Metoclopramide is a commonly used antiemetic associated with extrapyramidal side effects, including akathisia. Although typically mild, severe presentations may mimic neurologic emergencies. We present an 81-year-old male with chronic obstructive pulmonary disease (COPD) admitted for respiratory syncytial virus (RSV) pneumonia who developed acute severe akathisia after a single dose of metoclopramide. The episode began with acute back pain followed by marked restlessness and nonrhythmic movements with preserved awareness, favoring a toxic-metabolic process over seizure. Laboratory evaluation revealed transient lactic acidosis (6.3 mmol/L), further confounding the diagnosis. Despite treatment with diphenhydramine and lorazepam, symptoms progressed, requiring intensive care unit (ICU) transfer due to worsening agitation and decreased awareness. Symptoms resolved completely within 24 hours. This case highlights the importance of recognizing medication-induced akathisia, which can mimic a seizure and lead to escalation of care, particularly in elderly patients with concurrent infection.

The quality of Surface-Enhanced Raman Chemical Imaging (SER-CI) rely on several parameters, among which the uniform deposition of metallic nanoparticles impacts greatly the result. Optimizing deposition protocols for biological samples is challenging due to inherent spatial heterogeneity, preventing the distinction between deposition artefacts and true analyte distribution. However, to optimize the deposition parameters, it is necessary to have a controlled experimental model. This study presents the development of a repeatable dried gelatine-agarose hydrogel as a controlled analytical substrate with the uniform spatial homogeneity of diphenhydramine hydrochloride as the experimental model for further nanoparticle deposition optimization. With its skin-mimicking Raman fingerprint, the proposed hydrogel enables the systematic evaluation of deposition techniques without biological variability. Confocal Raman imaging performances are as follows: the normalization-based ratio (I1003/I1469) achieved an intra-day RSD of 3.6-8.2%, inter-day RSD of 6.5%, and intra-day pixel-wise RSD (%) of 8.3-12.3%. The Distribution Homogeneity Index (DHI) confirmed the analyte's uniform distribution. Drying kinetics modelling revealed a diffusion-based dehydration process, with repeatable batch production. Application of dried hydrogels for SERS chemical imaging confirmed diphenhydramine hydrochloride detectability inside the polymeric matrix, with the proportionality of intensity based on the diphenhydramine hydrochloride concentration. A preliminary performance comparison of nanoparticle deposition by drop-casting and spray-coating demonstrates the applicability of the developed model. This standardized matrix provides a reference platform for evaluating deposition homogeneity, distinguishing method performance from sample artefacts and accelerating chemical imaging method development and performance through optimization.

Background: Nausea and vomiting in pregnancy affects up to 80% of pregnant women and may progress to hyperemesis gravidarum, leading to maternal morbidity and adverse pregnancy outcomes. Despite numerous pharmacological and non-pharmacological options, the comparative efficacy and safety of these interventions remain unclear. Methods: We conducted a systematic review and network meta-analysis of randomized controlled trials assessing pharmacological and non-pharmacological interventions for nausea and vomiting in pregnancy. The databases searched included CENTRAL, PubMed, and EMBASE (up to 28 May 2024). Eligible trials compared interventions with a placebo in pregnant women with nausea and vomiting in pregnancy. The primary outcomes were symptom severity, assessed using validated tools. Safety outcomes included adverse effects. Data were pooled using frequentist pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool, and the certainty of evidence was evaluated using the CINeMA framework. Results: Of 9844 records screened, 24 randomized controlled trials (3017 participants) met the inclusion criteria, encompassing 16 intervention categories. Network analysis ranked quince, vitamin B6 with pomegranate and mint, acupressure P6, dimenhydrinate, and acupuncture combined with doxylamine-pyridoxine as the most effective interventions for reducing symptoms of nausea and vomiting in pregnancy, with considerable uncertainty and low-to-moderate quality of evidence. Reporting of adverse events was limited. Risk of bias was low to moderate. Discussion: Most interventions demonstrated significant benefit over a placebo. However, high heterogeneity and sparse reporting of adverse effects warrant caution when translating these results into clinical practice. Conclusions: This study indicates that both pharmacological (vitamin B6, metoclopramide, dimenhydrinate) and non-pharmacological (ginger, quince, acupressure, acupuncture) interventions might be effective in reducing symptoms of nausea and vomiting in pregnancy.

Diphenhydramine and cyclizine are over-the-counter (in many countries) antihistamines that have considerable sedative effects. Therefore, they can be used in drug-facilitated crimes to incapacitate victims. There is a knowledge gap regarding detection possibilities and concentration levels of these antihistamines in hair. This study aimed to investigate whether a single dose of diphenhydramine and cyclizine could be quantified in head hair, and for how long. A single-dose study was conducted in which 12 adult volunteers ingested a single dose of diphenhydramine (25 mg) and cyclizine (44 mg). Hair samples were collected before drug intake and at 1, 3, 5, and if possible, 12 months after intake. To quantify a single dose of antihistamines in head hair, a validated LC-MS/MS method with a lower limit of quantification of 1 pg/mg was applied. Both antihistamines and their main metabolites, N-demethyldiphenhydramine and norcyclizine, were detected in all hair samples collected up to 5 months after intake. Twelve months after intake, diphenhydramine was quantifiable in 25% and cyclizine in 62.5% of available hair samples. The concentrations found in hair within 1 year after intake ranged from 0 to 610 pg/mg for diphenhydramine and from 0 to 590 pg/mg for cyclizine. The median decrease in concentration over 2, 4, and 11 months was 43%, 70%, and 100% for diphenhydramine and 40%, 64%, and 98% for cyclizine. The data obtained provided indicative concentration ranges for a single oral dose of diphenhydramine and cyclizine in hair, thereby improving the interpretation of hair analyses in forensic casework.

BackgroundHeadache following traumatic brain injury (TBI) is a common, yet disabling, disorder with diverse mechanisms and treatment needs that remain poorly defined. Pharmacological regimens are the primary source of remedies for individuals with post-traumatic headaches (PTH). The main objective of this review is to describe the efficacy of pharmacological medications for the treatment of PTH with a specific focus on the effect of these medications on headache characteristics and headache-related quality of life (QoL).MethodsThis systematic review (CRD42024537719) followed PRISMA and SWiM guidelines. PubMed, CINAHL, Scopus, PsycINFO and the Cochrane Library were searched in April 2024 for peer-reviewed articles published in English between 2009 and 2024. Eligible studies included randomized controlled trials, controlled cohort studies, and systematic reviews or meta-analyses evaluating pharmacological treatments for PTH in adults. Studies were excluded if they did not assess outcomes related to PTH pain, only included pediatric populations, used animal models, investigated only non-pharmacological interventions, were case reports, narrative reviews, editorials or conference abstracts, or did not involve human participants with TBI-related headache. Risk of bias was assessed using RoB-2 for Randomized controlled trials (RCTs) and ROBINS-I for the non-randomized studies of the effects of interventions.ResultsSixteen studies were included in the final review, comprising retrospective observational (n = 7), non-randomized prospective (n = 4) and randomized controlled trials (n = 5). Most studies reported some improvements in headache frequency and intensity following pharmacological treatment, although findings for headache-related QoL were inconsistent. Erenumab showed potential benefits for persistent PTH in small, uncontrolled studies of civilian samples. However, findings on its impact on headache-related QoL should be interpreted with caution, given the high discontinuation rate observed. Prazosin demonstrated similar benefits in military populations, with minimal side effects. In the acute care setting, metoclopramide, co-administered with diphenhydramine to minimize side effects, was associated with short-term relief of headache symptoms. Of the RCTs, only two had a low risk of bias, of which only one specifically focused on PTH.ConclusionsPharmacological treatments for PTH may provide improvements in headache frequency and intensity; however, evidence for their efficacy is limited and inconsistent. Given the limited high-quality evidence overall, no specific clinical recommendations can be made at this time. Future research should prioritize rigorous, controlled studies, particularly comparative effectiveness trials, and explore holistic, personalized approaches that incorporate treatment of psychiatric comorbidities and consider patient context.

Acute laryngeal dystonia (ALD) is a rare but potentially fatal extrapyramidal adverse effect of high-dose antipsychotic medications like haloperidol. It presents with sudden contraction of laryngeal muscles that causes narrowing of the airway, which rapidly progresses to respiratory failure if not promptly recognized. We report a 45-year-old male patient with schizophrenia who developed respiratory distress and inspiratory stridor within 15 minutes of receiving haloperidol for postoperative agitation following emergent abdominal surgery. Initial management with epinephrine failed to improve symptoms. Given the temporal association with haloperidol administration, an acute dystonic reaction was suspected, and the patient was promptly treated with intravenous diphenhydramine and benztropine, resulting in immediate improvement of respiratory distress. Anticholinergic therapy was continued for one week with no recurrence of symptoms. This case highlights the importance of early recognition of ALD in postoperative and critical care settings, as timely administration of anticholinergic agents can be life-saving and may prevent unnecessary endotracheal intubation. It is recommended to continue anticholinergic agents for a prolonged period of time, even after haloperidol discontinuation, to prevent the recurrence of symptoms that have been reported in many cases in the past.

Identification of bioaccumulative chemicals has largely relied on models and empirical data describing bioaccumulation of nonionizable organic chemicals in fish, but bioaccumulation research has remained understudied in other aquatic taxa, particularly for ionizable organic chemicals. We examined the influences of pH on uptake and elimination kinetics, bioconcentration factors, and internal disposition of diphenhydramine (DPH), a weakly basic pharmaceutical, in signal crayfish Pacifastacus leniusculus. After a 10-day bioconcentration experiment (7 days of uptake, followed by 3 days of elimination) at pH 6.7 and 8.7, we analyzed DPH in water, crayfish hemolymph, and whole-body tissues using liquid chromatography with tandem mass spectrometry. We then derived a hemolymph: water partition coefficient and estimated the apparent volume of distribution (VD) for DPH in crayfish. Consistent with previous observations in freshwater and estuarine fish, pH significantly (P < 0.05) altered DPH tissue levels and bioconcentration factors (BCF) in signal crayfish. However, hemolymph: water partitioning and steady state and kinetic-based BCFs for DPH were lower than similar observations in fish, and apparent VD values were markedly higher in crayfish (416 - 451) than in fish and humans. Our findings indicate that signal crayfish represent a suitable crustacean model to advance an understanding of ionizable organic contaminant bioaccumulation in invertebrates.

Anaphylaxis is a rarely reported yet potentially fatal adverse effect of apixaban. This case involves a patient in her 60s who presented with left leg swelling and was diagnosed with bilateral deep vein thrombosis. Less than an hour after ingestion of therapeutically indicated apixaban, she experienced dyspnoea, hypoxia, hypotension and an urticarial rash. She was promptly treated with epinephrine, diphenhydramine and methylprednisolone and found to have an elevated tryptase level, a reliable marker for anaphylactic reactions. She clinically improved, transitioned to enoxaparin and was discharged the following day. This case encourages healthcare providers to consider anaphylaxis as a rare but potentially lethal side effect of apixaban.