Two-week Course Of Treatment Research Articles

Anti-suicidal effects of IV ketamine in a real-world setting

The current study evaluated the effectiveness of intravenous ketamine treatment for suicidality in a community-based clinical sample of 295 outpatients (mean age= 40.37; 58.6 % male). We conducted growth mixture modeling to estimate latent classes of changes in symptoms of suicidality measured by the Concise Health Risk Tracking – Self-Report (CHRT-SR) across five infusions in a two-week course of treatment. Best-fit indices indicated three trajectory groups demonstrating non-linear, quadratic changes in CHRT-SR scores during ketamine treatment. The largest group of patients (n= 170, 57.6 %) had moderate CHRT-SR scores at baseline and showed gradual improvement during treatment. The other two groups of patients had severe CHRT-SR scores at baseline and diverged into one group with no improvement throughout treatment (n = 63, 21 %) and one group with rapid improvement (n = 62, 21 %). Of the clinical and demographic variables available and tested, only higher scores pertaining to active thoughts of death and/or plan were found to predict which of the patients with severe CHRT-SR scores at baseline would not benefit from treatment. The present study provides an important contribution to the knowledge of ketamine's effects on symptoms related to suicide over time. providing support for the possible effectiveness of ketamine in a proportion of patients.

Chitosan-based composite film dressings with efficient self-diagnosis and synergistically inflammation resolution for accelerating diabetic wound healing

Diabetic wounds with delayed healing are highly susceptible to microbial infection and this seriously affects the life quality of patients. Thus, the development of novel wound dressings featured with rapid diagnosis, effective bacteria eradication, and satisfying biocompatibility is highly desirable to alleviate this issue yet remains critically challenging. In this work, we designed a multi-component composite film by integrating pH-sensitive purple cabbage anthocyanins (PCA), photothermal agent copper sulfide (CuS) nanoparticles, and broad-spectrum antibiotic gentamicin (Gent) into chitosan (CS) film, described as CS/CuS/Gent/PCA film. The composite film dressings are highly sensitive to the pH environment, which could effectively aid the patient to assess the level of infection. Moreover, in vitro experiments showed that the synergistic contributions from the mild photothermal ability under NIR irradiation to CuS and the photothermal-promoted release of Gent could result in an effective bactericidal effect, with a 95.73 % antibacterial ratio. In vivo test further verified that the film dressing with high biosafety could promote the recovery of infected defective skin of diabetic rats, which could heal approximately 92.05 % of open wounds over a two-week course of treatment. Our work provided a promising strategy for the design of advanced wound dressings with smart sensing and anti-information therapy.

Efficacy of a 1% malic acid spray for xerostomia treatment: A systematic review and meta-analysis.

To assess the efficacy of topical sialogogue spray containing malic acid 1% for treating xerostomia. We searched PubMed, Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases. Literature search, screening, study selection, data collection, data extraction and assessment of bias risk were independently conducted by two reviewers. The study appraisal was performed by Cochrane Collaboration's tool for assessing bias risk. The systematic review registration number was PROSPERO-CRD42021241322. All statistical analyses were performed using Review Manager version 5.4. Five original articles involving 244 patients with xerostomia who received topical sialogogue spray (malic acid 1%) or placebo for two weeks were included in this review. Based on the questionnaire survey, the topical sialogogue spray (malic acid 1%) improved the symptoms of dry mouth significantly better than the placebo, which was reflected in the Dry Mouth Questionnaire (DMQ), Xerostomia Inventory (XI) and Visual Analogue Scale (VAS) scores. Regarding the increase in unstimulated and stimulated saliva flow rates, the intervention group was also better than the placebo group after a two-week course of treatment. Although the included studies are limited, our results show that topical sialogogue spray (malic acid 1%) is an effective method for the treatment of xerostomia. Additional randomised controlled trials in the future are needed to provide high-quality evidence of this therapy and to improve clinical practice guidelines.

EFFECTIVENESS OF WET COMBING COMPARED WITH 1% PERMETHRIN LOTION FOR THE TREATMENT OF PEDICULOSIS CAPITIS

Objective: Pediculus humanus capitis is an ectoparasite that sucks blood from the patient’s scalp. Gamma-hexachlorocyclohexane is an effective treatment but its use has been discontinued because of its neurotoxicity. Although the replacement pediculicide is permethrin, this is not affordable for everyone, and thus the recommended treatment is wet combing. The aim of this study is to evaluate the effectiveness of permethrin compared with wet combing for eliminating pediculosis.
 Methods: This study was a randomized controlled trial (RCT) conducted in a boarding school in Bogor District; the data were collected in July–August, 2018. Subjects were regarded as infested if lice were found during examination. Infested subjects were divided into two groups. In the permethrin group, the hair was wetted with permethrin lotion and left for 10 min. Afterwards, a fine-toothed comb was used to remove lice, and then the subjects were instructed to wash their hair with shampoo. On day 14, each subject’s head was reexamined to determine the cure rate. The wet-combing group was treated similarly but using conditioner instead of permethrin.
 Results: Of 121 subjects, 88.4% were infested with head lice. The cure rate after one week of treatment was 66% in the permethrin group and 63% in the wet-combing group. After a two-week course of treatment, the cure rate increased to 94% in permethrin group and 89% in the wet-combing group. There was no significant difference in cure rate between permethrin and wet combing after a one-(P = 0.740) or two-week (P = 0.507) course of treatment.
 Conclusion: The prevalence of pediculosis capitis in a boarding school in Bogor District was 88.4%. Wet combing treatment was as effective as permethrin for treating pediculosis capitis.

Impact of the Professor Kozyavkin Method on Gross Motor Functions in Children with Cerebral Palsy

Background and Aim: Changes of gross motor function during the course of intensive neurophysiological rehabilitation by the Professor Kozyavkin Method were studied in 61 patients with spastic forms of Cerebral Palsy at the age of 2 to 15 years. Material and Methods: All patients were examined before and at the end of a two-week course of treatment, using the Gross Motor Function Measurement GMFM-66 Item Sets test to calculate of scores of motor development. Results: Statistical analysis indicated a significant increase in the level of motor development of children after treatment from 45.1 to 47.6 (p> 0.01). The most significant progress was noted in patients at level II of Gross Motor Function Classification System. The score of motor development has increased from 66.2 to 69.6 with a difference of 3.42 points (p <0.01). Conclusions: The results suggest the effectiveness of the Professor Kozyavkin Method for the improvement of gross motor functions in patients with cerebral palsy. It is necessary to continue this study and conduct blinded randomized clinical trial according to the requirements of evidence based medicine.

Change in Movement-Related Cortical Potentials Following Constraint-Induced Movement Therapy (CIMT) After Stroke

Abstract. Patients with chronic stroke were given Constraint-Induced Movement Therapy (CIMT) over an intensive two-week course of treatment. The intervention resulted in a large improvement in use of the more-affected upper extremity in the laboratory and in the real-world environment. High-resolution electroencephalography (EEG) showed that the treatment produced marked changes in cortical activity that correlated with the significant rehabilitative effects. Repetitive unilateral self-paced voluntary movements showed a large increase after treatment in the amplitudes of the late components of the Bereitschaftspotential (BP) both in the hemisphere contralateral to the more-affected arm and in the ipsilateral hemisphere. Simultaneous electromyographic recordings (EMG) and other aspects of the data indicate that the emergence of the movement-related neural source in the healthy hemisphere was not due to mirror movements of the non-test hand and that the increase in BP amplitudes was not the result of an increase in the force or effort of the response pre- to post-treatment. The results are consistent with the rehabilitation treatment having produced a use-dependent cortical reorganization and is a case where the physiological data interdigitates with and provides additional credibility to the clinical data.

YK-4-279 effectively antagonizes EWS-FLI1 induced leukemia in a transgenic mouse model.

Ewing sarcoma is an aggressive tumor of bone and soft tissue affecting predominantly children and young adults. Tumor-specific chromosomal translocations create EWS-FLI1 and similar aberrant ETS fusion proteins that drive sarcoma development in patients. ETS family fusion proteins and over-expressed ETS proteins are also found in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. Transgenic expression of EWS-FLI1 in mice promotes high penetrance erythroid leukemia with dense hepatic and splenic infiltrations. We identified a small molecule, YK-4-279, that directly binds to EWS-FLI1 and inhibits its oncogenic activity in Ewing sarcoma cell lines and xenograft mouse models. Herein, we tested in vivo therapeutic efficacy and potential side effects of YK-4-279 in the transgenic mouse model with EWS-FLI1 induced leukemia. A two-week course of treatment with YK-4-279 significantly reduced white blood cell count, nucleated erythroblasts in the peripheral blood, splenomegaly, and hepatomegaly of erythroleukemic mice. YK-4-279 inhibited EWS-FLI1 target gene expression in neoplastic cells. Treated animals showed significantly better overall survival compared to control mice that rapidly succumbed to leukemia. YK-4-279 treated mice did not show overt toxicity in liver, spleen, or bone marrow. In conclusion, this in vivo study highlights the efficacy of YK-4-279 to treat EWS-FLI1 expressing neoplasms and support its therapeutic potential for patients with Ewing sarcoma and other ETS-driven malignancies.

Evidence of use: A selective COX-2 inhibitor in the treatment of experimental chronic pancreatitis induced by Dibutyltin dichloride

Abstract The search for new prophylactic and therapeutic drugs for the treatment of chronic pancreatitis (CP) is an urgent problem in current pancreatology. A promising direction in CP therapy may be the use of nonsteroidal anti-inflammatory drugs. Hence, the aim of the present study was to investigate the selective inhibition properties of COX-2 rofecoxib on the development of pancreas fibrosis in rats with experimental chronic pancreatitis induced by Dibutyltin dichloride (DBTC). The 60 male albino Wistar rats of our study were placed into three groups of 20 animals in each: I - the intact control; II - that which received an intraperitoneal injection (i.p.) of DBTC (6 mg/g); III - those which, 28 days after administration of DBTC (6 mg/g, i.p.), received a two-week course of treatment of rofecoxib (5 mg/kg, i.p). One day after rofecoxib treatment was completed, analysis was undertaken regarding the level of amylase, as well as the pancreatic amylase and lipase in the blood serum and the prostaglandin E2 in the pancreatic tissue. In addition, the morphological condition of the pancreas was ascertained. The obtained data suggest that administration of Rofecoxib reduces the development of fibrosis and improves the morpho-functional state of the pancreas in rats with chronic pancreatitis induced by DBTC. Thus, treatment with a selective COX-2 inhibitor could be a possible strategy for improving the clinical outcome of patients with CP.

Corticosteroids for parasitic eosinophilic meningitis.

Angiostrongylus cantonensis (A. cantonensis) is the major cause of infectious eosinophilic meningitis. Dead larvae of this parasite cause inflammation and exacerbate symptoms of meningitis. Corticosteroids are drugs used to reduce the inflammation caused by this parasite. To assess the efficacy and safety of corticosteroids for the treatment of eosinophilic meningitis. We searched CENTRAL (2014, Issue 11), MEDLINE (1950 to November Week 3, 2014), EMBASE (1974 to December 2014), Scopus (1960 to December 2014), Web of Science (1955 to December 2014), LILACS (1982 to December 2014) and CINAHL (1981 to December 2014). Randomised controlled trials (RCTs) of corticosteroids versus placebo for eosinophilic meningitis. Two review authors (SiT, SaT) independently collected and extracted study data. We graded the methodological quality of the RCTs. We identified and analysed outcomes and adverse effects. We did not identifiy any new trials for inclusion or exclusion in this 2014 update. One study involving 110 participants (55 participants in each group) met our inclusion criteria. The corticosteroid (prednisolone) showed a benefit in shortening the median time to resolution of headaches (five days in the treatment group versus 13 days in the control group, P value < 0.0001). Corticosteroids were also associated with smaller numbers of participants who still had headaches after a two-week course of treatment (9.1% versus 45.5%, P value < 0.0001). The number of patients who needed repeat lumbar puncture was also smaller in the treatment group (12.7% versus 40%, P value = 0.002). There was a reduction in the median time of analgesic use in participants receiving corticosteroids (10.5 versus 25.0, P value = 0.038). There were no reported adverse effects from prednisolone in the treatment group. Corticosteroids significantly help relieve headache in patients with eosinophilic meningitis, who have a pain score of four or more on a visual analogue scale. However, there is only one RCT supporting this benefit and this trial did not clearly mention allocation concealment and stratification. Therefore, we agreed to grade our included study as a moderate quality trial. Future well-designed RCTs are necessary.

The improved resistance to high salinity induced by trehalose is associated with ionic regulation and osmotic adjustment in Catharanthus roseus

The effects of exogenous trehalose (Tre) on salt tolerance of pharmaceutical plant Catharanthus roseus and the physiological mechanisms were both investigated in this study. The results showed that the supplement of Tre in saline condition (250 mM NaCl) largely alleviated the inhibitory effects of salinity on plant growth, namely biomass accumulation and total leaf area per plant. In this saline condition, the decreased level of relative water content (RWC) and photosynthetic rate were also greatly rescued by exogenous Tre. This improved performance of plants under high salinity induced by Tre could be partly ascribed to its ability to decrease accumulation of sodium, and increase potassium in leaves. The exogenous Tre led to high levels of fructose, glucose, sucrose and Tre inside the salt-stressed plants during whole the three-week treatment. The major free amino acids such as proline, arginine, threonine and glutamate were also largely elevated in the first two-week course of treatment with Tre in saline solution. It was proposed here that Tre might act as signal to make the salt-stressed plants actively increase internal compatible solutes, including soluble sugars and free amino acids, to control water loss, leaf gas exchange and ionic flow at the onset of salt stress. The application of Tre in saline condition also promoted the accumulation of alkaloids. The regulatory role of Tre in improving salt tolerance was optimal with an exogenous concentration of 10 mM Tre. Larger concentrations of Tre were supra-optimum and adversely affected plant growth.

Irestatin, a potent inhibitor of IRE1α and the unfolded protein response, is a hypoxia-selective cytotoxin and impairs tumor growth

3514 Background: The unfolded protein response (UPR) is an adaptive response to the toxic accumulation of misfolded proteins in the endoplasmic reticulum (ER), and is activated in solid tumors. IRE1a is a core component of the UPR and responds to ER stress through activation of its dual kinase and endonuclease domains. The IRE1a endonuclease splices the mRNA for XBP-1, generateing a potent transcription factor that is required for tumor growth. Methods: We developed a fibrosarcoma cell line expressing a fusion of unprocessed XBP-1 inserted upstream of firefly luciferase. Under ER stress, IRE1a catalyzes the removal of a 26-nt intronic sequence from the XBP-1 mRNA, introducing a shift in reading frame that permits translation of luciferase. We screened a chemical library of 66,000 small molecules for inhibitors of XBP-luciferase activity and identified 12 molecules, termed irestatins, which consistently inhibited the IRE1a signaling module without affecting the activity of a control CMV-luciferase reporter. We pursued several of the most potent irestatins, including irestatin 9389, which inhibited XBP-luciferase activity with an IC50 of ∼25 nM. Results: Irestatin-mediated inhibition of the IRE1a endonuclease impairs the growth of malignant myeloma cells and inhibits the survival of oxygen-starved tumor cells in vitro. Exposure to irestatin 9389 (2.5 μM) had a negligible effect on the survival of HT1080 cells cultured under normal oxygen conditions. However, in cells cultured under hypoxia for 48 hours, irestatin 9389 inhibited colony formation by nearly 80-fold (48% vs. 0.62%). A two-week course of treatment with single-agent irestatin 9389 (50 mg/kg) administered every other day by i.p. bolus injection was well tolerated and strongly inhibited the growth of subcutaneous HT1080 tumor xenografts (1790 ± 380 mm3 vs. 480 ± 210 mm3; P&lt;0.01). Conclusion: Irestatins define a novel class of hypoxia- and ER stress-selective agents targeted to the underlying physiological response to the tumor microenvironment. Intratumoral inhibition of the UPR can potentiate cell death and impair tumor growth. Molecular intervention against central components of the UPR may represent an effective therapeutic strategy in cancer treatment. No significant financial relationships to disclose.

TREATMENT OF EOSINOPHILIC MENINGITIS WITH A COMBINATION OF PREDNISOLONE AND MEBENDAZOLE

To study the efficacy of the combination of prednisolone and mebendazole for the treatment of eosinophilic meningitis, we conducted a pilot study among Thai patients with eosinophilic meningitis. Patients were given a two-week course of prednisolone, 60 mg/day, and mebendazole, 10 mg/kg/day. The primary observation parameter was the number of patients who still had headaches after the two-week course of treatment. Forty-one patients were enrolled in the study. Four (10%) patients still had headaches after the two-week course of treatment and the median length of time until complete disappearance of headaches was three days. Serious side effects were not detected. Treatment for two weeks with the combination regimen of prednisolone and mebendazole is safe and beneficial in relieving headaches in patients with eosinophilic meningitis.

Evaluation of treatment modalities for septic arthritis with histological grading and analysis of levels of uronic acid, neutral protease, and interleukin-1.

We compared the effectiveness of antibiotics alone and in combination with arthroscopy, arthroscopy with debridement, arthrotomy, or needle aspiration for the treatment of septic arthritis. Each modality has its proponents, but, to our knowledge, no comparative studies have been conducted in animals. We used biochemical and histological analysis to compare these methods of treatment in an experimental model. The right hind knee of thirty goats was injected with 1 x 10(5) Staphylococcus aureus bacilli. The left hind knee was not inoculated and served as the normal control. Seventy-two hours after inoculation, a two-week course of treatment with intramuscular administration of cefuroxime sodium, either alone or in combination with another mode of treatment, was initiated in each of five groups. The cartilage was evaluated histologically with biochemical, enzymatic, and interleukin-1 analyses. Despite the early therapeutic intervention, on the average, there was a 25 per cent loss of uronic acid (t test, p < 0.001) and a 43 per cent increase in neutral protease activity (signed-rank test, p = 0.003) in the treatment groups. There were no significant intergroup differences with regard to the histochemical-histological rating or the levels of uronic acid, neutral protease, or interleukin-1.

Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis

In a prospective study, a two-week course of antibiotics (cloxacillin 2 g/4 h plus amikacin 7.5 mg/kg/12 h) was evaluated in the therapy of right-sided infective endocarditis in intravenous drug users (IVDU). All IVDU admitted to hospital during the study period who fulfilled the strict criteria for diagnosis of infective endocarditis were analysed. A subgroup of patients with right-sided endocarditis caused by Staphylococcus aureus who had a good prognosis were selected as being eligible for the two-week course of treatment. In a total of 139 episodes of infective endocarditis in IVDU, 72 (51.8%) cases were eligible for the two-week treatment. Of this group, 67 were cured, 4 needed prolongation of treatment to cure the infection and 1 died in hospital of respiratory distress syndrome on day 10 of treatment. In patients not eligible for the two-week treatment, the mortality was higher (24.2% versus 0.7%; p = 0.00015). Drug toxicity in the treated group was low. It can be concluded that administration of cloxacillin and amikacin parenterally for 14 consecutive days was successful in the therapy of right-sided endocarditis in IVDU.