To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
There is growing interest in using composite individualized treatment rules (ITRs) to guide depression treatment selection, but best approaches for doing this are not widely known. We develop an ITR for depression remission based on secondary analysis of a recently published trial for second-line antidepression medication selection using a cutting-edge ensemble machine learning method.
Data come from the SUN(^_^)D trial, an open-label, assessor blinded pragmatic trial of previously-untreated patients with major depressive disorder from 48 clinics in Japan. Initial clinic-level randomization assigned patients to 50 or 100 mg/day sertraline. We focus on the 1549 patients who failed to remit within 3 weeks and were then rerandomized at the individual-level to continuation with sertraline, switching to mirtazapine, or combining mirtazapine with sertraline. The outcome was remission 9 weeks post-baseline. Predictors included socio-demographics, clinical characteristics, baseline symptoms, changes in symptoms between baseline and week 3, and week 3 side effects.
Optimized treatment was associated with significantly increased cross-validated week 9 remission rates in both samples [5.3% (2.4%), p = 0.016 50 mg/day sample; 5.1% (2.7%), p = 0.031 100 mg/day sample] compared to randomization (30.1–30.8%). Optimization was also associated with significantly increased remission in both samples compared to continuation [24.7% in both: 11.2% (3.8%), p = 0.002 50 mg/day sample; 11.7% (3.9%), p = 0.001 100 mg/day sample]. Non-significant gains were found for optimization compared to switching or combining.
An ITR can be developed to improve second-line antidepressant selection, but replication in a larger study with more comprehensive baseline predictors might produce stronger and more stable results.
Depression is increasingly recognized as a chronic and relapsing disorder. However, an important minority of patients who start treatment for their major depressive episode recover to euthymia. It is clinically important to be able to predict such individuals.
The study is a secondary analysis of a recently completed pragmatic megatrial examining first- and second-line treatments for hitherto untreated episodes of non-psychotic unipolar major depression (n = 2011). Using the first half of the cohort as the derivation set, we applied multiply-imputed stepwise logistic regression with backward selection to build a prediction model to predict remission, defined as scoring 4 or less on the Patient Health Quetionnaire-9 at week 9. We used three successively richer sets of predictors at baseline only, up to week 1, and up to week 3. We examined the external validity of the derived prediction models with the second half of the cohort.
In total, 37.0% (95% confidence interval 34.8–39.1%) were in remission at week 9. Only the models using data up to week 1 or 3 showed reasonable performance. Age, education, length of episode and depression severity remained in the multivariable prediction models. In the validation set, the discrimination of the prediction model was satisfactory with the area under the curve of 0.73 (0.70–0.77) and 0.82 (0.79–0.85), while the calibration was excellent with non-significant goodness-of-fit χ2 values (p = 0.41 and p = 0.29), respectively.
Patients and clinicians can use these prediction models to estimate their predicted probability of achieving remission after acute antidepressant therapy.
We aimed to elucidate the accuracy and optimal cut-off point of the self-diagnosis of influenza and the associated clinical symptoms of children by their guardians, compared with those of the rapid influenza diagnostic test (RIDT).
Seasonal influenza is a common outpatient problem during the winter season. A paediatric influenza epidemic has socio-economic impacts like temporary school closure, school event cancellations, and unscheduled work absences among parents. Hence, early identification and assessment of influenza to prevent its spread is important from a societal perspective.
We performed a cross-sectional observational study in a rural clinic in Japan every winter season from December 2013 to March 2016. We retrospectively extracted information from the medical records and pre-examination checklists of 24 patients aged <12 years (mean age, 5.4 years; men, 54.2%). The data extracted from the medical records and pre-examination checklist included the baseline characteristics (age, sex and past medical history of influenza), clinical signs and symptoms, diagnosis by guardians (%) and RIDT results.
The optimal cut-off point of the self-diagnosis of influenza by guardians was 80%, with a sensitivity and specificity of 63.6% (95% confidence interval: 30.8–89.1) and 92.3% (64.0–99.8). At a 50% cut-off point, the sensitivity and specificity were 90.9% (58.7–99.8) and 53.8% (25.1−80.8). The accuracy of feeling severely sick, as estimated by the guardians showed a sensitivity and specificity of 90.9% (58.7–99.8) and 69.2% (38.6–90.9). Our study indicates that the diagnosis of seasonal influenza by guardians to their children would be useful in the establishment of both confirmatory diagnoses when it has high probability above the optimal cut-off point (80%), and exclusion diagnosis when it has low probability (50%). Not feeling severely sick, estimated by the guardians might be a useful indicator for the exclusion of paediatric influenza.
The antiviral effects of both a live and non-live Lactobacillus acidophilus strain L-92 (L-92) were investigated by oral administration (10 mg/mouse per d) daily for 21 d in a mouse model infected intranasally with influenza virus (H1N1). Virus titres in the lung of mice administered either live or non-live L-92 cells daily for 15 d were repressed 6 d after virus infection compared with the control group. Natural killer (NK) activity in the orally administered non-live L-92 group was higher compared with that of the control group before virus infection and on day 6. In contrast, NK activity in the live L-92 group compared with the control group was not significantly changed on both days, but was significantly higher on day 1. In contrast, live L-92 showed a greater repression of virus proliferation compared with non-live L-92, 6 d after the infection. Live L-92 decreased the number of neutrophils in the lung and suppressed lung weight, leading to the consequent deterioration of consolidation scores of the lung. These results indicated that pretreatment of live or non-live L-92 cells had protective effects against influenza virus infection. Among the measured cytokines and chemokines, eotaxin, macrophage colony-stimulating factor, IL-1β, RANTES (regulated on activation, normal T cell expressed and secreted) and interferon-α were significantly increased in the lung: IL-17 was significantly increased in Peyer's patch of the live L-92 group compared with the control group. A mechanistic study suggested that the enhancement of NK activity in the lung caused by stimulating various antiviral cytokines and chemokines after the oral administration of L-92 cells might be important in protecting against virus infection.
Effect of quantity and nutritional quality of dietary proteins on the content of mRNA of insulin-like growth factor-binding protein-1 (IGFBP-1) was studied in rat liver and kidney. IGFBP-1 mRNA content per unit RNA increased in liver and kidney of rats fed on a protein-free diet and in those of fasted rats compared with that in the rats fed on a casein diet. When rats were given a gluten diet for 7 d, IGFBP-1 mRNA content in liver did not change significantly but that in kidney increased considerably compared with that in those organs of the rats fed on the casein diet. Because IGFBP-1 mRNA has been demonstrated both in liver parenchymal and non-parenchymal cells (Takenaka et al. 1991), the effect of the protein-free diet on these two types of cells has been studied. An increase in IGFBP-1 mRNA content under protein deprivation was observed in both liver parenchymal and non-parenchymal cells, suggesting that these two types of cells are regulated in a similar mode as far as IGFBP-1 mRNA content is concerned. The physiological and nutritional significance of the previously stated results on protein anabolism are discussed when considered together with our previous observations on the plasma concentrations of IGF-1 (Takahashi et al. 1990) and IGFBP (Umezawa et al. 1991) and insulin-like growth factor-1 mRNA content in liver (Miura et al. 1991).
Effects of quantity and quality of dietary proteins on plasma immunoreactive insulin-like growth factor-1 (IGF-1) concentration, and content of IGF-1 mRNA in rat liver were investigated in rats. Plasma immunoreactive IGF-1 concentration in rats given a casein diet was higher than that in rats given a soya-bean-protein or protein-free diet. The IGF-1 mRNA content in liver was estimated by the Northern blot hybridization technique employing 32P-labelled rat IGF-1 complementary DNA (cDNA). At least four molecular species of IGF-1 mRNA of different molecular weight were found in rat liver. The sizes were 0·8–1·2, 2·0, 3·6–4·0 and 7·4 kb. Most of the mRNA species decreased in the livers of rats given a gluten diet (120 g gluten/kg diet) compared with rats given the casein diet. In particular, mRNA of 7·4 kb decreased markedly. When rats were fed on the protein-free diet, mRNA of all species decreased significantly. The estimated IGF-1 mRNA in the livers of rats fed on the gluten or protein-free diet was almost 0·4 of that of the rats given the casein diet. Feeding the soya-bean-protein diet did not result in a marked effect on the hepatic content of mRNA species of IGF-1. The results showed that liver IGF-1 mRNA content is sensitively regulated by quantity and nutritional quality of dietary proteins.
The effect of protein deprivation on plasma concentration of insulin-like growth factor-binding proteins (IGFBP) was studied in rats. A significant decrease in the concentration of IGFBP of molecular weight (mass) approximately 40 kDa was observed in protein-deprived rats. There was no prominent effect of protein deprivation on the concentration of IGFBP with molecular weights of about 30 kDa or 22–24 kDa. The binding capacity to plasma IGFBP of exogenously-added 125I-labelled insulin-like growth factor-1 (125I-IGF-1) was also studied. IGFBP of molecular weight about 30 and 22–24 kDa (the native form of this protein is presumed to be 29 kDa) in protein-deprived rat plasma bound more 125I-IGF-1 than those in protein-fed rat plasma. This suggested that these IGFBP in protein-deprived rat plasma are relatively unsaturated by endogenous IGF-1. The response of IGFBP to protein deprivation which was elucidated in the present investigations add further evidence to our previous assumption that IGFBP play an important role in protein nutrition.
The relations between the urinary excretion of acid-soluble peptide (ASP)-form amino acids, the rate of whole body protein synthesis and plasma immunoreactive insulin-like growth factor-1/somatomedin C concentration were investigated in rats. The urinary ASP-form leucine plus valine excretion correlated well with the rate of whole body protein synthesis and with the plasma immunoreactive insulin-like growth factor-1 concentration. The results provide further evidence for the hypothesis that urinary excretion of ASP is an excellent index of the status of protein metabolism in animals.
1. Nutritional factors affecting the urinary excretion of acid-soluble peptides (ASP) were studied in rats. The ratio, total urinary nitrogen: ASP-form leucine + valine was lowest in the rats fed on a protein-free diet and increased as retained N: absorbed N decreased. The ratio was not affected by dietary protein level when the level was below the National Research Council (1978) recommended requirement, but increased greatly when it exceeded the recommended requirement.
2. The excretion of ASP-form leucine + valine per kg body-weight was significantly lower in the protein- deficient rats than in those fed on protein-adequate diets. This variable decreased during the stage of rapid growth, but did not change as markedly after the onset of adolescence. It increased again when the rats became older. The patterns of change in the rate of excretion of ASP-form amino acids during growth and that of Nr-methylhistidine were different.
3. When labelled amino acids were injected into rats, the largest amount of the ASP-form label was excreted on the 1st day of injection. From the 2nd day the excretion of ASP-form label decreased exponentially.
4. The findings suggest that the rate of urinary excretion of ASP-form amino acids can be employed as an index of protein metabolism, particularly as a simple index of the assessment of the status of protein nutrition.
Email your librarian or administrator to recommend adding this to your organisation's collection.