BACKGROUND: Clozapine is recommended by national and international guidelines for people with treatment-resistant schizophrenia. However, available meta-analyses of randomised controlled trials have not shown superior efficacy of clozapine when compared with other second-generation antipsychotics, with heterogeneity identified between the original studies. We aimed to use individual patient data (IPD) to account for potential reasons of variability and to synthesise an adjusted estimate for the difference in efficacy between clozapine and other second-generation antipsychotics for treatment-resistant schizophrenia. METHODS: In this systematic review and IPD meta-analysis, we searched the Cochrane Schizophrenia Group's Study-Based Register from inception to Jan 24, 2024, and previous reviews for blinded randomised controlled trials comparing clozapine with other second-generation antipsychotics in participants with treatment-resistant schizophrenia. Trials were eligible if they included patients with treatment-resistant schizophrenia and had a duration of at least 6 weeks. IPD were requested from trial investigators. The primary outcome was change in overall schizophrenia symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) between clozapine and other second-generation antipsychotics after 6-8 weeks of treatment. The effect size measure for the primary outcome was mean difference with 95% credible interval (CrI). We fitted a Bayesian random-effects IPD meta-regression model that included duration of illness, baseline severity, and sex as potential prognostic factors or treatment effect modifiers. Confidence in the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). People with lived experience of mental illness were involved in this study. This study is registered with PROSPERO, CRD42021254986. FINDINGS: We screened 13 876 references and included 19 studies with data for 1599 participants; IPD were available for 12 of 19 trials (n=1052; mean age 37·67 years [SD 11·24; range 10-66]; 348 [33·08%] women and 704 [66·92%] men). Data on ethnicity were not available. The estimated mean difference in change from baseline PANSS total score was -0·64 points (95% CrI -3·97 to 2·63; τ=2·68) in favour of other second-generation antipsychotics. Shorter duration of illness and higher baseline severity were prognostic factors associated with a larger reduction in symptoms, but neither those factors nor sex were found to modify the relative effect between clozapine and other second-generation antipsychotics. The confidence in the evidence was graded as very low. INTERPRETATION: This IPD meta-analysis found a small and uncertain advantage of other second-generation antipsychotics, mainly olanzapine and risperidone, and so did not provide evidence for superior efficacy of clozapine compared with other second-generation antipsychotics in treatment-resistant schizophrenia. It is limited by unavailability of IPD for some studies, uncaptured sources of variance, and uncertainty due to premature study discontinuation. Given the side-effects of clozapine, the observed uncertainty regarding clozapine's superiority warrants prudent use and further research. FUNDING: German Ministry of Education and Research.
- MeSH
- antipsychotika * terapeutické užití MeSH
- dospělí MeSH
- klozapin * terapeutické užití MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- refrakterní schizofrenie * farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
BACKGROUND: This is a multicentre, European, prospective trial evaluating the diagnostic accuracy of One Step Nucleic Acid Amplification (OSNA) compared to sentinel lymph nodes histopathological ultrastaging in endometrial cancer patients. METHODS: Centres with expertise in sentinel lymph node mapping in endometrial cancer patients in Europe will be invited to participate in the study. Participating units will be trained on the correct usage of the OSNA RD-210 analyser and nucleic acid amplification reagent kit LYNOAMP CK19 E for rapid detection of metastatic nodal involvement, based on the cytokeratin 19 (CK19) mRNA detection. Endometrial cancer patients ≥ 18 years listed for surgical treatment with sentinel lymph node mapping, with no history of other types of cancer and who provide a valid written consent will be considered potentially eligible for the study. However, they will only be enrolled if a successful sentinel lymph node mapping is retrieved. Each node will be processed according to the study protocol and assessed by both OSNA and ultrastaging. DISCUSSION: The accuracy of OSNA (index test) will be assessed against sentinel lymph node histopathological ultrastaging (reference test). This European study has the potential to be the largest study on the use of OSNA in endometrial cancer to date. OSNA could represent a modern diagnostic alternative to sentinel lymph node ultrastaging with the added benefits of standardisation and fast results. TRIAL REGISTRATION: The study was registered in the German Clinical Trial Register - Nr. DRKS00021520, registration date 25th of May 2020, URL of the trial registry record: https://drks.de/search/en/trial/DRKS00021520 .
- MeSH
- biopsie sentinelové lymfatické uzliny metody MeSH
- keratin-19 genetika MeSH
- lidé MeSH
- lymfatické metastázy * diagnóza patologie MeSH
- lymfatické uzliny patologie MeSH
- multicentrické studie jako téma MeSH
- nádory endometria * patologie genetika diagnóza MeSH
- prospektivní studie MeSH
- sentinelová uzlina * patologie MeSH
- staging nádorů MeSH
- techniky amplifikace nukleových kyselin * metody MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
- Geografické názvy
- Evropa MeSH
Low temporal stability may complicate the interpretation of survey measures of conspiracy theories (CTs). Current study examines the stability of endorsement of CTs on a popular set of items addressing COVID-19-related CTs. An online survey tapping two CTs about COVID-19 was administered to 179 students of general medicine. The same items were presented twice in March 2022 and once in May 2022. The mean endorsement of the CTs did not differ between March and May. The correlation between answers provided in March and May was low (.5 < r < .7). Most of those reporting agreement with CTs in March reported disagreement in May. Conspiracy believers' responses did not change between two measurements in March but were different in May, suggesting that the low temporal stability was due to situational factors rather than erroneous or random answers. Poor temporal stability of responses endorsing CTs may problematize interpretation of survey data. Respondents' endorsement of CTs may be affected by situational factors, inflating agreement with CTs, and correlations with other survey-based measures.
- MeSH
- COVID-19 * epidemiologie MeSH
- dospělí MeSH
- lidé MeSH
- průzkumy a dotazníky MeSH
- SARS-CoV-2 MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Triple-negative breast cancer (TNBC) is associated with poor prognosis, and new treatment options are urgently needed. About 34%-39% of primary TNBCs show a low expression of human epidermal growth factor receptor 2 (HER2-low), which is a target for new anti-HER2 drugs. However, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC. PATIENTS AND METHODS: We retrospectively included patients with TNBC from five European countries for this international, multicenter analysis. Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years before metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ without ERBB2 gene amplification. Survival probabilities were calculated by the Kaplan-Meier method, and multivariable hazard ratios (HRs) were estimated by Cox regression models. RESULTS: In total, 691 patients, diagnosed between January 2006 and February 2021, were assessable. The incidence of HER2-low was 32.0% [95% confidence interval (CI) 28.5% to 35.5%], with similar proportions in metastases (n = 265; 29.8%) and primary tumors (n = 425; 33.4%; P = 0.324). The median overall survival (OS) in HER2-low and HER2-0 TNBC was 18.6 and 16.1 months, respectively (HR 1.00; 95% CI 0.83-1.19; P = 0.969). Similarly, in multivariable analysis, HER2-low had no significant impact on OS (HR 0.95; 95% CI 0.79-1.13; P = 0.545). No difference in prognosis was observed between HER2 IHC 0/1+ and IHC 2+ tumors (HR 0.89; 95% CI 0.69-1.17; P = 0.414). CONCLUSIONS: In this large international dataset of metastatic TNBC, the frequency of HER2-low was 32.0%. Neither in univariable nor in multivariable analysis HER2-low showed any influence on OS.
- MeSH
- lidé MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- triple-negativní karcinom prsu * farmakoterapie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
AIMS: To evaluate the 3-year follow-up results of two children delivered at our institution in 2019 from mothers with a transplanted uterus. METHODS: Observational data on pregnancy outcomes, neonatal course, and growth trajectory in two children born to mothers after uterus transplantation, including 3-year follow-up and neurodevelopmental status assessed using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). RESULTS: Both children were born prematurely via uneventful caesarean sections, to mothers with Mayer-Rokitansky-Küster-Hauser syndrome and a transplanted uterus. An acute caesarean section was performed in one mother because of the onset of regular uterine contractions at 34 weeks and 6 days of pregnancy; in the other mother, an elective caesarean section was performed at 36 weeks and 2 days of gestation. The children were born healthy with no congenital malformations. They had an uneventful postnatal course and showed a normal growth trajectory during 3 years of follow-up. The Bayley-III neurodevelopmental scores of both children were within the normal ranges at ages 2 and 3 years. CONCLUSION: Though pregnancy after uterus transplantation is associated with the risk of premature delivery, no abnormalities were observed in the neonatal course and 3-year follow-up results, including the neurodevelopmental status, of two children born prematurely to mothers with a transplanted uterus. This is the first report on neurodevelopmental outcomes in children born after uterus transplantation. More data on children born after this radical procedure of uterine factor infertility treatment are required to support our promising results.
- MeSH
- císařský řez * škodlivé účinky MeSH
- kojenec MeSH
- lidé MeSH
- matky MeSH
- následné studie MeSH
- novorozenec MeSH
- těhotenství MeSH
- uterus transplantace MeSH
- ženská infertilita * MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
OBJECTIVES: The primary aim was to test the hypothesis that physical interpersonal violence is decreased during the lockdown period in comparison with comparable control periods. The secondary aims were to explore the effects of gender and alcohol consumption on the violence during the lockdown. METHODS: Nationwide records of hospitalizations secondary to an assault were analyzed using quasipoisson regression. Assault rates in two lockdown periods, defined as a national emergency state, were compared to baseline data between 2017 and 2020, controlling for seasonal fluctuations and pandemic-related effects other than lockdown. To validate the findings on independent data, differences between lockdown and baseline in Police records of violent criminality between 2017 and 2021 were examined using one-way ANOVA. RESULTS: The rates of hospitalizations secondary to an assault decreased substantially during lockdowns (IRR = .43; P < .001) and the duration of lockdown did not affect assault rates (P = .07). The decrease in assault rates was more pronounced in males than females (IRR = .77; P < .05) and was weakened in patients with history of alcohol abuse (IRR = 1.83; P < .001). Violent crime rate decreased by 19% during the lockdowns compared to prepandemic baseline (P < .001). CONCLUSION: We found that physical interpersonal violence decreased during the COVID-19 lockdown periods. The reduction is significantly greater in males. Emerging evidence suggests an increased risk of alcohol use and intoxication during the lockdowns. Violent crime rate decreased during the lockdown.
- MeSH
- COVID-19 * epidemiologie prevence a kontrola MeSH
- dospělí MeSH
- hospitalizace statistika a číselné údaje MeSH
- karanténa psychologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- násilí * statistika a číselné údaje MeSH
- pití alkoholu epidemiologie MeSH
- registrace * statistika a číselné údaje MeSH
- senioři MeSH
- sexuální faktory MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Mayer-Rokitansky-Küster-Hauser syndrome is a rare female congenital anomaly that presents with an inability to have coital sexual intercourse and absolute uterine factor infertility. Both surgical and nonsurgical approaches have been described for the treatment of vaginal agenesis to allow satisfactory coitus. Transplantation of the uterus has the challenge of achieving pregnancy and delivery of her own genetic and biological children in a woman without a natural uterus. Women of reproductive age with a congenital form of absolute uterine factor infertility are considered appropriate recipients of a uterus in the experimental phase of uterus transplantation trials. A neovagina in the normal anatomic position covered by natural non-keratinized mucosa is one of the main assumptions for surgical and reproductive success in transplant recipients. More than 70 uterine transplants have been performed to date, and more than 25 childbirths have been achieved by several research centers in the recipients of a uterus with uterine agenesis. In women with Mayer-Rokitansky-Küster-Hauser syndrome, skin-graft neovagina, Vecchietti's vaginoplasty, and self-dilation using Frank's and Ingram's methods are appropriate techniques to create a neovagina if transplantation of the uterus is intended in the future.
BACKGROUND AND AIMS: Uterine transplantation (UTx) is an experimental sterility treatment method in women with absolute uterine factor infertility. This article describes the current trends and risks in UTx and provides an overview of our experience with this method, to date. METHODS: Based on our experience with the Czech UTx trial and the published results of other trials, we describe the possibilities and risks of this perspective method in the treatment of absolute uterine factor infertility (AUFI). RESULTS: Twelve healthy babies were born in 2014-2018 after more than 40 uterine transplantations. There is no general consensus whether it is more suitable to transplant uteri from living or deceased donors, and nulliparous or parous women (with proven obstetrical functionality). Most centers prefer to collect at least ten frozen embryos from in vitro fertilization (IVF) cycles before transplantation. The serious complication of a surgically successful uterine transplantation is posttransplant partial stenosis of the uterine-vaginal anastomosis that may be a technical problem for embryo transfer, outflow of menstrual blood, and sexual satisfaction due to the narrowed and shortened vagina. This paper concludes that, currently, procurement of the uterus and the transplant procedure are surgically feasible and that none of the transplanted uteri have been lost due to rejection but only because of graft thrombosis or infection. CONCLUSION: Uterine transplantation, after optimization of surgical methods, selection of suitable donors, standardization of immunosuppressive therapy, adjustment of assisted reproductive technologies and obstetrical proceedings might be an effective therapeutic method for women with AUFI who wish to have their own biological child.
- MeSH
- asistovaná reprodukce * MeSH
- lidé MeSH
- těhotenství MeSH
- uterus transplantace MeSH
- výběr dárců * MeSH
- výsledek těhotenství MeSH
- ženská infertilita chirurgie MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
INTRODUCTION: There is still a lack of organs for kidney transplantation. The aim of our experimental animal study was to improve the quality of the kidney grafts from donors after cardiac death (DCD) using immediate start of machine perfusion instead of perfusion based on hydrostatic pressure. METHODS: Ten rabbits were used as an experimental model. In group A, 5 kidneys after ischemic injury were perfused in situ using hydrostatic pressure. In group B, 5 kidneys were perfused in situ using machine pulsatile perfusion. After nephrectomy kidney parenchyma was histologically analyzed. We have evaluated the maximum perfusion flow rate, temperature drop rate, and degree of parenchymal injury. RESULTS: The flow rate in the group of machine-perfused animals (group B) was significantly higher than in the control group (group A), and temperature was significantly decreased in group B (P < .001). Qualitative histopathologic evaluation of the perfusion quality of the grafts was statistically significant, again in favor of machine perfusion in group B (P = .005). DISCUSSION: According to our results, the immediate start of machine perfusion is a superior method of kidney graft preservation in DCDs. All observed modalities were superior in the group with machine perfusion compared with usual clinical practice.
- MeSH
- dárci tkání MeSH
- králíci MeSH
- ledviny * MeSH
- modely nemocí na zvířatech MeSH
- nefrektomie MeSH
- odběr tkání a orgánů metody MeSH
- perfuze metody MeSH
- pulzatilní průtok MeSH
- smrt MeSH
- transplantace ledvin metody MeSH
- transplantáty MeSH
- uchovávání orgánů metody MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
