Real-world study of intranasal ketamine for use in patients with refractory chronic migraine: a retrospective analysis.

INTRODUCTION: Subanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal ketamine may be an alternative option for outpatient care. METHODS: A retrospective study was conducted at a single tertiary headache center to assess the clinical effectiveness and tolerability of intranasal ketamine in patients with refractory chronic migraine. Candidates who received intranasal ketamine between January 2019 and February 2020 were screened through an electronic medical record query. Manual chart reviews and structured telephone interviews were conducted on obtaining informed consent. RESULTS: Of 242 subjects screened, 169 (79.9% women) of median (IQR) age 44 (22) years were interviewed. They reported a median (IQR) of 30 (9) monthly headache days and tried 4 (1) classes of preventive medications. Overall, they used 6 (6) sprays per day, with a median (IQR) of spray use of 10 (11) days per month. Intranasal ketamine was reported as 'very effective' in 49.1% and the quality of life was considered 'much better' in 35.5%. At the time of the interview, 65.1% remained current intranasal ketamine users and 74.0% reported at least one adverse event. CONCLUSION: In this descriptive study, intranasal ketamine served as an acute treatment for refractory chronic migraine by reducing headache intensity and improving quality of life with relatively tolerable adverse events. Most patients found intranasal ketamine effective and continued to use it despite these adverse events. Given the potential for overuse, it should be reserved for those clearly in need of more effective rescue treatment with appropriate safety precautions. Well-designed prospective placebo-controlled trials are necessary to demonstrate the efficacy and safety of intranasal ketamine in patients with migraine.

Cocaine abuse during pregnancy.

Cocaine abuse during pregnancy is a significant public health problem but is infrequently discussed between physicians and patients. The impact of in utero cocaine exposure on pregnancy and the baby has received significant media attention in preceding decades because of fears of teratogenicity, long-term health consequences, and poor cognitive and neurodevelopmental outcomes. We sought to review the medical literature examining these phenomena. We identified risks to the pregnancy and baby in women abusing cocaine during pregnancy. These include preterm birth, placenta-associated syndromes (e.g., placental abruption, preeclampsia, and placental infarction), and impaired fetal growth. Long-term neurodevelopmental and cognitive deficits include (but are not limited to) poorer language development, learning and perceptual reasoning, behavioural problems, and adverse effects on memory and executive function. However, these results should be interpreted cautiously because cocaine abuse may be accompanied by many other maternal and sociodemographic risk factors, so it is difficult to ascertain the effect of cocaine alone. Therefore, it is critical to counsel patients about potential risk, and perhaps more importantly, to treat addiction and to better understand, and advocate for improvements to, these patients' high-risk environment.

Bien que la consommation de cocaïne pendant la grossesse constitue un problème de santé publique considérable, elle ne fait que peu fréquemment l'objet de discussions entre les médecins et leurs patientes. Les effets de l'exposition in utero à la cocaïne sur la grossesse et l'enfant se sont mérités une attention médiatique considérable au cours des dernières décennies, en raison de préoccupations au sujet de la tératogénicité de la cocaïne, de ses conséquences à long terme sur la santé et de son influence sur l'obtention de piètres issues cognitives et neurodéveloppementales. Nous avons cherché à analyser la littérature médicale examinant ces phénomènes. Nous avons identifié des risques pour la grossesse et l'enfant attribuables à la consommation de cocaïne pendant la grossesse. Parmi ces risques, on trouve l'accouchement préterme, des syndromes associés au placenta (p. ex. décollement placentaire, prééclampsie et infarctus placentaire) et l'altération de la croissance fœtale. Parmi les déficits cognitifs et neurodéveloppementaux à long terme, on trouve (entre autres) des difficultés quant au développement langagier, à l'apprentissage et au raisonnement perceptif, des problèmes comportementaux et des effets indésirables sur la mémoire et la fonction exécutive. Toutefois, ces résultats devraient être interprétés avec prudence, puisque la consommation de cocaïne pourrait s'accompagner de nombreux autres facteurs de risque maternels et sociodémographiques; il est donc difficile de déterminer l'effet qui est seulement attribuable à la cocaïne. Ainsi, il est d'une importance cruciale de conseiller les patientes au sujet des risques potentiels d'une telle pratique et, ce qui est peut-être encore plus important, d'assurer la prise en charge de l'assuétude et de mieux comprendre les conditions de vie à risque élevé de ces patientes (et de promouvoir la mise en œuvre de mesures permettant de les améliorer).

Elevated blood pressure: Our family's fault? The genetics of essential hypertension.

AIM: To provide an updated review on current genetic aspects possibly affecting essential hypertension (EH), and to further elucidate their role in EH. METHODS: We searched for genetic and epigenetic factors in major studies associated with EH between Jan 2008-Oct 2013 using PubMed. We limited our search to reviews that discussed mostly human studies, and were accessible through the university online resource. We found 11 genome wide association studies (GWAS), as well as five methylation and three miRNA studies that fit our search criteria. A distinction was not made between genes with protective effects or negative effects, as this article is only meant to be a summary of genes associated with any aspect of EH. RESULTS: We found 130 genes from the studies that met our inclusion/exclusion criteria. Of note, genes with multiple study references include: STK39, CYP17A1, MTHFR-NPPA, MTHFR-NPPB, ATP2B1, CSK, ZNF652, UMOD, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, CSK-ULK3, CYP1A2, NT5C2, CYP171A, PLCD3, SH2B3, ATXN2, CACNB2, PLEKHA7, SH2B3, TBX3-TBX5, ULK4, and HFE. The following genes overlapped between the genetic studies and epigenetic studies: WNK4 and BDKRB2. Several of the identified genes were found to have functions associated with EH. Many epigenetic factors were also correlated with EH. Of the epigenetic factors, there were no articles discussing siRNA and its effects on EH that met the search criteria, thus the topic was not included in this review. Among the miRNA targets found to be associated with EH, many of the genes involved were also identified in the GWAS studies. CONCLUSION: Genetic hypertension risk algorithms could be developed in the future but may be of limited benefit due to the multi-factorial nature of EH. With emerging technologies, like next-generation sequencing, more direct causal relationships between genetic and epigenetic factors affecting EH will likely be discovered creating a tremendous potential for personalized medicine using pharmacogenomics.

Risks of untreated depression in pregnancy.

QUESTION: In my family practice, I tell my female patients of reproductive age who have depression that untreated depression in pregnancy might be more harmful than the unproven risks of antidepressants. However, I recently read in a national news magazine that there is actually no evidence for this advice. Have I missed something? ANSWER: You did not miss anything, so you should continue to advise your pregnant patients as before. News magazines can have substantial bias, as the reporters often only interview "experts" who support their beliefs, as was probably the case in this article. Most glaringly, in this instance, no perinatal psychiatrists were interviewed and none of the experts were clinically involved with pregnant women. We believe that media statements like the one you mentioned might lead women to abruptly discontinue their antidepressants, putting themselves at risk of relapse, hospitalization, and even suicide. Your balancing role in providing your patient with evidence-based information is critical.

Hot yoga and pregnancy: fitness and hyperthermia.

QUESTION: One of my pregnant patients wishes to continue her hot yoga exercises during pregnancy. Is this practice safe? ANSWER: With the increased risk of neural tube defects and possibly of other malformations among fetuses exposed to excessive heat, pregnant women should avoid practising hot yoga during pregnancy.

Synthesis of fatty acid ethyl esters in mammalian tissues after ethanol exposure: a systematic review of the literature.

The ability to undergo non-oxidative metabolism from ethanol to fatty acid ethyl esters (FAEEs) varies greatly among tissues and organs. To gain a greater understanding of non-oxidative ethanol metabolism to FAEE, we aimed to collect all published data on FAEE synthesis in mammalian organs and tissues to identify all tissues, organs, and enzymes that are known to, or likely possess FAEE-synthetic activity. A systematic search for relevant papers was performed and two independent reviewers examined potentially relevant abstracts (articles on FAEEs that pertain to ethanol exposure) to determine whether they met the inclusion criteria. Information on FAEE synthesis was retrieved from papers meeting the inclusion/exclusion criteria and summarized by organ/tissue/matrix examined. The systematic search through four databases yielded 78 articles that investigated FAEE synthesis by tissues, tissue fractions and cell lines, and 29 articles that attempted to purify and/or characterize the enzymes involved in FAEE synthesis. Two enzyme activities have been studied: FAEE synthase (FAEES, which conjugates ethanol and free fatty acid) and acyl-CoA: ethanol O-acyltransferase (AEAT, which conjugates ethanol and fatty acyl-CoA). Both activities are expressed by a variety of different enzymes. FAEES activity is the most widely studied and has been purified from several tissues and shown to be associated with several well-known enzymes, while the identity of enzymes possessing AEAT activity remains unknown. The organs and tissues that have been shown to synthesize FAEEs are discussed, with special emphasis on the studies that attempted to elucidate the enzymology of FAEE synthesis in those tissues.

Cocaethylene as a biomarker to predict heavy alcohol exposure among cocaine users.

BACKGROUND: Cocaethylene (CE) is a cocaine metabolite formed during alcohol and cocaine co-consumption. There are no previous studies to assess the effectiveness of hair CE as a biomarker indicating chronic alcohol consumption among individuals who have consumed cocaine. OBJECTIVES: To establish the ability of CE to predict chronic alcohol use among individuals testing positive for cocaine. METHODS: We studied all cases referred to our laboratory where both chronic cocaine and alcohol consumption were sought, and values of hair cocaine, benzoylegconine (BE), CE, and FAEEs (as marker of chronic alcohol consumption ) were available. Cocaine, BE and CE were screened by ELISA and confirmed using headspace-solid phase microextraction (HS-SPME) and GC-MS. FAEE were analyzed using HS-SPME and GC-MS/EI. Sensitivity, specificity, and predictive values of CE as a marker of alcohol consumption among cocaine users were calculated using different FAEE cutoffs. RESULTS: Cocaine (P<0.001) and BE (P<0.001) concentrations were associated with increased FAEE. The positive predictive value of CE to identify alcohol consumption was 0.66 for excessive drinking and 0.76 for chronic drinking among positive cocaine users. Negative CE ruled out almost completely excessive alcohol consumption. CONCLUSION: Positive hair CE results had high specificity for chronic excessive alcohol consumption among cocaine users. With no established safe level of alcohol in pregnancy, identification of CE in hair of pregnant women who have used cocaine can serve as a biomarker for fetal alcohol spectrum disorder.

Safety of azathioprine use during pregnancy.

QUESTION: Quite a few of my female patients with rheumatic diseases and inflammatory bowel disease are using azathioprine. They are afraid to take a "cancer drug" during pregnancy. What is known about the risks? ANSWER: An increasing body of evidence from prospective cohort studies suggests that azathioprine is safe for the fetus during pregnancy.