One lithium level >1.0 mmol/L causes an acute decline in eGFR: findings from a retrospective analysis of a monitoring database

Objectives Lithium is a mainstay of bipolar disorder treatment, however, there are still differences in opinion on the effects of lithium use on renal function. The aim of this analysis was to determine if there is an association between short-term exposure to various elevated lithium levels and estimated-glomerular filtration rate (eGFR) at ≤3 months, 6 months (±3 months) and 1 year (±3 months) follow-up. Setting Norfolk-wide (UK) lithium register and database. Participants 699 patients from the Norfolk database. Primary outcome measures eGFR change from baseline at ≤3 months, 6 months (±3 months) and 1 year (±3 months) after exposure to a lithium level within these ranges: 0.81–1.0 mmol/L (group 2), 1.01–1.2 mmol/L (group 3) and 1.21–2.0 mmol/L (group 4). The reference group was patients whose lithium levels never exceeded 0.8 mmol/L. Results Compared to the reference group, groups 3 and 4 showed a significant decrease in eGFR in the first 3 months after exposure (p=0.047 and p=0.040). At 6 months (±3 months) postexposure group 4 still showed a decline in eGFR, however, this result was not significant (p=0.298). Conclusions These results show for the first time that a single incident of a lithium level >1.0 mmol/L is associated with a significant decrease in eGFR in the following 3 months when compared to patients whose lithium levels never exceeded 0.8 mmol/L. It is still not known whether the kidneys can recover this lost function and the impact that more than a single exposure to a level within these ranges can have on renal function. These results suggest that lithium level monitoring should be undertaken at least every 3 months, in line with current UK guidelines and not be reduced further until the impact of more than one exposure to these lithium levels has been fully established

Jointly structuring triadic spaces of meaning and action:book sharing from 3 months on

This study explores the emergence of triadic interactions through the example of book sharing. As part of a naturalistic study, 10 infants were visited in their homes from 3-12 months. We report that (1) book sharing as a form of infant-caregiver-object interaction occurred from as early as 3 months. Using qualitative video analysis at a micro-level adapting methodologies from conversation and interaction analysis, we demonstrate that caregivers and infants practiced book sharing in a highly co-ordinated way, with caregivers carving out interaction units and shaping actions into action arcs and infants actively participating and co-ordinating their attention between mother and object from the beginning. We also (2) sketch a developmental trajectory of book sharing over the first year and show that the quality and dynamics of book sharing interactions underwent considerable change as the ecological situation was transformed in parallel with the infants' development of attention and motor skills. Social book sharing interactions reached an early peak at 6 months with the infants becoming more active in the coordination of attention between caregiver and book. From 7-9 months, the infants shifted their interest largely to solitary object exploration, in parallel with newly emerging postural and object manipulation skills, disrupting the social coordination and the cultural frame of book sharing. In the period from 9-12 months, social book interactions resurfaced, as infants began to effectively integrate object actions within the socially shared activity. In conclusion, to fully understand the development and qualities of triadic cultural activities such as book sharing, we need to look especially at the hitherto overlooked early period from 4-6 months, and investigate how shared spaces of meaning and action are structured together in and through interaction, creating the substrate for continuing cooperation and cultural learning

Relation of delayed recovery of myocardial function after takotsubo cardiomyopathy to subsequent quality of life

Takotsubo cardiomyopathy (TTC) has generally been regarded as a relatively transient disorder, characterized by reversible regional left ventricular systolic dysfunction. However, most patients with TTC experience prolonged lassitude or dyspnea after acute attacks. Although this might reflect continued emotional stress, myocardial inflammation and accentuated brain-type natriuretic peptide (BNP) release persist for at least 3 months. We therefore tested the hypotheses that this continued inflammation is associated with (1) persistent contractile dysfunction and (2) consequent impairment of quality of life. Echocardiographic parameters (global longitudinal strain [GLS], longitudinal strain rate [LSR], and peak apical twist [AT]) were compared acutely and after 3 months in 36 female patients with TTC and 19 age-matched female controls. Furthermore, correlations were sought between putative functional anomalies, inflammatory markers (T2 score on cardiovascular magnetic resonance, plasma NT-proBNP, and high-sensitivity C-reactive protein levels), and the physical composite component of SF36 score (SF36-PCS). In TTC cases, left ventricular ejection fraction returned to normal within 3 months. GLS, LSR, and AT improved significantly over 3-month recovery, but GLS remained reduced compared to controls even at follow-up (-17.9 ± 3.1% vs -20.0 ± 1.8%, p = 0.003). Impaired GLS at 3 months was associated with both persistent NT-proBNP elevation (p = 0.03) and reduced SF36-PCS at ≥3 months (p = 0.04). In conclusion, despite normalization of left ventricular ejection fraction, GLS remains impaired for at least 3 months, possibly as a result of residual myocardial inflammation. Furthermore, perception of impaired physical exercise capacity ≥3 months after TTC may be explained by persistent myocardial dysfunction

Video Evidence That London Infants Can Resettle Themselves Back to Sleep After Waking in the Night, as well as Sleep for Long Periods, by 3 Months of Age

Objective: Most infants become settled at night by 3 months of age, whereas infants not settled by 5 months are likely to have long-term sleep-waking problems. We assessed whether normal infant development in the first 3 months involves increasing sleep-period length or the ability to resettle autonomously after waking in the night. Methods: One hundred one infants were assessed at 5 weeks and 3 months of age using nighttime infrared video recordings and parental questionnaires. Results: The clearest development was in sleep length; 45% of infants slept continuously for 5 hours or more at night at 3 months compared with 10% at 5 weeks. In addition, around a quarter of infants woke and resettled themselves back to sleep in the night at each age. Autonomous resettling at 5 weeks predicted prolonged sleeping at 3 months suggesting it may be a developmental precursor. Infants reported by parents to sleep for a period of 5 hours or more included infants who resettled themselves and those with long sleeps. Three-month olds fed solely breast milk were as likely to self-resettle or have long sleep bouts as infants fed formula or mixed breast and formula milk. Conclusions: Infants are capable of resettling themselves back to sleep in the first 3 months of age; both autonomous resettling and prolonged sleeping are involved in “sleeping through the night” at an early age. Findings indicate the need for physiological studies of how arousal, waking, and resettling develop into sustained sleeping and of how environmental factors support these endogenous and behavioral processes

Clinical implications of discordant early molecular responses in CML patients treated with imatinib

A reduction in BCR-ABL1/ABL1IS transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3-and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values >10% at 3 months but <1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; p < 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (75% vs. 18.2%; p < 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values <1% at 6 months (p < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points

Mother's stress, mood and emotional involvement with the infant: 3 months before and 3 months after childbirth

Adverse effects of maternal anxiety and depression are well documented, namely on the foetus/child behaviour and development, but not as much attention has been given to the mother's emotional involvement with the offspring. To study mother's prenatal and postpartum stress, mood and emotional involvement with the infant, the State-Trait Anxiety Inventory, the Edinburgh Postnatal Depression Scale and the Mother-to-Infant Bonding Scale were filled in and cortisol levels were measured, 3 months before and 3 months after childbirth, in a sample of 91 Portuguese women. From pregnancy to the postpartum period, mother's cortisol levels, anxiety and emotional involvement toward the child decrease. No significant change was observed regarding mother's depression. Mother's depression predicted a worse emotional involvement before childbirth, while mother's anxiety predicted a worse emotional involvement with the infant after childbirth. Additionally, pregnant women with a worse emotional involvement with the offspring are at risk of poorer emotional involvement with the infant and higher anxiety and depression at 3 months postpartum. It should be given more attention to mother's poor emotional involvement with the offspring during pregnancy, as it interferes with her emotional involvement with the infant and her psychological adjustment 3 months after childbirth.We would like to thank the Human Development and Health Service of the Calouste Gulbenkian Foundation (Ref. 48914), the Bial Foundation (Ref. 58/02) and all the mothers that participated in this study

Radio variability of 1st 3-months Fermi blazars at 5 GHz: affected by interstellar scintillation?

Blazars from the first-three-months Fermi-AGN list were observed with the Urumqi 25m radio telescope at 5GHz in IDV (Intra-Day Variability) mode and inter-month observation mode. A significant correlation between the flux density at 5GHz and the gamma-ray intensity for the Fermi-LAT detected blazars is seen. There is a higher IDV detection rate in Fermi detected blazars than those reported for other samples. Stronger variability appears at lower Galactic latitudes; IDV appears to be stronger in weaker sources, indicating that the variability is affected by interstellar scintillation.Comment: 4 pages, 4 figures, in proceedings of 'Multiwavelength Variability of Blazars' in Guangzhou Uni. of China, 22-24, Sep. 2010, to appear in JA

Duration of adjuvant chemotherapy for stage III colon cancer

BACKGROUND Since 2004, a regimen of 6 months of treatment with oxaliplatin plus a fluoropyrimidine has been standard adjuvant therapy in patients with stage III colon cancer. However, since oxaliplatin is associated with cumulative neurotoxicity, a shorter duration of therapy could spare toxic effects and health expenditures. METHODS We performed a prospective, preplanned, pooled analysis of six randomized, phase 3 trials that were conducted concurrently to evaluate the noninferiority of adjuvant therapy with either FOLFOX (fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin) administered for 3 months, as compared with 6 months. The primary end point was the rate of disease-free survival at 3 years. Noninferiority of 3 months versus 6 months of therapy could be claimed if the upper limit of the two-sided 95% confidence interval of the hazard ratio did not exceed 1.12. RESULTS After 3263 events of disease recurrence or death had been reported in 12,834 patients, the noninferiority of 3 months of treatment versus 6 months was not confirmed in the overall study population (hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15). Noninferiority of the shorter regimen was seen for CAPOX (hazard ratio, 0.95; 95% CI, 0.85 to 1.06) but not for FOLFOX (hazard ratio, 1.16; 95% CI, 1.06 to 1.26). In an exploratory analysis of the combined regimens, among the patients with T1, T2, or T3 and N1 cancers, 3 months of therapy was noninferior to 6 months, with a 3-year rate of disease-free survival of 83.1% and 83.3%, respectively (hazard ratio, 1.01; 95% CI, 0.90 to 1.12). Among patients with cancers that were classified as T4, N2, or both, the disease-free survival rate for a 6-month duration of therapy was superior to that for a 3-month duration (64.4% vs. 62.7%) for the combined treatments (hazard ratio, 1.12; 95% CI, 1.03 to 1.23; P=0.01 for superiority). CONCLUSIONS Among patients with stage III colon cancer receiving adjuvant therapy with FOLFOX or CAPOX, noninferiority of 3 months of therapy, as compared with 6 months, was not confirmed in the overall population. However, in patients treated with CAPOX, 3 months of therapy was as effective as 6 months, particularly in the lower-risk subgroup. (Funded by the National Cancer Institute and others.

Psychodynamic approaches to teaching medical students about the doctor-patient relationship: Randomised controlled trial

Aims and method: To evaluate the effectiveness of two psychodynamic psychotherapy teaching methods, a student psychotherapy scheme (SPS) and participation in a Balint group, in teaching first-year clinical medical students about doctor-patient communication and the doctor-patient relationship. The 28 students, who were randomly allocated to three groups (SPS group, Balint group starting at baseline and Balint group starting at 3 months and acting as partial controls), were rated on a questionnaire testing their knowledge of emotional and psychodynamic aspects of the doctor-patient relationship administered at baseline, at 3 months and at 1 year. Results: At 3 months, students in the SPS and Balint groups scored higher than the partial control group, the difference approaching significance at the 5% level. At 1 year, participation in either teaching method led to significantly higher scores compared with baseline. Clinical implications: Psychodynamic psychotherapy teaching methods are effective in increasing students’ knowledge of the doctor-patient relationship and potentially also improving their communication skills