-ECMO resulted in hemodynamic stabilization, enabling vasopressor withdrawal and decannulation after three days. The patient survived the acute toxic phase without irreversible neurological injury. However, the course was complicated by vascular complications, prolonged mechanical ventilation, renal replacement therapy, severe functional decline and eventually death eight months later. This case illustrates that VA-ECMO may provide effective temporary circulatory support in severe reversible toxic cardiogenic shock, even in elderly patients with significant comorbidity. However, the substantial burden of long-term morbidity and prolonged recovery should be carefully weighed during multidisciplinary decision-making.

In recent years, the analysis and identification of benzodiazepines and Z-drugs have presented significant challenges in forensic medicine and pharmaceutical analysis due to their widespread use. Notably, some of these substances are classified as new psychoactive substances (NPS) by the UNODC. Hair was chosen as a biological matrix for monitoring long-term drug intake in this study. We aimed to develop and validate a rapid and sensitive method for simultaneous determination of 40 benzodiazepines and Z-drugs in hair using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). All the analytes were detected within 11 min. The method was validated with linear calibration curves over the range of 5-500 pg mg[-1] (coefficient of determination, r[2] > 0.99). The limits of detection (LOD) were 1-3 pg mg[-1], and the limits of quantification (LOQ) were 5 pg mg[-1]. The method demonstrated acceptable selectivity, accuracy, and precision (< 20%). Matrix effects ranged from -29.8-23.5%, and recoveries ranged from 77.9% to 119.9%. The method was successfully applied to six authentic hair samples, detecting nine substances: Nitrazepam, Temazepam, Lorazepam, 7-Aminoflunitrazepam, Clobazam, Lormetazepam, α-Hydroxyalprazolam, 7-Aminoclonazepam, and Zolpidem. Benzodiazepines concentrations ranged from 5.6 to 436.1 pg mg[-1], while zolpidem concentrations ranged from 11.1 to 113.8 pg mg[-1]. This method provided a reliable tool for detecting benzodiazepines and Z-drugs in hair and addresses the requirements of routine forensic practice.

Pharmaceutical contamination of surface water is a serious concern, posing a threat to ecosystem stability. This study focuses on assessing the occurrence and environmental impact of diazepam and its active metabolites oxazepam, temazepam, and nordazepam in two Czech rivers, identifying the main sources of pollution, and evaluating the effectiveness of root-zone wastewater treatment plant (WWTP) in removing these contaminants. Benzodiazepines were detected in 72% to 100% of the water samples, with oxazepam concentrations peaking at 67.50 ng/L, particularly at the conventional WWTP effluent. Although root-zone plants are often reported to be effective in removing organic pollutants, the investigated plant failed to effectively remove oxazepam, likely due to insufficient maintenance. Ecotoxicological assessments revealed that multiple sites exhibited hazard quotient values of moderate to high environmental risk, suggesting the persistence and bioaccumulative nature of these contaminants. The findings highlight the limitations of current wastewater treatment technologies in fully eliminating benzodiazepines, which continue to be detected even after treatment, leading to potential long-term ecological consequences. This research calls for the development and implementation of more effective, scalable, and cost-efficient WWTP solutions to reduce pharmaceutical pollution and for ongoing monitoring of aquatic environments to protect freshwater resources and safeguard biodiversity.

Chronic insomnia is a common condition that significantly burdens patients and increases the risk of various comorbidities. Cognitive Behavioral Therapy for Insomnia (CBT-I) is the recommended first-line treatment and has shown strong, long-lasting effects with fewer side effects compared to medication. This article presents a representative case study of a woman with long-term insomnia,illustrating the core components and practical implementation of CBT-I, including the combination with medication tapering. CBT-I targets the maintaining factors of insomnia through behavioral techniques (e.g. sleep restriction) and cognitive interventions, and restoring daytime balance. Up to 80% of patients experience clinically relevant improvements, even with comorbid conditions. In contrast, sleep medications like temazepam or zolpidem should be used cautiously, for no longer than 2-4 weeks. CBT-I leads to more sustainable outcomes and supports patient autonomy. Wider implementation in clinical practice is hindered by limited awareness, access, and reimbursement, despite strong evidence for its effectiveness.

This study investigated the bioaccumulation and elimination dynamics of diazepam in various tissues of carp (Cyprinus carpio) exposed to environmentally relevant concentrations, along with assessing the potential human exposure risks associated with carp consumption. The residues of diazepam in carp skin muscle exceeded regulatory thresholds when the water concentration surpassed 100 ng/L. The tissue-specific accumulation levels followed the order: liver > kidney > gill > plasma > skin muscle. Steady-state bioconcentration factors (BCFss) were found to be 7.18 L/kg and 8.26 L/kg at exposure concentrations of 200 ng/L and 500 ng/L, respectively. The uptake constants (K1) for the skin muscle were measured at 0.70 L/(kg·d) and 0.75 L/(kg·d), while the elimination constants (K2) were 0.10 h[-1] and 0.085 h[-1], corresponding to half-lives of 6.37 h and 10.57 h, respectively. During the depuration phase, diazepam was predominantly detected compared to other main metabolites including nordazepam, oxazepam and temazepam. Risk assessments revealed that the counsumption of skin muscle posed acceptable risks, whereas the consumption of liver and kidney raised significant concerns. These findings provide a theoretical basis for pollution control, risk assessment, and the scientific management of diazepam in aquaculture.