The Effects of Radiotherapy on the Sequence and Eligibility of Breast Reconstruction: Current Evidence and Controversy.

Immediate breast reconstruction (IBR) following a mastectomy, combined with radiotherapy, presents a multifaceted approach to breast cancer treatment, balancing oncological safety and aesthetic outcomes. IBR, typically involving the use of implants or autologous tissue, aims to restore breast morphology directly after a mastectomy, minimizing the psychological and physical impacts. However, integrating radiotherapy with IBR is complex due to the potential adverse effects on reconstructed tissues. Radiotherapy, essential for reducing local recurrence, can induce fibrosis, capsular contracture, and compromised aesthetic results. This narrative review covers the current trends in the sequencing of breast reconstruction and radiotherapy. We discuss patient selection, timing of radiotherapy, and reconstructive techniques, with special attention paid to quality-of-life outcomes that are increasingly reported in clinical trials. Emerging evidence supports the feasibility of IBR with careful patient selection and tailored therapeutic approaches, although ongoing research is necessary to refine protocols and enhance outcomes. Overall, IBR in the context of radiotherapy remains a promising but intricate treatment modality, requiring a nuanced balance between cancer control and aesthetic restoration.

Cost-Effectiveness of a Culturally Adapted Manual-Assisted Brief Psychological Intervention for Self-Harm in Pakistan: A Secondary Analysis of the Culturally Adapted Manual-Assisted Brief Psychological Randomized Controlled Trial.

OBJECTIVES: Self-harm is a serious public health problem. A culturally adapted manual-assisted problem-solving training (C-MAP) intervention improved and sustained a reduction in suicidal ideation, hopelessness, and depression compared with treatment as usual (TAU) alone. Here, we evaluate its cost-effectiveness. METHODS: Patients admitted after an episode of self-harm were randomized individually to either C-MAP plus TAU or TAU alone in Karachi. Improvement in health-related quality-adjusted life-years (QALYs) was measured using the EQ-5D with 3 levels instrument at baseline, 3 months, and 6 months after randomization. The primary economic outcome was health service cost per QALY gained as the incremental cost-effectiveness ratio, based on 2019 US$ and a 6-month time horizon. Nonparametric bootstrapping was used to assess uncertainties and sensitivity analysis to examine the impact of hospitalization costs. RESULTS: A total of 108 and 113 participants were enrolled among the intervention and standard arms, respectively. The intervention resulted in 0.04 (95% confidence interval [CI] 0.00-0.08) more QALYs 6 months after enrolment. The mean cost per participant in the intervention arm was $1001 (95% CI 968-1031), resulting in an incremental cost of the intervention of $640 (95% CI 595-679). The incremental cost-effectiveness ratio for the C-MAP intervention versus TAU was $16 254 (95% CI 7116-99 057) per QALY gained. The probability that C-MAP is cost-effective was between 66% and 83% for cost-effective thresholds between $20 000 and $30 000. Cost-effectiveness results remained robust to sensitivity analyses. CONCLUSIONS: C-MAP may be a valuable self-harm intervention. Further studies with longer follow-up and larger sample sizes are needed to draw reliable conclusions.

Cost-Effectiveness of a Culturally Adapted Manual-Assisted Brief Psychological Intervention for Self-Harm in Pakistan: A Secondary Analysis of the Culturally Adapted Manual-Assisted Problem-Solving Training Randomized Controlled Trial.

OBJECTIVES: Self-harm is a serious public health problem. A culturally adapted manual-assisted problem-solving training (C-MAP) intervention improved and sustained the reduction in suicidal ideation, hopelessness, and depression compared with treatment as usual (TAU) alone. Here, we evaluate its cost-effectiveness. METHODS: Patients admitted after an episode of self-harm were randomized individually to either C-MAP plus TAU or TAU alone in Karachi. Improvement in health-related quality-adjusted life years (QALYs) was measured using the Euro Qol-5D-3L instrument at baseline and at 3 months and 6 months after randomization. The primary economic outcome was health service cost per QALY gained as the incremental cost-effectiveness ratio, based on 2019 US dollars and a 6-month time horizon. Nonparametric bootstrapping was used to assess uncertainties, and sensitivity analysis to examine the impact of hospitalization costs. RESULTS: A total of 108 and 113 participants were enrolled among the intervention and standard arms, respectively. The intervention resulted in 0.04 more QALYs (95% confidence interval [CI] 0.00-0.08) 6 months after enrolment. The mean cost per participant in the intervention arm was US $1001 (95% CI 968-1031), resulting in an incremental cost of the intervention of US $640 (95% CI 595-679). The incremental cost-effectiveness ratio for the C-MAP intervention versus TAU was US $16 254 (95% CI 7116-99 057) per QALY gained. The probability that C-MAP is cost-effective was between 66% and 83% for cost-effective thresholds between US $20 000 and US $30 000. Cost-effectiveness results remained robust to sensitivity analyses. CONCLUSIONS: C-MAP may be a valuable self-harm intervention. Further studies with longer follow-up and larger sample sizes are needed to draw reliable conclusions.

Demographic and psychosocial characteristics of self-harm: The Pakistan perspective.

Self-harm is a major public health issue in Pakistan, yet the characteristics of those who self-harm are under-explored. This is a secondary analysis from a large randomized control trial on the prevention of self-harm, exploring demographic, clinical and psychological characteristics of people who self-harm in Pakistan. A total of 221 participants with a history of self-harm were recruited from medical wards of three major hospitals in Karachi. The Beck Scale for Suicidal Ideation (BSI), Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), and Suicide Attempt Self Injury Interview (SASII) assessment scales were completed. The sample consisted predominantly of females (68.8%) in their 20's. Interpersonal difficulties were most commonly reported as the main antecedent to the self-harm, followed by financial difficulties. Participants had high severity scores on BSI, BDI and BHS. Pesticide and insecticide use were (n = 167, 75.6%) the most common methods of self-harm. The findings indicate that some characteristics of those who self-harm in Pakistan are comparable to other populations. This may raise the possibility of common causal mechanisms and processes. Future research needs to examine the efficacy of interventions targeting these risk factors in reducing rates of self-harm and thus suicide.

SCN10A/Nav1.8 modulation of peak and late sodium currents in patients with early onset atrial fibrillation.

AIMS: To test the hypothesis that vulnerability to atrial fibrillation (AF) is associated with rare coding sequence variation in the SCN10A gene, which encodes the voltage-gated sodium channel isoform NaV1.8 found primarily in peripheral nerves and to identify potentially disease-related mechanisms in high-priority rare variants using in-vitro electrophysiology. METHODS AND RESULTS: We re-sequenced SCN10A in 274 patients with early onset AF from the Vanderbilt AF Registry to identify rare coding variants. Engineered variants were transiently expressed in ND7/23 cells and whole-cell voltage clamp experiments were conducted to elucidate their functional properties. Resequencing SCN10A identified 18 heterozygous rare coding variants (minor allele frequency ≤1%) in 18 (6.6%) AF probands. Four probands were carriers of two rare variants each and 14 were carriers of one coding variant. Based on evidence of co-segregation, initial assessment of functional importance, and presence in ≥1 AF proband, three variants (417delK, A1886V, and the compound variant Y158D-R814H) were selected for functional studies. The 417delK variant displayed near absent current while A1886V and Y158D-R814H exhibited enhanced peak and late (INa-L) sodium currents; both Y158D and R818H individually contributed to this phenotype. CONCLUSION: Rare SCN10A variants encoding Nav1.8 were identified in 6.6% of patients with early onset AF. In-vitro electrophysiological studies demonstrated profoundly altered function in 3/3 high-priority variants. Collectively, these data strongly support the hypothesis that rare SCN10A variants may contribute to AF susceptibility.

Detecting maternal depression in a low-income country: comparison of the self-reporting questionnaire and the edinburgh postnatal depression scale.

OBJECTIVE: To validate the Self-Reporting Questionnaire (SRQ-20) and the Edinburgh Postnatal Depression Scale (EPDS) against the Clinical Interview Schedule-Revised (CIS-R). DESIGN: Two-phase design. SUBJECTS AND METHODS: 664 mothers were approached, 601 of them completed the EPDS and SRQ questionnaires. The CIS-R was administered to confirm the diagnosis for depression. The diagnostic accuracy was compared using the receiver operating characteristic analysis. RESULTS: At the threshold of 11, the SRQ had better sensitivity, negative predictive values and positive predictive values compared with the EPDS optimal threshold of 14. CONCLUSION: Both measures (EPDS and SRQ) have adequate validity to screen for depression in mothers in Pakistan. However, the SRQ performed better, with participants finding it easy to understand. The scales can be of great value to detect maternal depression in primary care and pediatric settings in low-income countries.