Concordance Study of Diagnoses and Therapeutic Management for Military Personnel Evacuated for Medico-psychological Reasons: From the Theater of Operations to the Military Training Hospital.

INTRODUCTION: The evolving global landscape has led to increased involvement of the French armed forces, exposing military personnel to operational challenges that can affect their mental well-being. As a result, psychiatry has become the second most common reason for Medical Evacuation (MEDEVAC). In war zones where specialized medico-psychological consultations may not be readily available, medical officers play a vital role in providing initial care. Therefore, there is a growing emphasis on the precise evaluation of these practices. MATERIALS AND METHODS: In this retrospective observational study, we analyzed MEDEVAC request files from the Operational Health Headquarters (Patient Medical Request sheets), Aeromedical Evacuation Mission Order sheets, and hospital records from the entire military hospital complex in the Île-de-France region for French military personnel who underwent low-priority MEDEVAC (P3) for medico-psychological reasons from a non-metropolitan area to metropolitan France. The study spanned from January 1, 2013, to December 31, 2016. The primary objective is to evaluate the concordance of diagnoses between general practitioners and psychiatrists. The secondary objective is a detailed description of the introduction of psychotropic drugs, especially benzodiazepines, by the medical officer in the field. RESULTS: In total, our study included 610 patients. Significant differences were observed between diagnoses made by military general practitioners and military psychiatrists, except for "psychotic disorders" and "other diagnoses" categories. During hospitalization, benzodiazepines were prescribed to 26.5% of repatriated patients, antidepressants to 12.7%, hypnotics to 17.6%, neuroleptics to 24.23%, and hydroxyzine to 18.8%. Upon discharge, benzodiazepines were prescribed to 23.5% of patients, antidepressants to 17.8%, hypnotics to 9.9%, neuroleptics to 28.9%, and hydroxyzine to 19.7%. The chi-squared test revealed significant differences in prescription between military operations and hospitalization for all molecules except hydroxyzine. Among patients diagnosed with Psychological Disorder Related to a Traumatic Event (TPRET) (<1 and >1 month) by psychiatrists during hospitalization, 66.2% were prescribed benzodiazepines during operational theaters, 24.3% continued during hospitalization, and 16.8% received a prescription upon discharge.The duration of missions often hinders precise psychiatric diagnoses, leading medical officers to transmit clinical data for optimized specialized care at military training hospitals. Furthermore, significant differences in therapeutic administration between medical officers and psychiatrists, particularly in benzodiazepine prescriptions for patients with TPRET, highlight the importance of prioritizing psychotropic prescription modalities in the training of medical officers on mental disorders. Strengthening operational preparations in recent years could enable more practitioners to benefit from these measures. CONCLUSIONS: We suggest several measures to enhance the transmission of medical information between medical officers and military psychiatrists. First, optimizing the drafting of Patient Movement Requests could involve implementing pre-filled drop-down menus or providing an adapted bilingual lexicon, facilitating the optimal transmission of clinical information for repatriated patients. Second, strengthening the training of medical officers before deployment and sharing the "Emergency Psy Kit," a comprehensive support tool developed by French military psychiatrists, would further enhance the tool kit available to field practitioners for judiciously prescribing psychiatric drugs.

Drug-induced delusion: A comprehensive overview of the WHO pharmacovigilance database.

INTRODUCTION: A number of prescribed medicines have been reported in cases of drug-induced delusion, such as dopaminergic agents or psychostimulants. But to this day, most studies are based on a limited number of cases and focus on a few drug classes, so a clear overview of this topic remains difficult. To address this issue, we provide in this article a comprehensive analysis of drug-induced delusion, based on the World Health Organization (WHO) pharmacovigilance database. METHODS: We performed a disproportionality analysis of this database using the information component (IC). The IC compares observed and expected values to find associations between drugs and delusion, using disproportionate Bayesian reporting. An IC0.25 (lower end of the IC 95% credibility interval) > 0 is considered statistically significant. RESULTS: Here we present an analysis of 4559 suspected drug-induced delusion reports in the WHO pharmacovigilance database. These results identified 66 molecules statistically associated with delusion and an extensive analysis of confounding factors and coprescriptions was performed, using full database as background with an IC0.25 > 0. The main drug classes involved were antidepressants, antiepileptics, dopaminergic agents, opioids, antiinfective agents, benzodiazepines, anti-dementia drugs and psychostimulants. CONCLUSION: These results will help clinicians identify potential suspected drugs associated with delusion and decide which drug to discontinue and eventually lead to a re-evaluation of drug labels for some molecules.

In-depth gas chromatography/tandem mass spectrometry fragmentation analysis of formestane and evaluation of mass spectral discrimination of isomeric 3-keto-4-ene hydroxy steroids.

RATIONALE: The aromatase inhibitor formestane (4-hydroxyandrost-4-ene-3,17-dione) is included in the World Anti-Doping Agency's List of Prohibited Substances in Sport. However, it also occurs endogenously as do its 2-, 6- and 11-hydroxy isomers. The aim of this study is to distinguish the different isomers using gas chromatography/electron ionization mass spectrometry (GC/EI-MS) for enhanced confidence in detection and selectivity for determination. METHODS: Established derivatization protocols to introduce [2 H9 ]TMS were followed to generate perdeuterotrimethylsilylated and mixed deuterated derivatives for nine different hydroxy steroids, all with 3-keto-4-ene structure. Formestane was additionally labelled with H2 18 O to obtain derivatives doubly labelled with [2 H9 ]TMS and 18 O. GC/EI-MS spectra of labelled and unlabelled TMS derivatives were compared. Proposals for the generation of fragment ions were substantiated by high-resolution MS (GC/QTOFMS) and tandem mass spectrometry (MS/MS) experiments. RESULTS: Subclass-specific fragment ions include m/z 319 for the 6-hydroxy and m/z 219 for the 11-hydroxy compounds. Ions at m/z 415, 356, 341, 313, 269 and 267 were indicative for the 2- and 4-hydroxy compounds. For their discrimination the transition m/z 503 → 269 was selective for formestane. In 2-, 4- and 6-hydroxy steroids loss of a TMSO radical takes place as cleavage of a TMS-derived methyl radical and a neutral loss of (CH3 )2 SiO. Further common fragments were also elucidated. CONCLUSIONS: With the help of stable isotope labelling, the structures of postulated diagnostic fragment ions for the different steroidal subclasses were elucidated. 18 O-labelling of the other compounds will be addressed in future studies to substantiate the obtained findings. To increase method sensitivity MS3 may be suitable in future bioanalytical applications requiring discrimination of the 2- and 4-hydroxy compounds.

Mass spectral fragmentation analyses of isotopically labelled hydroxy steroids using gas chromatography/electron ionization low-resolution mass spectrometry: A practical approach.

RATIONALE: Gas chromatography coupled to electron ionization mass spectrometry (GC/EI-MS) is used for routine screening of anabolic steroids in many laboratories after the conversion of polar groups into trimethylsilyl (TMS) derivatives. The aim of this work is to elucidate the origin and formation of common and subclass-specific fragments in the mass spectra of TMS-derivatized steroids. Especially in the context of metabolite identification or analysis of designer drugs, isotopic labelling is helpful to better understand fragment ion generation, identify unknown compounds and update established screening methods. METHODS: Stable isotope labelling procedures for the introduction of [2 H9 ]-TMS or 18 O were established to generate perdeuterotrimethylsilylated, mixed deuterated and 18 O-labelled derivatives for 13 different hydroxy steroids. Fragmentation proposals were substantiated by comparison of the abundances of isotopically labelled and unlabelled fragment ions in unit mass resolution GC/MS. Specific fragmentations were also investigated by high-resolution MS (GC/quadrupole time-of-flight MS, GC/QTOFMS). RESULTS: Methyl radical cleavage occurs primarily from the TMS groups in saturated androstanes and from the steroid nucleus in the case of enol-TMS of oxo or α,ß-unsaturated steroid ketones. Loss of trimethylsilanol (TMSOH) is dependent on steric factors, degree of saturation of the steroid backbone and the availability of a hydrogen atom and TMSO group in the 1,3-diaxial position. For the formation of the [M - 105]+ fragment ion, methyl radical cleavage predominates from the angular methyl groups in position C-18 or C-19 and is independent of the site of TMSOH loss. The common [M - 15 - 76]+ fragment ion was found in low abundance and identified as [M - CH3 - (CH3 )2 SiH - OH]+ . For the different steroid subclasses further diagnostic fragment ions were discussed and structure proposals postulated. CONCLUSIONS: Stable isotope labelling of oxo groups as well as derivatization with deuterated TMS groups enables the detection of structure-related fragment ion generation in unit mass resolution GC/EI-MS. This may in turn allow us to propose isomeric assignments that are otherwise almost impossible using MS only.

Reconsidering mass spectrometric fragmentation in electron ionization mass spectrometry - new insights from recent instrumentation and isotopic labelling exemplified by ketoprofen and related compounds.

RATIONALE: In various fields of chemical analyses, structurally unknown analytes are considered. Proper structure confirmation may be challenged by the low amounts of analytes that are available, e.g. in early stage drug development, in metabolism studies, in toxicology or in environmental analyses. In these cases, mass spectrometric techniques are often used to build up structure proposals for these unknowns. Fragmentation reactions in mass spectrometry are known to follow definite pathways that may help to assign structural elements by fragment ion recognition. This work illustrates an investigation of fragmentation reactions for gas chromatography/electron ionization mass spectrometric characterization of benzophenone derivatives using the analgesic drug ketoprofen and seven of its related compounds as model compounds. METHODS: Deuteration and 18 O-labelling experiments along with high-resolution accurate mass and tandem mass spectrometry (MS/MS) were used to further elucidate fragmentation pathways and to substantiate rationales for structure assignments. Low-energy ionization was investigated to increase confidence in the identity of the molecular ion. RESULTS: The high-resolution mass analyses yielded unexpected differences that led to reconsideration of the proposals. Site-specific isotopic labelling helped to directly trace back fragment ions to their respective structural elements. The proposed fragmentation pathways were substantiated by MS/MS experiments. CONCLUSIONS: The described method may offer a perspective to increase the level of confidence in unknown analyses, where reference material is not (yet) available.

[Nutritional supplements in sports - sense, nonsense or hazard?] / Nahrungsergänzungsmittel im Sport ­ Sinn, Unsinn oder Gefahr?

The excessive sale of dietary supplements (DSs) has become a global multi-billion market as more and more people turn to DSs for a healthy lifestyle or for aesthetic reasons. DSs are also increasingly popular among athletes; 50-85% of recreational and 35-100% of competitive athletes report taking DSs, the latter more regularly. Unless pathological deficiencies are detected, the intake of DSs for recreational athletes is not recommended. While it may be advisable for competitive athletes to supplement their diet with certain macronutrients (proteins and carbohydrates), many micronutrients (vitamins, minerals) as well as allegedly performance enhancing DSs may only show minimal impact under specific conditions and for certain sports. However, most products lack proof of their effectiveness. In some cases, DSs may even have negative effects and reduce performance. Furthermore, competitive athletes should be aware of the fact that DSs may lead to positive doping tests, as they bear the risk of being contaminated with banned substances, or components may be banned substances themselves. Every single case of taking DSs should therefore be critically assessed and discussed with experts prior to use. DSs cannot replace a balanced diet and hard practice.