Duration-related Effect Research Articles

Secondary Infections After Diagnosis of Severe Radiation Pneumonitis (SRP) Among Patients With Non-Small Cell Lung Cancer: Pathogen Distributions, Choice of Empirical Antibiotics, and the Value of Empirical Antifungal Treatment

This study aimed to assess pathogen distributions and antimicrobial sensitivity characteristics in patients with non-small cell lung cancer (NSCLC) with severe radiation pneumonitis (SRP) and secondary infections. Data from 1746 patients with NSCLC and SRP after thoracic radiation therapy from January 2009 to December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in patients with secondary lung infections were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and receiver operating characteristic curves. Overall, 44.5% of patients with NSCLC and SRP (777 of 1746 patients) were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (n=206; 27%), Klebsiella pneumonia (n=200; 26.2%), and Pseudomonas aeruginosa (n=104; 13.6%) being the most common. Carbapenem and cefoperazone-sulbactam resistance rates of 52.7% and 32.2%, 28.8% and 26.4%, and 23.7% and 20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% of patients with SRP. Independent risk factors for infection-related death included poor performance status scores, inappropriate empirical antimicrobial treatment, bacteria/fungal coinfection, and lack of empirical antifungal treatment. Receiver operating characteristic curves showed that the cutoff value of empirical antifungal treatment duration was 9 (area under the curve: 0.819). For patients with SRP and secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. Although this represents a promising treatment approach for patients with SRP and secondary lung infections before antibacterial susceptibility testing, further prospective validation is essential.

A Rare Case of Ethambutol Induced Optic Neuritis in a Peripheral Health Institute of Northern India

Ethambutol (EMB) is one of the first-line drugs in the treatment of tuberculosis. EMB induces ocular toxicity which is a rare side-effect that is either dose-related or duration-related effect and is often reversible on therapy discontinuation. The toxicity has been reported at 4 to 12 months of the initiation of the therapy. We reported a rare case of EMB-induced optic neuritis after 1 month of initiation of the therapy. After the withdrawal of the drug, there was complete recovery of the patient. This case description would improve the understanding of the clinical presentation as well as the treatment of ethambutol optic neuritis, especially in recourse-limited settings. It would also enrich the knowledge regarding the prevention strategies and timely recognition of the side effect. Keywords: Ethambutol, Optic neuritis, Isoniazid.

Photo-pollution disrupts reproductive homeostasis in female rats: The duration-dependent role of selenium administrations.

Although selenium is known to be essential for reproductive function, studies have indicated the adverse effect with its prolonged use. The present study investigated the duration-related effect of selenium administrations on reproductive hormones and estrous cycle indices in adult female Wistar rats exposed to a model of light pollution using altered photoperiod (AP). Ninety-six cyclic female Wistar rats displaying 4-5 days' estrous cycle length (ECL) and weighing 148-152 g were randomly divided into short and long experimental cohorts consisting of six groups each and spanning for 1 and 8 weeks, respectively. Each consisted of control, high selenium dose (HSE), low selenium dose (LSE), AP, AP + HSE, and AP + LSE. The rats were orally administered high dose (150 μg/kg) and low dose (100 μg/kg) of sodium selenite once per day. The estrous cycle indices were monitored. Plasma levels of follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E), progesterone (P), prolactin, E/P ratio, and histology of ovary and uterine horn were evaluated. The statistical analysis was performed using Statistical Package for the Social Sciences. In AP rats, HSE and LSE caused no significant effect on LH, E, P, and E/P ratio, ECL, estrus interval (EI), and estrous cycle ratio (ECR). The effect of HSE and LSE on LH, E, P, E/P ratio, and ECL showed no duration-dependent increase, but there was a duration-dependent increase in EI and ECR at low dose. The study indicated that administration of HSE of selenium improved reproductive function in photo-pollution-exposed rats irrespective of the duration of treatment.

Toxicological Potential of Cadmium Impact on Rainbow Trout (Oncorhynchus mykiss) in Early Development.

Cadmium (Cd) is a toxic element widely distributed in the aquatic environment and producing a wide variety of harmful effects. In this study, the acute toxicity (96h LC50) of Cd to rainbow trout Oncorhynchus mykiss embryos and larvae was determined. The obtained results showed that hatched larvae were the most sensitive to Cd exposure. After 4days of exposure, embryos were found to have accumulated greater concentrations of Cd than larvae. Exposure to Cd at sublethal concentrations produced deleterious, exposure duration-related effects on biological parameters (mortality, heart rate and gill ventilation frequency) of larvae. Cd induced a significant elevation of all the studied geno- and cytotoxicity endpoints in larval erythroblasts.

Effect of the duration of protease inhibitor therapy in HIV-infected individuals on the severity of obstructive sleep apnea.

Background:Protease inhibitors (PIs) are a vital part of the antiretroviral therapy. Long-term use of PIs may cause lipodystrophy, a clinical syndrome characterized by peripheral lipoatrophy and central fat accumulation, which may increase the risk of developing obstructive sleep apnea (OSA) in HIV-infected patients. We hypothesize that a longer duration of PIs’ use might be associated with increasing severity of OSA in HIV-infected patients.Materials and Methods:This was a retrospective cohort study of HIV-infected patients who were treated with PIs, who presented with symptoms suggestive of OSA, and underwent nocturnal polysomnography. The primary objective of the study is to evaluate the association between the duration of PIs’ use and the severity of OSA. The duration of PIs’ use measured in months was recorded for each patient. The primary outcome of interest was the apnea–hypopnea index (AHI) obtained at the time of the sleep study. Data were analyzed using univariate and multivariate linear regression between AHIs with PIs’ use as well as other predictors.Results:A total of 54 patients diagnosed with HIV and OSA were included in the study cohort for the analysis. Sleep study body mass index (BMI; P = 0.042) and change in BMI (ΔBMI; P = 0.027) were the only statistically significant independent predictors of AHI. The association between AHI and PIs’ use duration was found to be nonlinear and nonsignificant. Gender differences evaluation suggested possible duration-related effect relationship between PIs and OSA severity among HIV-infected men exposed to PIs within a 66-month duration.Conclusion:We did not observe a significant association between PIs’ use duration and the severity of OSA.

Case-control study examining the association between herpes zoster and oral corticosteroids use in older adults.

Little research focuses on the association between herpes zoster and oral corticosteroids use in older adults. The aim of the study was to explore this issue. We performed a case-control study using the database of the Taiwan National Health Insurance Program. There were 10,912 participants aged 65years and older with newly diagnosed herpes zoster in 2000-2013 as the cases. We randomly selected 42,676 sex-matched and age-matched participants without herpes zoster as the controls. Ever use of oral corticosteroids was defined as participants who at least had a prescription for oral corticosteroids before the index date. Never use was defined as participants who did not have a prescription for oral corticosteroids before the index date. The odds ratio (OR) and 95% confidence interval (CI) for herpes zoster associated with oral corticosteroids use were estimated using the logistic regression model. The adjusted OR of herpes zoster was 3.13 for participants with ever use of oral corticosteroids (95% CI 2.84-3.46), compared with never use. In a further analysis, the adjusted ORs of herpes zoster were 3.10 for cumulative duration of oral corticosteroids use < 12months (95% CI 2.81-3.42) and 3.65 for cumulative duration ≥ 12months (95% CI 3.20-4.18). Older adults with oral corticosteroids use are associated with a threefold increase in odds of herpes zoster in Taiwan. There is a duration-related effect of oral corticosteroids use on the risk of herpes zoster.

Risk of hospital admission for liver injury in users of NSAIDs and nonoverdose paracetamol: Preliminary results from the EPIHAM study.

The SALT study found similar per-user risks of acute liver failure (ALF) leading to transplantation (ALFT) between NSAIDs and a threefold higher risk in nonoverdose paracetamol (NOP) users. The objective of EPIHAM was to identify the risks of hospital admission for acute liver injury (ALI) associated with NSAIDs and NOP. Case-population study in the 1/97 sample of the French population claims database. Acute liver injury was identified from hospital discharge summaries, from 2009 to 2013. Exposure for cases was dispensing of NSAID or NOP resulting in exposure within 30days before admission. Population exposure was the number of patients using the drugs over the study timeframe and total number of DDD dispensed. Of 63 cases of ALI, 13 had been exposed to NSAIDs and 24 to NOP. Events per million DDD (95% CI) ranged from 0.46 (0.09-1.34) (ketoprofen) to 1.43 (0.04-7.97) (diclofenac combinations), 0.43 (0.23-0.73) all NSAIDs combined, 0.58 (0.37-0.86) for NOP. There was no association with average duration of treatment. Per patient risk ranged from 19.5 (5.31-49.9) (ibuprofen) per million users to 37.2 (19.8-63.6) all NSAIDs combined, 58.0 (37.2-86.3) for NOP. There was a linear relationship between average treatment duration and per-user risk (R2 =0.51, P<.05 for NSAIDs, R2 =0.97, P<.01 for NOP). Risk of hospital admission for ALI with NSAIDs and NOP was similar and indicative of a dose and duration-related effect (pharmacological) effect. Acute liver injury rates were not predictive of ALFT risk.

Immune responses to different patterns of exposure to ovalbumin in a mouse model of allergic rhinitis.

Allergic rhinitis (AR) has been a significant healthcare burden on individuals and society. However, the detailed effect of different patterns of allergen exposure on the development of AR remains controversial. A mouse model of AR was established to address the complex relationships between allergen exposure and the development of AR. Allergic symptom, OVA-specific IgE in serum and nasal lavage fluid, allergic inflammation in nasal tissues were evaluated after intranasal sensitization and challenge of ovalbumin (OVA) in mice treated with two different doses of allergen for different sensitized durations. Exposure to different doses and sensitized durations of OVA were capable of inducing allergic nasal response. Repetitive OVA exposure in the sensitization phase induced the recruitment of eosinophils and goblet cell hyperplasia. The level of OVA-specific IgE in serum depended on OVA exposure and was mediated in a duration-related manner. In addition, mice treated with low-dose OVA for prolonged duration manifested the major features of human local allergic rhinitis. There were dose- and duration-related effects of allergen exposure on the development of AR. LAR was associated with repetitive exposure to low-dose allergen. Thus, allergen avoidance should be an important aim of AR management.

Hot and cold executive functions in pure opioid users undergoing methadone maintenance treatment: Effects of methadone dose, treatment duration, and time between last methadone administration and testing.

Methadone maintenance is a standard treatment for opiate-dependent individuals. However, deficits in cognitive functioning have been associated with this treatment. This study aimed to determine the dose and treatment duration-related effects of methadone on executive functions. Pure male opioid users with no considerable history of other drug abuse, undergoing methadone maintenance treatment (MMT) were recruited from a major government-run de-addiction center. Hot executive functions including decision-making and emotion recognition were assessed using the Iowa gambling task and Ekman faces test, whereas cold executive functions including working memory (WM), cognitive flexibility, and response inhibition were assessed using n-back, Wisconsin card sorting test, and the GO/NOGO task, respectively. Statistical Analyses Used: Descriptive statistics, Pearson's correlation coefficients, and multiple regression analysis were used to test the hypotheses of the study. Methadone dose and length of MMT were found to be associated with greater impairment in executive functions. Impairment in cognitive performance was also found to be inversely related to time since dosing. Regression analyses revealed that methadone dosage and time since dosing accounted for a significant proportion of the variance in cognitive flexibility, while the total amount of methadone administered was able to predict deficits in WM, methadone treatment duration predicted psychomotor speed, and time since dosing predicted decision-making ability. To keep cognitive impairment at a minimum, methadone dose and treatment duration will have to be customized considering the history of opiate abuse so that impairment attributable to long-term opiate use may be differentiated from acute methadone dosing.

Influence of Intensity and Duration of Invasion by Amur Honeysuckle (Lonicera maackii) on Mixed Hardwood Forests of Indiana

AbstractThe expansion of populations of invasive species continues to compromise the ecological and economic integrity of our natural resources. The negative effects of invasive species on native biota are widely reported. However, less is known about how the duration (i.e., age of oldest invaders) and intensity (i.e., density and percent cover) of an invasion influences native plant diversity and abundance at the microsite scale. We examined the influence of density, percent cover, and age of Amur honeysuckle (a nonnative invasive shrub), and several environmental factors on native plant taxa at 12 mixed hardwood forests in Indiana, USA. Overall, study sites with the greatest taxonomic diversity (Shannon's Diversity; H′), richness (S), percent cover, and density of native vegetation also had the lowest percent cover of Amur honeysuckle in the upper vertical stratum (1.01 to 5 m). Based on linear mixed model analyses, percent cover of Amur honeysuckle in the upper vertical stratum was consistently and negatively correlated with H′, S, total percent cover, and woody seedling density of native taxa at the microsite scale (P &lt; 0.05). Duration of Amur honeysuckle at the microsite scale was not significant when percent cover of Amur honeysuckle in the upper vertical stratum was included in models. However, duration of Amur honeysuckle invasion was significantly correlated with dependent variables and with upper-stratum honeysuckle cover, suggesting that older Amur honeysuckle in a microsite resulted in greater light competition from above for native understory plant species. Beyond increased cover and shading, our results do not provide evidence of duration-related effects from long-term dominance of honeysuckle in our sampled mixed hardwood forest sites.

A rare case report on ethambutol induced optic neuritis

Ethambutol (EMB) is one of the first-line drugs in the treatment of tuberculosis. EMB induced ocular toxicity is a rare side-effect that observed as either dose or duration related effect and reversible on therapy discontinuation. We report a rare case of EMB-induced optic neuritis, even though the dose and duration are not related to it. After withdrawal of the drug, we observed there is a recovery and mapping of the central visual field showed only slight enlargement of the blind spot in the right eye. If there is no vision improvement, but ocular toxicity is not severe, isoniazid should also be stopped.

Nitrous Oxide–related Postoperative Nausea and Vomiting Depends on Duration of Exposure

Inclusion of nitrous oxide in the gas mixture has been implicated in postoperative nausea and vomiting (PONV) in numerous studies. However, these studies have not examined whether duration of exposure was a significant covariate. This distinction might affect the future place of nitrous oxide in clinical practice. PubMed listed journals reporting trials in which patients randomized to a nitrous oxide or nitrous oxide-free anesthetic for surgery were included, where the incidence of PONV within the first 24 postoperative hours and mean duration of anesthesia was reported. Meta-regression of the log risk ratio for PONV with nitrous oxide (lnRR PONVN2O) versus duration was performed. Twenty-nine studies in 27 articles met the inclusion criteria, randomizing 10,317 patients. There was a significant relationship between lnRR PONVN2O and duration (r = 0.51, P = 0.002). Risk ratio PONV increased 20% per hour of nitrous oxide after 45 min. The number needed to treat to prevent PONV by avoiding nitrous oxide was 128, 23, and 9 where duration was less than 1, 1 to 2, and over 2 h, respectively. The risk ratio for the overall effect of nitrous oxide on PONV was 1.21 (CIs, 1.04-1.40); P = 0.014. This duration-related effect may be via disturbance of methionine and folate metabolism. No clinically significant effect of nitrous oxide on the risk of PONV exists under an hour of exposure. Nitrous oxide-related PONV should not be seen as an impediment to its use in minor or ambulatory surgery.

INTERNATIONALIZATION AND PERFORMANCE: DEGREE, DURATION AND SCALE OF OPERATIONS.

The article examines the relationship between degree of internationalization (DOI) and performance before and after controlling for duration-related effects. A sample of 4,486 observations of 786 U.S. internationalized firms from 1979 to 1996 was analyzed. It is hypothesized that the relationship between DOI and performance is monotonically negative, with negative consequences slowing down at initial degrees and speeding up at higher levels of DOI. It is argued that an internationalizing firm does not achieve a performance higher than a comparable non-internationalized counterpart at any stage of internationalization.

Influence of control selection in nested case‐control studies: the example of exposure to antiretroviral treatment (ART) and the risk of myocardial infarction (MI) in the French Hospital Database on HIV (FHDH‐ANRS CO4)

Soon after availability of protease inhibitors (PIs), a duration-related effect relationship between PI and myocardial infarction (MI) was shown. New antiretroviral treatments (ARTs) have allowed more individualized regimens. To study their influence established risk factors of MI and additional therapeutic options such as lipid-lowering drugs will have to be taken into account. A nested case-control is an interesting alternative raising the choice of controls. With the previous full cohort analysis as reference, we investigated the influence of control selection in nested case-control studies sampled in this cohort by testing nine sampling scenarios. During the period 1996-1999, 49 MI occurred among male patients exposed to PI and followed-up in the French Hospital Database on HIV (FHDH-ANRS CO4). For each case, controls were selected using incidence-density sampling. The influence of additional matching criteria was tested. Random sampling and analysis was repeated 100 times with varying control-case ratios. When controls were randomly selected among patients of the same age who were free of MI at the date MI was diagnosed in the case, we observed a duration-related effect relationship between PI and MI in agreement with the results of the full cohort analysis. The use of four controls per case was sufficient. Estimates obtained with simple sampling were more precise than those obtained when controls were also matched for year of enrollment, initial CD4 cell count and HIV transmission group. To study ARTs as MI risk factors, nested case-control using incidence-density sampling without additional matching is one appropriate option.

Estimation of time‐dependent rate ratios in case‐control studies: comparison of two approaches for exposure assessment

In pharmacoepidemiology, it is well recognized that the rate of adverse events may vary as a function of the cumulative duration of the drug exposure and/or the time since the end of the exposure. In case-control studies, two different approaches have been used to estimate temporal effects of drug exposure: the time-windows (T-Ws) approach and the duration-specific (D-S) approach. We decided to conduct a simulation study to compare the two approaches when the rate ratios (RRs) vary as a function of the cumulative duration of exposure and/or the time since the end of exposure. We generated three cohorts of 500,000 individuals in which the rate of the event was varying as a function of the cumulative duration of exposure and the time since the end of exposure. For each cohort, a nested case-control analysis was performed using both the D-S and the T-Ws approaches. In the T-Ws approach, a RR is estimated within specific periods of time prior to the outcome, while a RR is estimated within periods of cumulative duration of exposure and time since the end of exposure in the D-S approach. We found that the RRs obtained from the D-S approach exactly corresponded to the RRs obtained from the cohort analyses, while the RRs obtained from the T-Ws approach generally not. RRs obtained from the T-Ws approach were difficult to interpret in terms of the effect of the duration and timing of the exposure. The D-S approach should be used to investigate the duration-related effects of exposure in case-control studies.

Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men

In the current context of dyslipidaema, hyperglycaema and lipodystrophia observed among HIV-seropositive subjects, it is important to study the risk of myocardial infarction (MI) in this population. The French Hospital Database on HIV, which includes a large number of seropositive subjects followed for substantial periods, offers the opportunity to analyse the impact of protease inhibitors (PI) on the risk of MI among men. Cox model was used to study the risk factors of MI occurrence. Standardized morbidity ratios (SMR) in men exposed to PI were calculated with data from the French general male population (FGMP) of the same age as reference. Between 1996 and 1999, MI was diagnosed in 60 men among 88 029 person-years (PY), including 49 cases among men exposed to PI. In the Cox model, exposure to PI was associated with a higher risk of MI [relative hazard (RH), 2.56; 95% confidence interval (CI), 1.03-6.34]. The expected incidence in the FGMP was 10.8/10,000 PY. The SMR relative to the FGMP was 0.8 (95% CI, 0.5-1.3) for men exposed to PI for < 18 months (G1), 1.5 (95% CI, 0.8-2.5) for men exposed for 18-29 months (G2) and 2.9 (95% CI, 1.5-5.0) for men exposed for >or= 30 months (G3). With G1 as reference, the SMR was 1.9 (95% CI, 1.0-3.1) for G2 and 3.6 (95% CI, 1.8-6.2) for G3. Our results point to a duration-related effect relationship between PI and MI, with a higher MI incidence rate among men exposed to PI for 18 months or more.

Dose- and treatment duration-related effects of p-tert-octylphenol on female rats

We conducted a study to investigate the relation between estrogenic effects of p-tert-octylphenol (OP) and serum concentration as well as treatment duration. Adult ovariectomized rats were given daily subcutaneous injections of OP for 2 and 14 days. 17β-Estradiol was also administrated at a dose of 5 μg/kg. OP was detected in serum at doses of 25 mg/kg and above for 2 days and with multiple doses (14 days) of 12.5 mg/kg. Uterine weights and luminal epithelial height were increased although the effects were weak compared to 17β-estradiol. Estrous conversion of the vaginal smear was detected only in 14-day-treated animals. OP-treatment for 2 days caused a dose-related increase in proliferation of uterine luminal, glandular, and stromal cells and vaginal epithelial cells. From the 14-day experiment, the minimum estrogenic dose level of OP was concluded to be 25 mg/kg/day and the serum level at the dose was determined to be about 80 ng/ml. These findings demonstrated that OP exerts estrogenic activity in the female reproductive tract of ovariectomized rats only at high levels of exposure and that the effects are fundamentally related to serum OP levels.

Prostaglandin f 2α induced termination of pregnancy and its reversal by prolactin or progesterone in rats

Intrauterine insertion of a Silastic-PVP tube containing 400 μg PGF 2α terminated midterm pregnancy in 100 percent of the animals. Progesterone (2 mg/day) or prolactin (PRL) reversed the abortifacient effect of PGF 2α. A dose- and duration-related effect of the PRL on PGFinduced termination of pregnancy was evident. The results suggest that PP 2 and PRL are antagonistic to each other and multiple doses of PRL are needed to neutralize the luteolytic action of PGF 2α.