Duration Of Treatment Period Research Articles

Is Posterior Nasal Nerve Neurectomy Really a Ray of Hope for the Patients of Allergic Rhinitis.

Allergic rhinitis significantly affects the quality of life, it contributes to missed or unproductive time at school or work, disturbed sleep pattern and day time somnolence. Rhinitis is defined clinically as having two or more symptoms of anterior or posterior rhinorrhoea, sneezing, nasal blockage and/or itching of the nose during two or more consecutive days for more than 1 h on most days (International rhinitis management working group, 1994). Allergic rhinitis is diagnosed when these symptoms are caused by allergen exposure leading to an IgE mediated reaction. Nerve irritation causes sneezing and itching, the loss of mucosal integrity causes causes rhinorrhoea and the vascular engrogment leads to nasal blockage. Medical modalities are symptomatically effective in mild cases, with temporary relief and addressable adverse effects. Prolonged treatment with allergy immunotherapy causes a sustainable financial burden while remaining inaccessible at smaller towns. Posterior nasal nerve neurectomy is short, easy and effective alternative. The basic procedure is to selectively cut nerve bundles at the level of the sphenopalatine foramen (SPF) with a trans nasal approach. By denervating the nasal mucosa one renders it unresponsive to any sorts of allergen or allergic reaction. The aim of the study was to evaluate the outcome of posterior nasal nerve neurectomy in cases of severe allergic rhinitis by assessing its impact on the total nasal symptom score. The study is a hospital based prospective study, conducted on 15 patients who presented to the ENT department of Mahatma Gandhi Hospital from march 2021 to October 2021 (6months) suffering from allergic rhinitis and did not show any satisfactory improvement even after 1year of medical treatment. Adult patients in the age group of 20-45 yrs. diagnosed with allergic rhinitis were enrolled into the study after obtaining a due written consent. These included patients having 2 or more symptoms of allergic rhinitis and refractoriness to medical therapy for > 1year along with significantly affected quality of life and elevated IgE level. Patients with drug induced & hormonal causes of rhinitis, chronic rhinosinusitis and any anatomical feature which precipitates to rhinitis such as deviated nasal septum, hypertrophied turbinates, blocked osteomeatal unit, polypoidal nasal mucosa and sinonasal polyposis were excluded from the study. During our study period from march 2021-September 2021, 15 patients were enrolled in the study. All the patients were followed up at 2nd and 6th month postoperatively. Amongst these patients, there were 11 females (73.34%) and 4 were male (26.67%)The mean age of patients was 35.2years. Subjective nasal symptoms of all 15 patients improved over the period of 6months. The mean TNSS improved from 12.067 preoperatively to 8.66 at the end of 2nd month, i.e., 23.1% improvement. By the end of the 6th postoperative month there was a consistent reduction in the tnss, which further reduced to a mean of 3.4 (70.2% reduction) indicating a further improvement in symptoms with time. With the advancement & popularity of endoscopic sinus surgery in the past decade, endoscopic resection of the posterior nasal nerve is emerging as a safe and less invasive technique with long standing results. Medical treatment usually provides mild and symptomatic relief with long duration of treatment period. Thus, PNN is safer, economical & easier alternative to current trend of treatment of allergic rhinitis, proving to be highly efficient in cases of intractable allergic rhinitis.

Safety and Efficacy of Acetyl-DL-Leucine in Certain Types of Cerebellar Ataxia

Cerebellar ataxia is a neurodegenerative disease impairing motor function characterized by ataxia of stance, gait, speech, and fine motor disturbances. To investigate the efficacy, safety, and tolerability of the modified essential amino acid acetyl-DL-leucine in treating patients who have cerebellar ataxia. The Acetyl-DL-leucine on Cerebellar Ataxia (ALCAT) trial was an investigator-initiated, multicenter, double-blind, randomized, placebo-controlled, clinical crossover trial. The study was conducted at 7 university hospitals in Germany and Austria between January 25, 2016, and February 17, 2017. Patients were aged at least 18 years and diagnosed with cerebellar ataxia of hereditary (suspected or genetically confirmed) or nonhereditary or unknown type presenting with a total score of at least 3 points on the Scale for the Assessment and Rating of Ataxia (SARA). Statistical analysis was performed from April 2018 to June 2018 and January 2020 to March 2020. Patients were randomly assigned (1:1) to receive acetyl-DL-leucine orally (5 g per day after 2 weeks up-titration) followed by a matched placebo, each for 6 weeks, separated by a 4-week washout, or vice versa. The randomization was done via a web-based, permuted block-wise randomization list (block size, 2) that was stratified by disease subtype (hereditary vs nonhereditary or unknown) and site. Primary efficacy outcome was the absolute change of SARA total score from (period-dependent) baseline to week 6. Among 108 patients who were randomly assigned to sequence groups (54 patients each), 55 (50.9%) were female; the mean (SD) age was 54.8 (14.4) years; and the mean (SD) SARA total score was 13.33 (5.57) points. The full analysis set included 105 patients (80 patients with hereditary, 25 with nonhereditary or unknown cerebellar ataxia). There was no evidence of a difference in the mean absolute change from baseline to week 6 in SARA total scores between both treatments (mean treatment difference: 0.23 points [95% CI, -0.40 to 0.85 points]). In this large multicenter, double-blind, randomized, placebo-controlled clinical crossover trial, acetyl-DL-leucine in the investigated dosage and treatment duration was not superior to placebo for the symptomatic treatment of certain types of ataxia. The drug was well tolerated; and ALCAT yielded valuable information about the duration of treatment periods and the role of placebo response in cerebellar ataxia. These findings suggest that further symptom-oriented trials are needed for evaluating the long-term effects of acetyl-DL-leucine for well-defined subgroups of cerebellar ataxia. EudraCT 2015-000460-34.

Correlation between Hemostasis Profile and Sepsis Outcome

Sepsis is an organ dysfunction caused by infection. Excessive cytokine activation, which causes hemostasis disorder israted by Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), fibrinogen, and D-dimer tests. Hemostasisdisorder can affect several sepsis outcomes (mortality and duration of treatment period). This study aimed to determine thecorrelation between hemostasis profile and sepsis outcome. This research was an analytical-observational withretrospective cohort study design with subjects consisting of 76 sepsis patients at Dr. Mohammad Hoesin Hospital,Palembang. The data were obtained by medical record observation and analyzed by Chi-Square and Spearman tests. From76 sepsis patients, 76.7% of subjects had normal PT; 88.2% had normal aPTT; 71.1% had elevated fibrinogen, and 100% hadelevated D-dimer. The patients' sepsis outcomes showed that 67.1% survived, and 32.9% has died, and the duration of thetreatment period without much differences is as long as ≤ 12 days and > 12 days. The statistical analysis showed that therewas no significant relationship between PT, mortality, duration of the treatment period (p=1.000; p=0.418), between aPTT,mortality, duration of the treatment period (p=0.709; p=0.480), between fibrinogen, mortality, duration of the treatmentperiod (p=0.350; p=1.000), and there was a weak negative correlation between D-dimer mortality and duration of thetreatment period (p=0.459; p=0.939). It could be concluded that there was no significant correlation between hemostasisprofile and sepsis outcome.

Injectable Disease Modifying Agents in Multiple Sclerosis: Pattern of Medication Use and Clinical Effectiveness.

The objective of this study was to assess long-term use, adherence and efficacy of injectable disease modifying agents (DMAs). Multiple Sclerosis (MS) patients diagnosed during 2002-2010 with early treatment start and at least one year in first choice medication were included in a large university district in Finland. Annualized relapse rates (ARR) during each treatment period were studied, and number of switches by medication evaluated. Use of health care facilities during 2002-2010 was assessed. In the study were included 113 MS patients; 15 (13%) switched medication. The mean duration of treatment period (128) was 3.8 years. In 77% (98/128) the treatment continued with the first DMA for (mean) 3.8 years, in 19% (25/128) with the second for 3.5 years and in 4% (5/128) with the third for 4.8 years. Mean ARR was 0.26, with 54% (69/128) of the periods relapse free. Mean ARR during the treatment periods with product switch was 0.41 before, and 0.28 after the switch, showing a trend towards better efficacy with the second DMA. The usage of health care resources remained within the guidelines. Long-term adherence to first choice DMA was observed, and a switch of product within the DMAs showed continuous adherence and efficacy. The efforts to seek a clinically effective and well tolerated agent within the first-line DMAs is warranted, leading to continued adherence and increased clinical effectiveness.

Physical comorbidity and 12-week treatment outcomes in Korean patients with depressive disorders: The CRESCEND study

ObjectivePhysical and depressive disorders frequently co-occur, but effects of physical health on depression treatment outcomes have received little research. This study aimed to compare treatment outcomes between people with depressive disorder with and without comorbid physical disorders. MethodsA Korean nationwide sample of 723 people with depressive disorder initiated on antidepressant treatment, and re-evaluated at 1, 2, 4, 8, and 12weeks later. Assessment scales for evaluating depressive symptoms (HAMD), anxiety (HAMA), global severity (CGI-s), and functioning (SOFAS) were administered at baseline and every follow-up visit. Achievement of remission or response was defined only when these were maintained to the 12week study endpoint or to the last follow-up examination, if earlier, with the date of the first observed remission point applied as the timing of remission. Logistic regression and Cox proportional hazards models were used. ResultsOf the sample, 247 (34%) had at least one physical disorder. This was associated with lower socioeconomic status and more severe depressive symptoms at baseline, but was not associated with any treatment related characteristics including antidepressant type and regimen, concomitant medications, side effects, and duration of treatment period. After adjustment, patients with physical comorbidity responded more slowly and less often — particularly in domains of anxiety, global severity, and functioning (all p-values <.005). ConclusionMore intensive assessment and integrated treatment approaches are needed to facilitate treatment responses for depressive disorders in people with physical comorbidity. Future comparative studies between conventional and integrated treatment approaches are indicated for depressive disorders with physical comorbidity.

Comparison of ocular hypotensive actions of fixed combinations of brimonidine/timolol and dorzolamide/timolol

Objective:To compare brimonidine/timolol fixed combination (BrTFC; Combigan with dorzolamide/timolol fixed combination (DTFC; Cosopt in terms of ability to lower intraocular pressure (IOP) in primary open-angle glaucoma (POAG).Methods:This was a prospective, randomized, double-masked, crossover study. After 6 weeks of therapy with timolol maleate 0.5% twice daily, patients were randomized to BrTFC twice daily or DTFC twice daily for 6 weeks, before being crossed over to the other treatment arm for a further 6 weeks. At all follow-up visits, IOP was measured at 09.00 (pre-instillation) 12.00 and 16.00.The primary outcome measure was change in mean diurnal IOP from baseline at 6 weeks. The secondary outcome was percentage of patients with IOP <18 mmHg at 6 weeks. Data were analyzed from all patients who completed the study.Results:Twenty-five patients were randomized and 20 completed the study. Mean diurnal IOP (mean ± standard deviation [SD]) was 20.28 ± 2.03 mmHg at timolol-treated baseline. After 6 weeks, mean diurnal IOP was 16.28 ± 2.07 mmHg following BrTFC and 17.23 ± 2.29 mmHg following DTFC (difference: 0.95 mmHg, 95% CI 0.10–1.80, p = 0.03). Mean IOP at 09.00 was 20.95 ± 2.31 mmHg at baseline. This was reduced to 15.85 ± 2.56 mmHg following BrTFC and 17.55 ± 2.67 mmHg following DTFC (difference: 1.70, 95% CI 0.80–2.60, p = 0.001). For the 12.00 and 16.00 timepoints, the mean changes from baseline in the two arms were comparable. Percentages of patients achieving a target IOP of <18 mmHg were 85% following BrTFC and 60% following DTFC (p = NS [not significant]). No treatment-related adverse events were reported with either therapy. Key limitations include the small size of the study population and the 6-week duration of treatment periods, which prevents drawing conclusions regarding long-term therapy.Conclusion:Reductions from baseline in mean diurnal IOP and morning IOP were greater with BrTFC than with DTFC.

Influence of two different inhalation devices on therapy compliance in asthmatic patients

Objective - To examine the influence of inhalation device (Autohaler versus metered dose inhaler) and patients' subjective opinion towards the different devices, as well as daily frequency and duration of treatment on medication compliance. Design - Prospective study measuring compliance in the same patients of the Autohaler twice daily with the metered dose inhaler twice daily, as well the Autohaler twice daily with the Autohaler four times daily. Setting - Primary health care. Subjects - 34 subjects with asthma. Main outcome measures - Patients preference and compliance. Results - Patients preferred the Autohaler. The percentage of patients with a negative opinion towards the metered dose inhaler was 38% compared with 12% towards the Autohaler. The median values of the compliance rate of the Autohaler with twice and four times daily frequency were 90.8% (25-75th percentile 61.6-98.0%) and 78.5% (25-75th percentile 49.0%-91.2%), respectively (p < 0.001). The duration of treatment period had a significant negative influence on compliance when four times daily dosage frequency was prescribed (p = 0.05). Conclusion - In conclusion, the devices (metered dose inhaler and Autohaler) and the patients' opinion about the devices did not significantly contribute to the compliance rates. Compliance towards the medication treatment, however, is negatively influenced by a high daily frequency.

Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C.

The population pharmacokinetics of ribavirin were assessed in patients with chronic hepatitis C virus (HCV) infection treated with interferon alpha-2b and ribavirin in four clinical efficacy studies. The authors collected 3450 ribavirin serum concentrations from 1105 patients at different treatment weeks for inclusion in the analysis. Population factors included gender, age, body weight, serum creatinine, creatinine clearance, and previous interferon treatment history. Ribavirin apparent clearance (CL/F) was calculated from individual patients' daily doses divided by concentration values, and the influence of these factors was assessed by multiple regression. Body weight, gender, age, and serum creatinine affected CL/F. Population mean CL/F estimates were 17.9 L/h (female) and 21.5 L/h (male) assuming an age of 40 years and body weight of 70 kg. Ribavirin apparent clearance increased as a function of body weight and decreased at ages greater than 40 years. Serum creatinine had little influence on CL/F, which may reflect the relatively normal renal function of these patients. Total CL/F variability was approximately 28%. The four covariates in the model explained 27% of this variability, and were thus of limited clinical significance because of the substantial residual variability not accounted for by the model. In assessing the relationship between pharmacokinetics and pharmacodynamics, the week 4 hemoglobin nadir value was negatively associated with week 4 ribavirin concentrations. The percentage of reduction from baseline was positively associated with ribavirin concentrations, although these data were highly variable. Loss of HCV-RNA at 24 weeks after completion of treatment was considered a response to interferon and ribavirin treatment in a logistic regression analysis of clinical and pharmacokinetic variables and treatment response in the interferon-naive patients. Hepatitis C virus genotype, pretreatment HCV-RNA titer, duration of treatment period, week 4 ribavirin concentration, and patient age affected the likelihood of response. Higher ribavirin concentrations at treatment week 4 were associated with a higher response rate. Variables that have predictive value for treatment outcome in patients treated with interferon and ribavirin are similar to those previously reported for interferon monotherapy.

Biochemical aspects of cesium administration in tumor-bearing mice.

The effect of pretreatment with CsCl on mice bearing sarcoma I implants was studied as a function of duration of treatment period, life span and tissue Cs+ and K+ levels. Treatment with CsCl for 14 consecutive days prior to sarcoma implantation resulted in initial reduction of the tumor-mediated mortality compared to controls and to a one week pretreatment period with identical doses of CsCl. A large accumulation of endogenous K+ was noted in tumor mass compared to nonmalignant tissue of the same animals or to tumor-free controls receiving identical Cs-treatment. The entry of exogenously administered Cs+ into malignant tissue was less than that accumulating in respective controls. The accumulation of Cs+ in tumor mass was dose-dependent. The ratio of K+:C+ was greater in tumor tissue than in nonmalignant tissue. The results suggest that a critical balance between these alkali metals may be required for adequate Cs effect against the tumor studied.

Methodological aspects of prophylactic drug trials in migraine.

The purpose of this paper is to analyse methodological aspects of prophylactic drug trials in migraine. A study of ferrum quartz in 33 patients provided the necessary data base. Migraine definitions, relation between interval headache and migraine, and a number of other clinical problems are discussed. A headache diary is presented which to a certain extent allows a separation of internal headache and migraine attacks. Virtually all patients with frequent migraine attacks have interval headaches. A statistical model which allows a separation of time effects and treatment effects is presented. The inter-patient variability was much greater than intra-patient variability. This indicates that it will be difficult to obtain sufficient power with a non-crossover design. The relation between duration of treatment periods and the necessary number of patients is shown to be inversely related.

Ovicidal activity of aliphatic amines and petroleum oil against two species of mosquitoes.

Most of the homologous series of primary lymphatic amines (long alkyl chains) proved highly effective against eggs of Anopheles albimanus Wireman, but only one of these (solely Maine) proved effective against eggs of the southern house mosquito, Culex pippins quinquefasciatus Say. A beta Maine (beta penta decane amine) also proved effective at 10 ppm concentration against the former species but not against the latter. Species specificity may be attributed to the variations in chorion and micropylar structures and their functioning in the 2 species. Age of eggs as well as duration of treatment period influenced level of susceptibility of eggs to oleyl amine and Neopynamin® (2,2-dimethyl-3-(2-methylpropenyl)cyclopro-panecarboxylic acid ester with N -(hydroxymethyl)-1-cyclo-hexene-1,2-dicarboximide). The younger eggs (1-8 hours old) were more susceptible than older eggs. Longer treatment period (48 hours) produced higher kill of the eggs than a shorter treatment period (24 hours). Exposure periods of shorter than 24 hours produced no marked effects. A kerosene-type petroleum oil (Toxisol J. A. (Jet Aviation grade)) killed eggs of C. p. quinquefasciatus at concentrations of 25 ppm or higher. At these higher concentrations the surface tension of water and/or eggs was lowered to such an extent that the egg rafts sank and mortality in these eggs was high. Mechanical sinking of egg rafts caused similar high mortality of eggs. Embryonic development in eggs treated with effective concentrations was generally retarded. Most of the embryos treated showed no differentiation or were found at the earlier stages of differentiation. However, some embryos in the treated eggs reached full maturity but were not able to emerge.