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This random-effects model meta-analysis of double-blind, randomized placebo-controlled trials compared recurrence rates in bipolar disorder (BD) patients between antipsychotic/mood stabilizer discontinuation and maintenance groups.
We conducted systematic literature search of Embase, PubMed, and CENTRAL databases without language restriction from inception until 22 May 2020. Independent investigators assessed studies and extracted data. We calculated risk ratios (RRs) and numbers needed to benefit or harm (NNTB/NNTH). Primary outcome was the recurrence rate of any mood episode at 6 months. Secondary outcomes were recurrence rates of depressive episodes and manic/hypomanic/mixed episodes and all-cause discontinuation at 6 months. We also investigated these outcomes at 1, 3, 9, 12, 18, and 24 months.
We identified 22 studies (n = 5462) receiving aripiprazole, asenapine, divalproex, long-acting injectable (LAI)-aripiprazole, LAI-risperidone, lamotrigine, lithium, olanzapine, paliperidone, or quetiapine. Mean study duration was 64.50 ± 69.35 weeks. The maintenance group demonstrated lower recurrence rates of any mood episode, depressive episodes, and manic/hypomanic/mixed episodes as well as reduced all-cause discontinuation at every observational point. The RRs (95% confidence interval, NNTB/NNTH) of recurrence rate at 6 months were 0.61 (0.54–0.70, 5) for any mood episode, 0.72 (0.60–0.87, 13) for depressive episodes, and 0.45 (0.36–0.57, 6) for manic/hypomanic/mixed episodes. The RR for all-cause discontinuation at 6 months was 0.71 (0.61–0.82, 6).
Maintaining drug treatment during clinically stable BD prevented recurrence for up to 24 months. Discontinuation of medications for ⩾1 month significantly increased recurrence risk. However, 47.3% of patients who discontinued drugs for 6 months did not experience recurrence.
Though Jean Toomer's Cane (1923) is one of the best-known texts of the Harlem Renaissance, it has rarely been discussed with the text alongside which it was initially imagined: Waldo Frank's Holiday (1923). These works were inspired by a joint trip to Spartanburg, South Carolina and were conceptualized as a shared project, what the authors termed “Holiday + Cane.” This essay tracks their coproduction with particular attention to their parallax vision of lynching to theorize what we call, building on Achille Mbembe's work, “sex under necropolitics.” This dispensation does not take shape within a privatized notion of sexuality, but instead is “ungendered” and unindividuated in the ways that Hortense Spillers has described through the notion of the flesh. We take up her work to suggest that black bodily practices and corporeal intimacies are governed by a regime other than sexuality. In this essay, we map the contours of this regime and its effects on both sides of the color line. Our new cartography promises to reconfigure understandings of the sexuality of Toomer and Frank and of the Harlem Renaissance, and to clarify the relationship between (white) queer theory and queer-of-color critique.
Discontinuation of antipsychotics predisposes patients with remitted/stable first-episode psychosis (FEP) to a higher risk of relapse, but it remains unclear how long discontinuation increases the relapse rate in these patients compared with maintenance.
This meta-analysis of randomized controlled trials (RCTs) compared relapse rates in FEP patients between antipsychotic treatment discontinuation and maintenance groups at 1, 2, 3, 6, 9, 12 (primary), and 18–24 months. The risk ratio (RR) and numbers needed to treat/harm (NNT/NNH) were calculated using a random-effects model.
Ten RCTs were identified (n = 776; mean study duration, 18.6 ± 6.0 months). The antipsychotics were discontinued abruptly in four RCTs (which reported data only at 12 months) and after tapering off gradually over several months (mean length, 3 months) in six RCTs. Compared with the discontinuation group, the maintenance group experienced significantly fewer relapses at all time points except 1 month [RR (NNT): 2 months, 0.49 (13); 3 months, 0.46 (9); 6 months, 0.55 (6); 9 months, 0.48 (3); 12 months, 0.47 (3); and 18–24 months, 0.57 (4)]. The maintenance group was associated with higher discontinuation due to adverse events (RR, 2.61; NNH, not significant).
Maintaining antipsychotic treatment prevented relapse for up to 24 months in FEP patients. Discontinuation of antipsychotics for ⩾2 months significantly increased the risk of relapse. However, 45.7% of patients who discontinued antipsychotics for 12 months (39.4% after 18–24 months) did not experience a relapse.
I introduce a minimum innovation size required for patents into a Schumpeterian growth model. We show that to satisfy the patentability requirement for minimum innovation size, each research and development (R&D) firm targets only industries in which the incumbent's technology is of sufficient obsolescence. This is because the technological gap between innovator and incumbent is greater in industries using older technologies. Although the increase in minimum innovation size reduces the number of industries targeted for R&D, it also increases the amount of R&D investment directed at those targeted industries. Consequently, introducing a minimum innovation size has a nonmonotonic (or negative) effect on the aggregate flow of innovations. Further, by deriving the endogenous long-run distribution of innovation size, we show that an increase in minimum innovation size reduces the mean innovation size. This implies that even if the patent office only grants patents for superior innovations, it causes innovators to produce generally inferior-quality innovations.
The objective of this study was to determine whether a combination of crude glycerin (CG) and soyabean oil (SO) could be used to partially replace maize in the diet of Nellore steers while maintaining optimum feed utilisation. Eight castrated Nellore steers fitted with ruminal and duodenal cannulas were used in a double 4×4 Latin square design balanced for residual effects, in a factorial arrangement (A×B), when factor A corresponded to the provision of SO, and factor B to the provision of CG. Steers feed SO and CG showed similar DM intake, DM, organic matter and neutral-detergent fibre digestibility to that of steers fed diets without oil and without glycerine (P>0·05). Both diets with CG additions reduced the acetate:propionate ratio and increased the proportion of iso-butyrate, butyrate, iso-valerate and valerate (P<0·05). Steers fed diets containing SO had less total N excretion (P<0·001) and showed greater retained N expressed as % N intake (P=0·022). SO and CG diet generated a greater ruminal abundance of Prevotella, Succinivibrio, Ruminococcus, Syntrophococcus and Succiniclasticum. Archaea abundance (P=0·002) and total ciliate protozoa were less in steers fed diets containing SO (P=0·011). CG associated with lipids could be an energy source, which is a useful strategy for the partial replacement of maize in cattle diets, could result in reduced total N excretion and ruminal methanogens without affecting intake and digestibility.
The preselection of highly developmentally competent oocytes for in vitro maturation (IVM) is crucial for improving assisted reproductive technology. Although several intrinsic markers of oocyte quality are known to be closely related to the onset of nuclear maturation (germinal vesicle break down, GVBD), a direct comparison between GVBD timing and oocyte quality has never been reported. In this study, we established a non-invasive oocyte evaluation method based on GVBD timing for preselecting more developmental competent oocytes in mice. Because the O2 concentration during IVM may affect the nuclear kinetics, all experiments were performed under two distinct O2 concentrations: 20% and 5% O2. First, we determined the time course of changes in nuclear maturation and preimplantation developmental competence of in vitro-matured oocytes to estimate GVBD timing in high developmental competent oocytes. Two-thirds of oocytes that underwent GVBD in early IVM seemed to mainly contribute to the blastocyst yield. To confirm this result, we compared the preimplantation developmental competence of the early and late GVBD oocytes. Cleavage and blastocyst formation rates of early GVBD oocytes (80.2% and 52.7% under 20% O2, respectively, and 67.6% and 47.3% under 5% O2, respectively) were almost double those of late GVBD oocytes (44.8% and 26.0% under 20% O2, respectively, and 40.4% and 17.9% under 5% O2, respectively). With no observable alterations by checking the timing of GVBD in preimplantation developmental competence, oocyte evaluation based on GVBD timing can be used as an efficient and non-invasive preselection method for high developmental competent oocytes.
The International Clearinghouse for Birth Defects, Surveillance and Research reports a rise in the prevalence rate of spina bifida in Japan. We determined first-trimester folate status of Hokkaido women and identified potential predictors. Participants were 15 266 pregnant women of the Hokkaido Study on Environment and Children’s Health Cohort. Data were extracted from self-reported questionnaires and biochemical assay results. Demographic determinants of low folate status were younger maternal age (adjusted OR (AOR) 1·48; 95 % CI 1·32, 1·66), lower educational level (AOR 1·27; 95 % CI 1·17, 1·39) and lower annual income (AOR 1·11; 95 % CI 1·01, 1·22). Plasma cotinine concentrations of 1·19–65·21 nmol/l increased the risk of low folate status (AOR 1·20; 95 % CI 1·10, 1·31) and concentrations >65·21 nmol/l further increased the risk (AOR 1·91; 95 % CI 1·70, 2·14). The most favourable predictor was use of folic acid (FA) supplements (AOR 0·19; 95 % CI 0·17, 0·22). Certain socio-demographic factors influence folate status among pregnant Japanese women. Modifiable negative and positive predictors were active and passive tobacco smoking and use of FA supplements. Avoiding both active and passive tobacco smoking and using FA supplements could improve the folate status of Japanese women.
There is little expert consensus as to which drugs should comprise the first-line pharmacological treatment for delirium. We sought to assess experts’ opinions on the first-line oral and injection drugs for delirium associated with a diverse range of clinical features using a rating-based conjoint analysis.
We conducted a cross-sectional study. We mailed a questionnaire to all consultation-liaison psychiatrists/educators certified by the Japanese Society of General Hospital Psychiatry.
Of 136 experts (response rate: 27.5%), more than 68% recommended the use of risperidone or quetiapine administered orally for hyperactive delirium, except in patients with comorbid diabetes and renal dysfunction. More than 67% recommended the use of haloperidol administered intravenously for hyperactive delirium if an intravenous line has been placed. No oral or injection drugs were recommended by over half of experts for treatment of hypoactive delirium with any clinical features.
In the absence of a definitive treatment trial, there are both areas of agreement and a lack of consensus regarding the first-line drug. Efforts are needed to routinely collect information that would allow a comparison of the effectiveness and safety of various drugs in real-world clinical practice.
A meta-analysis of the serotonin1A (5-HT1A) receptor partial agonist of the azapirone class as an anxiolytic drug for the treatment of major depressive disorder (MDD) has not previously been reported.
We carried out a systematic review of the literature available in PubMed, the Cochrane Library database and PsycINFO up to 12 October 2013, and conducted a meta-analysis of randomized controlled trials (RCTs) comparing 5-HT1A agonists with placebo and RCTs of 5-HT1A agonist augmentation therapies for MDD treatment. We calculated the risk ratio (RR), number needed to treat (NNT)/number needed to harm (NNH) and 95% confidence intervals (CIs).
Fifteen RCTs comparing 5-HT1A agonists with placebo (total n = 2469, four studies with buspirone, seven with gepirone, three with ipsapirone and one with zalospirone) were identified. Pooled 5-HT1A agonists had significantly more responders (RR 0.74, 95% CI 0.65–083, p < 0.00001, NNT = 6, 12 trials, n = 1816) than placebo. Pooled 5-HT1A agonists were superior to placebo in discontinuation due to inefficacy (RR 0.49, p = 0.02, NNH = 16, p = 0.03, 10 trials, n = 1494) but were inferior to placebo in discontinuation due to side-effects (RR 1.88, p < 0.0001, NNH = 17, p = 0.001, 13 trials, n = 2196). However, all-cause discontinuation was similar in both groups (RR 0.99, p = 0.85, 14 trials, n = 2402). Four 5-HT1A agonist augmentation studies were identified (total n = 365, three buspirone studies and one tandospirone study). There were no statistically significant effects of 5-HT1A agonist augmentation therapies on response rate (RR 0.98, p = 0.85, four trials, n = 341). 5-HT1A agonist-related side-effects including gastrointestinal symptoms, dizziness, insomnia, palpitation, paresthesia and sweating were greater than with placebo (p < 0.00001 to p = 0.03).
Our results suggest that 5-HT1A agonist has a more beneficial effect on MDD than placebo, but has several side-effects.
We investigated an association between the polymorphism of brain-derived neurotrophic factor (BDNF) gene Val66Met and the response to mirtazapine in Japanese patients with major depressive disorder (MDD). We also examined mirtazapine's effects on the serum BDNF and plasma levels of catecholamine metabolites in these patients.
Eighty-four patients who met the DSM-IV-TR criteria for MDD were treated with only mirtazapine for 4 weeks. The BDNF Val66Met polymorphism was detected by direct sequencing in the region, and serum BDNF levels and plasma levels of catecholamine metabolites were measured by ELISA and HPLC-ECD, respectively.
Mirtazapine treatment for 4 weeks significantly increased serum BDNF levels in the responders, whereas nonresponders showed significant decreases. No association was found between either of the two genotypes (Val/Val vs. Met-carriers) and the response to mirtazapine at T4 or the serum BDNF levels at T0. Mirtazapine did not alter the plasma levels of homovanillic acid (HVA) or 3-methoxy-4-hydroxyphenylglycol (MHPG).
The dynamics of serum BDNF levels, but not plasma levels of HVA and MHPG, reflect the response to mirtazapine treatment; the BDNF Val66Met polymorphism in patients with depression is, however, associated with neither a particular response to mirtazapine treatment nor baseline serum BDNF levels.
Serum BDNF levels, but not plasma levels of HVA or MHPG, and BDNF Val66Met polymorphism are related to the mirtazapine response in MDD.
Epidemiological studies have suggested that the condition of recurrent pregnancy loss (RPL) may be multifactorial, with both genetic predisposition and environmental factors potentially involved in its pathogenesis. The aim of this study is to elucidate the associations between maternal folate, alcohol and energy metabolism-related gene polymorphisms and the risk of RPL. This case–control study, which involved 116 cases with two or more instances of RPL and 306 fertile controls, was performed in the city of Sapporo, Japan. The associations between eight single nucleotide polymorphisms of folate, alcohol and energy metabolism-related genes [methylenetetrahydrofolate reductase (MTHFR), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR), alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), beta-3-adrenergic receptor (ADRB3) and peroxisome proliferator-activated receptor gamma (PPARG)], and RPL were assessed. Without consideration of cigarette smoking or alcohol use, the risk of RPL significantly decreased in women with the MTHFR rs1801133 TT, MTR rs1805087 AG or ALDH2 rs671 AA genotype (P < 0.05). The risk of RPL associated with cigarette smoking and alcohol use decreased significantly in women carrying the MTHFR rs1801133 T allele [odds ratio (OR), 0.51; 95% confidence interval (CI), 0.27–0.95]. Similarly, the risk of RPL significantly decreased in women carrying the MTR rs1805087 G allele (OR, 0.44; 95% CI, 0.23–0.85). Our findings suggest that maternal gene polymorphisms related to folate metabolism may decrease the risk of RPL. Molecular epidemiological studies are needed to unequivocally elucidate the multifactorial effects of both genetic and environmental factors on human fecundity.
Only a few benign tumours of the middle ear have been reported to lead to the development of facial palsy. Here, we describe a patient with middle-ear cavernous lymphangioma and facial palsy.
Single case study.
A 61-year-old man presented with left-sided hearing impairment and incomplete left facial palsy. A tumour was confirmed to be occupying the epi- to mesotympanum and to be joined to the facial nerve. The tumour was removed along with facial nerve tissue, which was resected at its horizontal portion, and the remaining facial nerve was fixed by end-to-end anastomosis. Complete facial paralysis occurred after the operation, but the patient's House–Brackmann grade gradually improved to grade III. Post-operative histopathological examination revealed infiltration of the lymphangioma into the facial nerve tissue, together with mild neural atrophy of the facial nerve.
These findings suggested that tumour invasion was the cause of facial palsy in this patient.
Let n(≥ 3) be an odd integer. Let k:= be the imaginary quadratic field and k′:= the real quadratic field. In this paper, we prove that the class number of k is divisible by 3 unconditionally, and the class number of k′ is divisible by 3 if n(≥ 9) is divisible by 3. Moreover, we prove that the 3-rank of the ideal class group of k is at least 2 if n(≥ 9) is divisible by 3.
Aeromonas has recently been recognized as an important enteropathogen. In faecal specimens the organism is readily identified and differentiated from coliforms by the positive oxidase reaction. However, few media have proved useful for foods and environmental specimens. Bile salts brilliant green starch agar (BBGS) was studied for this purpose by testing artificially contaminated foods as well as natural potential sources. The results indicate the suitability of the medium for the isolation of Aeromonas from foods and from environmental sources.
To investigate long-term trends in dietary intakes of vitamins A, C and E in Japanese adults.
Time series by community-based nutrition survey.
Two rural communities (Ikawa and Kyowa) between 1974 and 2001 in Japan.
A total of 3713 men and 3726 women aged 40–69 years.
Dietary intake data were collected by the 24 h dietary recall.
In Ikawa, mean intake of vitamin A (β-carotene and retinol) increased by 13–40 %; vitamins C and E increased by approximately 23–33 % among men and women from 1974–1977 to 1998–2000. In Kyowa, mean intake of vitamin A, primarily retinol, increased by 13–21 % among men and women; vitamin C from fruits decreased by 16 % among men; and vitamin E increased by 29 % among women from 1982–1986 to 1998–2001. Mean intake of vitamin E in the latest survey period was lower than the Adequate Intake among men and women in both communities. Generally, there were increased intakes of β-carotene and vitamin C from green/yellow and other vegetables; increased retinol intake from fish/shellfish, eggs, milk/dairy products and fats/oils; and increased vitamin E intake from green/yellow and other vegetables, fish/shellfish, eggs, milk/dairy products and fats/oils.
Mean intakes of the antioxidant vitamins A, C and E increased among middle-aged Japanese men and women between the 1970s and the 1990s except for decreased vitamin C among Kyowa men. The lower mean intake of vitamin E than the Adequate Intake should be considered a potential public health issue for the prevention of CVD.
MecA, a structural gene located on the chromosome of Staphylococcus aureus, characterizes methicillin-resistant S. aureus (MRSA), and femA and femB(fem) genes encode proteins which influence the level of methicillin resistance of S. aureus. In order to examine effectiveness of detecting mecA and fem genes in identification of MRSA, the presence of these genes in 237 clinically isolated strains of staphylococci was investigated by polymerase chain reaction (PCR). An amplified mecA DNA fragment of 533 base pairs (bp) was detected in 100% of oxacillin-resistant S. aureus, in 16·7 % of oxacillin-sensitive S. aureus, in 81·5% of S. epidermidis, and in 58·3% of other coagulase-negative staphylococci (CNS). While the PCR product of femA (509 bp) or femB (651 bp) was obtained from almost all the S. aureus strains except for five oxacillin-resistant strains (2·5%), neither of these genes were detected in CNS. Therefore, the detection of femA and femB together with mecA by PCR was considered to be a more reliable indicator to identify MRSA by differentiating it from mecA-positive CNS than single detection of mecA.
Low-affinity penicillin-binding protein PBP-2a encoded by mecA is closely related to methicillin resistance in staphylococci, and expression of PBP-2a is controlled by regulator elements encoded by mecRl and mecI which are located adjacent to mecA on the chromosome. Deletion or mutation which occurred in mec regulator gene is considered to be associated with constitutive production of PBP-2a. The distribution of the mec regulator genes in 176 strains of Staphylococcus aureus and 33 strains of S. epidermidis isolated from a single hospital was studied by polymerase chain reaction amplification. Most clinical isolates of methicillin-resistant S. aureus (MRSA) (94.3 %) and S. epidermidis (MRSE) (83.9 %) possessed both mecI and mecR1 genes (type I), whereas no mec regulator genes were detected in mecA-negative isolates. In contrast, 7 MRSA and 5 MRSE isolates were found to have incomplete regulator genes, and they were classified into three groups; strains which lacked only mecI gene (type II), strains which lacked mecIand 3'-end of mecR1 gene (type III), and strains which lacked both regulator genes (type IV). Analysis of mecI gene from all the strains having mecI by restriction fragment length polymorphism after Mse I digestion indicated that three MRSA strains possessed one of the known point mutations identified previously. These findings indicated the predominance of a single type of MRSA possessing both mecI and mecR1 in the study period and also suggested a high genomic diversity in mec regulator region of staphylococci.