Changes in the prescribing pattern of antidepressant drugs in elderly patients: an Italian,nationwide, population-based study

Background

Despite the high use of antidepressants (ADs) among the elderly, there is limited information about the prescribing pattern of these drugs in the Italian elderly population. The aim of this study was to analyze the trend in the use of ADs in the Italian elderly patients in the years 2003-2009, and specifically, to evaluate rates and predictors of AD treatment discontinuation in depressed older patients.

Methods

The nationwide general practice Health Search Database (HSD) was used to identify AD users aged 65 years old and over from 2003 to 2009. ADs were categorized as (1) selective serotonin reuptake inhibitors (SSRIs); (2) serotonin-norepinephrine reuptake inhibitors (SNRIs); (3) tricyclic antidepressants (TCAs); (4) noradrenergic and specific serotonergic antidepressants (NaSSAs); and (5) other ADs. Incidence and prevalence of AD use per 1,000 inhabitants was calculated by drug class and single compound. We also measured rates and predictors of AD discontinuation (i.e., treatment gap?≥?60 days) during the first year of therapy.

Results

Overall, 39,557 AD users ≥65 years (17 % of the total HSD elderly population) were included in the study. SSRIs were increasingly and most frequently prescribed ADs (102.7-195.3 per 1,000 over seven years). The most common indications for AD use were depression and anxiety. Overall, 14 % of AD users continued their AD medication without treatment gaps, 27 % were intermittent AD users and 58 % discontinued their ADs during the first year of follow-up. Specific AD classes such as TCAs and ‘other ADs were found to be predictors of discontinuation. In depressed patients, the use of NaSSas, TCAs and ‘other ADs as well the concomitant use of >5 drugs (other than ADs) and living in Southern Italy were more likely to predict discontinuation.

Conclusion

ADs, especially SSRIs, are widely and increasingly prescribed in elderly Italian patients in recent years. The observed high AD discontinuation rates are likely to impact the achievement of a therapeutic endpoint in depressed patients. Patients who are at high risk of AD discontinuation such as those receiving multi-drug therapy or living in Southern Italy should be monitored more closely to improve benefits of AD treatments.     

Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only proven curative therapy for juvenile myelomonocytic leukemia (JMML). We, the European Working Group on Childhood MDS (EWOG-MDS) and the European Blood and Marrow Transplantation (EBMT) Group, report the outcome of 100 children (67 boys and 33 girls) with JMML given unmanipulated HSCT after a preparative regimen including busulfan, cyclophosphamide, and melphalan. Forty-eight and 52 children received transplants from an HLA-identical relative or an unrelated donor (UD), respectively. The source of hematopoietic stem cells was bone marrow, peripheral blood, and cord blood in 79, 14, and 7 children, respectively. Splenectomy had been performed before HSCT in 24 children. The 5-year cumulative incidence of transplantation-related mortality and leukemia recurrence was 13% and 35%, respectively. Age older than 4 years predicted an increased risk of disease recurrence. The 5-year probability of event-free survival for children given HSCT from either a relative or a UD was 55% and 49%, respectively (P = NS), with median observation time of patients alive being 40 months (range, 6 to 144). In multivariate analysis, age older than 4 years and female sex predicted poorer outcome. Results of this study compare favorably with previously published reports. Disease recurrence remains the major cause of treatment failure. Outcome of UD-HSCT recipients is comparable to that of children receiving transplants from an HLA-identical sibling. (Blood. 2005;105:410-419)      

Decoding ultrafast polarization responses in lead halide perovskites by the two-dimensional optical Kerr effect

The ultrafast polarization response to incident light and ensuing exciton/carrier generation are essential to outstanding optoelectronic properties of lead halide perovskites (LHPs). A large number of mechanistic studies in the LHP field to date have focused on contributions to polarizability from organic cations and the highly polarizable inorganic lattice. For a comprehensive understanding of the ultrafast polarization response, we must additionally account for the nearly instantaneous hyperpolarizability response to the propagating light field itself. While light propagation is pivotal to optoelectronics and photonics, little is known about this in LHPs in the vicinity of the bandgap where stimulated emission, polariton condensation, superfluorescence, and photon recycling may take place. Here we develop two-dimensional optical Kerr effect (2D-OKE) spectroscopy to energetically dissect broadband light propagation and dispersive nonlinear polarization responses in LHPs. In contrast to earlier interpretations, the below-bandgap OKE responses in both hybrid CH₃NH₃PbBr₃ and all-inorganic CsPbBr₃ perovskites are found to originate from strong hyperpolarizability and highly anisotropic dispersions. In both materials, the nonlinear mixing of anisotropically propagating light fields results in convoluted oscillatory polarization dynamics. Based on a four-wave mixing model, we quantitatively derive dispersion anisotropies, reproduce 2D-OKE frequency correlations, and establish polarization-dressed light propagation in single-crystal LHPs. Moreover, our findings highlight the importance of distinguishing the often-neglected anisotropic light propagation from underlying coherent quasiparticle responses in various forms of ultrafast spectroscopy.

Understanding the ultrafast polarization response to light fields and the subsequent generation of charge carriers or excitons is key to establishing the photophysical mechanisms in the excellent optoelectronic material system of lead halide perovskites (LHPs) (1). The two ionic polarization contributions by the reorientational motion of organic cations and the deformation of the inorganic cages have been discussed within dynamic screening models (2–4) and large polaron formation (5), respectively and jointly, whereas the immediate electronic polarization response to the light field itself has been neglected so far. In many optoelectronic applications, nevertheless, not only charge carrier transport but also light propagation right below the bandgap is essential. In LHP nanowire lasers, the lasing modes are known to be redshifted from excitonic resonances due to efficient coupling to plasmon emission (6). In LHP-based exciton–polariton devices, light–matter coupling redshifts the hybrid state on the lower polariton branch (7). Propagation of subgap light is known to boost the efficiency of LHP photovoltaic cells and light-emitting devices by the so-called “photon recycling” (8). Light propagation strongly influences the function of LHP photonic devices in general (9, 10). A key feature of light propagation near the bandgap is its strong photon energy dependence, as is obvious from the classic Lorentzian model for the dielectric function near an optical resonance (11). However, most photophysical experiments probing carrier/exciton formation, screening, scattering, and nonlinear optical responses employ ultrashort excitation pulses with inherently broad energy distribution and thus convoluted spectral responses. Here, we develop a Fourier-transform-based laser spectroscopy technique, two-dimensional optical Kerr effect (2D-OKE), to investigate light propagation and nonlinear polarization responses directly in the time domain with superior excitation energy resolution near the electronic bandgap.The third-order nonlinear electric polarization P(3) serves as an in situ probe of a material’s polarizability and governs the ultrafast macroscopic response to an incident light field. This is employed in a variety of spectroscopies, such as (magneto-) OKE (12, 13), coherent phonon spectroscopy (14, 15), and four-wave mixing (FWM) in general (11). Recently, OKE has been applied to LHP single crystals: Below the bandgap, the dominating nonoscillatory Kerr response of MAPbBr₃ (MA = CH₃NH₃) compared to its all-inorganic counterpart CsPbBr3 was previously attributed to the transient polarization anisotropy caused by liquidlike reorientation dynamics of organic cations (2) and lattice disorder (5). The exponentially decaying responses with above-gap excitations were discussed in relation to polaron formation in both materials (5). Interestingly, for excitation energies close to the bandgap in CsPbBr₃ at room temperature, time-resolved OKE reveals complex oscillatory features. Such oscillatory transient birefringence signals are usually attributed to coherently excited collective modes, such as phonons (15–17) or magnons (18, 19), but the strong dependence of the oscillatory frequency on pump-photon energy in OKE seems to contradict these origins in LHPs (5). In this work, we unveil a unified source for the Kerr responses in single-crystal LHPs by tracing contributions from hyperpolarizability and the peculiar light propagation close to electronic transitions.     

Factors affecting left ventricular remodelling and mechanics in the long-term follow-up after successful repair of aortic coarctation

AIMS: To identify factors predisposing to abnormal left ventricular geometry and mechanics in 52 patients after successful repair of aortic coarctation. METHODS AND RESULTS: We evaluated left ventricular remodelling, systolic midwall mechanics, and isthmic gradient by echo-Doppler, systemic blood pressure at rest/exercise and by ambulatory blood pressure monitoring, and the aortic arch by magnetic resonance imaging. Echocardiographic findings were compared with those of 142 controls. The patients with aortic coarctation showed an increased indexed left ventricular end-diastolic volume, increased mass index, increased ratio of mass to volume and systolic chamber function. The contractility, estimated at midwall level, was increased in 21 percent of the patients. In 26 (50 percent) of the patients, we found abnormal left ventricular geometry, with 9 percent showing concentric remodelling, 33 percent eccentric hypertrophy, and 8 percent concentric hypertrophy. These patients were found to be older, underwent a later surgical repair, and to have higher systolic blood pressures at rest and exercise as well as during ambulatory monitoring. The relative mural thickness and mass index of the left ventricle showed a significant correlation with different variables on uni- and multivariate analysis. Age and diastolic blood pressure at rest are the only factors associated with abnormal left ventricular remodelling. CONCLUSIONS: Patients who have undergone a seemingly successful surgical repair of aortic coarctation may have persistently abnormal geometry with a hyperdynamic state of the left ventricle. This is more frequent in older patients, and in those with higher diastolic blood pressures.     

Does age influence the success of intra-tympanic steroid treatment in idiopathic sudden deafness?

Conclusions: The present study shows that AGE, DELAY, and PTA_PRE may be considered factors influencing therapeutic success in intra-tympanic steroid therapy. Objective: The aim of the study is to evaluate the relationship between the therapeutic success of intra-tympanic prednisolone therapy and age, in patients affected by idiopathic sudden sensorineural hearing loss (ISSNHL), considering the influence of factors such as delay, gender, and pure tone average (PTA) pre-therapy. Method: This retrospective study involved 402 consecutive patients, affected by unilateral ISSNHL between January 2009 and January 2014. Patients were divided into two groups based on age: group one with 94 patients aged over 65 years and group two with all 402 patients enrolled in the study, including those over 65. Results: PTA recorded before the beginning of the therapy (PTA_PRE) in group one was worse than for group two. In both groups the therapy was significantly effective in improving hearing thresholds, even if PTA_PRE was significant and negatively correlated with success rate. This effect disappeared within the population over 65. On average, each day of DELAY from the onset of hearing loss to the beginning of therapy cuts almost 2% of the possibility to recover. AGE was negative and significant when specified continuously for group two.     

Clinical and biological effects of treatment with amifostine in myelodysplastic syndromes

We treated six patients with primary myelodysplastic syndrome (MDS) with amifostine (200 mg/m(2) i.v./three times a week for three consecutive weeks). Neutrophil counts were more frequently increased than platelet and reticulocyte counts, but no reduction of the transfusion requirement was observed. Significant reduction of the marrow blasts was observed in one case of refractory anaemia with excess of blasts. In vitro stimulation of haematopoiesis was observed in five cases. The apoptotic rate of marrow cells was significantly diminished even after the first course. Our findings show fairly good clinical and biological response to amifostine in MDS.