Epidemiology of cutaneous porphyria in Israel: a nationwide cohort study.

BACKGROUND: From a dermatologist's perspective, there are four major types of cutaneous porphyrias (CPs): porphyria cutanea tarda (PCT), erythropoietic protoporphyria (EPP), variegate porphyria (VP) and hereditary coproporphyria (HCP). Scarce data are available regarding the epidemiology of CPs. OBJECTIVES: To describe the epidemiology of CPs in Israel, including distribution, incidence and prevalence rates of major types. METHODS: This retrospective study includes all patients who were diagnosed with CPs between the years 1988-2018. It is based on data from Israel's National Service for the Biochemical Diagnoses of Porphyrias, and Israeli patients' nationwide electronic medical charts. Incidence and prevalence rates were calculated. RESULTS: Of 173 patients with CPs diagnosed during a 30-year period, 65 (38%) had VP, 62 (36%) had PCT, 31 (18%) had HCP and 15 (9%) had EPP; with incidence rates of 0.29, 0.30, 0.17, 0.07, and prevalence rates of 6.3, 4.8, 2.9, 1.6, respectively, per million population. Characteristics of patients with PCT differed from those with other CPs with regard to lack of family history, older mean age at diagnosis [51 vs. 36 (VP), 35 (HCP) and 25 (EPP) years] and male predominance (81% vs. similar distribution). All patients with PCT were diagnosed at adulthood, while 20%, 19% and 15% of patients with VP, HCP and EPP, respectively, were diagnosed during childhood or adolescence. CONCLUSIONS: Variegate porphyria and PCT were found to be the most prevalent in Israel; however, CPs might be underdiagnosed, thus dermatologists' awareness of these rare disorders is highly important.

Prevalence of New Psychoactive Substances (NPS) and conventional drugs of abuse (DOA) in high risk populations from Paris (France) and its suburbs: A cross sectional study by hair testing (2012-2017).

BACKGROUND: The aim of the present study is to describe the prevalence of NPS and conventional DOA in Paris and its suburbs over a six-year period using hair testing approach. METHOD: Hair was sampled in patients admitted to different departments of Paris hospitals between 2012 and 2017. Two high-risk populations were mainly considered: 1) drug-dependent and 2) acutely intoxicated patients. Segmental hair analysis was performed by validated LC-MS/MS method to screen for DOA and 83 NPS. RESULTS: 480 patients (280 M/200 F, 15-70 years) were included. 141 patients tested positive for NPS (99 M/42 F; median age: 33). NPS prevalence was 29%, that of amphetamines, cocaine and opioids were 32%, 38.5% and 52%, respectively. 27 NPS were identified, 4-MEC and mephedrone (number of cases n = 24 each) were the most detected cathinones. JWH-122 (n = 1) was the only detected synthetic cannabinoid while ketamine (n = 104) was present in numerous NPS users (67%). 3-fluorofentanyl (n = 1), furanylfentanyl (n = 1), N-ethylpentylone (n = 2), pentedrone (n = 2), mexedrone (n = 1), methcathinone (n = 3), 6-APDB (n = 2), TFMPP (n = 2), 2-CE (n = 1), 3,4-MD-αPHP (n = 1) and dextromethorphan (n = 27) were identified for the first time in hair. Users were found to have more than one NPS in 53% of cases, mostly in combination with conventional DOA. The number of detected NPS rose from 5 in 2012 to 42 in 2017. A broad range of hair concentrations (0.001-318 ng/mg) was found, but the low median concentrations seem to show an occasional exposure more than chronic use. CONCLUSION: NPS screening should be assessed in routine clinical practice, especially in high-risk populations.

[Which psychiatric comorbidities in cannabis dependence during adolescence? Comparison of outpatients and controls]. / Quelles comorbidités psychiatriques dans la dépendance au cannabis à l'adolescence ? Comparaison de patients consultants et de témoins.

BACKGROUND: The use of illicit substances, in particular cannabis, among French adolescents and young adults has become an important public health concern. A better understanding of the mechanisms involved in pathological substance use is nowadays critical. Psychiatric comorbidities have been previously reported in adult substance abusers but are less documented in adolescents, especially regarding cannabis dependence. OBJECTIVES: We investigated mental health problems in adolescents and young adults, seeking treatment for their problematic cannabis use, comparatively to healthy controls, taking into account the participant's gender and age. Moreover, we explored the relationships between psychiatric diagnosis and substance use modalities. METHODS: In total, 100 young patients (80 males - mean age 18.2 (SD=2.9; [14 to 25] years old)) with a cannabis dependence (DSM-IV-TR criteria) seeking treatment in an addiction unit, and 82 healthy control subjects (50 males - mean age 18.3 (SD=3.4; [14 to 25] years old)) with no substance misuse diagnostic other than for alcohol, participated in the study. The MINI was administered to evaluate cannabis dependence, and DSM-IV axis I comorbid diagnosis, and a semi-structured interview was used to determine psychoactive substance use. RESULTS: Statistical analyses revealed that 79 % of the patients reported at least one other non-drug or alcohol comorbid diagnosis, versus 30.5 % in the control group (χ2=16.83; P<0.001). Logistic regression indicated that participants with a psychiatric diagnosis had an 8.6 times higher risk (P<0.001; OR 95 % CI=[4.38-16.81]) of being patients. Significant inter-group differences and OR were noted for several diagnoses: dysthymia over the previous 2years (χ2=14.06; P<0.001; OR=10.63; OR 95 % CI=[2.41-46.87]), life-time panic attack disorder (χ2=4.15; P<0.042; OR=3.59; OR 95 % CI=[0.98-13.19]), alcohol abuse (χ2=47.72; P<0.001; OR=66.27; OR 95 % CI=[8.87-495.11]) and dependence (V=0.230; P=0.001) and generalized anxiety disorder (χ2=7.46; P=0.006-OR=3.57; OR 95 % CI=[1.37-9.30]). On the whole, the females (n=20) of our clinical sample presented significantly more comorbid diagnoses than the males (n=80) (95 % versus 75 %; χ2=6.25, P=0.011). These significant gender differences were found for life-time eating disorder (V=0.352; P=0.007) and generalized anxiety disorder diagnoses (V=0.278; P=0.013). Moreover, young adult patients (19-25years old; n=35) presented, on the whole, significantly more comorbid diagnoses than adolescent patients (14-18years old; n=65) (70.8 % versus 94.3 %; χ2=7.58, P=0.006). These age inter-group differences were found for several diagnoses: alcohol dependence (6.2 % versus 20 %; V=0.211, P=0.047), dysthymia over the past 2years (13.8 % versus 34.3 %; χ2=5.73, P=0.017) and generalized anxiety disorder (12.3 % versus 40 %; χ2=10.17, P=0.001). Various associations were observed between psychiatric comorbid diagnosis and substance use indicators. CONCLUSION: This study demonstrates that cannabis dependence in adolescents and young adults is related to great psychological distress and puts emphasis on the importance of substance use prevention as early as middle school. Moreover, the psychiatric features of adolescents and young adults need to be taken into consideration for treatment planning.

Do assisted conception twins have an increased risk for anencephaly?

BACKGROUND: The incidence rates of anterior neural tube defects, anencephaly and encephalocele appear increased among twins compared with singletons. The current study aimed to evaluate whether the etiology of this phenomenon is related to twinning, assisted reproductive technology (ART), or both. METHODS: The study cohort consisted of parturient women who were referred to our ultrasonography unit between January 1998 and December 2009 due to suspicion of severe fetal abnormality. The study cohort was divided into two subgroups based on mode of conception: spontaneous and ART (including IVF and ICSI). The subgroups were further subdivided into singleton and multiple pregnancies. We also compared pregnancies diagnosed with anencephaly in the study group to all live births in the Department of Obstetrics and Gynecology. RESULTS: Anencephaly was diagnosed in 43 fetuses out of 1154 (3.7%) pregnancies diagnosed with severe fetal anomaly. Anencephaly was diagnosed in 9 out of 78 twin pregnancies (11.5%); of these, 8 of 45 (17.8%) were ART conceived and 1 of 33 (3%) spontaneously conceived. A significant correlation was found between twinning and anencephaly, with an odds ratio (OR) of 3.4 [confidence interval (CI) = 1.3-8.9, P= 0.011], while no significant correlation was found between ART and anencephaly. A significant correlation was found between anencephaly and the combination of ART conception and twinning (OR of 6.6, CI = 2.8-15.3, P< 0.01). Analyzing the distribution of pregnancies diagnosed with anencephaly in the study group compared with the total number of live births in the department revealed a significant correlation between twinning and anencephaly, with an OR of 11.4 (CI = 4.9-26.5, P< 0.01), with no significant correlation between ART and anencephaly. Among all live births, a significant correlation was found between anencephaly and the combination of ART conception and twinning (OR of 24.6, CI = 11.4-53.2, P< 0.01). CONCLUSIONS: Our data suggest that twin pregnancies conceived by ART constitute a high-risk group for anencephaly, due to a possible synergistic effect of twinning and ART.

[Enterobacter cloacae spondylodiscitis through misuse of high-dose intravenous buprenorphine]. / Spondylodiscite à Enterobacter cloacae par mésusage intraveineux de la buprénorphine haut dosage.

INTRODUCTION: We report a case of Enterobacter cloacae spondylodiscitis related to risk practices in intravenous drug addicts (IVDA). OBSERVATION: The patient, a former heroin addict, was receiving long-term, high-dose buprenorphine maintenance treatment. He had been misusing the treatment, injecting it daily for several months. The clinical course included several uncommon features that are usually found in IVDA patients: subacute infection, apyrexia, and minimal inflammatory syndrome. This infection also led to the discovery of his HIV infection. DISCUSSION: Any dorsolumbar pain in IVDA patients, including those receiving regular drug maintenance treatment and especially those with HIV infection, should suggest spondylodiscitis, because of these patients' enhanced sensitivity to infection and the frequent bacteremia caused by persistent or transitory relapse involving injection (exchange of material, reuse of needles, syringes, cotton swabs, and risk of contamination through the hands or saliva).

Slow metabolism and long half life of methadone in a patient with lung cancer and cirrhosis.

In a patient on methadone maintenance treatment, admitted for lung cancer suspicion, a slight decrease in pain dose response to morphine have necessitated adjustments of methadone treatment founded on clinical check-up and methadone assay. Plasma methadone concentrations were 4 fold higher than mean plasma concentration for control population at the same dose. Half-life was above 70 hours and clearance and metabolic index were strongly decreased. In this patient, daily dose methadone occurred in progressive accumulation and neuro-physiological tolerance without clinical incidence, except decrease in morphine effectiveness compared to our knowledge. Cancer, cirrhosis and adjuvant therapy contributions (fluconazole, omeprazole) to this original methadone kinetic are discussed. Methadone and morphine dose clinical adjustments are described. However, the main objective of this case report is focused on plasma methadone assay contribution to therapeutic adjustment of the interval dose in a single patient with a complex clinical situation.

[The health of prisoners]. / La santé des détenus.

In twenty years, the prison population, from the mother country and the overseas departments, has more than doubled, in spite of reprieve and amnesty decisions. This increase is more a consequence of longer penalties than of a rise in the number of imprisoned people The law no. 94-43, dated january 18th 1994, concerning the prisoners' medical care and welfare is an unprecedented health revolution. It comes in addition to provisions from 1986 and 1987 for the programme "13,000" prisons and those endowed with a regional medical and psychological service (SMPR). The prisoners' health must urgently be dealt with and particularly as regards infectious diseases, vaccination check-up, campaign against drug addiction health and nutrition education and dental care. As soon as incarceration has begun, the exist must be prepared and taken into consideration by the different interveners inside and outside the prison, in order to make sure of an efficient medical follow-up. As the number of intervening medical and social personnel, is increasing in prisons, a coordination inside the their walls as well as on the regional and national levels, would prove useful.

Sweat testing in opioid users with a sweat patch.

For many years, toxicologists have detected the presence of drugs of abuse in biological materials using blood or urine. In recent years, remarkable advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional samples such as sweat. In a study conducted in a detoxification center, sweat patches were applied to 20 known heroin abusers. Subjects wore the patch with minimal discomfort for five days. During the same period, two urine specimens were also collected. Target drugs analyzed either by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) included opiates (heroin, 6-monoacetylmorphine, morphine, codeine), cocaine (cocaine, benzoylecgonine, ecgonine methyl ester), delta 9-tetrahydrocannabinol, benzodiazepines (nordiazepam, oxazepam), amphetamines (amphetamine, methamphetamine, methylenedioxyamphetamine [MDA], methylenedioxymethamphetamine [MDMA], methylenedioxyethylamphetamine [MDEA]), and buprenorphine. Patches were positive for opiates in 12 cases. Heroin (37-175 ng/patch) and/or 6-acetylmorphine (60-2386 ng/patch) were identified in eight cases, and codeine exposure (67-4018 ng/patch) was determined in four cases. When detected, heroin was always present in lower concentrations than 6-acetylmorphine, which was the major analyte found in sweat. Cocaine (324 ng/patch) and metabolites were found in only one case. delta 9-Tetrahydrocannabinol (4-38 ng/patch) was identified in nine cases. Benzodiazepine concentrations were very low, ranging from 2 to 44 and from 2 to 15 ng/patch for nordiazepam and oxazepam, respectively. MDEA (121 ng/patch) and its metabolite, MDA (22 ng/patch), were detected in one case. Buprenorphine, which was administered as therapy under close medical supervision, was detected in the range 1.3-153.2 ng/patch with no apparent relationship between the daily dose and amount excreted in sweat. All the urine tests were consistent with the sweat findings, but to identify the same drugs it was necessary to test two urine specimens along with only one sweat specimen. It was concluded that sweat testing appears to offer the advantage of being a relatively noninvasive means of obtaining a cumulative estimate of drug exposure over the period of a week. This new technology may find useful applications in the treatment and monitoring of substance abusers, as the patch provides a long-term continuous monitor of drug exposure or noncompliance.

Characterization of dextromoramide (Palfium) abuse by hair analysis in a denied case.

By providing information on exposure to drugs over time, hair analysis is useful in verifying the history of drug use. In a clinical case, where drug abuse was denied, it was possible to identify dextromoramide in the hair of the subject. After acid hydrolysis of the hair with 0.1 M HCl, in the presence of SKF 525A as an internal standard, the drug was extracted at pH 8.4 with chloroform-isopropanol-n-heptane (50:17:33 v/v) and quantified by gas chromatography/mass spectrometry. The hair strands were cut into 3 sections of 2.5 cm, corresponding to a growth period of 2 months. Concentrations were 1.09, 1.93 and 1.48 ng/mg from the root to the end, respectively. This is the first report on dextromoramide testing in human hair.

Hair analysis for buprenorphine and its dealkylated metabolite by RIA and confirmation by LC/ECD.

Hair samples were obtained from 14 subjects admitted 2 or 3 months previously to a detoxification center. All reported an history of intravenous heroin abuse. After decontamination by two dichloromethane washes, about 50 mg hair were pulverized in a ball mill and incubated at 56 degrees C overnight in 1 mL 0.1 HCl. After neutralization, buprenorphine analyzed by RIA was in the range of 0.01 to 0.47 ng/mg. To confirm buprenorphine, liquid chromatography was used. After neutralization, drugs were extracted with toluene at pH 8.5 during a 3-step extraction procedure. A portion of the reconstituted residue was injected into a Lichrosorb CN column, with a mobile phase of phosphate buffer (pH 4.0)-acetonitrile-1-heptane sulfonic acid-butylamine (85:17:2:0.01, v/v). Detection was achieved by coulometry, and the potential of the electrodes was 0.15 and 0.50 V, respectively. Linear calibration curves were obtained from 0.02 to 2.0 ng/mg with a correlation coefficient r > 0.99 for both drugs. The detection limit for the major metabolite was about 0.01 ng/mg and 0.02 ng/mg for buprenorphine, using a 50 mg hair sample. Recovery (at 0.2 ng/mg) was 54 and 62% for norbuprenorphine and buprenorphine, respectively. Drugs concentrations in hair were in the range 0.02-0.59 and not detected--0.15 ng/mg for buprenorphine and norbuprenorphine, respectively. Results suggest that a dose-response relationship exists between the concentration of buprenorphine in hair and the administered dose.