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The Japanese package insert (J-PI) for nirmatrelvir/ritonavir (N/r) (specially approved pharmaceutical) includes numerous warnings about drug interactions. However, discrepancies in the information on drug interaction are reported between J-PI and foreign databases. This study aimed to evaluate various information sources on N/r drug interactions. We categorized and compared information on N/r drug interactions from the J-PI, prescribing information from foreign regulatory agencies, guidance from the National Institutes of Health and University Health Network, the Ontario coronavirus disease 2019 (COVID-19) Science Advisory Table, University of Liverpool, Lexicomp, and the Japanese Society of Pharmaceutical Health Care and Sciences (JSPHCS). We assessed information quantity, missing data in J-PI, predicted change of the area under the blood concentration-time curve (AUC) for nirmatrelvir or co-administered drugs, and the information source consistency. From these information sources, we compiled a dataset with 115 contraindications and 203 precautions for N/r co-administration, and 51 contraindications are missing in J-PI. Among them, at least 12 drugs have large predicted AUC changes with N/r (AUC ≥5-fold or <1/5 of the baseline value). Nine of these 12 drugs are included as contraindications in Lexicomp and the JSPHCS. The consistency among the information sources is low. Information in the J-PI alone may be insufficient and Lexicomp or the JSPHCS guidelines should be useful because of their large amounts of information and wide coverage of drugs with large AUC changes. Due to low source consistency, multiple sources are needed for clinical management.
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Combinación de Medicamentos , Interacciones Farmacológicas , Ritonavir , Ritonavir/administración & dosificación , Humanos , Tratamiento Farmacológico de COVID-19 , Lopinavir , Área Bajo la Curva , Japón , IndazolesRESUMEN
Detailed examinations of the internal structure of tablets are imperative for comprehending their formulation, physical attributes, and ensuring their safe utilization. While X-ray computed tomography (CT) is valuable for noninvasively analyzing internal structural changes, the influence of humidity on these structural changes remains unexplored. Accordingly, we aimed to assess the viability of X-ray CT in non-destructively evaluating the internal structure of humidified magnesium oxide (MgO) tablets. MgO tablets were subjected to conditions of 40 °C and 75% humidity for 7 days, weighed pre- and post-humidification, and subsequently stored at room temperature (22-27 °C) until day 90. Their internal structure was evaluated using X-ray CT. We observed a substantial increase in the weight of MgO tablets concomitant with moisture absorption, with minimal changes observed upon storage at room temperature. The skewness reduced immediately post-moisture absorption, remained almost the same post-storage at room temperature, and failed to revert to pre-humidification levels during the storage period. These findings highlight the utility of X-ray CT as an effective tool for non-destructive, three-dimensional, and detailed evaluation of internal structural transformations in MgO tablets.
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Óxido de Magnesio , Tomografía Computarizada por Rayos X , Óxido de Magnesio/química , Fenómenos Químicos , Comprimidos/química , HumedadRESUMEN
Low-density lipoprotein apheresis (LDL-A) is a blood purification therapy used to treat refractory ulcers in patients with arteriosclerosis obliterans. We describe a case of vancomycin treatment in a patient undergoing maintenance hemodialysis and LDL-A therapy and assess its impact on serum vancomycin concentration. The patient underwent LDL-A twice a week (Mondays and Fridays) and maintenance dialysis three times a week (Tuesdays, Thursdays, and Saturdays) for diabetic nephropathy associated with type 1 diabetes mellitus. Following the wound culture results, vancomycin was initiated with a 1.75 g administration post-dialysis. Serum vancomycin levels before and after LDL-A, measured on the subsequent day, exhibited only slight fluctuations within the intermeasurement variability range. Despite continuing vancomycin administration at the standard dose in patients undergoing hemodialysis, the serum concentration remained consistent, suggesting a minimal impact of LDL-A on vancomycin pharmacokinetics.
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Antibacterianos , Eliminación de Componentes Sanguíneos , Lipoproteínas LDL , Diálisis Renal , Vancomicina , Humanos , Vancomicina/sangre , Vancomicina/uso terapéutico , Vancomicina/farmacocinética , Eliminación de Componentes Sanguíneos/métodos , Antibacterianos/sangre , Antibacterianos/uso terapéutico , Antibacterianos/farmacocinética , Antibacterianos/administración & dosificación , Lipoproteínas LDL/sangre , Masculino , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/complicaciones , Persona de Mediana EdadRESUMEN
AIMS: Many patients who are transferred to the convalescent rehabilitation ward of Kawasaki Kokoro Hospital (hereinafter, our hospital) are on psychotropics prescribed for delirium by their physicians at acute care hospitals. In this study, psychiatrists and pharmacists collaborated with rehabilitation physicians to reduce the use of psychotropics. METHODS: The basic information and psychotropics prescription statuses of 88 patients discharged from the convalescent rehabilitation ward of our hospital between April 1, 2021 and March 31, 2022 were derived from their medical records. RESULTS: At admission, psychotropics were prescribed to 55 patients and the number of prescribed drugs was 2 (median). At discharge, psychotropics were prescribed to 41 patients and the number of prescribed drugs was 1 (median), showing a significant decrease (p < 0.05). Compared with those at admission, prescribed psychotropic doses at discharge were significantly higher for lemborexant but significantly lower for antipsychotics, benzodiazepine/nonbenzodiazepine hypnotics, antidepressants, suvorexant, ramelteon, and sodium valproate (p < 0.05). CONCLUSIONS: These results suggest that it may be possible to reduce the types and doses of psychotropics prescribed at acute care hospitals in convalescent rehabilitation wards. However, further investigation is needed because the number of patients in this study was limited, and selection bias due to different patient characteristics cannot be ruled out.
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Antipsicóticos , Psicotrópicos , Humanos , Antidepresivos , Hospitales , Alta del PacienteRESUMEN
We describe herein topological mRNA capture using branched oligodeoxynucleotides (ODNs) with multiple reactive functional groups. These fragmented ODNs efficiently formed topological complexes on template mRNA in vitro. In cell-based experiments targeting AcGFP mRNA, the bifurcated reactive ODNs showed a much larger gene silencing effect than the corresponding natural antisense ODN.
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Silenciador del Gen , Oligodesoxirribonucleótidos , ARN Mensajero/genética , Expresión GénicaRESUMEN
The Aedes aegypti mosquito, is an arbovirus vector that can spread dengue, chikungunya, Zika, and yellow fever. Pyrethroids are widely used to control mosquitoes. The voltage-gated sodium channel (Vgsc) is the target of pyrethroids, and amino acid substitutions in this channel attenuate the effects of pyrethroids. This is known as knockdown resistance (kdr). Recently, we found that Ae. aegypti with concomitant Vgsc mutations L982W + F1534C exhibit extremely high levels of pyrethroid resistance. L982 is located in a highly conserved region of Vgsc in vertebrates and invertebrates. This study aimed to evaluate the viability of Ae. aegypti, with concomitant L982W + F1534C mutations in Vgsc. We crossed a resistant strain (FTWC) with a susceptible strain (SMK) and reared it up to 15 generations. We developed a rapid and convenient genotyping method using a fluorescent probe (Eprobe) to easily and accurately distinguish between three genotypes: wild-type and mutant homozygotes, and heterozygotes. As generations progressed, the proportion of wild-type homozygotes increased, and only 2.9% of mutant homozygotes were present at the 15th generation; the allele frequencies of L982W + F1534C showed a decreasing trend over generations. These observations show that these concomitant mutations have some fitness costs, suggesting that mosquitoes can potentially recover pyrethroid susceptibility over time without pyrethroid selection pressure in the field.
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Aedes , Insecticidas , Piretrinas , Canales de Sodio Activados por Voltaje , Infección por el Virus Zika , Virus Zika , Animales , Insecticidas/farmacología , Aedes/genética , Alelos , Resistencia a los Insecticidas/genética , Piretrinas/farmacología , Mutación , Canales de Sodio Activados por Voltaje/genética , Infección por el Virus Zika/genética , Mosquitos Vectores/genéticaRESUMEN
BACKGROUND: One-dose packaging is frequently used in Japan for elderly patients who are prescribed several medications. It is useful for easy administration and the prevention of misuse or missed medications. Hygroscopic medications are not suitable for one-dose packaging because moisture absorption may alter their properties. Plastic bags with desiccating agents are sometimes used to store hygroscopic medicines in one-dose packaging. However, the relationship between the quantity of desiccating agents and their safety in the storage of hygroscopic medications is poorly understood. Furthermore, older adults might accidentally consume desiccating agents used in food preservation. In this study, we developed a bag that suppresses the moisture absorption of hygroscopic medications without the use of desiccating agents. METHODS: The bag was manufactured using polyethylene terephthalate, polyethylene, and aluminum film on the outside, and unified with a desiccating film on the inside. RESULTS: The relative humidity (RH) in the bag was maintained at approximately 30-40% when the bag was stored at 75% RH and 35 °C. The manufactured bag's moisture suppressing effect was better than that of plastic bags with desiccating agents when the hygroscopic medications, potassium aspartate and sodium valproate tablets, were stored at 75% RH and 35 °C for 4 weeks. CONCLUSIONS: The moisture-suppression bag effectively stored and preserved hygroscopic medications and was more effective in inhibiting moisture absorption than plastic bags with desiccating agents under high temperature and humidity conditions. The moisture-suppression bags are expected to be useful for elderly patients who are prescribed several medications in one-dose packaging.
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Deglutition aid foods are used to help patients with dysphagia take oral medications. Yoghurt is occasionally used to help swallow medications; however, its influence on pharmacokinetics is poorly understood. Yoghurt made with Lactococcus cremoris subsp. cremoris FC has a characteristic viscous texture that facilitates bolus formation and deglutition due to its metabolite exopolysaccharide. We assessed yoghurt prepared with L. cremoris FC as a food deglutition aid. We performed a dissolution test using famotidine powder mixed with yoghurt and a food thickener. Famotidine dissolution rates without deglutition-assisting foods and with yoghurt or food thickener were 102.3 ± 1.7, 85.7 ± 4.6, and 46.4 ± 1.1% after 15 min, respectively. Next, we orally administered famotidine powder with water, yoghurt, and food thickener to rats and measured plasma famotidine levels. We observed no significant differences between all test groups. The Tmax of famotidine mixed with a food thickener was significantly lower than that with yoghurt. These results suggest that yoghurt with L. cremoris FC did not remarkably affect the dissolution and pharmacokinetic profiles of famotidine powder. Thus, the administration of famotidine with yoghurt might be a suitable alternative to powder administration as a deglutition aid for patients.
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Deglución , Famotidina , Ratas , Animales , Famotidina/farmacología , Solubilidad , Polvos/farmacología , YogurRESUMEN
We examined the methods for recovering residual anticancer drugs in medical settings to prevent health hazards caused by exposure to anticancer drugs. Presently, the lactose hydrate recovery rates(Lac, an alternative sample for an anticancer drug)were determined using 2 drug recovery methods that are based on a procedure manual(procedure manual method) and smart remote support(remote support method). Using the procedure manual method, 5 healthcare workers recovered Lac after receiving a detailed face-to-face methodological explanation. Using the remote support method, 3 healthcare workers recovered Lac regarded by an instructor waiting at a remote site without using a procedure manual. As a result, the Lac recovery rates were>80% for both methods; however, they showed the need for improvement. Eventually, the issues found presently will be resolved to improve the working environments of healthcare workers, caregivers, and medical service providers.
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Antineoplásicos , Condiciones de Trabajo , Humanos , Personal de Salud , Cuidadores , Antineoplásicos/uso terapéuticoRESUMEN
Aedes aegypti (Linnaeus, 1762) is the main mosquito vector for dengue and other arboviral infectious diseases. Control of this important vector highly relies on the use of insecticides, especially pyrethroids. The high frequency (>78%) of the L982W substitution was detected at the target site of the pyrethroid insecticide, the voltage-gated sodium channel (Vgsc) of A. aegypti collected from Vietnam and Cambodia. Alleles having concomitant mutations L982W + F1534C and V1016G + F1534C were also confirmed in both countries, and their frequency was high (>90%) in Phnom Penh, Cambodia. Strains having these alleles exhibited substantially higher levels of pyrethroid resistance than any other field population ever reported. The L982W substitution has never been detected in any country of the Indochina Peninsula except Vietnam and Cambodia, but it may be spreading to other areas of Asia, which can cause an unprecedentedly serious threat to the control of dengue fever as well as other Aedes-borne infectious diseases.
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Aedes , Enfermedades Transmisibles , Dengue , Insecticidas , Piretrinas , Animales , Insecticidas/farmacología , Resistencia a los Insecticidas/genética , Mutación , Aedes/genética , Asia , Dengue/epidemiología , Dengue/genéticaRESUMEN
Olanzapine, a second-generation antipsychotic used in the treatment of schizophrenia, is classified as a multi-acting receptor-targeted antipsychotic. Abnormal weight gain is one of the most common side effects of this drug, along with an increased appetite and food intake. However, weight gain has also been reported in patients taking olanzapine without an increase in appetite. Olanzapine has been reported to be directly associated with enhanced adipogenesis; however, whether olanzapine increases lipid content in adipocytes under weak stimulus conditions, such as low glucose concentrations and weak differentiation and/or maturation conditions, is poorly understood. The present study examined the stimulatory effect of olanzapine during the differentiation and maturation of 3T3-L1 pre-adipocytes under low-glucose and weak stimulation conditions by evaluating the expression levels of PPARγ by western blotting and oil red O staining. Western blotting revealed that olanzapine suppressed perilipin phosphorylation, which is an important lipolysis step in adipocytes. The findings of the present study provide novel insights to explain weight gain in patients taking olanzapine but not presenting with increased food intake.
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In the past two decades, minimally invasive spine surgery (MISS) techniques have been developed for spinal surgery. Historically, minimizing invasiveness in decompression surgery was initially reported as a MISS technique. In recent years, MISS techniques have also been applied for spinal stabilization techniques, which were defined as minimally invasive spine stabilization (MISt), including percutaneous pedicle screws (PPS) fixation, lateral lumbar interbody fusion, balloon kyphoplasty, percutaneous vertebroplasty, cortical bone trajectory, and cervical total disc replacement. These MISS techniques typically provide many advantages such as preservation of paraspinal musculature, less blood loss, a shorter operative time, less postoperative pain, and a lower infection rate as well as being more cost-effective compared to traditional open techniques. However, even MISS techniques are associated with several limitations including technical difficulty, training opportunities, surgical cost, equipment cost, and radiation exposure. These downsides of surgical treatments make conservative treatments more feasible option. In the future, medicine must become "minimally invasive" in the broadest sense-for all patients, conventional surgeries, medical personnel, hospital management, nursing care, and the medical economy. As a new framework for the treatment of spinal diseases, the concept of minimally invasive spinal treatment (MIST) has been proposed.
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Enfermedades de la Columna Vertebral , Fusión Vertebral , Humanos , Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Neuroquirúrgicos/métodos , Fusión Vertebral/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the disintegration of wet- and dry-compressed orally disintegrating (OD) tablets, with synchrotron radiation as the X-ray source. SIGNIFICANCE: Pharmaceutical tablets are vital for the treatment of various diseases. Therefore, they are constantly developed to ensure desirable characteristics. In particular, OD tablets need to disintegrate immediately after absorbing saliva. How these tablets absorb saliva is key to enhancing rapid product development. Recently, absorption processes have been investigated using various noninvasive techniques, including X-ray radiography and X-ray computed tomography. However, X-ray radiography studies on how water without a contrast agent is absorbed, moves, and causes a tablet to swell are scarce. The use of a contrast agent is associated with some shortcomings, including complex data analysis in some instances, alterations in the viscosity of water, and potential influence on fluid transport inside the tablet, thus possibly affecting the disintegration process. METHODS: Real-time X-ray radiography was used to monitor the disintegration of various tablets, while X-ray computed tomography and software were used to create 3 D images. RESULTS: We demonstrated how pure water penetrated the wet-compressed tablet faster than inside the dry-compressed tablet, and how the latter swelled more. X-ray computed tomography showed the presence of voids in the tablets following water absorption. CONCLUSION: Our methods are promising for nondestructive fluid absorption and transport investigations inside OD tablets.
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Medios de Contraste , Tomografía Computarizada por Rayos X , Administración Oral , Solubilidad , Comprimidos , Agua , Rayos XRESUMEN
Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the most common procedure in minimally invasive spine stabilization (MISt), details of the technique remain unclear. This technical report shows the mid-long-term clinical outcomes in patients who underwent posterior oblique square decompression (POSDe) with the three-step wanding technique of tubular MIS-TLIF for degenerative lumbar disease. Tubular MIS-TLIF (POSDe) was performed on 50 patients (males, 19; age, 69.2 ± 9.6 years), and traditional open surgery was performed (OS) on 27 (males, 4; age, 67.9 ± 6.6 years). We evaluated the clinical outcomes using the Visual Analog Scale for back pain, Japanese Orthopedic Association (JOA) scores, and JOA Back Pain Evaluation Questionnaire. We also assessed the fusion rate using the Bridwell grading system with computed tomography or plain radiography for at least 2 years postoperatively. Although there was no significant difference in the improvement rate of JOA scores between the two groups, the mean operation time and blood loss were significantly lower with MIS-TLIF than with OS. In the tubular MIS-TLIF group, there were no cases of deep wound infection; four cases had a pseudarthrosis, two had dural injury, and three had cage retropulsion. We revealed good clinical outcomes in patients who underwent POSDe.
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A 75-year-old woman underwent L4-L5 lateral interbody fusion for L4-5 foraminal stenosis with the use of percutaneous pedicle screws. On the day after the surgery, she was in shock. Emergency contrast-enhanced CT showed active extravasation from the 4th lumbar artery with a transverse process fracture. A radiologist performed a successful transarterial embolization, and the patient then began walking training on the 4th day post-surgery. Close attention should be paid to the insertion of a percutaneous pedicle screw, as it may cause a lumbar artery injury; in such a case, transarterial embolization is the preferred treatment.
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Arterias/lesiones , Vértebras Lumbares/lesiones , Tornillos Pediculares/efectos adversos , Anciano , Femenino , Humanos , Vértebras Lumbares/cirugía , Hemorragia Posoperatoria/etiologíaRESUMEN
Background and Objectives: Clinicians are required to manage a growing number of elderly patients with several medical comorbidities, and invasive surgical treatments are sometimes not advisable for these patients. The aim of this study was to evaluate the efficacy of minimally invasive intraspinal canal treatment, trans-sacral canal plasty (TSCP), for patients with and without failed back surgery syndrome (FBSS). Materials and Methods: A multicenter analysis was conducted. TSCP was performed in patients with chronic low back pain and leg pain due to lumbar spinal disorders. An adhesiolysis by TSCP was carried out, then a mixture of steroid and local anesthesia was injected. Visual Analog Scales (VAS) for low back pain and leg pain, and complications were evaluated. Results: A total of 271 patients with a minimum 6-month follow-up were enrolled. There were 80 patients who had a history of previous lumbar spinal surgery (F group), and 191 patients without previous lumbar spinal surgery (N group). There were no significant differences in sex and age between the two groups. VAS scores for low back pain (N group/F group) preoperatively, immediately postoperatively, and 1 month, 3 months and 6 months postoperatively, were 51/52 mm, 24/26 mm, 33/34 mm, 30/36 mm, and 30/36 mm, respectively. VAS scores for leg pain were 69/67 mm, 28/27 mm, 39/41 mm, 36/43 mm, and 32/40 mm, respectively. Both VAS scores for low back pain and leg pain were significantly decreased from baseline to final follow-up in both groups (p < 0.01). However, VAS scores for leg pain at 3 months and 6 months postoperatively were significantly higher in F group (p < 0.05). There were three catheter breakages (2/3 in F group), and one dural tear in F group. Conclusions: TSCP significantly reduced both VAS scores for low back and leg pain in patients with and without FBSS. However, co-existence of intractable epidural adhesion might be associated with less improvement in FBSS.
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Síndrome de Fracaso de la Cirugía Espinal Lumbar , Dolor de la Región Lumbar , Anciano , Síndrome de Fracaso de la Cirugía Espinal Lumbar/complicaciones , Síndrome de Fracaso de la Cirugía Espinal Lumbar/cirugía , Humanos , Dolor de la Región Lumbar/etiología , Dolor de la Región Lumbar/cirugía , Vértebras Lumbares/cirugía , Dimensión del Dolor , Adherencias Tisulares , Resultado del TratamientoRESUMEN
Patients with dysphagia have difficulty swallowing oral medications. Swallowing aid foods, such as deglutition aid jellies and food thickeners, are often used to help such patients take oral medications. Yogurt is occasionally used to help swallow medications. It is also advantageous as it is nutritious and easy to swallow. However, the influence of yogurt on the pharmacokinetics of oral medications is poorly understood. In this study, we aimed to evaluate yogurt as a potential swallowing aid for the intake of oral tablets, by comparing the physical properties and effects of yogurt on disintegration and dissolution profiles of various oral tablets with deglutition aid jelly and xanthan gum-based food thickener. Yogurt and the food thickener were found to extend the disintegration time of several tablets; however, this increase was unremarkable. Although dissolution of magnesium oxide tablets decreased by 6%, 14%, and 25% after immersion in deglutition aid jelly, food thickener, and yogurt, respectively, at 15 min, this impact on dissolution reduced over time (dissolution rates of all samples at 120 min were over 90%). Rheological measurements showed that yogurt and food thickeners have a weak gel structure and therefore have better fluidity than deglutition aid jelly. The adhesiveness and dynamic viscosity of yogurt were higher than those of the food thickener, which delayed tablet disintegration and reduced the dissolution rate. However, these effects were not substantial. We can thus conclude that yogurt may be a useful swallowing aid for patients with deglutition disorders who take oral medications.
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Deglución , Yogur , Aditivos Alimentarios/química , Humanos , Solubilidad , Comprimidos/químicaRESUMEN
BACKGROUND/AIMS: Gastric acid secretion is suspected to be a pivotal contributor to the pathogenesis of functional dyspepsia. The present study investigates the potential association of the gastric acid secretion estimated by measuring serum pepsinogen with therapeutic responsiveness to the prokinetic drug acotiamide. METHODS: Dyspeptic patients consulting participating clinics from October 2017 to March 2019 were prospectively enrolled in the study. The dyspeptic symptoms were classified into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Gastric acid secretion levels were estimated by the Helicobacter pylori infection status and serum pepsinogen using established criteria and classified into hypo-, normo-, and hyper-secretion. Each patient was then administered 100 mg acotiamide thrice daily for 4 weeks, and the response rate to the treatment was evaluated using the overall treatment efficacy scale. RESULTS: Of the 86 enrolled patients, 56 (65.1%) and 26 (30.2%) were classified into PDS and EPS, respectively. The estimated gastric acid secretion was not significantly different between PDS and EPS. The response rates were 66.0% for PDS and 73.1% for EPS, showing no significant difference. While the response rates were stable, ranging from 61.0% to 75.0% regardless of the estimated gastric acid secretion level among subjects with PDF, the rates were significantly lower in hyper-secretors than in non-hyper-secretors among subjects with EPS (42.0% vs 83.0%, P = 0.046). CONCLUSION: Although acotiamide is effective for treating EPS as well as PDS overall, the efficacy is somewhat limited in EPS with gastric acid hypersecretion, with gastric acid suppressants, such as proton pump inhibitors, being more suitable.
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Lithium carbonate is used to increase white blood cell counts as a means of counteracting leukopenia caused by the administration of antipsychotic drugs. To evaluate the effect of antipsychotics on the leukocyte-enhancing effect of lithium, we compared white blood cell counts, serum lithium levels, and lithium dosage in patients receiving antipsychotics and lithium in combination and patients receiving lithium alone. Chlorpromazine equivalent values were used as an indicator of the antipsychotic dose. Lithium serum levels were measured in 41 hospitalized patients. The lithium dose in the combination group (median, 800 mg) was significantly higher than that in group receiving only lithium (median, 400 mg) (P = 0.03). The lithium doses in the combination group receiving ≥1000 mg chlorpromazine equivalents (overdosing; median lithium dose 800 mg) and the combination group treated with 600-999 mg chlorpromazine equivalents (high dosing; median lithium dose 800 mg) were significantly higher than the group that was not treated with antipsychotic medication, with median lithium dose 400 mg (P < 0.05).There were no significant differences in the white blood cell counts and serum lithium levels. Because of the large variety of antipsychotic drugs used in combination with lithium and the various doses used, it was difficult to evaluate the effects of lithium, with or without antipsychotic administration, on leukocyte count enhancement. We are planning to study a larger number of patients and, since renal function could not be assessed in this study, we will also focus on renal function, including urine output.
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Antipsicóticos , Leucopenia , Antipsicóticos/uso terapéutico , Humanos , Recuento de Leucocitos , Leucopenia/inducido químicamente , Leucopenia/tratamiento farmacológico , Litio/efectos adversos , Carbonato de Litio/efectos adversosRESUMEN
Bed bug control highly depends on insecticides with a limited number of modes of action, especially since the global prevalence of pyrethroid resistance. De facto insecticide options against bed bugs in Japan are acetylcholinesterase inhibitors (AChEis) that consist of organophosphates and carbamates. However, the status of AChEi resistance and the mechanisms involved have not been ascertained. An amino acid substitution mutation, F348Y (or F331Y in standard numbering), occurring at an acyl-binding site of the paralogous AChE gene (p-Ace), was identified among AChEi-resistant colonies of both common and tropical bed bugs (Cimex lectularius and C. hemipterus, respectively). This mutation was genetically associated with propoxur and fenitrothion resistance in F348Y-segregating colonies of C. hemipterus. Inhibition of heterologously expressed C. lectularius p-Ace with insecticides revealed that the sensitivities of F348Y-carrying AChE decreased by orders of 10- to more than 100-fold for diazoxon, carbaryl, fenitroxon, paraoxon, chlorpyrifos-methyl, malaoxon, azamethiphos, methyl-paraoxon, and propoxur. In contrast, the mutant AChE showed a slightly decreased degree of sensitivity for dichlorvos and almost unchanged sensitivity for metoxadiazone. Further studies are needed to ascertain whether the practical efficacies of dichlorvos and metoxadiazone are ensured against F348Y-carrying bed bugs and whether other resistance mechanisms are involved.