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Objectives: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). Methods: We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual‐energy X‐ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. Results: In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479–800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new‐onset metabolic syndrome. Conclusions: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to assess the effect of tenofovir alafenamide (TAF) on kidney and bone biomarkers in patients who developed proximal renal tubulopathy (PRT) while receiving tenofovir disoproxil fumarate (TDF). Methods: Individuals with a history of TDF‐associated PRT and currently suppressed HIV infection on a tenofovir‐sparing regimen were randomized 1:1 to continue current antiretroviral therapy or initiate emtricitabine (F)/TAF with discontinuation of nucleoside reverse transcriptase inhibitors (NRTIs) as appropriate. Renal and bone biomarkers were analysed at baseline, week 4 and week 12. The primary outcome was the mean difference between study arms in urine retinol‐binding protein:creatinine ratio (RBPCR) change from baseline to week 12. Data were analysed using linear regression, with robust standard errors (primary outcome), and repeated measures mixed effects models (secondary outcomes). The trial was registered under European Union Drug Regulating Authorities Clinical Trials Database 2016‐003345‐29. Results: We randomized 31 individuals [mean age 52.4 (standard deviation 0.3) years; 97% male; 90% white); all completed the study. At 12 weeks, there was no difference in change in RBPCR (β 19.6; 95% confidence interval −35.3, 74.5; P = 0.47), and no difference in change in estimated glomerular filtration rate (eGFR) (based on creatinine or cystatin C), albuminuria, proteinuria, renal phosphate or urea handling, (fasting) urine osmolality, parathyroid hormone and bone turnover markers in the control versus the F/TAF exposed groups. No cases of PRT were observed. Conclusions: In people with a history of proximal renal tubulopathy while on TDF, 12‐week exposure to TAF did not adversely affect renal tubular function. These data support continued evaluation of the long‐term safety of TAF in this group of patients. [ABSTRACT FROM AUTHOR]

Introduction: Management of bipolar disorder (BD) include assessment of non-adherence (Berk et al., 2010). Knowledge about lithium therapy has been shown to improve adherence and reduce the risk of toxicity. Objectives: Better understand patient's knowledge level and attitudes towards lithium; verify the variables which could influence adherence. Methods: At admission BD patients completed the Italian versions of the Lithium Knowledge Test (LKT) and Lithium Attitudes Questionnaire (LAQ): adapted translations of a validated psychiatric survey. Scores were correlated to clinical, demographic, pharmacological variables as well as patient's plasma lithium levels. Results: 16.5% showed good lithium knowledge. Knowledge positive correlated with education level (p < 0,04). 21.7% expressed negative attitudes towards lithium therapy: obstacles to adherence were younger age (for side effects <0,01), earlier onset of illness (doubt efficacy <0,04), and late onset of lithium prophylaxis (with poor concept of illness <0,05). Lithiemia positively correlated with duration of illness (p < 0,02), duration of lithium treatment (p<0,01), good lithium knowledge (p<0,04) and positive attitude towards lithium (p<0.04). Duration of lithium therapy positively correlated with general attitude towards lithium (p<0,02), lithium therapy specifically (p<0,01), and severity of illness insight (p<0,009) Conclusions: A low percentage of patients had a good lithium knowledge. Duration of lithium therapy seems to be a protective factor for adherence; younger patients, earlier age of onset, late addition of lithium to therapy could represent barriers for adherence and topics for psychoeducational individual support. [ABSTRACT FROM AUTHOR]

Twenty-eight individuals who experienced proximal renal tubulopathy (PRT, Fanconi syndrome) while receiving tenofovir disoproxil initiated tenofovir alafenamide (TAF) and were followed for 5 years. None developed recurrent PRT or experienced significant changes in estimated glomerular filtration rate (by creatinine or cystatin-C), albuminuria, proteinuria, retinol-binding proteinuria, fractional excretion of phosphate, alkaline phosphatase, or bone mineral density at the lumbar spine. These data suggest that TAF is a well tolerated treatment option for individuals vulnerable to developing PRT., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People living with human immunodeficiency virus (HIV) are disproportionately impacted by socioeconomic deprivation and are at increased risk of developing other long-term conditions (LTCs). These illnesses require transformative action to tackle the adverse effects on their health. Data on lived experiences of LTCs among people living with HIV of Black African and Black Caribbean ethnicities are sparse, and how people with LTCs are impacted by social determinants of health (SDoH)., Methods: Through a phenomenological study design this qualitative study, conducted in 2022, comprised four focus group discussions (FGDs) with 20 people of Black ethnicities living with HIV were purposively invited from a community organisation (CO) in London, including four semistructured interviews with CO staff. Following transcription, qualitative data were analysed thematically and measures to validate the findings were implemented., Results: The findings are presented in terms of the following four levels of SDoH: (1) individual determinants (such as the impact of SDoH on lifestyle modification and self-management); (2) interpersonal determinants (such as positive experiences of accessing healthcare for LTCs); (3) clinical determinants (such as care pathway barriers) and (4) systemic determinants (such as systemic barriers related to race/ethnicity)., Conclusions: It is necessary to provide ongoing and interactive education to community members who live with HIV, focusing on risks and management of LTCs. Additionally, individuals would benefit from support to navigate increasingly complex and fragmented health services. Health Service staff require cultural competence when caring for patients of Black African and Black Caribbean ethnicities with complex health and psychosocial needs., Patient or Public Contribution: The research team collaborated with an HIV CO in South London from the very start of the project to agree the study design and learn about the realities of their daily lived experiences. Community collaborators helped to develop the semistructured interview and FGD topic guides, and were directly involved in the data gathering, analysis and validation., (© 2024 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Objective: Social determinants of health (SDH) are important determinants of long-term conditions and multimorbidity in the general population. The intersecting relationship between SDH and multimorbidity in people with HIV remains poorly studied., Design: A cross-sectional study investigating the relationships between eight socio-economic parameters and prevalent comorbidities of clinical significance and multimorbidity in adults of African ancestry with HIV aged 18-65 years in South London, UK., Methods: Multivariable logistic regression analysis was used to evaluate associations between SDH and comorbidities and multimorbidity., Results: Between September 2020 and January 2022, 398 participants (median age 52 years, 55% women) were enrolled; 85% reported at least one SDH and 72% had at least one comorbidity. There were no associations between SDH and diabetes mellitus or kidney disease, few associations between SDH (job and food insecurity) and cardiovascular or lung disease, and multiple associations between SDH (financial, food, housing and job insecurity, low educational level, social isolation, and discrimination) and poor mental health or chronic pain. Associations between SDH and multimorbidity mirrored those for constituent comorbidities., Conclusion: We demonstrate strong associations between SDH and poor mental health, chronic pain and multimorbidity in people of black ethnicities living with HIV in the UK. These findings highlight the likely impact of enduring socioeconomic hardship in these communities and underlines the importance of holistic health and social care for people with HIV to address these adverse psychosocial conditions., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

More than 10 years ago, the discovery of the antidepressant effects of Ketamine opened the opportunity to develop a novel class of antidepressants. Ketamine induces dissociative symptoms as a major side effect. This rapid-acting antidepressant is available as an endovenous racemic compound and as an intranasal S-enantiomer: Esketamine; which is four-fold more potent for the NMDA receptor. Here we present the critical case of a patient who took both molecules experiencing remission just with endovenous Ketamine, whose impact in terms of dissociative symptoms was greater. In this short report, we discuss the differences between the two drugs and the possibility of dissociative features to predict their efficacy., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dysfunctional glutamatergic neurotransmission has been proposed both, as a biological underpinning of mood disorder and as a target for rapid-acting antidepressant treatments. Total sleep deprivation and light therapy (TSD + LT) can prompt antidepressant response in drug-resistant bipolar depression. Here we explored the effects of TSD + LT on dorsolateral prefrontal cortex (DLPFC) glutamate and/or glutamine+glutamate (Glx) levels., Methods: We studied single voxel 1 H-MRS measures of DLPFC Glu and Glx levels of 48 healthy participants and 55 inpatients with a major depressive episode in course of Bipolar Disorder, a subset of which (N = 23) underwent three cycles of repeated TSD + LT and were evaluated before and after treatment. Treatment effects of mood and on Glu and Glx concentrations were analyzed in the context of the Generalized Linear Model (GLM), correcting for age, sex and ongoing lithium treatment., Results: Higher concentration of Glu (adjusted Z = -2189, p = 0,0285) and Glx (adjusted Z = -3,13, p = 0,0017) were observed in BD patients compared to HC. Treatment caused a significant rapid reduction of depressive symptom severity over time (F = 63.98, p < 0.01). Change in depression levels after TSD + LT treatment was significantly influenced by delta change in Glu levels (LR χ 2  = 4.619, p = 0.0316) and in Glx levels (LR χ 2  = 4.486, p = 0.0341)., Conclusion: A reduction in Glu and Glx levels associated with depression could contribute to the mechanism of action of TSD + LT, directly acting on glutamatergic neurons, or to the interaction between the glutamatergic system and dopamine (DA) and serotonin (5-HT) levels, known to be targeted by TSD. This is in line with several studies showing a glutamatergic modulation effects of antidepressants and mood stabilizing agents. This finding deepens our understanding of antidepressant effect of chronoterapeutics., Competing Interests: Declaration of Competing Interest The authors of this paper report no biomedical financial interests or other potential conflicts of interest. All authors have approved the final article., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The aim of this study is to objectively evaluate sleep architecture changes of depressed bipolar subjects treated with chronoterapeutics. Eleven depressed bipolar inpatients received 3 cycles of Total Sleep Deprivation, followed by daily light therapy sessions for one week. Polysomnography was performed before and after the treatment. Depressive symptoms significantly reduced, and sleep architecture changed with significant differences in N2% and N3% and REM density. Change in N3% was also positively correlated to depressive symptoms reduction. Although, previous studies reported sleep architecture changes after chronoterapeutics in unipolar depression, this is the first study to demonstrate changes also in bipolar depressed subjects., Competing Interests: Declaration of Competing Interest The authors report no conflict of interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). The aim of the study was to evaluate changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG)., Methods: We conducted a randomized controlled trial in which women aged ≥ 40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. We analysed changes in BMD at the hip and lumbar spine from baseline to week 96 using linear regression, and markers of bone turnover and kidney function using repeated measures mixed effects models with multiple imputation for missing data. We conducted exploratory analyses of weight, mental health, sleep and symptoms attributed to HIV infection and antiretroviral therapy., Results: Ninety-one women [mean (standard deviation) age 50.4 (6.6) years] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in BMD at the lumbar spine (but not the neck of the femur or the total hip), bone resorption markers and proteinuria (total protein, albumin and retinol-binding protein) and modest weight gain without changes in body mass index. Although mean anxiety, depression and sleep scores did not differ between the two study arms, anxiety, depression and sleep disturbance at baseline predicted ABC/3TC/DTG discontinuation for neuropsychiatric side effects [odds ratios (95% confidence intervals) 11.9 (2.0-71.6), 16.0 (2.6-97.9) and 10.0 (1.8-56.0), respectively]., Conclusions: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG improved the BMD of the lumbar spine and kidney function. These benefits need to be balanced against modest weight gain and the need for antiretroviral therapy substitutions in a proportion of participants., (© 2021 British HIV Association.)

Objectives: We performed a randomized single-blinded study to assess the superiority of the combination strategy of repetitive Transcranial Magnetic Stimulation (rTMS) and Bright Light Therapy (BLT) over rTMS treatment alone in reducing depressive symptoms in treatment-resistant depression (TRD). Methods: We enrolled 80 inpatients with a diagnosis of TRD. All patients were randomly assigned into two groups: group A was treated with rTMS, compared to group B treated with a combination of rTMS and BLT. Depressive symptoms were weekly assessed (T0, T1, T2, T3) through the 17-item Hamilton depression rating scale (HDRS-17). Results: rANOVA (F=2.766, p=0.043) and post-hoc in HDRS-17 showed significant better scores in favour of group B every week (p<0.025, T1: 22.075 vs 17.200; T2: 16.100 vs 12.775; T3: 12.225 vs 8.900). Conclusions: The antidepressant effect of rTMS was enhanced and accelerated by its combination with BLT in treating resistant depression.KEYPOINTSAlmost one third of depressed patients does not respond to antidepressants; emerging neuromodulation and chronobiological techniques are effective antidepressant augmentation treatments.The aim of this study was to assess the superiority of the combination strategy of Light Therapy and TMS over TMS treatment alone in a group of treatment resistant depressed patients.The implication of this study in clinical practice is that a safe, low risk and cost-effective treatment, as Light Therapy, improves and accelerates the antidepressant effect of TMS.

Background: Proximal renal tubulopathy (PRT) is an infrequent complication of tenofovir disoproxil fumarate (TDF). It remains to be established whether tenofovir alafenamide (TAF) can be safely administered to individuals who experienced PRT on TDF., Methods: Individuals with a history of TDF-associated PRT and current estimated glomerular filtration rate (eGFR) over 30 mL/min/1.73 m2 initiated TAF and were followed for 96 weeks. The primary outcome of interest was recurrent PRT. Secondary outcomes were changes in kidney biomarkers, bone biomarkers, and bone mineral density (BMD). Data were analyzed using multilevel mixed-effects linear regression models. The trial was registered under EudraCT 2016-003345-29., Results: All 31 participants [median age 55 (inter-quartile range 51, 60) years, 97% men, 87% White ethnicity] remained on TAF at week 96, and none developed glycosuria or recurrent PRT. Participants experienced small declines in eGFR-creatinine [-1.9 (95% confidence interval: -3.5 to -0.3) mL/min/1.73 m2/yr; P = 0.024], but not in eGFR-cystatin C [-0.9 (-2.1 to 0.4) mL/min/1.73 m2/yr; P = 0.16]. Ten (32%) and 5 (16%) participants experienced rapid (>5 mL/min/1.73 m2/yr) decline in eGFR-creatinine and eGFR-cystatin C. No significant change in other kidney biomarkers, bone turnover, or BMD was observed (P > 0.2)., Conclusions: In individuals with a history of PRT on TDF, 96 weeks of TAF was not associated with recurrent PRT or adverse effects on renal tubular function, bone turnover, or BMD. These data suggest that TAF is a treatment option for this vulnerable population., Competing Interests: L.H. reports personal fees from Gilead Sciences; R.J. reports personal fees from Gilead Sciences, ViiV Healthcare, Janssen Pharmaceuticals and MSD outside the submitted work; A.W. reports research grants, honoraria, or speaker fees from ViiV Healthcare, Janssen, Gilead Sciences, and BMS; F.A.P. reports grants and personal fees from Gilead Sciences, grants and personal fees from ViiV Healthcare, and grants and personal fees from MSD outside the submitted work. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Mood disorders associate with peripheral markers of low-grade inflammation, among which circulating levels of interleukin-1β (IL-1β) consistently predict diagnosis and poor outcomes. Antidepressant chronotherapeutics (total sleep deprivation and light therapy, TSD+LT) prompts response in drug-resistant bipolar depression, but its effect on peripheral inflammation were never assessed. Here we explored the effects of TSD+LT on IL-1β signaling., Methods: We studied the ratio between IL-1β and its receptor antagonist (IL-1β:IL1ra) in 33 healthy participants, and in 26 inpatients with a major depressive episode in course of Bipolar Disorder, before and after treatment with three cycles of repeated TSD+LT, interspersed with sleep recovery nights, administered during 1 week. Treatment effects of mood and on IL-1β:IL1ra were analyzed in the context of the Generalized Linear Model (GLM)., Results: At baseline, patients had higher IL-1β, IL1ra, and IL-1β:IL1ra than controls. Treatment significantly decreased IL-1β:IL1ra, by decreasing IL-1β and increasing IL1ra, the effect being proportional to baseline levels and normalizing values. Patients with higher baseline levels showed the highest decrease in IL-1β:IL-1ra, which associated with the immediate antidepressant response at the first cycle; while patients with lower baseline values showed negligible changes in the IL-1β:IL-1ra, unrelated to treatment response., Conclusion: We observed a parallel change of inflammatory biomarkers and severity of depression after chronotherapeutics, suggesting that a reduction in inflammation associated with depression could contribute to the mechanism of action of TSD+LT, and warranting interest for controlled studies addressing the role of inflammation in the recovery from bipolar depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Benedetti, Dallaspezia, Melloni, Lorenzi, Zanardi, Barbini and Colombo.)

Background: Despite the impact of depression in terms of personal suffering and socioeconomic burden, most currently available treatment options are often ineffective. A particularly difficult-to-treat depressive disorder characteristic of the elderly is vascular depression, a late-life depressive syndrome related to a variety of potential vascular mechanisms. Transcranial Direct Current Stimulation (tDCS), a non-invasive and effective somatic approach to depression, also showed positive effects on cognitive deficits., Aim: We performed a double-blind randomized study to investigate the efficacy of tDCS as augmentation strategy to sertraline in the treatment of vascular depression, hypothesizing a positive effect in both depressive symptoms and cognitive functions., Methods: We enrolled 93 inpatients over 60 years of age with a diagnosis of vascular depression. Depressive symptoms were weekly assessed (T0, T1, T2) with the 21-items Hamilton depression rating scale (HDRS). Cognitive functioning was evaluated with the Milan Overall Dementia Assessment (MODA) at baseline and after the treatment protocol. All patients were randomly assigned into three groups, Group I: one tDCS stimulation per day, Group II: two tDCS stimulations per day, Sham group: one sham tDCS stimulation per day. Stimulation was performed for 10 consecutive working days., Results: A significant interaction time∗treatment was observed on HDRS scores (F = 14, p < 0.001). All groups improved at T1 but whereas Group II significantly differed from the Sham group (p < 0.001) we observed no difference between Sham and Group I. At T2 all groups improved but Group II showed the greater improvement (vs. Sham p < 0.001; vs. Group I p < 0.001) and the Sham group the smallest (vs. Group I p = 0.005). A significant interaction time∗treatment was also observed on MODA scores (F = 3.31, p = 0.04). Only subjects treated with tDCS improved at T2 (Group I: p < 0.001; Group II: p = 0.007). However, no difference between Group I and II was shown., Conclusion: tDCS as augmentation treatment of an adequate pharmacotherapy is a potential strategy in the management of vascular depression, a disease known to be often unresponsive to antidepressants only. Non-invasiveness, the absence of severe side effects and the possibility of administering it to outpatients at an affordable price make tDCS an important tool in clinical practice., Competing Interests: Declaration of competing interest No known conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The spread of COVID-19 throughout Italy, particularly Lombardy, led to adopt quarantine measures, known to exacerbate pre-existing psychiatric conditions. We described a telephone-based surveillance on 101 euthymic Mood Disorder outpatients in Milan by a non-standardized survey to evaluate reactions to lockdown measures and the presence of quarantine stressors. Frustration was the most represented quarantine stressor. Being jobless was significantly related to the presence of frustration, somatization, increased alertness, psychic anxiety and low mood; younger age to the presence of psychic anxiety, alertness and financial concerns. No recurrences were observed at the time of writing., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Diffusion tensor imaging (DTI) measures suggest a widespread alteration of white matter (WM) microstructure in patients with bipolar disorder (BD). The chronotherapeutic combination of repeated total sleep deprivation and morning light therapy (TSD+LT) can acutely reverse depressive symptoms in approximately 60% of patients, and it has been confirmed as a model antidepressant treatment to investigate the neurobiological correlates of rapid antidepressant response., Methods: We tested if changes in DTI measures of WM microstructure could parallel antidepressant response in a sample of 44 patients with a major depressive episode in course of BD, treated with chronoterapeutics for one week. We used both a tract-wise and a voxel-wise approach for the whole-brain extraction of DTI measures of WM microstructure: axial (AD), radial (RD), and mean diffusivity (MD), and fractional anisotropy (FA)., Results: Compared to baseline level, at one-week follow up we observed a significant increase in average FA measures paralleled by a significant decrease in MD measures of several WM tracts including cingulum, corpus callosum, corona radiata, cortico-spinal tract, internal capsule, fornix and uncinate fasciculus. The degree of change was associated to clinical response., Conclusions: This is the first study to show changes of individual DTI measures of WM microstructure in response to antidepressant treatment in BD. Our results add new evidence to warrant a role for chronotherapeutics as a first-line treatment for bipolar depression and contribute identifying generalizable neuroimaging-based biomarkers of antidepressant response., Competing Interests: Declaration of Competing Interest The authors of this paper report no biomedical financial interests or other potential conflicts of interest. All authors have approved the final article., (Copyright © 2020. Published by Elsevier B.V.)

Background and Aim of the Work: electroconvulsive therapy is a psychiatric procedure requiring general anesthesia. The choice of the hypnotic agent is important because the success of the intervention is associated to the occurrence and duration of motor convulsion. However, all available anesthetic agents have anti-convulsant activity. We compared the effect of thiopental and propofol on seizures., Methods: We designed a retrospective study at Mood Disorders Unit of a teaching Hospital. Fifty-six consecutive patients undergoing electroconvulsive therapy were enrolled. Patients received fentanyl followed by either thiopental or propofol. We evaluated the incidence and the duration of seizure after electric stimulus at the first session of electroconvulsive therapy for each patient. Adverse perioperative effects were recorded., Results: Patients were 60±12.1 years old and 64% was female. There was a statistically significant higher number of patients who had motor convulsion activity in the thiopental group when compared to the propofol group (25 vs 13, p=0.023). Seizure duration was statistically significant longer in the thiopental group than in the propofol group (35 sec vs 11 sec, p=0.046). No hemodynamic instability, oxygen desaturation episodes, prolonged recovery time from anesthesia and adverse effects related to anesthesia were recorded., Conclusions: Thiopental induction has a favourable effect on seizure when compared to propofol in patients undergoing electroconvulsive therapy.