[Adjustment of healthcare and telemedicine in times of lockdown and COVID-19 pandemic: Feedback from a "Maison des Adolescents" (Teenager's House)]. / Adaptation des soins et télémédecine en période de confinement et de pandémie de COVID-19 : retour d'expérience d'une Maison des Adolescents.

BACKGROUND: The COVID-19 sanitary crisis has imposed a major reorganization of the health care system in France. Lockdown could be a factor in the emergence or deterioration of psychological disorders; it can be even more fragilizing during the specific period of adolescence. The « Maisons des Adolescents ¼ (Teenagers' Houses) had to urgently adjust their practices to provide continuity of care for adolescents suffering from physical or mental disorders. The « Maisons des Adolescents ¼ are pluridisciplinary care centres for adolescents and their families that provide assessments and services for medical, psychological, socio-educational, educational and legal needs. How did care continue for adolescents during lockdown? What adjustments occurred in the « Maisons des Adolescents ¼ during the health crisis? METHODS: This article presents the case of an adolescent who suffered a significant deterioration of her anorexia nervosa during confinement. Through this case, we describe the reorganization of care within the different units (consultations - day hospital - hospitalization unit) of a Parisian « Maison des Adolescents ¼ during the COVID-19 pandemic. FINDINGS: In this service, the rapid implementation of the telemedicine system in the context of the COVID-19 pandemic made possible provision of continuity in care for vulnerable adolescents and families. Based on the existing literature, we discuss the advantages and limitations of telemedicine and the practical issues for the future organization of care for adolescents. PERSPECTIVES: In contrast to pediatric medicine or child psychiatry, there is no protocol describing the application of telemedicine in adolescent medicine and psychiatry. There is an urgent need for further evaluation of the use of telemedicine for this population. This kind of research will improve knowledge about the effectiveness, acceptability and limitations of using a teleconsultation device in adolescent psychiatry in a crisis context. Certain remote care modalities implemented during the sanitary crisis could thus be maintained over time and become routine in the field of adolescent medicine and psychiatry.

Pharmacokinetics of tedizolid in subjects with renal or hepatic impairment.

Two open-label, single-dose, parallel-group studies were conducted to characterize the pharmacokinetics of the novel antibacterial tedizolid and the safety of tedizolid phosphate, its prodrug, in renally or hepatically impaired subjects. Tedizolid pharmacokinetics in subjects with severe renal impairment without dialysis support was compared with that of matched control subjects with normal renal function. Effects of hemodialysis on tedizolid pharmacokinetics were determined in a separate cohort of subjects undergoing long-term hemodialysis. Effects of hepatic impairment on tedizolid pharmacokinetics were determined in subjects with moderate or severe hepatic impairment and compared with those of matched control subjects with normal hepatic function. Each participant received a single oral (hepatic impairment) or intravenous (renal impairment) dose of tedizolid phosphate at 200 mg; hemodialysis subjects received two doses (separated by 7 days), before and after dialysis, in a crossover fashion. The pharmacokinetics of tedizolid was similar in subjects with severe renal impairment and controls (∼8% lower area under the concentration-time curve [AUC], with a nearly identical peak concentration) and in subjects undergoing hemodialysis before and after tedizolid phosphate administration (∼9% lower AUC, with a 15% higher peak concentration); <10% of the dose was removed during 4 h of hemodialysis. Tedizolid pharmacokinetics was only minimally altered in subjects with moderate or severe hepatic impairment; the AUC was increased approximately 22% and 34%, respectively, compared with that of subjects in the control group. Tedizolid phosphate was generally well tolerated in all participants. These results suggest that tedizolid phosphate dose adjustments are not necessary in patients with any degree of renal or hepatic impairment. (This study has been registered at ClinicalTrials.gov under registration numbers NCT01452828 [renal study] and NCT01431833 [hepatic study].).

In vitro, in vivo, and clinical studies of tedizolid to assess the potential for peripheral or central monoamine oxidase interactions.

Tedizolid phosphate is a novel oxazolidinone prodrug whose active moiety, tedizolid, has improved potency against Gram-positive pathogens and pharmacokinetics, allowing once-daily administration. Given linezolid warnings for drug-drug and drug-food interactions mediated by monoamine oxidase (MAO) inhibition, including sporadic serotonergic toxicity, these studies evaluated tedizolid for potential MAO interactions. In vitro, tedizolid and linezolid were reversible inhibitors of human MAO-A and MAO-B; the 50% inhibitory concentration (IC50) for tedizolid was 8.7 µM for MAO-A and 5.7 µM for MAO-B and 46.0 and 2.1 µM, respectively, with linezolid. Tedizolid phosphate was negative in the mouse head twitch model of serotonergic activity. Two randomized placebo-controlled crossover clinical studies assessed the potential of 200 mg/day tedizolid phosphate (at steady state) to enhance pressor responses to coadministered oral tyramine or pseudoephedrine. Sensitivity to tyramine was determined by comparing the concentration of tyramine required to elicit a ≥ 30-mmHg increase in systolic blood pressure (TYR30) when administered with placebo versus tedizolid phosphate. The geometric mean tyramine sensitivity ratio (placebo TYR30/tedizolid phosphate TYR30) was 1.33; a ratio of ≥ 2 is considered clinically relevant. In the pseudoephedrine study, mean maximum systolic blood pressure was not significantly different when pseudoephedrine was coadministered with tedizolid phosphate versus placebo. In summary, tedizolid is a weak, reversible inhibitor of MAO-A and MAO-B in vitro. Provocative testing in humans and animal models failed to uncover significant signals that would suggest potential for hypertensive or serotonergic adverse consequences at the therapeutic dose of tedizolid phosphate. Clinical studies are registered at www.clinicaltrials.gov as NCT01539473 (tyramine interaction study conducted at Covance Clinical Research Center, Evansville, IN) and NCT01577459 (pseudoephedrine interaction study conducted at Vince and Associates Clinical Research, Overland Park, KS).

Incorporating serotypes into family based association studies using the MFG test.

Family based association tests are widely used to detect genetic effects. The focus of this paper is the maternal-fetal genotype (MFG) incompatibility test, a family based association test which can be used to detect genetic effects that contribute to disease, including alleles in the child that increase disease risk, maternal alleles that increase disease risk in the child, and maternal-fetal genotype incompatibilities. Consideration of incomplete data resulting from using serotypes could expand the power of the MFG test for detecting genetic effects. Serotypes may be all that are available in certain families, or preferred because of convenience or low cost, and thus a modification of the MFG test will allow optimal use of such data. The modified MFG likelihood can accommodate the incomplete data that result from using serotypes rather than the corresponding codominant genotypes. The modified MFG test was evaluated with serotypes and genotypes from families with members affected with schizophrenia. In addition, simulation studies were performed. Results of the data analyses and simulation studies showed that serotypes can be used to augment genotypes within a sample, to increase power to detect effects when the candidate gene produces serotypes.

Decreased macular leukocyte velocity in human immunodeficiency virus-infected individuals.

PURPOSE: To determine whether human immunodeficiency virus (HIV)-infected individuals have decreased macular capillary blood flow in vivo. DESIGN: Case control study. METHODS: Macular leukocyte velocity and perceived leukocyte density were determined in 41 HIV-infected individuals without cytomegalovirus retinitis and 31 HIV-negative control subjects using the blue field simulation technique (BFS-2000, Oculix, Inc., Jenkintown, PA). Velocity and density measurements for HIV-infected individuals were compared to current and lowest previous CD4+ T-lymphocyte counts, HIV RNA blood levels, and blood leukocyte counts. RESULTS: Mean macular leukocyte velocity was lower in HIV-infected individuals than in controls (P = 0.0006). No correlations were identified between velocity measurements and the following factors in HIV-infected individuals: current or lowest previous CD4+ T-lymphocyte count; or HIV RNA blood level. Mean perceived leukocyte density in HIV-infected individuals was lower than in controls (P = 0.003), but was not correlated with blood leukocyte count in HIV-infected individuals. No relationships were identified between macular leukocyte velocity and duration of medication use or duration of elevated CD4+ T-lymphocyte count in patients receiving potent antiretroviral therapy. CONCLUSIONS: Reduced macular leukocyte velocity may have important implications for understanding the retinal microvasculopathy of HIV disease, the pathogenesis of opportunistic retinal infections, and visual dysfunction in HIV-infected individuals who do not have opportunistic retinal infections. We found no evidence that macular leukocyte velocity increased with immune reconstitution.

Viability of Chlamydia trachomatis in fallopian tubes of patients with ectopic pregnancy.

OBJECTIVE: To use standard molecular methods to define the prevalence and metabolic characteristics of Chlamydia trachomatis during infection of fallopian tubes in women with ectopic pregnancies. DESIGN: Polymerase chain reaction (PCR)- and reverse transcription-PCR (RT-PCR)-based assessment of presence of chlamydial DNA and various RNA species in fallopian tube biopsy samples. SETTING: Hospital and molecular genetics laboratory. PATIENTS: Ten women of varying ages, each presenting with ectopic pregnancy. MAIN OUTCOME MEASURE(S): Positive signal in specific chlamydia-directed PCR and RT-PCR assays. RESULT(S): Nucleic acid preparations from 7 of the 10 fallopian tube patient samples were PCR-positive for C. trachomatis DNA. Each of the 7 PCR-positive samples also showed the presence of several transcripts from the bacterium, including primary transcripts from the ribosomal RNA operons. CONCLUSION(S): A higher proportion of ectopic pregnancies than was believed previously may be attributable to infection of the fallopian tubes by C. trachomatis. The presence of various chlamydial RNA molecules suggests that viable, metabolically active bacteria were present in fallopian tubes of the patients studied.

Free and protein-bound progesterone during normal and luteal phase defective cycles.

OBJECTIVES: New methods for the measurement of the percent free (%FreeP) and percent corticosteroid binding globulin-bound (%CBG-B) fractions of plasma progesterone (P) are described. METHODS: Modifications of previously reported equilibrium dialysis and charcoal adsorption assays were used. P binding was analyzed in single midluteal samples of 16 infertile women with endometrial biopsy proven luteal phase defect (LPD) and 10 infertile women with a normal luteal phase. RESULTS: %FreeP, %CBG-B, percent nonspecific protein-bound P (%NSP), total P and total plasma estradiol (E2) were measured during the normal ovulatory cycles of 5 women. The mean follicular phase %FreeP was found to be lower than in the luteal phase due to a decline in the late follicular phase. This decline correlated with the preovulatory rise in E2. The mean absolute concentration of free P (FreeP) rose significantly in the luteal phase, positively correlating with total P in both phases. Mean %CBG-B and %NSP were unchanged throughout the cycle. P was lower in LPD vs. normal cycles, but %FreeP and %CBG-B were not different. E2 highly correlated with P but not with %FreeP and %CBG-B. CONCLUSIONS: In normal cycles a small but significant decrease in %FreeP occurs in the late follicular phase and is associated with increasing E2. Changes in total P during the ovulatory cycle reflect changes in the concentration of bioactive P. There were no data to support an association of LPD with changes in the bioactive fraction of P.

Chlamydia antibody by enzyme-linked immunosorbent assay and associated severity of tubal factor infertility.

We have evaluated the clinical utility of the serum chlamydial antibody value by ELISA in predicting the severity of tubal factor infertility quantified by the use of a previously reported pelvic scoring system. Significant differences in salpingitis scores, tubal occlusion scores, adhesion scores, and pelvic stages were found with increasing chlamydia antibody grades. The level of ELISA value strongly correlated with salpingitis, tubal occlusion, and total pelvic scores and pelvic stages. The serum chlamydia antibody level by ELISA now appears to be a useful prognostic tool for predicting the severity of tubal factor infertility in addition to its value in screening for its presence.

Comparative evaluation of the neuromuscular and cardiovascular effects of pipecuronium, pancuronium, atracurium, and vecuronium under isoflurane anesthesia.

The neuromuscular and cardiovascular effects of intubating doses of pipecuronium 80 micrograms/kg, pancuronium 100 micrograms/kg, atracurium 500 micrograms/kg, and vecuronium 100 micrograms/kg were compared in 62 patients under isoflurane (end-tidal concentration = 0.5-1%) anesthesia. Pipecuronium, pancuronium, and vecuronium had no significant effect on systolic or diastolic blood pressure. In one patient the administration of atracurium resulted in significant hypotension. Heart rate was significantly increased only after the administration of pancuronium. The neuromuscular-blocking effect of pipecuronium and pancuronium appears to be twice as long as that of vecuronium and atracurium. Administration of neostigmine resulted in significantly faster recovery of muscle function in patients receiving vecuronium or atracurium. Although pipecuronium's neuromuscular-blocking effect is similar to that of pancuronium, its lack of cardiovascular effects more closely resembles that of vecuronium.

Treatment of postoperative nausea and vomiting with ondansetron: a randomized, double-blind comparison with placebo.

Postoperative nausea and vomiting are common after recovery from general anesthesia. The antiemetic effect and safety of ondansetron, a selective serotonin type 3 (5-HT3) receptor antagonist, was determined in 36 patients suffering from nausea or vomiting during recovery from intravenous anesthesia by giving either a single intravenous dose of ondansetron (8 mg, n = 18) or placebo (n = 18) over 2-5 min in a randomized, double-blind manner. A "rescue" antiemetic was provided in case of continued vomiting or at the patient's request. Antiemetic efficacy was defined as no request for rescue antiemetic and/or no vomiting episode during the next 4 h. There was no significant difference in the demographic data between the groups. Administration of ondansetron or placebo had no significant effect on vital signs. Ondansetron was an effective antiemetic in 78% (14/18) and placebo was effective in 28% (5/18) of the patients. Laboratory studies 24 h later showed no signs of hematologic, hepatic, or renal alterations. Ondansetron at a dose of 8 mg administered intravenously over 2-5 min appears to be a safe and effective antiemetic for the treatment of nausea and/or vomiting after intravenous anesthesia.

Chlamydial antibody, as determined with an enzyme-linked immunosorbent assay, in tubal factor infertility.

Serum chlamydial antibody (CA), as determined with an enzyme-linked immunosorbent assay (ELISA), was evaluated as a predictor for the presence or absence of tubal factor infertility. Two hundred fifty-eight infertile women had CA drawn at the initial visit of an infertility workup. Of them, 46.3% were CA positive (CA+). One hundred forty-five patients underwent laparoscopy (LPY). Tubal factor was diagnosed in 87.2% of CA+ patients and 13.6% of CA negative (CA-) ones (P less than .001), with a rising frequency by CA positivity. CA correctly predicted the presence or absence of tubal factor in 86.9% of patients. The frequency of abnormal hysterosalpingograms (HSG) was higher in CA+ patients. The predictive values for tubal factor with low, mid and high CA+ were 62.5%, 97.5% and 95.8%, respectively, and for no tubal factor with CA- was 72.3%. Combining HSG with CA- increased that value. Agreement between the LPY and HSG findings by the CA result showed a high correlation. A history of pelvic inflammatory disease (PID) or intrauterine device use was more common in CA+ patients, but only 25.3% of patients with tubal factor had a history of PID. The frequency of positive cervical chlamydial cultures was 0.8%. CA determined with ELISA appears to be an accurate screening test for tubal factor infertility and can be used to reliably select the procedure of choice for tubal evaluation.

Pyrophosphate analogues in pyrophosphorolysis reaction catalyzed by DNA polymerases.

It is demonstrated here that rat liver DNA polymerase beta catalyzes the pyrophosphorolysis reaction with pyrophosphate (PPi) and its analogues. The substrate specificity of the PPi-binding site of several DNA polymerases was investigated. It was discovered that the ability of DNA polymerases to utilize PPi analogues instead of PPi in the pyrophosphorolysis reaction was markedly restricted. Only imidodiphosphate and methylenediphosphonate were demonstrated as participating in this process. Oxodiphosphonate and phosphonoformate inhibited DNA synthesis, but probably not via the interaction with the PPi-binding site of DNA polymerases.

Assessment of infertility surgery by a pelvic scoring system.

A pelvic scoring and staging system previously reported was used to evaluate 77 major microsurgical procedures during a 3-year period. Pregnancy rates by clinical assessment groups were (a) surgery indicated for tubo-ovarian adhesions (SGY:F) = 50%; (b) surgery indicated with other pelvic pathology, such as adnexal masses or myoma (SGY:F/etc) = 23%; and (c) surgery questionably indicated (SGY:?) = 18%. Using the scoring system, pregnancy rates by stage were 75%, 41%, and 14% for Stages I, II, and III, respectively. The pregnancy rate was higher in the pure tubal factor group as compared with those with additional infertility factors. Pelvic scores and stages correlated well with clinical expectations. Life-table analysis of cumulative pregnancy rates showed that all subsequent pregnancies occurred within the 24 months following surgery. A significant correlation noted between pelvic scores and cumulative pregnancy rates illustrates the system's usefulness in predicting reproductive potential postoperatively. This method can be used to assist the surgeon in establishing a couple's prognosis and to compare results between surgeons or different surgical techniques.

Urinary follicle stimulating hormone treatment for luteal phase defect.

A deficiency in follicle stimulating hormone (FSH) levels during the early follicular phase of the menstrual cycle has been shown to result in luteal phase defect (LPD). A short course of human urinary FSH (uFSH) (Metrodin, Serono Laboratories) was given for a maximum of six cycles to 18 women with endometrial-biopsy-proven (EBX-proven) LPD. Adjunctive therapy in the form of midcycle human chorionic gonadotropin was given after the third therapy cycle. The uFSH therapy reduced the mean EBX lag time (2.0 +/- 0.6 days with therapy vs. 4.1 +/- 0.4 pretherapy, P less than .01), normalized the follicular phase length (15 +/- 0.4 days vs. 17.2 +/- 0.8 pretherapy, P less than .25) and increased the luteal phase length (12.7 +/- 0.4 days vs. 10.8 +/- 0.2 pretherapy, P less than .001). Twelve of 46 cycles (26%) in which uFSH was given without adjunctive therapy were anovulatory. Seven patients conceived; the result was seven viable pregnancies, all delivered at term. The cumulative pregnancy rate approached 48% by the sixth therapy cycle. uFSH therapy is useful for the correction of LPD and yields an acceptable pregnancy rate.

The integrated luteal progesterone: an assessment of luteal function.

An integrated luteal progesterone (ILPL) was calculated on the basis of a luteal progesterone (P) level with the assumption that the daily plasma P level in the luteal phase closely approximates a sine curve. The midluteal P-amplitude (K) was also obtained mathematically. Daily luteal P levels from five normal ovulatory cycles were assessed for the biologic variation of ILPL and K, then compiled to construct a normogram of the ILP during the luteal phase. The coefficient of variation of K and total ILPL in each cycle ranged from 9.7% to 24.3% and 3.5% to 13.2%, respectively. Fifty-two infertility patients were evaluated for their luteal function by the luteal P and estradiol (E2) level, K, ILPL, endometrial biopsy (EBX)-lag-day, as well as the lengths of follicular phase, luteal phase (L#), and cycle. Thirty-nine patients had EBX-lag day less than or equal to 2 days and were designated as infertile-normal (INF-NL) luteal phase, while the remaining 13 patients who had EBX-lag day greater than 2 days were considered as luteal phase defect (LPD). Significant (P less than 0.05) differences were observed between INF-NL and LPD in: luteal length (13.2 +/- 0.31 versus 11.0 +/- 0.58 days, respectively), and total ILPL (170 +/- 8.3 versus 113 +/- 8.5 ng/ml-day, respectively). No differences were seen in luteal P, E2 and K levels, nor in follicular and cycle length. Significant (P less than 0.05) correlations were observed between total ILPL and luteal P, E2, L#, and K; while a negative correlation was noted between follicular and luteal length.(ABSTRACT TRUNCATED AT 250 WORDS)

Properties of 2',3'-dideoxy-2',3'-dehydrothymidine 5'-triphosphate in terminating DNA synthesis catalyzed by several different DNA polymerases.

2',3'-dideoxy-2',3'-dehydrothymidine 5'-triphosphate (dddTTP) shows termination substrate properties in the DNA synthesis catalyzed by E. coli DNA polymerase I KF, rat liver DNA polymerase beta, reverse transcriptases of avian myeloblastosis virus and Raus sarcoma virus and calf thymus terminal deoxynucleotidyl transferase. This implies that the mononucleotide residue of dddTTP incorporates into 3'-termini of newly synthesized DNA chains. However, dddTTP has no influence on the DNA synthesis catalyzed by calf thymus DNA polymerase alpha. In the case of some DNA polymerases dddTTP was one order of magnitude more effective in comparison with the other known termination substrates.

Leiomyomatosis peritonealis disseminata. A case report and literature review.

Leiomyomatosis peritonealis disseminata is a rare disorder characterized by the presence of multiple small nodules, consisting of benign smooth muscle, scattered over the abdominopelvic viscera and peritoneum. The case described below is the 21st reported in the medical literature to our knowledge. The condition generally occurs in menstruating, parous women in the third decade of life, and the symptoms are similar to those of uterine leiomyomata. There is a very high association with excess exogenous and endogenous female gonadal steroids, specifically estrogen and progesterone. Leiomyomatosis peritonealis disseminata is a benign condition for which conservative management is indicated, particularly if fertility is desired.