RESUMO
STUDY QUESTION: Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? SUMMARY ANSWER: Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol. WHAT IS KNOWN ALREADY: Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION: In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A). MAIN RESULTS AND THE ROLE OF CHANCE: Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] -2.4 [95% CI -4.1 to -0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM -1.8 [95% CI -3.1 to -0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM -1.5 [95% CI -2.6.1 to -0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM -0.07 [95% CI -0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM -0.07 [95% CI -0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8-38.1%] and a 35% [95% CI 26.6-43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist. LIMITATIONS, REASONS FOR CAUTION: The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between. WIDER IMPLICATIONS OF THE FINDINGS: In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V., F.M., and I.R. declared no conflicts of interest. TRIAL REGISTRATION NUMBER: The study was registered at Clinical Trials Gov. (NCT04108039).
Assuntos
Hormônio Liberador de Gonadotropina , Indução da Ovulação , Ploidias , Progesterona , Feminino , Humanos , Indução da Ovulação/métodos , Progesterona/administração & dosagem , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Adulto , Estudos Prospectivos , Gravidez , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/farmacologia , Blastocisto/efeitos dos fármacos , Taxa de Gravidez , Recuperação de Oócitos , Transferência Embrionária/métodos , Administração Oral , Injeções de Esperma Intracitoplásmicas/métodosRESUMO
BACKGROUND: Investigations into neurochemical mechanisms of opioid addiction are difficult due to the complexity of behavior and multiplicity of involved neurotransmitter and hormonal systems. The aim of this study was to examine the benefits of structured analysis of these mechanisms using the framework of the neurochemical model Functional Ensemble of Temperament (FET) and the example of maternal behavior under the condition of opium consumption in pregnancy. The FET differentiates between (a) endurance, (b) speed of integration, and (c) emotionality aspects of behavior suggesting that these systems are differentially regulated by (a) serotonin-neuropeptides-brain-derived neurotrophic factor (BDNF), (b) dopamine-GABA, and (c) opioid receptor systems, correspondingly. The FET also suggests that mu-opioid receptors (MORs) binding the endorphines (including opium's ingredient morphine) have a stronger association with regulation endurance, whereas delta-OR have a stronger association with integration of behavior and kappa-OR - with the perceptual mobilization seen in anxiety. To test the predictions of this model, we compared the impact of massive MOR dysregulation on 3 behavioral aspects of behavior and on serotonin, BDNF, and corticosterone levels. METHODS: The study used 24 female white Wistar rats which were randomly divided into (1) control group: pregnant rats without any intervention; (2) opium-exposed group: animals that were exposed to opium during pregnancy and after the delivery until the end of the study. At the end of the study, the levels of BDNF, serotonin (5-HT) in the hippocampus of the mother's brain, and serum corticosterone, as well as 12 aspects of the maternal behavior were evaluated. The differences between control and experimental groups were assessed using the t test for independent samples. RESULTS: The BDNF and serotonin concentrations in the hippocampus of the mother rats which were exposed to opium were lower than in the control group; the mean corticosterone in exposed mothers was higher than in the control group. Behaviorally, opium-consuming mothers showed lower endurance in 4 distinct behavioral categories (nesting, feeding, grooming, and retrieval) than the mothers in the control group. Ease of integration of behavior was affected to a lesser degree, showing a significant effect only in 1 out of 5 applied measures. Self-grooming, seen as an emotionality-related aspect of behavior, was not affected. CONCLUSION: Opium exposure during pregnancy in our experiment primarily reduced the endurance of rat's maternal behavior, but the speed of integration of behavioral acts was less affected. This negative impact of opium on endurance was associated with a decrease of BDNF and serotonin levels in the hippocampus and an increase in corticosterone level in opium-consuming mothers. There is no effect of opium exposure on self-grooming behavior. This pattern supports the FET hypothesis about the role of 5-HT and BDNF in endurance, differential regulation of endurance, integrative and emotionality aspects of behavior, and differential association of the MOR system with endurance aspects, in comparison with kappa- and delta opioid receptors.
Assuntos
Comportamento Animal/fisiologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/sangue , Hipocampo/metabolismo , Comportamento Materno/fisiologia , Entorpecentes/farmacologia , Ópio , Serotonina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Comportamento Materno/efeitos dos fármacos , Entorpecentes/administração & dosagem , Gravidez , Ratos , Ratos WistarRESUMO
BACKGROUND: A bioassay with severely mercury-stressed duckweed (Lemna gibba L.) had revealed growth-inhibiting effects of homeopathically potentised mercury(II) chloride (Mercurius corrosivus, Merc-c.). We hypothesised that effects of potentised preparations are dependent on the stress level of the organisms used in the bioassay. The aim of the present investigation was to examine the response of duckweed to potentised Merc-c. at a lower stress level. METHODS: Duckweed was moderately stressed with 2.5 mg/L mercury(II) chloride for 48 hours. Afterwards plants grew in either Merc-c. (seven different potency levels, 24x-30x) or water controls (unsuccussed or succussed water) for 7 days. Growth rates of the frond (leaf) area were determined using a computerised image-analysis system for day 0-3 and 3-7. Three independent experiments with potentised Merc-c. and three systematic negative control experiments were performed. All experiments were randomised and blinded. RESULTS: Unsuccussed and succussed water did not significantly differ in their effects on duckweed growth rate. The systematic negative control experiments did not yield any significant effects, thus providing evidence for the stability of the experimental system. Data from the two control groups and the seven treatment groups (Merc-c. 24x-30x) were each pooled to increase statistical power. Duckweed growth rates for day 3-7 were enhanced (p < 0.05) after application of Merc-c. compared with the controls. Growth rates for day 0-3 were not influenced by the homeopathic preparations. CONCLUSIONS: Moderately mercury-stressed Lemna gibba L. yielded evidence of growth-enhancing specific effects of Merc-c. 24x-30x in the second observation period (day 3-7). This observation is complementary to previous experiments with severely mercury-stressed duckweed, in which a decrease in growth was observed in the first observation period (day 0-3). We hypothesise that the differing results are associated with the level of stress intensity (moderate vs. severe).
Assuntos
Materia Medica/uso terapêutico , Mercúrio/efeitos adversos , Pectinas/uso terapêutico , Reguladores de Crescimento de Plantas/farmacologia , Bioensaio/métodos , Materia Medica/normas , Mercúrio/administração & dosagem , Pectinas/normas , Plantas/efeitos dos fármacosRESUMO
INTRODUCTION: Urological chronic pelvic pain syndrome (UCPPS) represents a group of pain symptoms relating to patients with pelvic pain for which treatment is largely unsatisfactory. The objective of this study is to analyze the effects of a novel treatment strategy in males suffering from UCPPS. METHODS: This retrospective, institutional review board-approved study analyzed eight male patients aged 24 to 61 with UCPPS. All the patients had a trial of antibiotic therapy, NSAIDs, and pelvic floor physical therapy before the study. The Visual Analog scale (VAS) and Functional Pelvic Pain scale (FPPS) were collected pretreatment. While continuing physical therapy, patients underwent weekly ultrasound-guided pelvic floor trigger point injections to the iliococcygeus, pubococcygeus, and puborectalis with lidocaine 1%. Concomitantly, patients received peripheral nerve hydrodissection performed on the pudendal nerve and the posterior femoral cutaneous nerve. The first two injections combined 1% lidocaine with dexamethasone, while the next four injections consisted of 1% lidocaine with traumeel (a homeopathic, plant-derived anti-inflammatory medication). At the 6-week follow-up, each patient retook the VAS and FPPS. RESULTS: The mean age of our patients was 31.8 years and the average duration of symptoms of the UCPPS was 21 months. Pretreatment, the mean VAS was 3.3 (STD 1.7) and the mean VAS posttreatment was 1.8 (STD 1.4); P < .05; 95% CI, 0.73 to 2.27. The mean FPPS pretreatment was 11.0 (STD 8.0) and the mean FPPS posttreatment was 6.3 (STD 5.3); P < .05; 95% CI, 0.03 to 9.22. CONCLUSION: Our results show promise for a novel, nonopioid-based treatment for UCPPS.
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Dor Crônica/tratamento farmacológico , Lidocaína/uso terapêutico , Dor Pélvica/tratamento farmacológico , Adulto , Dor Crônica/diagnóstico , Dor Crônica/fisiopatologia , Feminino , Humanos , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Medição da Dor , Diafragma da Pelve/fisiopatologia , Dor Pélvica/diagnóstico , Dor Pélvica/fisiopatologia , Modalidades de Fisioterapia , Nervo Pudendo/fisiopatologia , Estudos Retrospectivos , Pontos-Gatilho , Ultrassonografia de Intervenção , Escala Visual Analógica , Adulto JovemRESUMO
BACKGROUND The aim of this study was to analyze the clinical application of cortex phellodendri compound fluid (CPCF) in the treatment of diabetic foot ulcers. MATERIAL AND METHODS From January 2012 to December 2015, a total of 720 cases of diabetic foot ulcers (DFU) were randomly assigned into an experimental group (n=540) that was treated by CPCF and a control group (n=180) that was treated by a Kangfuxin solution (KFS). After 4 weeks of treatment, their ulcer area, serum growth factor, clinical total effective rate, and incidence of adverse events were assessed. RESULTS There were 720 patients who completed the trial. The experimental group was superior to the control group in reducing ulcer area, increasing growth factor content, and total effective rate (P<0.05). There was no significant difference in the adverse events rates between the 2 groups. CONCLUSIONS CPCF external treatment of diabetic foot ulcer can promote ulcer healing and increase the concentration of growth factors, and it is safe and reliable.
Assuntos
Pé Diabético/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Materia Medica/administração & dosagem , Materia Medica/efeitos adversos , Phellodendron/química , Fitoterapia/efeitos adversos , Administração Cutânea , Idoso , Pé Diabético/sangue , Fator de Crescimento Epidérmico/sangue , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangue , Cicatrização/efeitos dos fármacosRESUMO
Skeletal muscle injuries in competitive sports cause lengthy absences of athletes from tournaments. This is of tremendous competitive and economic relevance for both the athletes and their respective clubs. Therapy for structural muscle lesions aims to promote regeneration and fast-track return-to-play. A common clinical treatment strategy for muscle injuries is the intramuscular injection of calf blood compound and the homeopathic drug, Tr14. Although the combination of these two agents was reported to reduce recovery time, the regulatory mechanism whereby this occurs remains unknown. In this in vivo study, we selected a rat model of mechanical muscle injury to investigate the effect of this combination therapy on muscle regeneration. Gene expression analysis and histological images revealed that this combined intramuscular injection for muscle lesions can enhance the expression of pro-myogenic genes and proteins and accelerate muscle regeneration. These findings are novel and depict the positive effects of calf blood compound and the homeopathic drug, Tr14, which are utilized in the field of Sports medicine.
Assuntos
Heme/análogos & derivados , Minerais/farmacologia , Músculo Esquelético/efeitos dos fármacos , Extratos Vegetais/farmacologia , Regeneração/efeitos dos fármacos , Animais , Traumatismos em Atletas/fisiopatologia , Traumatismos em Atletas/prevenção & controle , Expressão Gênica/efeitos dos fármacos , Heme/administração & dosagem , Heme/farmacologia , Homeopatia , Humanos , Injeções Intramusculares , Masculino , Minerais/administração & dosagem , Modelos Animais , Músculo Esquelético/lesões , Músculo Esquelético/fisiopatologia , Proteína MyoD/genética , Proteína MyoD/metabolismo , Fator Regulador Miogênico 5/genética , Fator Regulador Miogênico 5/metabolismo , Extratos Vegetais/administração & dosagem , Ratos Wistar , Regeneração/genética , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologiaRESUMO
Lamb farming is generally a secondary activity for farmers, and many breeding systems suffer from management failures that impair production. One reason for decline in performance is enteritis, usually affecting newborn lambs. Enteritis can be fatal, especially in dairy herds. Generally, lambs are fed sucrose or unprocessed milk from sheep or cow that is heated and fed to animals two or three times a day in baby bottles. However, on most farms, milk temperature differs among feeds, as often the process of alteration among diet adaptations is deficient, contributing to enteritis and consequent diarrhea. Therefore, the objective of the present study was to verify the administration of the homeopathic product (Dia 100®) in newborn and bottle-fed lambs, in order to prevent or minimize the occurrence of diarrhea. We studied 60 lambs, divided into two groups with ten repetitions each (nâ¯=â¯30) and during the nursing period (1-45 days of life). Animals in the treated group received the homeopathic product (36â¯g) orally divided into three doses (1, 7 and 14 days of life). We measured weight gain, mortality, bacterial counts (Escherichia coli and total coliforms) in feces, hematological analysis (leukocytes, hematocrit, hemoglobin and erythrocytes) and biochemical analyses (glucose, triglycerides, cholesterol, albumin, globulin, urea and total protein) at four time-points. There were no differences in weight gain between groups (Pâ¯>â¯0.05); however, there was a higher mortality rate in the control group (13%) than in the treated group (6%). E. coli counts were significantly higher in the stools of control group lambs on days 15 and 45 of the experiment (Pâ¯<â¯0.05). Total leukocyte counts were greater in treated animals due to greater numbers of lymphocytes on day 15 of the experiment (Pâ¯<â¯0.05). In the treated group, we found higher serum levels of total protein, urea (day 15), globulin and triglycerides (days 15 and 30). In the period of administration of the homeopathic product, there was substantial and significant reduction of cases of diarrhea (up to day 14); however, after this period, there were no difference between groups. Based on these results, we concluded that the homeopathic product had moderate efficacy in terms of control of diarrhea. The treated lambs made better use of nutrients, contributing to the development of their immune responses.
Assuntos
Diarreia/prevenção & controle , Materia Medica/administração & dosagem , Doenças dos Ovinos/prevenção & controle , Administração Oral , Animais , Animais Recém-Nascidos , Carga Bacteriana , Células Sanguíneas , Análise Química do Sangue , Peso Corporal , Fezes/microbiologia , Ovinos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Postoperative ureteroscopy patients can develop bladder spasms, complaints of pain, and the urgent need to void during emergence from anesthesia. Discomfort leads to patient agitation, resulting in a risk to patient safety. The purpose of this study was to determine the effectiveness of a preemptive preoperative belladonna and opium (B + O) suppository on postoperative bladder comfort, narcotic requirements, and length of stay of ureteroscopy patients. DESIGN: A prospective double-blind study was conducted. METHODS: Fifty adult outpatients scheduled for ureteroscopy were assigned to routine care or a B + O suppository immediately after anesthesia induction. Urinary urgency and pain were assessed every 15 minutes. FINDINGS: Urgency significantly decreased in the B+O group, with less than half reporting urgency at discharge. CONCLUSIONS: Pre-emptive preoperative administration of a B + O suppository before ureteroscopy results in decreased urinary urgency during the postoperative recovery. Pre-emptive preoperative interventions can result in positive outcomes before discharge.
Assuntos
Atropa belladonna/química , Ópio/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Cuidados Pré-Operatórios/métodos , Ureteroscopia/métodos , Adulto , Idoso , Analgésicos Opioides/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , SupositóriosRESUMO
Context: Kangfuxin (KFX) is widely used for the treatment of gastric and duodenal ulcer; however, more research is needed to determine the protective mechanisms of KFX in ameliorating gastric ulcer.Objective: To investigate the efficacy and potential mechanism of Kangfuxin liquid (KFX) in water-immersion and restraint stress (WIRS)-induced gastric ulcer.Materials and methods: Seventy rats were randomly divided into seven groups (n = 10) as follows: the control group (normal saline, i.g.), the model group (normal saline, i.g.), the KFX groups (2.5, 5 and 10 mL/kg, i.g.), the omeprazole group (20 mg/kg, i.p.) and Sanjiuweitai Granules group (1850 mg/kg, i.g.). The WIRS model was applied to induce stress ulcers after 7 days of drug administration. Afterwards, rats were sacrificed at 10 h induced by WIRS.Results: Pre-treatment with KFX (5,10 mL/kg) could effectively reduce the area of gastric ulcers and improve the pathological changes of ulcerated tissue. Moreover, KFX (5,10 mL/kg) increased the prostaglandin E2 (52%) and cyclooxygenase-1 (30%) levels, and improved malondialdehyde (54%), superoxide dismutase (58%), catalase (39%), and nitric oxide (11%) and TNF-α (9%), IL-6 (11%), MMP-9 (54%) and MMP-2 (53%) of ulcer tissue. Furthermore, pre-treatment with KFX dramatically increased IGF-1, PTEN, and Akt protein expression.Conclusions: Our results suggest that KFX has protective effects on WIRS-induced gastric ulcer via inflammatory reactions, oxidative stress inhibition, and pro-survival action, which were the results of activating the IGF-1/PTEN/Akt signalling pathway. Our results provide evidence of KFX for treating gastric ulcer.
Assuntos
Anti-Inflamatórios/farmacologia , Antiulcerosos/farmacologia , Materia Medica/farmacologia , Úlcera Gástrica/prevenção & controle , Animais , Anti-Inflamatórios/administração & dosagem , Antiulcerosos/administração & dosagem , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamação/prevenção & controle , Masculino , Materia Medica/administração & dosagem , Omeprazol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Restrição Física , Estresse Psicológico/complicaçõesRESUMO
OBJECTIVE: To describe an outbreak of lead poisoning among opium users in the Islamic Republic of Iran and estimate the number of affected people in the country. METHODS: We used data from the country's largest poison treatment centre to illustrate the epidemiology of an outbreak of lead poisoning in oral opium users. We describe the government's referral and treatment guidelines in response to the outbreak. Based on the number of individuals treated and previous studies on the prevalence of oral opium use we estimated the total number of people at risk of lead-contaminated opium nationwide. FINDINGS: In February 2016, we noticed a steep increase in the numbers of oral opium users referred to our poison treatment centre with abdominal pain, anaemia and constipation. Numbers peaked in June 2016 but the outbreak was ongoing in August 2017. The mean blood lead level in a sample of 80 patients was 140.3 µg/dL (standard deviation: 122.6). Analysis of an illegal opium sample showed 3.55 mg lead in 1 g opium. Treatment was exposure reduction with opioid substitutes and laxatives, or chelation therapy if indicated. Over 7 months, 4294 poison cases were seen at main referral hospitals in Tehran out of an estimated 31 914 oral opium users in the city. We estimate more than 260 000 out of 773â¯800 users nationwide remain untreated and at risk of poisoning. CONCLUSION: Lead-contaminated opium and heroin that has transited through the Iranian markets is a global risk and highlights a need for better monitoring of illegal drug supplies.
Assuntos
Usuários de Drogas/estatística & dados numéricos , Intoxicação por Chumbo/epidemiologia , Chumbo/toxicidade , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Ópio/administração & dosagem , Adulto , Surtos de Doenças , Humanos , Irã (Geográfico)/epidemiologiaRESUMO
BACKGROUND: Prolonged treatment with benzodiazepines is common practice despite clinical recommendations of short-term use. Benzodiazepines are used by approximately 4% of the general population, with increased prevalence in psychiatric populations and the elderly. After long-term use it is often difficult to discontinue benzodiazepines due to psychological and physiological dependence. This review investigated if pharmacological interventions can facilitate benzodiazepine tapering. OBJECTIVES: To assess the benefits and harms of pharmacological interventions to facilitate discontinuation of chronic benzodiazepine use. SEARCH METHODS: We searched the following electronic databases up to October 2017: Cochrane Drugs and Alcohol Group's Specialised Register of Trials, CENTRAL, PubMed, Embase, CINAHL, and ISI Web of Science. We also searched ClinicalTrials.gov, the WHO ICTRP, and ISRCTN registry, and checked the reference lists of included studies for further references to relevant randomised controlled trials. SELECTION CRITERIA: We included randomised controlled trials comparing pharmacological treatment versus placebo or no intervention or versus another pharmacological intervention in adults who had been treated with benzodiazepines for at least two months and/or fulfilled criteria for benzodiazepine dependence (any criteria). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 38 trials (involving 2543 participants), but we could only extract data from 35 trials with 2295 participants. Many different interventions were studied, and no single intervention was assessed in more than four trials. We extracted data on 18 different comparisons. The risk of bias was high in all trials but one. Trial Sequential Analysis showed imprecision for all comparisons.For benzodiazepine discontinuation, we found a potential benefit of valproate at end of intervention (1 study, 27 participants; risk ratio (RR) 2.55, 95% confidence interval (CI) 1.08 to 6.03; very low-quality evidence) and of tricyclic antidepressants at longest follow-up (1 study, 47 participants; RR 2.20, 95% CI 1.27 to 3.82; low-quality evidence).We found potentially positive effects on benzodiazepine withdrawal symptoms of pregabalin (1 study, 106 participants; mean difference (MD) -3.10 points, 95% CI -3.51 to -2.69; very low-quality evidence), captodiame (1 study, 81 participants; MD -1.00 points, 95% CI -1.13 to -0.87; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -3.57 points, 95% CI -5.34 to -1.80; very low-quality evidence), tricyclic antidepressants (1 study, 38 participants; MD -19.78 points, 95% CI -20.25 to -19.31; very low-quality evidence), and flumazenil (3 studies, 58 participants; standardised mean difference -0.95, 95% CI -1.71 to -0.19; very low-quality evidence) at end of intervention. However, the positive effect of paroxetine on benzodiazepine withdrawal symptoms did not persist until longest follow-up (1 study, 54 participants; MD -0.13 points, 95% CI -4.03 to 3.77; very low-quality evidence).The following pharmacological interventions reduced symptoms of anxiety at end of intervention: carbamazepine (1 study, 36 participants; MD -6.00 points, 95% CI -9.58 to -2.42; very low-quality evidence), pregabalin (1 study, 106 participants; MD -4.80 points, 95% CI -5.28 to -4.32; very low-quality evidence), captodiame (1 study, 81 participants; MD -5.70 points, 95% CI -6.05 to -5.35; very low-quality evidence), paroxetine (2 studies, 99 participants; MD -6.75 points, 95% CI -9.64 to -3.86; very low-quality evidence), and flumazenil (1 study, 18 participants; MD -1.30 points, 95% CI -2.28 to -0.32; very low-quality evidence).Two pharmacological treatments seemed to reduce the proportion of participants that relapsed to benzodiazepine use: valproate (1 study, 27 participants; RR 0.31, 95% CI 0.11 to 0.90; very low-quality evidence) and cyamemazine (1 study, 124 participants; RR 0.33, 95% CI 0.14 to 0.78; very low-quality evidence). Alpidem decreased the proportion of participants with benzodiazepine discontinuation (1 study, 25 participants; RR 0.41, 95% CI 0.17 to 0.99; number needed to treat for an additional harmful outcome (NNTH) 2.3 participants; low-quality evidence) and increased the occurrence of withdrawal syndrome (1 study, 145 participants; RR 4.86, 95% CI 1.12 to 21.14; NNTH 5.9 participants; low-quality evidence). Likewise, magnesium aspartate decreased the proportion of participants discontinuing benzodiazepines (1 study, 144 participants; RR 0.80, 95% CI 0.66 to 0.96; NNTH 5.8; very low-quality evidence).Generally, adverse events were insufficiently reported. Specifically, one of the flumazenil trials was discontinued due to severe panic reactions. AUTHORS' CONCLUSIONS: Given the low or very low quality of the evidence for the reported outcomes, and the small number of trials identified with a limited number of participants for each comparison, it is not possible to draw firm conclusions regarding pharmacological interventions to facilitate benzodiazepine discontinuation in chronic benzodiazepine users. Due to poor reporting, adverse events could not be reliably assessed across trials. More randomised controlled trials are required with less risk of systematic errors ('bias') and of random errors ('play of chance') and better and full reporting of patient-centred and long-term clinical outcomes. Such trials ought to be conducted independently of industry involvement.
Assuntos
Benzodiazepinas/efeitos adversos , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Suspensão de Tratamento , Adulto , Antidepressivos/uso terapêutico , Ácido Aspártico/uso terapêutico , Benzodiazepinas/administração & dosagem , Buspirona/uso terapêutico , Carbamazepina/uso terapêutico , Etilaminas/uso terapêutico , Flumazenil/uso terapêutico , Homeopatia , Humanos , Imidazóis/uso terapêutico , Compostos de Lítio/uso terapêutico , Melatonina/uso terapêutico , Paroxetina/uso terapêutico , Pregabalina/uso terapêutico , Progesterona/uso terapêutico , Piridinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfetos/uso terapêuticoRESUMO
Context ⢠Pertussis cough (whooping cough) is distressing due to the intensity and chronicity of its cough. No specific drugs are available that can alleviate the cough's intensity or significantly shorten its duration. Homeopathic medicines are used for a wide variety of medical conditions, including cough. Objective ⢠The study investigated the benefits of homeopathic medicines for whooping cough, to alleviate the cough's intensity and to shorten its duration. Design ⢠The current study was a case series of patients with whooping cough. Setting ⢠The study took place at one of the suburban hospital clinics of the Ann & Robert H. Lurie Children's Hospital of Chicago (Chicago, IL, USA). Participants ⢠Participants were 20 patients aged 21 mo to 20 y, of whom 11 were female and 18 were male, who visited the hospital clinic for treatment of the chronic cough that is characteristic of whooping cough. The details of the cases of 3 representative participants are highlighted in the text. Intervention ⢠The 3 representative patients all received 1 dose weekly of a 30c dilution of homeopathic pertussinum and a 6c dilution of homeopathic Drosera 3 times daily. The homeopathic medicines most often used for the other participants were the same doses of pertussinum and Drosera. Outcome Measures ⢠Verbal feedback from patient or family were obtained at the follow-up visits. Results ⢠The intensity and duration of participant's coughs were alleviated within days to 1 wk in most cases. Conclusions ⢠Homeopathic medicines can alleviate the intensity or reduce the duration of whooping cough, with no adverse effects.
Assuntos
Materia Medica/uso terapêutico , Coqueluche/tratamento farmacológico , Coqueluche/fisiopatologia , Adolescente , Adulto , Chicago , Criança , Pré-Escolar , Drosera , Feminino , Humanos , Lactente , Masculino , Materia Medica/administração & dosagem , Adulto JovemRESUMO
BACKGROUND: Cancer-related fatigue has been described as a subjective feeling of physical, emotional, and/or cognitive tiredness. Homeopathy has been widely used to treat side effects of chemotherapy. The n-of-1 design is a single-patient trial method to study a clinical condition that is either short lived and reversible or is chronic and stable. The n-of-1 design requires a washout/reset period. The feasibility of performing an n-of-1 study in homeopathy has not previously been tested. METHODS: A feasibility n-of-1 trial of individualized homeopathic treatment for fatigue in a single adult undergoing chemotherapy administered periodically was performed. For each matched pair of treatments, the participant was randomly allocated either placebo or verum for the period between treatments. For the subsequent treatment period, the opposite allocation was given. Participant and practitioner were blinded to the allocation. Ongoing conventional treatments were permitted. The ability to recruit and retain was monitored and changes in fatigue and quality of life were measured using two validated outcome measures. RESULTS: Sixty-eight patients were assessed between February 2014 and February 2015. Four patients were eligible for the study and one consented to participate. The participant enrolled in the study for six cycles of chemotherapy and completed all treatment and outcome measures. There was no improvement under homeopathic treatment compared to placebo. There were multiple confounding events such as conventional medication changes and an adverse event unrelated to therapy. CONCLUSION: Adequate recruitment was not feasible in this setting. The n-of-1 study design is feasible in this population from the perspective of the ability to complete the trial. No conclusion on the efficacy of homeopathy for this individual can be made. It is unclear as to whether multiple treatments of chemotherapy would be an appropriate clinical situation in which to apply the n-of-1 trial methodology. Future studies should pilot adaptations to this study design.
Assuntos
Fadiga/terapia , Homeopatia/métodos , Materia Medica/administração & dosagem , Adulto , Método Duplo-Cego , Estudos de Viabilidade , Feminino , Humanos , Masculino , Neoplasias/complicações , Projetos Piloto , Medicina de Precisão/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Contact dermatitis (CD) is a frequently occurring medical condition, for which Vinca minor (VM) is one of the recommended homeopathic medicines. However, the symptoms indicating this medicine have not yet been assessed systematically. Likelihood ratio (LR), based on Bayesian statistics, may yield better estimation of a medicine's indication than the existing method of entry of symptoms into materia medica and repertories. METHODS: We investigated LRs of four CD symptoms of VM: (1) great sensitiveness of skin, with redness and soreness from slightest rubbing; (2) weeping eczema with foul, thick crusts; (3) itching amelioration in open air; and (4) CD of scalp. An observational, prospective, patient-outcome study was conducted in five different practice settings on 390 CD patients over 18 months using three outcomes-Glasgow Homeopathic Hospital Outcome Scale (GHHOS), Scoring Atopic Dermatitis (SCORAD), and Dermatology Life Quality Index (DLQI), assessed at baseline, after 3 and 6 months. The LR of each of the four symptoms was estimated as per the patient-rated outcomes on GHHOS. RESULTS: Seventy-four VM and 316 non-VM cases were analyzed. Estimated LRs were as follows: symptom 1, 1.29 (95% confidence interval [CI]: 0.65 to 2.60); symptom 2, 1.48 (95% CI: 0.80 to 2.74); symptom 3, 1.70 (95% CI: 0.94 to 3.07); symptom 4, 1.36 (95% CI: 0.74 to 2.51). There were statistically significant reductions in SCORAD and DLQI scores over 3 and 6 months. CONCLUSION: There was insufficient evidence to attribute any of the four assessed symptoms clearly to VM. Though non-significant, a high LR was observed for "itching amelioration in open air" (symptom 3). Symptoms in the homeopathic materia medica for VM are perhaps over-represented. More research of this nature is warranted.
Assuntos
Dermatite Atópica/tratamento farmacológico , Homeopatia/métodos , Materia Medica/administração & dosagem , Vinca , Adulto , Feminino , Seguimentos , Humanos , Masculino , Placebos , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Over-the-counter medicines may be proposed by pharmacists for children with acute cough. Study objectives were to describe the sociodemographic profile of children who were proposed a cough syrup by a pharmacist, the nature of the cough and type(s) of cough syrup proposed and to assess the evolution of the cough, tolerance and satisfaction with treatment. METHODS: Observational, prospective, longitudinal, multicentre study with 157 pharmacies in France. Children who were proposed a cough syrup by a pharmacist were recruited. Questionnaires were completed by the pharmacists and/or parents at inclusion and by the parents after 5 days of treatment. RESULTS: Four hundred fourteen children were included (mean age: 6.0±2.9 years); 45.9% had a dry and 43.3% a productive cough. 30.4% were proposed an allopathic antitussive syrup, 28.3% an allopathic expectorant syrup and 23.7% a homeopathic syrup. Children with a dry cough were more likely to be given an allopathic antitussive (55.2%) or homeopathic (28.2%) syrup. Children with a productive cough or cough of several days duration were more likely to be given an allopathic expectorant syrup (70.1%). Cough disappearance was more frequent with homeopathic syrups compared to allopathic expectorants (P=0.002), or allopathic antitussives (P=0.042). Adverse events were most common with allopathic antitussive syrups (18.7%) (P<0.001). Two-thirds of parents were satisfied with the treatment their child received. CONCLUSIONS: Pharmacists play an important role in the management of acute cough in children. Homeopathic cough syrups may have an interest in terms of public health.
Assuntos
Antitussígenos/administração & dosagem , Tosse/tratamento farmacológico , Expectorantes/administração & dosagem , Medicamentos sem Prescrição/administração & dosagem , Doença Aguda , Criança , Pré-Escolar , Serviços Comunitários de Farmácia , Feminino , França , Humanos , Estudos Longitudinais , Masculino , Satisfação do Paciente/estatística & dados numéricos , Farmacêuticos/estatística & dados numéricos , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Scopo della presente trattazione è promuovere la consapevolezza del pediatra nei confronti della sintomatologia legata alla dentizione nei bambini con il supporto delle evidenze più significative reperibili nella letteratura scientifica. Dopo la caratterizzazione dei disturbi più comuni, con la relativa incidenza e durata nella popolazione pediatrica, e del ruolo dell'infiammazione saranno definiti i limiti delle terapie attualmente disponibili. Saranno quindi illustrate le prerogative di un medicinale omeopatico, Camilia® (Boiron, Francia), che interviene sull'infiammazione locale e sistemica e sulla composita fenomenologia correlata al processo di dentizione, con il vantaggio di un'azione multifunzionale ed efficace e l'assenza di effetti indesiderati o rischi di interazione con altri farmaci.
Assuntos
Inflamação/etiologia , Materia Medica/administração & dosagem , Erupção Dentária , Humanos , Lactente , Inflamação/terapia , Pediatras/organização & administraçãoRESUMO
BACKGROUND: Primary tooth eruption in infants is associated with a range of local and systemic symptoms although this remains a subject of much debate. In addition, data are limited on the role of physicians in managing infant teething, and on the benefit of homeopathic treatments. METHODS: We conducted an observational, multicenter, prospective survey evaluating teething symptoms, and symptom course following routine medical management by French pediatricians in 597 infants aged from 3 to 24 months. We also examined the response to treatment with routinely prescribed teething medications; the homeopathic agent, Camilia® and topically applied gingival agents (Delabarre® or Dolodent®). RESULTS: Most infants (96.6%) had buccogingival symptoms and 93.3% had at least one general symptom. Fever (≥38 °C) was reported in 15.2% of infants. For teething, 212 infants were prescribed Camilia®, 172 a gingival solution (Delabarre® or Dolodent®) and 213 received Camilia® along with a gingival agent. Infants prescribed both a homeopathic and a gingival treatment had a significantly higher number of symptoms at presentation compared with those prescribed a single agent. There were no significant differences in symptom course across these three treatment groups. Systemic analgesics/antipyretics were prescribed in 68.8% of cases. Parent satisfaction with medical management and prescribed treatments was high. CONCLUSIONS: Teething is frequently associated with transient local and systemic upset in infants and is a significant concern to parents. Camilia® provides a similar benefit to topical therapy, and is frequently used by pediatricians in France.
Assuntos
Materia Medica/administração & dosagem , Pais/psicologia , Padrões de Prática Médica/estatística & dados numéricos , Erupção Dentária , Administração Tópica , Benzoatos/administração & dosagem , Pré-Escolar , Feminino , Febre/epidemiologia , Febre/etiologia , França , Humanos , Lactente , Estudos Longitudinais , Masculino , Pediatras/estatística & dados numéricos , Estudos Prospectivos , Inquéritos e Questionários , Resultado do TratamentoRESUMO
INTRODUCTION: At present, the usage of antimicrobial agents in organic dairy farming is a subject of controversial public debate because of its impact on animals, humans and the environment. This study shows how farms can be successfully managed without using antimicrobials for udder diseases. Thereby, animal welfare and targeted low bulk tank somatic cell counts should not be neglected. The operating data analysed in this study was collected during feeding and milking time on 18 swiss dairy farms that have not been treating diseased udders with antibiotics for at least 3 years. This study is a cross-sectional study. Farmers put the focus on breed characteristics such as a high life performance, low bulk tank somatic cell counts over several lactations, animals with a calm character, and small-formed cows with a deep flank. A trend towards dual-purpose breeds was observed. Few persons were involved in the milking process. Moreover, 94% of the farmers were raising their own young cattle directly on the farm. Consequently, animal transport has been minimized. Furthermore, clear management practices and work processes as well as a good animal observation influenced decisively the production success. additionally some farmers used phytotherapy, homeopathy and tried and true home remedies.
INTRODUCTION: Dans l'élevage laitier, les médicaments vétérinaires contenant des antibiotiques susceptibles d'avoir un effet sur l'homme, l'animal et l'environnement sont un sujet discuté de façon controversée dans le grand public. La présente étude veut démontrer comment fonctionnent des exploitations qui n'utilisent pas de préparations antibiotiques intra-mammaires. Cela doit se passer sans que ni le bien-être des animaux ni un nombre de cellules bas dans le lait ne soient affectés. Les données utilisées pour ce travail ont été collectées pendant l'affouragement et la traite sur 18 exploitations suisses qui, dans les 3 années précédentes, n'avaient pas utilisé d'antibiotiques au niveau de la mamelle. Il s'agit ici d'une étude transversale qui présente les prévalences. Les producteurs s'intéressent à des caractéristiques d'élevage tels que la production totale sur la durée de vie de l'animal, un nombre de cellules bas au cours de plusieurs lactations, un caractère paisible et des vaches de petit format avec une flanc profond. On a constaté une tendance en direction des races à deux fins. Les propriétaires portaient leur attention à ce qu'un petit nombre de personnes pratiquent la traite régulièrement. Vu l'élevage des propres jeunes animaux sur 94% des exploitations, le trafic des animaux a été réduit. D'autre part, des structures d'exploitation et des processus de travail clairs ainsi qu'une bonne observation des animaux avaient un effet décisif sur le succès de ce mode de production. Sur ces exploitations, des méthodes de traitement spécifiques, telles l'homéopathie ou la phytothérapie ainsi que des remèdes traditionnels étaient utilisés en soutien.
Assuntos
Bem-Estar do Animal , Antibacterianos/administração & dosagem , Doenças dos Bovinos/terapia , Indústria de Laticínios/métodos , Leite/metabolismo , Animais , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/metabolismo , Tratamento Conservador , Estudos Transversais , Feminino , Glândulas Mamárias Animais/fisiologia , Uso Excessivo de Medicamentos Prescritos/prevenção & controle , Qualidade de VidaRESUMO
Recurrent aphthous ulcer (RAU) is a common and frequently occurring disease in the Department of Stomatology. The clinical manifestations are localized ulcer of oral mucosa, and the ulcer mask is self limiting and easy to recur. In this paper, by adopting the randomized study method, the author study the effect of oral ulcer powder combined with traditional Chinese drugs on patients with recurrent aphthous ulcer, and analyze its effect on inflammatory factor. Kangfuxin liquid combined with oral ulcer powder helps reduce recurrent aphthous ulcer patients the levels of inflammatory factors, improve the symptoms of pain. The recurrence rate of the patients in the observation group for 6 months was 12.8%, which was significantly lower than that of the control group (31.42%). The difference was statistically significant (P<0.05). At the same time, the average TNF-a, IL-1 and IL-6 water in the observation group were significantly lower than that of the control group, proving that the treatment regimen could reduce the inflammatory response.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Materia Medica/uso terapêutico , Estomatite Aftosa/tratamento farmacológico , Adolescente , Adulto , Feminino , Humanos , Masculino , Materia Medica/administração & dosagem , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: By the search for new natural compounds with beneficial health effects, cephalopod ink has been considered as an attempt to develop new drugs and functional foods, which is an especially active field in Asia, where cephalopods are a major fishery catch, for which ink sacs are a bi-product and where homeopathic medicine has deep roots. There is a demand to evaluate the safety and influence to the organism. The specific composition and relative abundance of the gut microbiota, which is potentially a major modulator of host metabolism, drives the interaction between functional foods and host health. We explore the effects of melanin from Sepiella Maindroni, most common cuttlefish in China, on the intestinal microbiome of mice. RESULTS: ICR mice were randomly divided four groups, which were normal group (S), low melanin dose group (D; 120 mg/kg), medium melanin dose group (Z; 240 mg/kg), and high melanin dose group (G; 480 mg/kg). Melanin was delivered for 28 consecutive days. Fecal samples were used to generate 7715 operational taxonomic units (OTUs) via high-throughput sequencing. There were significant shifts in relative abundance of the dominant taxa at the phylum, class, order, family, and genus levels following melanin treatment. CONCLUSIONS: MSMI had no significant effect on the structure of intestinal flora in mice. The main effect was in the proportion of dominant bacterial communities. The effect positively correlated with the dose. From a health point of view, the use of melanin does not cause intestinal flora disorder. Our results may have important implications for MSMI as functional food component and potential therapeutic for manipulating gut microbiota.