Whole-family programmes for families living with parental mental illness: a systematic review and meta-analysis.

Several interventions have been developed to support families living with parental mental illness (PMI). Recent evidence suggests that programmes with whole-family components may have greater positive effects for families, thereby also reducing costs to health and social care systems. This review aimed to identify whole-family interventions, their common characteristics, effectiveness and acceptability. A systematic review was conducted according to PRISMA 2020 guidelines. A literature search was conducted in ASSIA, CINAHL, Embase, Medline, and PsycINFO in January 2021 and updated in August 2022. We double screened 3914 abstracts and 212 papers according to pre-set inclusion and exclusion criteria. The Mixed Methods Appraisal Tool was used for quality assessment. Quantitative and qualitative data were extracted and synthesised. Randomised-control trial data on child and parent mental health outcomes were analysed separately in random-effects meta-analyses. The protocol, extracted data, and meta-data are accessible via the Open Science Framework ( https://osf.io/9uxgp/ ). Data from 66 reports-based on 41 independent studies and referring to 30 different interventions-were included. Findings indicated small intervention effects for all outcomes including children's and parents' mental health (dc = -0.017, -027; dp = -0.14, -0.16) and family outcomes. Qualitative evidence suggested that most families experienced whole-family interventions as positive, highlighting specific components as helpful, including whole-family components, speaking about mental illness, and the benefits of group settings. Our findings highlight the lack of high-quality studies. The present review fills an important gap in the literature by summarising the evidence for whole-family interventions. There is a lack of robust evidence coupled with a great need in families affected by PMI which could be addressed by whole-family interventions. We recommend the involvement of families in the further development of these interventions and their evaluation.

HS3ST2 expression induces the cell autonomous aggregation of tau.

Heparan sulfates have long been known to intracellularly accumulate in Alzheimer's disease neurons, where they colocalize with neurofibrillary tangles made of abnormally phosphorylated and aggregated tau protein. However, the reasons and consequences of the heparan sulfates accumulation in the Alzheimer's cells are not yet well understood. Previously, we showed that the neural heparan sulfate 3-O-sulfotransferase HS3ST2 is critical for the abnormal phosphorylation of tau in Alzheimer's disease-related tauopathy. Using cell models of tauopathy we showed that intracellular 3-O-sulfatated heparan sulfates interact with tau inducing its abnormal phosphorylation. However, it is unknown whether HS3ST2 expression induces the intracellular aggregation of tau in cells. Here, by using replicative pEBV plasmids, we engineered HEK293 cells to stably express HS3ST2 together with human tau carrying or not the P301S mutation. We show that HS3ST2 gain of function induces the cell autonomous aggregation of tau not only in cells expressing tauP301S, but also in cells expressing the wild type tau. Our engineered cells mimicked both the HS intracellular accumulation observed in neurons of Alzheimer's disease and the tau aggregation characteristic of tauopathy development and evolution. These results give evidence that the neural HS3ST2 plays a critical role in the cell autonomous self-aggregation of tau.

A longitudinal, observational study of the features of transitional healthcare associated with better outcomes for young people with long-term conditions.

BACKGROUND: Most evidence about what works in transitional care comes from small studies in single clinical specialties. We tested the hypothesis that exposures to nine recommended features of transitional healthcare were associated with better outcomes for young people with long-term conditions during transition from child-centred to adult-oriented health services. METHODS: This is a longitudinal, observational cohort study in UK secondary care including 374 young people, aged 14-18.9 years at recruitment, with type 1 diabetes (n = 150), cerebral palsy (n = 106) or autism spectrum disorder with an associated mental health problem (n = 118). All were pre-transfer and without significant learning disability. We approached all young people attending five paediatric diabetes centres, all young people with autism spectrum disorder attending four mental health centres, and randomly selected young people from two population-based cerebral palsy registers. Participants received four home research visits, 1 year apart and 274 participants (73%) completed follow-up. Outcome measures were Warwick Edinburgh Mental Wellbeing Scale, Mind the Gap Scale (satisfaction with services), Rotterdam Transition Profile (Participation) and Autonomy in Appointments. RESULTS: Exposure to recommended features was 61% for 'coordinated team', 53% for 'age-banded clinic', 48% for 'holistic life-skills training', 42% for 'promotion of health self-efficacy', 40% for 'meeting the adult team before transfer', 34% for 'appropriate parent involvement' and less than 30% for 'written transition plan', 'key worker' and 'transition manager for clinical team'. Three features were strongly associated with improved outcomes. (1) 'Appropriate parent involvement', example association with Wellbeing (b = 4.5, 95% CI 2.0-7.0, p = 0.001); (2) 'Promotion of health self-efficacy', example association with Satisfaction with Services (b = - 0.5, 95% CI - 0.9 to - 0.2, p = 0.006); (3) 'Meeting the adult team before transfer', example associations with Participation (arranging services and aids) (odds ratio 5.2, 95% CI 2.1-12.8, p < 0.001) and with Autonomy in Appointments (average 1.7 points higher, 95% CI 0.8-2.6, p < 0.001). There was slightly less recruitment of participants from areas with greater socioeconomic deprivation, though not with respect to family composition. CONCLUSIONS: Three features of transitional care were associated with improved outcomes. Results are likely to be generalisable because participants had three very different conditions, attending services at many UK sites. Results are relevant for clinicians as well as for commissioners and managers of health services. The challenge of introducing these three features across child and adult healthcare services, and the effects of doing so, should be assessed.

Quality of life, support and smoking in advanced lung cancer patients: a qualitative study.

BACKGROUND: Lung cancer is the most common cancer and smoking is the principal cause. Due to poor survival rates, symptom palliation and promotion of health-related quality of life (HRQoL) are primary outcomes for lung cancer patients. Given the established relationship between smoking and lung cancer, patients who have smoked may feel stigmatised or guilty after diagnosis, and more pessimistic about their illness and likely outcomes. This may have adverse implications for HRQoL. OBJECTIVES: We explored HRQoL and support experiences among newly diagnosed patients with advanced lung cancer. DESIGN: Semistructured interviews were conducted with nine patients and analysed using interpretative phenomenological analysis. RESULTS: Patients described the physical, emotional and social impact of disease on HRQoL. Fear of compromising their immune system and adjusting to new relationship roles had a wide-ranging effect on patients' HRQoL. Patients acknowledged links between lung cancer and smoking but some continued to smoke. They were sensitive to the opinions of medical staff about smoking especially those who continued to smoke or recently quit. CONCLUSIONS: We conclude that staff should give clearer advice about the adverse implications of continued smoking. We discuss the potential value of diagnosis as a teachable moment for promoting smoking cessation among patients and family members.

Implications of sperm banking for health-related quality of life up to 1 year after cancer diagnosis.

BACKGROUND: Sperm banking is recommended for all men diagnosed with cancer where treatment is associated with risk of long-term gonadatoxicity, to offer the opportunity of fatherhood and improved quality of life. However, uptake of sperm banking is lower than expected and little is known about why men refuse. Our aims were to determine: (i) demographic and medical variables associated with decisions about banking and (ii) differences in quality of life between bankers and non-bankers at diagnosis (Time 1 (T1)) and 1 year later (Time 2 (T2)). METHODS: Questionnaires were completed by 91 men (response rate=86.67%) at T1 and 78 (85.71% response rate) at T2. RESULTS: In all, 44 (56.41%) banked sperm. They were younger and less likely to have children than non-bankers. In a subset of men who were not sure if they wanted children in the future (n=36), 24 banked sperm. Among this group, those who banked were younger, more satisfied with clinic appointments and less worried about the health of future children. At T2, there were no differences in quality of life between bankers and non-bankers. CONCLUSION: For those who are uncertain about future reproductive plans, decisions depend on their health on diagnosis and satisfaction with clinic care. We conclude that extra care should be taken in counselling younger men who may have given little consideration to future parenting. Results support previous findings that the role of the doctor is vital in facilitating decisions, especially for those who are undecided about whether they wanted children in the future or not.

Monitoring fertility (semen analysis) by cancer survivors who banked sperm prior to cancer treatment.

STUDY QUESTION: What medical and psychological variables predict why men with banked sperm do not return for semen analysis after their cancer treatment has ended? SUMMARY ANSWER: Men who decline the offer of semen analysis are less likely to have reported adverse side effects during cancer treatment, and have a more negative experience of banking sperm and a more negative attitude towards disposal of their stored semen than those who attend. WHAT IS KNOWN ALREADY: Previous authors have noted that male cancer survivors seem reluctant to have their fertility tested after their treatment has ended. Moreover, the utilization rates of banked sperm are very low (<10%) and the majority of samples are kept for many years without being used. STUDY DESIGN, SIZE AND DURATION: A cross-sectional study of 499 cancer survivors who were sent a questionnaire about their views on sperm banking, fertility and post-treatment semen analysis between April 2008 and December 2010. PARTICIPANTS AND SETTING: Men (aged 18-55 years) who had banked sperm in Sheffield and Nottingham (UK) prior to gonadotoxic treatment for cancer more than 5 years previously. MAIN RESULTS AND THE ROLE OF CHANCE: Completed questionnaires were received from 193 men (38.7% response rate) whose samples had been banked for 9.18 ± 3.70 years (range = 4.94-26.21) and whose current age was 35.08 ± 7.08 years (range = 21.58-54.34; mean ± SD). One-third (35.8%) had never attended for semen analysis. In multivariate analysis, the odds of not attending for semen analysis were significantly greater among men who did not experience adverse treatment side effects [odds ratio (OR) = 5.72, 95% confidence interval (CI) = 2.10-15.56], who reported a more negative experience of banking sperm (OR = 1.82, 95% CI = 1.17-2.82) and a more negative attitude to disposal of their stored semen (OR = 1.56, 95% CI = 1.01-2.42). LIMITATIONS AND REASONS FOR CAUTION: Only 38.7% of those eligible agreed to take part. We do not know the characteristics of men who declined to take part, if they agreed to attend semen analysis without completing the questionnaire or whether they had chosen to have semen analysis performed elsewhere (e.g. private sector). Some of the measures used (e.g. experience of banking sperm) relied on men's recall of events many years previously. WIDER IMPLICATIONS OF THE FINDINGS: New strategies are required to encourage these men to engage with fertility monitoring programmes if sperm banks are to be used cost-effectively and men are to be given appropriate fertility advice. STUDY FUNDING AND COMPETING INTERESTS: This paper was supported by funding from Cancer Research-UK to C.E., A.A.P. and R.R. (C481/A8141). The views expressed are those of the authors. No competing interests declared.

Finding out about sperm banking: what information is available online for men diagnosed with cancer?

Sperm banking is routinely offered to men where there is a risk of infertility following cancer treatment but uptake is lower than expected. Since these men may turn to the internet for information, we used the search engine www.google.com to identify the material available about sperm banking and fertility preservation options. Sixty-six resources (NHS/Private Clinic, Charity, Press Releases, General and Forums/Blogs) fulfilled the criteria for inclusion and were examined for quality including readability, layout and content. The most frequently reported information related to: (1) effects of cancer treatment on fertility (77.3%); (2) reasons to bank sperm (69.7%); and (3) fertility recovery after treatment (57.6%). Information about maintaining contact with the sperm bank (18.2%) and disposal of banked samples (10.6%) was less often included. The quality of information available on the Internet about sperm banking was variable. The readability of all resources was assessed as 'fairly difficult', i.e. reading skills required were too complex for the average member of the public to understand. Furthermore, visual presentation of material (e.g. lay out) did not facilitate easy reading. More attention should be given to information about longer-term issues, such as fertility recovery and the use or disposal of banked sperm.

Surgical educator preferences regarding key objective structured clinical examination topics.

BACKGROUND: Numerous methods are used for assessing the performance of surgical residents and students. Unfortunately, these same methods are often unsatisfactory. One technique that is gaining increased favor is the Objective Structured Clinical Examination (OSCE). It is unclear what areas of evaluation might best be included in such an examination so as to optimize its value. Therefore, this study evaluated the opinions of an international body of surgical educators. METHODS: A survey was distributed to 674 attending surgical educators; it asked respondents to select and rank the five most important topics from four areas. These areas included 84 topics from History Taking, Physical Examination, Data Interpretation, and Surgical Technique. A weighted score was calculated for each topic by assigning points according to a Likert scale ranking. RESULTS: Among 674 surveys distributed, 243 responses (36.1%) were received; 25 of the 243 responses were excluded, for a usable response rate of 218/674 (32.3%). The five highest ranked topics were (History Taking) "abdominal pain" 29.2%, "breast mass" 10.8%, "gastrointestinal bleeding" 8.5%, "bowel obstruction" 8.5%, "trauma" 7.2%; (Physical Examination) "acute abdomen" 28.9%, "trauma survey" 18.2%, "breast examination" 15.8%, "peripheral vascular" 8.9%, "cardiopulmonary" 7.5%; (Data Interpretation) "chest X ray" 21%, "abdominal series" 20.2%, "CT scan" 19.6%, "mammogram" 10.1%, "cervical spine films" 5.2%; and (Surgical Technique) "central line" 16.1%, "basic suture skills" 14.2%, "bowel anastomosis" 8.0%, "informed consent" 7.9%, "intubation" 6.4%. CONCLUSION: This survey offers useful data regarding those skills viewed as most important by experienced surgical educators, and offers guidelines for composition of surgical OSCEs.

Objective Structured Clinical Examination technical skill stations correlate more closely with postgraduate year level than do clinical skill stations.

Validity of an examination format is supported by its ability to distinguish levels of training among examinees. The Objective Structured Clinical Examination (OSCE) is a developing format generally composed of various types of task-oriented stations used to evaluate clinical skills of students and residents. The ideal composition of OSCE stations to maximize validity has not been determined. We examined the relative correlation between selected types of stations and level of resident postgraduate year (PGY). A 12-station OSCE was administered to surgical residents of all PGY levels at a university program. Individual station scores were correlated with PGY level. The overall correlation of the total examination score with PGY level was good (R = 0.681). Technical skill stations exhibited a significantly greater correlation with PGY level (0.679 vs 0.203) as compared with clinical skill stations (P < 0.05). These data suggest that technical skill evaluation is more sensitive in distinguishing level of training of surgical residents than is clinical skill evaluation.

Large-field, external beam irradiation as a surgical adjuvant for node-positive colon carcinoma: an Eastern Cooperative Oncology Group Pilot Study (PA285).

The Eastern Cooperative Oncology Group (ECOG) PA-285 study was designed as a pilot study to evaluate the effect of large-field, external beam abdominal irradiation as an adjuvant treatment for resectable stage C1 to C2 colon cancer. Eligible patients received 45 Gy directed to the tumor bed and periaortic lymph nodes, as well as 30 Gy to the liver. Patients were followed up for time to recurrence and for survival. Fourteen patients were enrolled. One elected not to have radiation after surgery; one died of acute hepatic radiation toxicity after a major deviation from protocol. Of the 12 remaining patients, seven survived longer than 10 years for a survival rate of 58%. Other than the fatal hepatic toxicity, side effects from radiation were moderate and of short duration. One patient failed to complete therapy because of ascites, had two episodes of partial bowel obstruction (successfully treated conservatively), and subsequently survived more than 10 years. Two of three patients with stage C1 tumors, four of eight with C2 tumors, and one with a C3 tumor were long-term survivors. This study demonstrates the feasibility and acceptable toxicity of this adjuvant regimen. The numbers are too limited to evaluate survival, but all seven survivors have lived more than 10 years.

Comparison of the Objective Structured Clinical Examination with the performance of third-year medical students in surgery.

BACKGROUND: The purpose of this study was to investigate the validity of the Objective Structured Clinical Examination (OSCE) as an evaluation technique by comparing medical student performance on the OSCE with traditional forms of evaluation. SUBJECTS AND METHODS: We analyzed the performance of 129 third-year medical students in the 1997-1998 academic year on clinical evaluations, oral examinations, and NBME subject examinations, and on OSCE, which was not included in the final grade. RESULTS: The OSCE showed high correlation with the final grades received for the clerkship. Seventy-one percent of students receiving High Pass or Honors had high OSCE scores whereas 67% of students with low OSCE scores received poor or Defer grades. Pearson product-moment correlations demonstrated significant bivariate correlations with the other test parameters. CONCLUSIONS: This study demonstrates that the OSCE is similar to the traditional methods in evaluating general ability and is also able to evaluate clinical ability in a standardized manner.

Thrombotic complications resulting from hypercoagulable states in chronic hemodialysis vascular access.

BACKGROUND: Vascular access-related complications are an important cause of morbidity, and they account for 14% to 17% of dialysis patients' hospitalizations with an annual cost in the United States of approximately $1 billion. Previous studies have related the major predisposing factor of thrombotic complications to stenosis of the graft anastomosis. Several recent reports suggest that antiphospholipid antibodies may cause frequent thrombotic complications. The broad spectrum of diseases that cause hypercoagulable states has not been correlated with frequent PTFE graft thrombosis. STUDY DESIGN: A retrospective case series study was performed to determine the frequency of hypercoagulable states in dialysis patients who had repeated thrombotic complications of their PTFE grafts. Between May 1996 and June 1998, 91 operations were performed on 34 patients with end-stage renal disease. All arteriovenous fistulas were created with PTFE grafts and placed by a single surgeon. All patients were evaluated at operation for anastomotic stenosis, and the majority of patients were studied for hypercoagulable states. Patients with a documented hypercoagulable state were considered for warfarin therapy. RESULTS: Twenty-two individuals (64.7%) developed 67 thrombotic complications. Twelve of the 14 patients tested (85.7%) were shown to have hypercoagulable states of various causes and degrees. Thirteen patients developed multiple thrombotic complications, 11 (81.8%) were tested and proved to be hypercoagulable. Thirty-eight of the thrombotic complications had nonanatomic causes and 28 (41.8%) had hypercoagulability as the only determinable cause. Ten of the 12 hypercoagulable patients (83.3%) were relegated to intermediate to high-intensity warfarin therapy to reduce the incidence of thrombotic events. Hypercoagulable patients not receiving warfarin had a thrombosis rate of 4.0 events per year; patients on warfarin had a rate of 1.2 events per year. Twenty-three thrombotic events occurred in the anticoagulated group all with an International Normalized Ratio (INR) less than 2.7. This incidence of vascular access thrombosis may be prevented when patients are maintained at an optimal INR of 2.7-3.0. CONCLUSIONS: Hypercoagulability has been a major etiologic factor in PTFE graft thrombosis. Hypercoagulable states are often found in patients with multiple graft thromboses and in patients with nonanatomic causes for thrombosis. Antiphospholipid antibodies are prevalent in the patients with PTFE graft thrombosis, as well as abnormalities in the Protein-C, Protein-S, and Antithrombin III systems. PTFE graft thrombosis has been a frequent cause of morbidity in patients on hemodialysis, and diagnostic evaluation should include a hypercoagulability profile. Based on our data, warfarin therapy should be instituted when hypercoagulable states are found, unless otherwise contraindicated, and INR maintained at 2.7-3.0 to decrease morbidity and frequency of graft thrombosis.

Phase II evaluation of treatment of complete resection of hepatic metastases from colorectal cancer and adjuvant hepatic arterial infusion of floxuridine: an Eastern Cooperative Oncology Group Study (PB083).

This study was designed to evaluate hepatic arterial infusion of floxuridine (FUDR) in patients with resected hepatic metastases from colorectal cancer. Patients who met eligibility criteria had an Infusaid pump (Infusaid Corporation, Sharon, MA, U.S.A.) implanted for intraarterial administration of chemotherapy. After complete surgical resection of hepatic metastases, FUDR (0.2 mg/kg/day) was given in 28-day cycles consisting of 14 days of treatment followed by 14 days of rest. Of 11 patients enrolled, one was ineligible, one received no treatment because of a blocked pump, and nine were treated per protocol. Of the nine treated patients, all are dead: one from hepatic toxicity, one from unrelated causes, and seven from progressive disease. Grade 3-4 toxicity included three cases of gastritis and two cases of hepatotoxicity from FUDR. Although this regimen was not successful, in part because of toxicity, the patient population studied here should be considered for future studies of adjuvant therapy.

Adjuvant radiation therapy for pancreatic cancer: a 15-year experience.

PURPOSE: A retrospective analysis to determine differences in survival of patients with pancreatic adenocarcinoma treated by radical surgery with and without adjuvant radiation therapy. METHODS AND MATERIALS: Between 1980 and 1995, 249 patients with pancreatic tumors were identified at the Medical College of Ohio. Forty-four of these patients underwent radical surgical procedures with curative intent. These patients were divided into four groups according to treatment: surgery alone (n = 14), surgery plus intraoperative radiation therapy (IORT) (n = 6), surgery plus external beam radiation therapy (EBRT) (n = 14), or surgery plus both IORT and EBRT (n = 10). Outcome and survival were analyzed among the four groups. RESULTS: The median survival time of patients treated with radical surgery alone was 6.5 months. The median survival time for the surgery plus IORT group was 9 months; however, 33.3% (two of six) of these patients survived longer than 5 years. This survival pattern was borderline significantly better than that for the surgery alone group (p = 0.0765). The surgery plus EBRT and the surgery plus IORT and EBRT groups had median survival times of 14.5 and 17.5 months, respectively. These were significantly better than that of the surgery alone group (p = 0.0004 and p = 0.0002, respectively). The addition of radiation therapy did not affect the treatment complication rate. CONCLUSION: The survival of patients who were treated with radical surgery alone was significantly poorer than that of patients who received adjuvant radiation therapy. These results are consistent with other studies in the literature. Patients treated with all three modalities (surgery, IORT, and EBRT) displayed the best median survival time.

Use of ileal urinary diversion in conjunction with intraoperative radiotherapy.

Intraoperative radiotherapy (IORT) was introduced in the 1970s as a new modality of cancer therapy. It has been especially useful after local irradiation or surgical failure. We report on the use of IORT in 13 patients with pelvic tumors requiring urinary diversion. All 13 were managed with ileal conduits. Despite the associated problems of prior abdominal procedures (11/13 patients), prior external beam radiation to the pelvis (11/13 patients), systemic chemotherapy (4/13 patients), and prolonged operative time (> 10 hours), perioperative mortality (1/13) and morbidity rates were low. We conclude that in cases of prior colonic resection and pelvic radiation, potentially irradiated ileum can be safely used for urinary diversion.

Expression and localization of elements of the plasminogen activation system in benign breast disease and breast cancers.

The malignant potential of solid tumors is related to the ability to invade adjacent tissue and to metastasize. These properties of cancer cells depend on the synthesis of proteolytic enzymes which are able to digest adjacent connective tissue and basement membranes. We hypothesized that all elements of the plasminogen activation system might be overexpressed in malignant human breast tumors, functioning as an essential element in tumor invasion and metastasis. As determined by histopathological methods, the malignant tumors showed statistically significantly higher expression of urokinase plasminogen activator (uPA), type-1 plasminogen activator inhibitor (PAI-1), and especially urokinase plasminogen activator receptor (uPAR) than benign tissues. All those elements were present in higher amounts in the cancer cells than in the cells of benign or normal breast tissues. High exhibition of tissue plasminogen activator (tPA) found in cancer seems to be random and not related to the malignant or benign state, since benign and malignant tumors show overexpression of tissue plasminogen activator with similar frequency. When the tumors express high amounts of uPA, they express a high amount of uPAR in 50% of cases and PAI-1 in 57.3% of cases. When urokinase is expressed in low amount, the receptor is low in 28.6% and inhibitor in 21.4% of malignant breast tumors. This statistically significant consensus, 78.6% in the case of urokinase and its receptor and 78.6% in case of urokinase and its inhibitor, suggests that these activities may be the result of a unique mechanism of control, activated in the last steps of malignant transformation.

Radiation therapy and 5-fluorouracil modulated by leucovorin for adenocarcinoma of the pancreas. A phase I study.

This Phase I study was designed to build on the Gastrointestinal Tumor Study Group's experience with combined modality therapy in patients with pancreatic cancer. Thirteen patients with adenocarcinoma of the pancreas received weekly 5-fluorouracil by rapid intravenous infusion midway through a 2-h infusion of high dose leucovorin during external beam radiation therapy. Twelve patients received 100% of planned external beam radiation; treatment delays occurred in only three. Four patients received 100% of planned chemotherapy doses. Leukopenia and thrombocytopenia caused reduction of the number of chemotherapy doses given during radiation in six patients; diarrhea, severe nausea and vomiting, and wound abscess caused reduction in three patients. Ten patients were evaluable for response; two had complete responses, one had a partial response, and two had minor responses. In this small series baseline and post-treatment CA 19-9 levels predicted and correlated with response. We conclude that radiation and 5-FU modulated by leucovorin is a tolerable treatment regimen for carcinoma of the pancreas, with preliminary suggestion of activity, that warrants further Phase II testing.