Destructive Groups: The Role of Projective Identification in Suicidal Groups of Young People

Group suicidal behaviour by young people has been attracting increasing worldwide attention, but the subject has rarely been studied from a clinical or psychodynamic perspective. Although etiological factors are not well understood, unconscious as well as conscious group processes likely contribute to self-destructive actions. In this article we discuss the role of projective identification in the development of suicidal behavior by individuals who are part of a destructive group. We consider how these factors may operate, illustrated through a case description of a young man involved with a group of high school students that included at least four who made serious suicide attempts. Recognition and understanding of these forms of communication have important implications for clinical practice and suicide prevention

Psychodynamic psychotherapy with suicidal adolescents

Although the treatment of suicidal adolescents is complex and may be daunting to many clinicians, it continues to play an important role in suicide prevention. In this paper we use case material to address questions that arise in psychotherapy, including the contending priorities of understanding the suicidal act in order to prevent repetition, versus connecting emotionally with the patient in the therapeutic relationship; and the use of an evolving understanding of the complexity of suicide that develops over time as patient and therapist engage in a deepening relationship which fosters life-sustaining development and psychic change. We present a case description of a patient in later adolescence, who began intensive psychoanalytic psychotherapy after a suicide attempt and explore key components of therapeutic action. From this discussion we emphasise the relational aspects of the transference and countertransference that enables interpretation and increased therapeutic receptivity through collaborative interaction. We conclude that collaborative interaction is foundational for therapeutic action with suicidal adolescents

Short-Term Psychodynamic Psychotherapy in Patients with “Male Depression” Syndrome, Hopelessness, and Suicide Risk: A Pilot Study

Objectives and Methods. This was an observational study of the efficacy of short-term psychodynamic psychotherapy (STPP) in a sample of 35 (30 women and 5 men) patients with moderate-to-severe “male depression” (Gotland Scale for Male Depression (GSMD) ≥ 13) comorbid with unipolar mood disorder (dysthymia and major depression) or anxiety disorder. Outcome measures were GSMD and BHS (Beck Hopelessness Scale) score changes from baseline. Results:. Patients had a strong response to STPP on the GSMD (estimated mean score change (± SE) = −9.08 ± 2.74; P < 0.01; partial eta squared = 0.50), but not on the BHS (estimated mean score change (± SE) = −0.92 ± 1.55; P = 0.57; partial eta squared = 0.03). BHS score changes were significantly associated with GSMD score changes (Pearson's r = 0.56; P < 0.001), even when controlling for the severity of hopelessness at the baseline (partial r = 0.62; P < 0.001). Conclusions:. STPP proved to be effective in patients suffering from “male depression” although hopelessness was only marginally reduced by this treatment which points to the need to better understand how STPP can be involved in the reduction of suicide risk

The effectiveness of psychoanalytic/psychodynamic psychotherapy for reducing suicide attempts and self-harm: systematic review and meta-analysis

Background: Preventing suicide and self-harm is a global health priority. Although there is a growing evidence base for the effectiveness of psychoanalytic and psychodynamic psychotherapies for a range of disorders, to date there has been no systematic review of its effectiveness in reducing suicidal and self-harming behaviours. Aims: To systematically review randomised controlled trials of psychoanalytic and psychodynamic psychotherapies for suicidal attempts and self-harm. Method: We searched PubMed, PsycINFO, Psycharticles, CINAHL, EMBASE and the Cochrane Central Register of Controlled Trials for randomise controlled trials of psychoanalytic and psychodynamic psychotherapies for reducing suicide attempts and self-harm. Results: Twelve trials (17 articles) were included in the meta-analyses. Psychoanalytic and psychodynamic therapies were effective in reducing the number of patients attempting suicide (pooled odds ratio, 0.469; 95% CI 0.274–0.804). We found some evidence for significantly reduced repetition of self-harm at 6-month but not 12-month follow-up. Significant treatment effects were also found for improvements in psychosocial functioning and reduction in number of hospital admissions. Conclusions: Psychoanalytic and psychodynamic psychotherapies are indicated to be effective in reducing suicidal behaviour and to have short-term effectiveness in reducing self-harm. They can also be beneficial in improving psychosocial well-being. However, the small number of trials and moderate quality of the evidence means further high-quality trials are needed to confirm our findings and to identity which specific components of the psychotherapies are effective. Declaration of interest: None

Safety and immunogenicity of a novel 10-valent pneumococcal conjugate vaccine candidate in adults, toddlers, and infants in The Gambia-Results of a phase 1/2 randomized, double-blinded, controlled trial.

BACKGROUND: A more affordable pneumococcal conjugate vaccine (PCV) that provides comparable protection to current PCVs is needed to ensure sustainable access in resource-limited settings. Serum Institute of India Pvt. Ltd.'s PCV candidate (SIIPL-PCV) has the potential to meet this need as manufacturing efficiency has been optimized and the vaccine targets the most prevalent disease-causing serotypes in Africa and Asia. We report SIIPL-PCV's safety, tolerability, and immunogenicity in adults, toddlers, and infants in The Gambia. METHODS: This phase 1/2, randomized, double-blind trial sequentially enrolled 34 PCV-naive adults (18-40?years old), 112 PCV (Prevenar 13® [PCV13])-primed toddlers (12-15?months old), and 200 PCV-naive infants (6-8?weeks old), who were randomized (1:1) to receive SIIPL-PCV or a licensed comparator vaccine. Infants received three-doses of SIIPL-PCV or PCV13 at 6, 10, and 14?weeks of age co-administered with routine Expanded Program on Immunization (EPI) vaccines. Reactogenicity was solicited through seven-days post-vaccination; unsolicited adverse events (AEs) were assessed throughout the study. The safety and immunogenicity of a matching booster at 10-14?months of age were evaluated in a subset of 96 infants. Immune responses were evaluated post-primary and pre- and post-booster vaccinations. RESULTS: Reactogenicity was primarily mild-to-moderate in severity. In infants, the most common solicited reactions were injection-site tenderness and fever, with no meaningful treatment-group differences. There were no serious or severe vaccine-related AEs and no meaningful trends in SAEs, vaccine-related AEs, or overall AEs. Infant post-primary seroresponse rates (IgG level???0.35?µg/mL) were ?89% for all serotypes except 6A (79%) in the SIIPL-PCV group. IgG GMCs were >1?µg/mL for all serotypes in both SIIPL-PCV and PCV13 groups. Post-booster GMCs were comparable between groups. CONCLUSION: SIIPL-PCV was well-tolerated, had an acceptable safety profile, and was immunogenic for all vaccine serotypes. Results support the evaluation of SIIPL-PCV in a phase 3 non-inferiority trial. Clinicaltrials.gov: NCT02308540

Risk of colorectal cancer for carriers of mutations in MUTYH, with and without a family history of cancer

We studied 2332 individuals with monoallelic mutations in MUTYH among 9504 relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We estimated CRC risks through 70 years of age of 7.2% for male carriers of monoallelic mutations (95% confidence interval [CI], 4.6%-11.3%) and 5.6% for female carriers of monoallelic mutations (95% CI, 3.6%-8.8%), irrespective of family history. For monoallelic MUTYH mutation carriers with a first-degree relative with CRC diagnosed by 50 years of age who does not have the MUTYH mutation, risks of CRC were 12.5% for men (95% CI, 8.6%-17.7%) and 10% for women (95% CI, 6.7%-14.4%). Risks of CRC for carriers of monoallelic mutations in MUTYH with a first-degree relative with CRC are sufficiently high to warrant more intensive screening than for the general population

Natural and hybrid immunity following four COVID-19 waves: A prospective cohort study of mothers in South Africa

BACKGROUND: More than half the global population has been exposed to SARS-CoV-2. Naturally induced immunity influences the outcome of subsequent exposure to variants and vaccine responses. We measured anti-spike IgG responses to explore the basis for this enhanced immunity. METHODS: A prospective cohort study of mothers in a South African community through ancestral/beta/delta/omicron SARS-CoV-2 waves (March 2020-February 2022). Health seeking behaviour/illness were recorded and post-wave serum samples probed for IgG to Spike (CoV2-S-IgG) by ECLISA. To estimate protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter for unvaccinated and vaccinated adults. FINDINGS: Despite little disease, 176/339 (51·9%) participants were seropositive following wave 1, rising to 74%, 89·8% and 97·3% after waves 2, 3 and 4 respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection with the greatest protection for beta and least for omicron. Vaccination induced higher CoV2-S-IgG in seropositive compared to naïve vaccinees. Amongst seropositive participants, proportions above the 50% protection against infection threshold were 69% (95% CrI: 62, 72) following 1 vaccine dose, 63% (95% CrI: 63, 75) following 2 doses and only 11% (95% CrI: 7, 14) in unvaccinated during the omicron wave. INTERPRETATION: Naturally induced CoV2-S-IgG do not achieve high enough levels to prevent omicron infection in most exposed individuals but are substantially boosted by vaccination leading to significant protection. A single vaccination in those with prior immunity is more immunogenic than 2 doses in a naïve vaccinee and may provide adequate protection. FUNDING: UK NIH GECO award (GEC111), Wellcome Trust Centre for Infectious Disease Research in Africa (CIDRI), Bill & Melinda Gates Foundation, USA (OPP1017641, OPP1017579) and NIH H3 Africa (U54HG009824, U01AI110466]. HZ is supported by the SA-MRC. MPN is supported by an Australian National Health and Medical Research Council Investigator Grant (APP1174455). BJQ is supported by a grant from the Bill and Melinda Gates Foundation (OPP1139859). Stefan Flasche is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant number 208812/Z/17/Z)

Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: A Prospective Cohort Study

To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P < .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P < .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P < .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P < .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P = .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P = .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P = .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P = .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P = .97). We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives

Immunogenicity and safety of a 10-valent pneumococcal conjugate vaccine administered as a 2 + 1 schedule to healthy infants in The Gambia: a single-centre, double-blind, active-controlled, randomised, phase 3 trial.

BACKGROUND: Three pneumococcal conjugate vaccines (PCVs) are currently licensed and WHO prequalified for supply by UN agencies. Here, we aimed to investigate the safety and immunogenicity of SIIPL-PCV compared with PHiD-CV and PCV13, when administered to infants according to a 2 + 1 schedule. METHODS: This single-centre, double-blind, active-controlled, randomised, phase 3 trial was done in Medical Research Council Unit The Gambia at the London School of Hygiene & Tropical Medicine clinical trial facilities within two government health centres in the western region of The Gambia. Healthy, PCV-naive infants aged 6-8 weeks were enrolled if they weighed at least 3·5 kg and had no clinically significant health complaints, as determined by history and clinical examination. Eligible infants were randomly assigned (1:1:1) to receive either SIIPL-PCV, PHiD-CV, or PCV13 using permuted blocks of variable size. Parents and the trial staff assessing all study outcomes were masked to vaccine group. The first PCV vaccine was given with other routine Expanded Programme on Immunization vaccines when infants were aged 6-8 weeks (visit 1). At visit 2, routine vaccines alone (without a PCV) were administered. At visit 3, the second dose of the PCV was administered alongside other routine vaccines. At visit 4, a blood sample was collected. Visits 1-4 took place at intervals of 4 weeks. The booster PCV was administered at age 9-18 months (visit 5), with final follow-up 4 weeks after the booster (visit 6). The primary immunogenicity outcome compared the serotype-specific IgG geometric mean concentrations (GMCs) generated by SIIPL-PCV with those generated by PHiD-CV and PCV13, 4 weeks after the booster. We used descriptive 95% CIs without adjustment for multiplicity. Immunogenicity analyses were done in the per protocol population (defined as all children who received all the assigned study vaccines, who had an immunogenicity measurement available, and who had no protocol deviations that might interfere with the immunogenicity assessment). This trial was registered with the Pan African Clinical Trials Registry, PACTR201907754270299, and ClinicalTrials.gov, NCT03896477. FINDINGS: Between July 18 and Nov 14, 2019, 745 infants were assessed for study eligibility. Of these, 85 infants (11%) were ineligible and 660 (89%) were enrolled and randomly assigned to receive SIIPL-PCV (n=220), PHiD-CV (n=220), or PCV13 (n=220). 602 infants (91%) were included in the per protocol immunogenicity population. The median age at vaccination was 46 days (range 42-56). 342 infants (52%) were female and 318 (48%) were male. Post-booster serotype-specific IgG GMCs generated by SIIPL-PCV ranged from 1·54 μg/mL (95% CI 1·38-1·73) for serotype 5 to 12·46 μg/mL (11·07-14·01) for serotype 6B. Post-booster GMCs against shared serotypes generated by PHiD-CV ranged from 0·80 μg/mL (0·72-0·88) for serotype 5 to 17·31 μg/mL (14·83-20·20) for serotype 19F. Post-booster GMCs generated by PCV13 ranged from 2·04 μg/mL (1·86-2·24) for serotype 5 to 15·54 μg/mL (13·71-17·60) for serotype 6B. Post-booster IgG GMCs generated by SIIPL-PCV were higher than those generated by PHiD-CV for seven of the eight shared serotypes (1, 5, 6B, 7F, 9V, 14, and 23F). The GMC generated by serotype 19F was higher after PHiD-CV. The SIIPL-PCV to PHiD-CV GMC ratios for shared serotypes ranged from 0·64 (95% CI 0·52-0·79) for serotype 19F to 2·91 (2·47-3·44) for serotype 1. The serotype 1 GMC generated by SIIPL-PCV was higher than that generated by PCV13, whereas serotype 5, 6A, 19A, and 19F GMCs were higher after PCV13. The SIIPL-PCV to PCV13 GMC ratios ranged from 0·72 (0·60-0·87) for serotype 19A to 1·44 (1·23-1·69) for serotype 1. INTERPRETATION: SIIPL-PCV was safe and immunogenic when given to infants in The Gambia according to a 2 + 1 schedule. This PCV is expected to provide similar protection against invasive and mucosal pneumococcal disease to the protection provided by PCV13 and PHiD-CV, for which effectiveness data are available. Generating post-implementation data on the impact of SIIPL-PCV on pneumococcal disease endpoints remains important. FUNDING: Bill & Melinda Gates Foundation