Personal and relational changes following deep brain stimulation for treatment-resistant depression: A prospective qualitative study with patients and caregivers.

OBJECTIVE: Deep brain stimulation (DBS) and whether it alters patient personality is a much-debated topic within academic literature, yet rarely explored with those directly involved. This study qualitatively examined how DBS for treatment-resistant depression impacts patient personality, self-concept, and relationships from the perspectives of both patients and caregivers. METHODS: A prospective qualitative design was used. Eleven participants were included (six patients, five caregivers). Patients were enrolled in a clinical trial of DBS of the bed nucleus of the stria terminalis. Semi-structured interviews were conducted with participants before DBS-implantation and 9-months after stimulation-initiation. The 21 interviews were thematically analysed. RESULTS: Three primary themes were identified: (a) impact of mental illness and treatment on self-concept; (b) device acceptability and usability, and (c) relationships and connection. Severe refractory depression had profoundly impacted who patients were, how they viewed themselves, and the quality and functioning of their relationships. Patients who benefited from DBS felt reconnected with their premorbid self, yet still far from their ideal self. While reductions in depression were broadly beneficial for relationships, the process of adjusting relationship dynamics created new challenges. All patients reported recharging difficulties and challenges adapting to the device. CONCLUSIONS: Therapeutic response to DBS is a gradual and complex process that involves an evolving self-concept, adjusting relationship dynamics, and growing connection between body and device. This is the first study to provide in-depth insight into the lived experience of DBS for treatment-resistant depression. Patient and caregiver narrative accounts should be routinely collected to guide more person-centred DBS clinical interventions.

"Nothing to Lose, Absolutely Everything to Gain": Patient and Caregiver Expectations and Subjective Outcomes of Deep Brain Stimulation for Treatment-Resistant Depression.

Background: How "success" is defined in clinical trials of deep brain stimulation (DBS) for refractory psychiatric conditions has come into question. Standard quantitative psychopathology measures are unable to capture all changes experienced by patients and may not reflect subjective beliefs about the benefit derived. The decision to undergo DBS for treatment-resistant depression (TRD) is often made in the context of high desperation and hopelessness that can challenge the informed consent process. Partners and family can observe important changes in DBS patients and play a key role in the recovery process. Their perspectives, however, have not been investigated in research to-date. The aim of this study was to qualitatively examine patient and caregivers' understanding of DBS for TRD, their expectations of life with DBS, and how these compare with actual experiences and outcomes. Methods: A prospective qualitative design was adopted. Semi-structured interviews were conducted with participants (six patients, five caregivers) before DBS-implantation and 9-months after stimulation initiation. All patients were enrolled in a clinical trial of DBS of the bed nucleus of the stria terminalis. Interviews were thematically analyzed with data saturation achieved at both timepoints. Results: Two primary themes identified were: (1) anticipated vs. actual outcomes, and (2) trial decision-making and knowledge. The decision to undergo DBS was driven by the intolerability of life with severe depression coupled with the exhaustion of all available treatment options. Participants had greater awareness of surgical risks compared with stimulation-related risks. With DBS, patients described cognitive, emotional, behavioral and physical experiences associated with the stimulation, some of which were unexpected. Participants felt life with DBS was like "a roller coaster ride"-with positive, yet unsustained, mood states experienced. Many were surprised by the lengthy process of establishing optimum stimulation settings and felt the intervention was still a "work in progress." Conclusion: These findings support existing recommendations for iterative informed consent procedures in clinical trials involving long-term implantation of neurotechnology. These rich and descriptive findings hold value for researchers, clinicians, and individuals and families considering DBS. Narrative accounts capture patient and family needs and should routinely be collected to guide patient-centered approaches to DBS interventions.

"He's Back so I'm Not Alone": The Impact of Deep Brain Stimulation on Personality, Self, and Relationships in Parkinson's Disease.

Deep brain stimulation (DBS) for Parkinson's disease successfully alleviates motor symptoms, but unanticipated changes in personality, self, and relationships can occur. Little is known about how these nonmotor outcomes affect patients and families. We prospectively examined the experience and meaning of DBS-related changes in personality and self for patients and caregivers. In-depth, semi-structured interviews were conducted with 22 participants (11 patient-caregiver dyads) before and 9 months after DBS and analyzed using thematic analysis. We identified three themes present prior to DBS that reflected a time of anticipation, while three themes present after DBS reflected a process of adjustment. Participants noted both positive and negative personality changes, with some, but not all, attributing them to the stimulation. The risk of stimulation-related personality change should be weighed against the procedure's motor benefits and considered in the context of disease- and medication-related personality changes. Clinical implications including perioperative education and follow-up management are discussed.

The influence of endogenous estrogen on high-frequency prefrontal transcranial magnetic stimulation.

BACKGROUND: The use of repetitive transcranial magnetic stimulation (rTMS) as both therapeutic and experimental tools has grown enormously over the past decade. However, variability in response to rTMS is one challenge that remains to be solved. Estrogen can impact neural plasticity and may also affect plastic changes following rTMS. The present study investigated whether estrogen levels influence the neurophysiological effects of high-frequency (HF) rTMS in the left dorsolateral prefrontal cortex (DLPFC). HYPOTHESIS: It was hypothesised that individuals with higher endogenous estrogen would demonstrate greater rTMS-induced changes in cortical reactivity. METHODS: 29 healthy adults (15M/14F) received HF-rTMS over left DLPFC. Females attended two sessions, one during a high-estrogen (HE) phase of the menstrual cycle, another during a low-estrogen (LE) phase. Males attended one session. Estrogen level was verified via blood assay. TMS-EEG was used to probe changes in cortical plasticity and comparisons were made using cluster-based permutation statistics and Bayesian analysis. RESULTS: In females, a significant increase in TMS-evoked P60 amplitude, and decrease in N45, N100 and P180 amplitudes was observed during HE. A less pervasive pattern of change was observed during LE. No significant changes in TEPs were seen in males. Between-condition comparisons revealed higher likelihood of the change in N100 and/or P180 being larger in females during HE compared to both females during LE and males. CONCLUSIONS: These preliminary findings indicate that a greater neuroplastic response to prefrontal HF-rTMS is seen in women when estrogen is at its highest compared to men, suggesting that endogenous estrogen levels contribute to variability in response to HF-rTMS.

Improving Response Rates and Representation of Hard-to-Reach Groups in Family Experience Surveys.

OBJECTIVE: Most US hospitals conduct patient experience surveys by mail or telephone after discharge to assess patient/family centeredness of care. Pediatric response rates are usually very low, especially for black, Latino, and low-income respondents. We investigated whether day of discharge surveying using tablets improves response rates and respondent representativeness. METHODS: This was a quasi-experimental study of parents of patients discharged from 4 units of a children's hospital. Parents were assigned to receive the Child Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) via an audio-enabled tablet before discharge or via mail at approximately 1 week postdischarge. Intervention and control conditions alternated by week. We compared response rates, child/respondent characteristics, and mean top-box scores between tablet and mail only arms. RESULTS: Administering Child HCAHPS on a tablet was administratively feasible and did not interfere with the discharge process (median completion time, 12.4 minutes). The response rate was 71.1% (424 of 596) for tablet versus 16.3% (96 of 588) for mail only. Although the tablet response rate was higher in every subgroup, tablet respondents were more likely to be fathers (20.4% vs 6.4%; P = .006), more likely to have a high school education or less (17.5% vs 8.4%; P = .002), less likely to be white (56.8% vs 71.9%; P = .006), and more likely to be publicly insured (31.4% vs 19.8%; P = .02). Tablet scores were significantly higher than mail only scores for 3 of 17 measures. CONCLUSIONS: The response rate for day of discharge tablet survey administration was >4-fold higher than with single-wave mail-only administration, with greater participation of hard-to-reach groups. These findings suggest tablet administration before discharge shows great promise for real-time feedback and QI and may transform the field of inpatient survey administration.

The influence of endogenous estrogen on transcranial direct current stimulation: A preliminary study.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique. Responses to tDCS differ substantially between individuals. Sex hormones that modulate cortical excitability, such as estrogen, may contribute to this inter-individual variability. The influence of estrogen on tDCS after-effects has not yet been researched. This study aimed to investigate whether endogenous estrogen levels influence cortical response to tDCS. Data from 15 male and 14 female healthy adults were analyzed. Males completed one experimental session. Females completed two, one during the early follicular phase of the menstrual cycle when estrogen was low, one during the mid-luteal phase when estrogen was high. Each session comprised 15-min of anodal tDCS delivered to the left dorsolateral prefrontal cortex (DLPFC). Response to stimulation was assessed using electroencephalography with DLPFC transcranial magnetic stimulation (TMS) administered before, immediately after, and 20-min after tDCS. Changes in amplitudes of N120 and P200 components of TMS-evoked potentials over time were compared between males, women with low estrogen and women with high estrogen. Blood assays verified estrogen levels. Women with high estrogen demonstrated a significant increase in P200 amplitude at both time points and change over time was greater for the high estrogen group compared with males. No significant differences were observed between males and women with low estrogen, or between women with low and high estrogen. These preliminary results indicate that greater neuroplastic response to DLPFC tDCS is seen in highest compared with lowest estrogen states, suggesting that endogenous estrogen levels contribute to inter-individual variability of tDCS outcomes.

Standards of practice, professional judgment, and scientific evidence to establish and extend a beyond-use date.

The establishment of both a beyond-use date and the extension of a beyond-use date need to be scientifically based. What is accepted as scientific evidence is at times misleading. The pharmacist may have the right to utilize some degree of professional judgment in both establishing and extending a beyond-use date, after a review of appropriate scientific literature. Notwithstanding this scientific review, it is the concept of professional judgment that seemingly needs to be better defined. A new-found appreciation for professional judgment will bring us to the understanding that a validated stability-indicating assay is the correct manner in which to extend a beyond-use date. This article addresses and discusses the recommendations and rigor required to establish and extend a beyond-use date. The perspectives of the pharmacist and physician are explored, as well as the impact of an extended beyond-use date, or lack thereof, are discussed. The application of a set of fundamental principles will be revealed, which will lead to finite conclusions as to the necessary methodology to establish as well as extend a beyond-use date.