Music therapy for supporting informal carers of adults with life-threatening illness pre- and post-bereavement; a mixed-methods systematic review.

BACKGROUND: Music therapy interventions with informal carers of individuals with life-threatening illness at pre- and post-bereavement is an increasingly important clinical area. This systematic review is the first to synthesise and critically evaluate the international evidence associated with music therapy with adult informal carers pre- and post-bereavement. Specifically, the objectives were: i) to describe the characteristics and effectiveness of music therapy interventions which aim to improve health-related outcomes for adult informal carers of adults with life-threatening illness (pre- and post-bereavement), and ii) to describe the experience of music therapy for adult informal carers of adults with life-threatening illness (pre- and post-bereavement). METHODS: Eligibility: adult informal carers of adults at end of life or bereaved; music therapy interventions for improving health-related outcomes; qualitative; mixed-method; and quantitative studies including comparators of any other intervention; published in English from 1998 onwards. Six databases were searched up to July 2022. A JBI mixed-methods systematic review approach was followed throughout, including quality appraisal, data extraction and a convergent segregated approach to synthesis and integration. RESULTS: A total of 34 studies were included, published between 2003 and 2022. Most were conducted in North America (n = 13), Australia (n = 10), or Europe (n = 8). No studies were conducted in low- and middle-income countries or in the UK. The majority were qualitative (n = 17), followed by quasi-experimental (n = 8), mixed-methods (n = 7) and two RCTs. The majority focused on carers of individuals with dementia (n = 21) or advanced cancer (n = 7). Seventeen studies were purely quantitative or included a quantitative component. During meta-synthesis, findings were aligned to core outcomes for evaluating bereavement interventions in palliative care and previously identified risk factors for complicated grief. Commonly targeted outcomes in quantitative studies included quality of life and mental wellbeing, showing equivocal effectiveness of music therapy with significant and non-significant results. Twenty-two studies either purely qualitative or with a qualitative component underwent meta synthesis and suggested a diverse range of improved pre- and post-bereavement outcomes for informal carers across all core outcomes, and across all risk and protective factors, including psychological, spiritual, emotional, and social outcomes. CONCLUSIONS: Qualitative studies provide moderate to strong evidence for improved health-related outcomes for adult informal carers of adults with life-threatening illness pre-bereavement. Limited studies including those bereaved negates conclusions for the bereavement phase. Comparisons and explanations for effectiveness across quantitative and qualitative studies are equivocal, with a high risk of bias and small samples in the limited number of quantitative studies, demonstrating a need for high-quality RCTs. SYSTEMATIC REVIEW PRE-REGISTRATION: PROSPERO [CRD42021244859].

Perspectives in adhesion prevention in gynaecological surgery.

Adhesions are a frequent, clinically relevant, and often costly complication of surgery that can develop in any body location regardless of the type of surgical procedure. Adhesions result from surgical trauma inducing inflammatory and coagulation processes and to date cannot be entirely prevented. However, the extent of adhesion formation can be reduced by using good surgical technique and the use of anti-inflammatory drugs, haemostats, and barrier agents. Strategies are needed in the short-, medium- and longer-term to improve the prevention of adhesions. In the short-term, efforts are needed to increase the awareness amongst surgeons and patients about the potential risks and burden of surgically induced adhesions. To aid this in the medium- term, a risk score to identify patients at high risk of adhesion formation is being developed and validated. Furthermore, available potentially preventive measures need to be highlighted. Both clinical and health economic evaluations need to be undertaken to support the broad adoption of such measures. In the longer- term, a greater understanding of the pathogenic processes leading to the formation of adhesions is needed to help identify effective, future treatments to reliably prevent adhesions from forming and lyse existing ones.

Total surgical time in laparoscopic supracervical hysterectomy with laparoscopic in-bag-morcellation compared to laparoscopic supracervical hysterectomy with uncontained morcellation.

Background: A possible solution to the problem of cell dissemination through laparoscopic uncontained morcellation during laparoscopic supracervical hysterectomy (LASH) is the use of laparoscopic in-bag morcellation. One criticism regarding the use of in-bag morcellation is the additional surgical time associated with this procedure. Objectives: In this retrospective study we compared the total surgical time in LASH with laparoscopic in-bag morcellation (107 cases from 2016-2018) and LASH with uncontained morcellation (47 cases from 2015-2017). Materials and Methods: All surgeries were performed in the same department of minimally invasive gynaecological surgery by a total of three experienced surgeons for the indication of bleeding disorder and / or dysmenorrhea. Main outcome measure: We measured and compared total surgical time, surgical outcome, blood loss and complications in LASH with in-bag morcellation and with uncontained morcellation. Results: Total surgical time in both procedures do not show a significant difference. Considering the learning curve in laparoscopic bag use, the total surgical time in LASH with laparoscopic in-bag morcellation is shorter than total surgical time in LASH with uncontained morcellation. Laparoscopic in-bag morcellation consumes time for bag use and handling, but saves time as it eliminates the need for meticulous sampling of lost tissue fragments and the complex lavage of the peritoneal cavity after morcellation. There is no difference between both groups in terms of blood loss, complications and surgical results. Conclusion / What is new?: We conclude that LASH with in-bag morcellation is not related to additional surgical time when compared to LASH with uncontained morcellation.

Extravascular Dispersion of Polyvinyl Alcohol Microsphere Particles in Uterine Artery Embolization.

Uterine artery embolization (UAE) is a common minimally invasive treatment of different uterine pathologies, such as fibroids, adenomyosis, and menorrhagia. The procedure involves the injection of embolic agents into the uterine arteries, whereby various particles can be used, such as polyvinyl alcohol (PVA). Complication of UAE is the dispersion of polyvinyl alcohol (PVA) microsphere particles in the uterine body which can lead to a granular vaginal discharge. We report the management of complications of PVA microspheres dispersed from the uterine body causing postprocedural discomfort due to the vaginal passage of microspheres or because of an induced fibroid-size enlargement. The dispersion of the PVA microspheres is one example of a minor UAE complication, which nevertheless causes significant distress to the patient and eventfully requires further surgical interventions.

Adhesions and Anti-Adhesion Systems Highlights.

The peritoneal and intrauterine cavities are lined by fragile membranes with a high-wound healing capacity, e.g. repairing the endometrium in its cyclical "injury and scar-free repair process" during menstruation. However, peritoneal and intrauterine fibrosis and adhesions can develop after surgical trauma through activation of molecular, immune and genetic mechanisms. During procedures with a high-risk of adhesions, the use of new peritoneal and intrauterine conditions in combination with anti-adhesion substances are promising measures to preserve peritoneal and endometrial function and avoid the most common complication of gynecological surgery. Highlights of adhesions and anti-adhesion prevention techniques in laparoscopic, laparotomic and hysteroscopic surgeries are discussed in this paper. Unfortunately, evidence is lacking to prove the superiority of one technique over its counterparts in terms of postoperative adhesions, such as instrumentation, type of energy, distending media, and intracavitary pressure. Additionally, there is limited evidence about the efficacy and outcomes of techniques and adjuvant measures used during adhesiolysis. The definition of a universal intrauterine adhesions classification scheme as well as a prognostic scoring system to identify women at high risk of postoperative adhesions are necessary for advising those who could benefit the most of the use of antiadhesion barriers.

Melanoma diagnosis and management after the introduction of a pigmented lesion clinic in the Mid-West of Ireland.

BACKGROUND: A pigmented lesion clinic (PLC) was introduced and Consultant Dermatology posts were increased in the Mid-West of Ireland with the aim of improving early detection of melanoma. METHODS: We analysed retrospectively the invasive melanomas excised in the Mid-West of Ireland over a 2-year period prior to (2010-2011) and after (2013-2014) the advent of the PLC. RESULTS: The number of melanomas excised almost doubled from 54 (2010-2011) to 107 (2013-2014). There was a significant rise in the rate of excision biopsies performed by Dermatologists compared to non-dermatology clinicians from 19 to 56% (p < 0.0001). There was a significant difference in the diagnostic accuracy of excised melanomas by Dermatologists compared to non-dermatology clinicians during both time periods (2010-2011: p = 0.001; 2013-2014: p < 0.0001). There was a non-significant decrease in the median Breslow thickness of melanomas from 1.3 mm (0.6-2.6) (2010-2011) to 1.0 mm (0.5-2.3) (2013-2014) (n = 145, p = 0.48). CONCLUSION: The PLC has led to an increase in the number of melanomas excised by Dermatologists in the Mid-West of Ireland which has led to higher diagnostic accuracy.

Adjuvant FOLFOX +/- cetuximab in full RAS and BRAF wildtype stage III colon cancer patients.

Background: RAS mutations have been shown to confer resistance to anti- epidermal growth factor receptor (EGFR) treatment. We analysed the results of the PETACC8 trial (cetuximab + FOLFOX vs FOLFOX) in full RAS and BRAF wildtype (WT) patients (pts) with resected stage III colon cancer. Patients and methods: Exons 2, 3 and 4 of KRAS and NRAS, and BRAF exons 11 and 15, were sequenced using the Ampliseq colon-lung cancer panel version 2, in PETACC8 trial pts who consented to translational research. The impact of cetuximab on time to recurrence (TTR), disease-free survival (DFS) and overall survival (OS) was investigated in pts with tumours harbouring RAS and BRAF WT, and RAS mutations. The prognostic value of each individual mutation was also tested. Results: Among the 2559 pts analysed, 745 pts (29%) were known to have KRAS exon 2 mutations and 163 pts (6.4%) the BRAF V600E mutation. Of the remaining 1651 pts, 1054 were assessed by NGS, showing that a further 227 pts (21%) had KRAS exon 2, 3, 4 or NRAS exon 2, 3, 4 mutations, and that 46 pts (4.4%) had a newly diagnosed BRAF mutation. Cetuximab added to FOLFOX did not significantly improve TTR, DFS or OS in pts with RAS WT or RAS and BRAF WT tumours (HR 0.77-1.03, all P > 0.05). Cetuximab addition was not either significantly deleterious in RAS mutant pts or in pts with rare RAS or BRAF mutations. In the overall trial population, NRAS and KRAS codon 61 mutations were the only rare mutations with the same pejorative prognostic value as KRAS exon 2 or BRAF V600E mutations. Conclusion: Though not significant, the clinically relevant 0.76 adjusted HR observed for DFS in favour of adding cetuximab to FOLFOX, in full RAS and BRAF WT stage III colon cancer pts, may justify a new randomized controlled trial testing EGFR inhibitors in this setting. Clinical trial number: This is an ancillary study of the PETACC8 trial: EUDRACT 2005-003463-23.

Determination of irinotecan and SN38 in human plasma by TurboFlow™ liquid chromatography-tandem mass spectrometry.

Irinotecan is a cytotoxic agent used in the treatment of metastatic colorectal cancer. Irinotecan is a prodrug when is converted in vivo to an active metabolite SN38, which has potent pharmacological activity. SN38 is then inactivated and excreted as SN38-glucuronide. High-performance liquid chromatography-mass spectrometry is a widely used bioanalysis technique that can be coupled to the turbulent-flow extraction line to shorten preparation time. A technique was developed to quantify irinotecan and its metabolite by liquid chromatography-tandem mass spectrometry coupled with a turbulent-flow online extraction method. Assays were performed on 100 µL of plasma after protein precipitation. The supernatant is injected directly into the extraction column, transferred to the chromatographic column, and analyzed by tandem mass spectrometry. Linearity, reproducibility and repeatability of the method were validated on a concentration range of 25-2500 ng/mL for irinotecan and 5-500 ng/mL for SN38. For the low limit of quantification of irinotecan and SN38, precision is 6.31% and 8.73%, and accuracy is 84.0% and 91.8%, respectively. The SN38-glucuronide determination protocol included a hydrolyzation step. This method was successfully used to quantify irinotecan, SN38 and SN38-G in human plasma in a clinical trial.

Assessing the benefit-risk of new treatments using generalised pairwise comparisons: the case of erlotinib in pancreatic cancer.

BACKGROUND: Efficacy and safety are the two considerations when characterising the effects of a new therapy. We sought to apply an innovative method of assessing the benefit-risk balance using data from a completed randomised controlled trial that compared erlotinib vs placebo added to gemcitabine in patients with advanced pancreatic cancer (NCIC CTG PA.3). METHODS: We applied generalised pairwise comparisons with several prioritised outcome measures (e.g., one or more benefit outcomes and one or more risk outcomes). Here, the first priority outcome was overall survival (OS) time. Differences in OS that exceeded 2 months were considered clinically meaningful. The second priority outcome was toxicity. The overall treatment effect was quantified using the proportion in favour of erlotinib, which can be interpreted as the net proportion of patients who have a better overall outcome with erlotinib as compared with placebo. Sensitivity analyses were performed. RESULTS: In this trial 569 patients were randomly assigned in a 1 : 1 ratio to receive gemcitabine plus either erlotinib or a matched placebo. Overall, the method indicated no statistically significant overall treatment effect in favour of erlotinib; if anything, the point estimate of the net proportion leaned in favour of the placebo group (overall proportion in favour of erlotinib=-3.6%, 95% CI, -14.2- 7.1%; P=0.51). The net proportion was never in favour of the erlotinib group throughout all sensitivity analyses. CONCLUSIONS: Generalised pairwise comparisons make it possible to assess the benefit-risk balance of new treatments using a single statistical test for any number of prioritised outcomes. The benefit-risk assessment was not in favour of adding erlotinib to gemcitabine for the treatment of patients with advanced pancreatic cancer.

Long-term net survival in patients with colorectal cancer in France: an informative contribution of recent methodology.

BACKGROUND: Net survival, the survival that might occur if cancer was the only cause of death, is a major epidemiological indicator. Recent findings have shown that the classical methods used for the estimation of net survival from cancer registry data, referred as to "relative-survival methods," provided biased estimates. OBJECTIVES: The aim of this study was to provide, for the first time, long-term net survival rates for colorectal cancer by using a population-based digestive cancer registry. DESIGN: This study is a population-based cancer registry analysis. The recently proposed unbiased nonparametric Pohar-Perme estimator was used. PATIENTS: Overall, 14,715 colorectal cancers diagnosed between 1976 and 2005 and registered in the population-based digestive cancer registry of Burgundy (France) were included. MAIN OUTCOME MEASURES: The primary outcome measured was cancer net survival, ie, the survival that might occur if all risks of dying of other causes than cancer were removed RESULTS: : Ten-year net survival increased from 31% during the 1976 to 1985 period to 47% during the 1986 to 1995 period and then leveled out (48% during the 1996-2005 period). There was a major improvement in 10-year net survival after resection for cure and for stage I to III. It was striking for stage III cancers, for which 10-year net survival increased from 21% (1976-1985) to 49% (1996-2005). The corresponding net survivals were 70% and 87% for stage I and 49% and 65% for stage II. These trends can be related to the decrease in operative mortality, the increase in the proportion of patients resected for cure, and the improvement in stage at diagnosis. They were mainly seen between 1976 and 1995, explaining why survival leveled out after 1995. LIMITATIONS: The study was limited by its retrospective and population-based nature. CONCLUSIONS: Further improvements for colorectal cancer management can be expected from more effective treatments and from the implementation of organized cancer screening.

Perfil genómico de riesgo en la práctica clínica / Genomic profile in clinical practice

En los últimos diez años se ha visto un aumento exponencial tanto de los conocimientos en genética médica como en la capacidad de analizar el genoma humano. En los próximos años es probable que estas tendencias continúen, haciendo necesaria la incorporación de estas herramientas en la práctica médica diaria. En estos momentos asistimos a los primerosintentos serios de aplicación de la genómica humana a la atención de la salud. El conocimiento de las bases genéticas, y las interacciones a nivel molecular que llevan a las enfermedades humanas, tiene potencialidades enormes para mejorar el diagnóstico, el pronóstico, el tratamiento y la prevención de las mismas, e implica el desafío de cómointerpretar esta información y cómo educar a los médicos para utilizarla.En este trabajo analizamos los últimos desarrollos, los beneficios y las limitaciones del análisis genómico en la clínica, las herramientas utilizadas para ello, esbozamos algunas tendencias y su extrapolación al futuro inmediato y, finalmente, analizamos la situación en nuestro medio.

Over the last ten years knowledge on medical genetics and the ability to analyze the human genome have showna steep block curve. This tendency is likely to continue in the coming years,and thus require the introduction of these tools in the every day medical practice. Today we witness the first serious attempts to apply human genomics to health care services. Knowledge on genetic bases, and interactions at molecular level leadingto human diseases have huge potential for improving their diagnosis, prognosis, treatment and prevention; and itimplies a challenge as to how to interpret this information and how to train medical doctors in their application.The present article comprises a study of the last progress made, and benefits and limitations of genomic analysis in clinical practice and its tools, and it also includesa sketch of tendencies and their extrapolation in the near future and, finally, the situation in our country isanalyzed.

Nos últimos dez anos observou-se um aumento exponencial tanto do conhecimento de genética médica como da capacidade de analisar o genoma humano. É provável que esta tendência se mantenha nos próximos anos, sendonecessário, portanto incorporar estas ferramentas na prática médica diária. Atualmente estamos assistindo àsprimeiras tentativas sérias de aplicar a genômica humana à atenção de saúde. O conhecimento das bases genéticas,e das interações a nível molecular que causam as doenças humanas, têm um potencial enorme para melhorar o diagnóstico, o prognóstico, o tratamento e a prevenção das mesmas, e gera o desafio para interpretar essa informaçãoe para educar os médicos sobre como utilizá-la. Neste trabalho analisamos os últimos progressos, os benefícios e as limitações da aplicação da análise genômica na clínica, as ferramentas utilizadas com esse fim, sugerimosalgumas tendências e fazemos algumas extrapolações para o futuro imediato, e finalmente, analisamos a situaçãono nosso meio.

Planned neck dissection before combined chemoradiation for pyriform sinus carcinoma.

CONCLUSIONS: A pretreatment neck dissection in a chemoradiation regimen for pyriform sinus carcinoma provides no delay for radiation, low complication rates, optimal radiation doses and a high nodal disease control. OBJECTIVES: The aims of this study were to evaluate the clinical feasibility, therapeutic consequences and neck nodes control of a pretreatment neck dissection in a chemoradiation regimen for organ preservation strategy for pyriform sinus carcinoma. PATIENTS AND METHODS: Seventy-six patients with untreated stage III and IV squamous cell carcinoma of the pyriform sinus were included in this study. Eighty neck dissections were performed according to the N status. Dose of radiotherapy was delivered according to the pathologic finding of neck dissections. RESULTS: The mean time between neck dissection and the chemoradiation was 24 days (+/-12 days). Only two patients (2.5%) experienced wound complications. A 'boost' radiation of 14 Gy was delivered after 49 neck dissections (61%) in patients with extracapsular spread. The rate of disease control within the regional nodes was 90%. The Kaplan-Meier 1- and 2- year overall survival rates were 78% and 43%, respectively, and specific survival rates were 88% and 67%, respectively.

Intermediate amyloid oligomers of lysozyme: Is their cytotoxicity a particular case or general rule for amyloid?

In the current study we investigated the molecular mechanisms of cytotoxicity of amyloid oligomers of horse milk lysozyme. We have shown that lysozyme forms soluble amyloid oligomers and protofibrils during incubation at pH 2.0 and 4.5 and 57 degrees C. These structures bind the amyloid-specific dyes thioflavin T and Congo Red, and their morphology and size were analyzed by atomic force microscopy. Monomeric lysozyme and its fibrils did not affect the viability of three cell types used in our experiments including primary murine neurons and fibroblasts, as well as neuroblastoma cell line IMR-32. However, soluble amyloid oligomers of lysozyme caused death of all these cell types, as estimated by flow-cytometry counting dead cells stained with ethidium bromide. The primary cell cultures appeared to be more sensitive to amyloid than neuroblastoma cell line IMR-32. Amyloid cytotoxicity depends on the size of oligomeric particles: samples containing 20-mers formed at pH 4.5 were more toxic than tetramers and octamers present in the solution at pH 2.0. Soluble amyloid oligomers can self-assemble into doughnut-like structures; however, no correlation was observed between the amount of the doughnut-like structures in the sample and its cytotoxicity. The fact that the intermediate oligomers of such an abundant protein as lysozyme display cytotoxicity confirms a hypothesis that cytotoxicity is a common feature of protein amyloid. Inhibition of intermediate oligomer formation is crucial in preventing amyloid pathogeneses.

Amyloidogenic properties of the artificial protein albebetin and its biologically active derivatives. The role of electrostatic interactions in fibril formation.

The artificial protein albebetin (ABB) and its derivatives containing biologically active fragments of natural proteins form fibrils at physiological pH. The amyloid nature of the fibrils was confirmed by far UV circular dichroism spectra indicating for rich beta-structure, thioflavin T binding assays, and examination of the obtained polymers by atomic force microscopy. Fusing of short peptides--octapeptide of human alpha(2)-interferon (130-137) or hexapeptide HLDF-6 (41-46) of human leukemia differentiation factor--with the N-terminus of ABB led to increased amyloidogenicity of the protein: the rate of fibril formation increased and the morphology of fibrils became more complex. The presence of free hexapeptide HLDF-6 in the ABB solution had the same effect. Increasing ionic strength also activated the process of amyloid formation, but to less extent than did the peptides fused with ABB or added to the ABB solution. We suggest an important role of electrostatic interactions in formation of ABB fibrils. The foregoing ways (addition of salt or peptides) allow decrease in electrostatic repulsion between ABB molecules carrying large negative charge (-12) at neutral pH, thus promoting fibril formation.

Acquired immune deficiency syndrome and the increase in non-Hodgkin lymphoma incidence in New Jersey from 1979 to 1996.

BACKGROUND: In New Jersey, the age-adjusted incidence rate of non-Hodgkin lymphoma (NHL) increased more than a third from 1979 to 1996, the largest increase among the major cancers. METHODS: Data from a linkage of New Jersey's population-based cancer and acquired immune deficiency syndrome (AIDS) registries were used to obtain two sets of annual age specific incidence rates and estimated average annual percentage changes in the incidence rates, for each of five adult age groups within each gender, from Poisson regression models that 1) included all the NHL cases and 2) excluded the cases of AIDS-NHL. RESULTS: During 1979-1996, of the NHL cases aged 15 years and older reported to the cancer registry, 687 (6%) of the 11,725 male cases and 139 (1%) of the 10,785 female cases were AIDS-NHL. The highest percentages of AIDS-NHL were in the younger age groups--15-29, 30-39, and 40-49 years. Among both men and women, average annual percentage increases in NHL occurred overall (3.1 and 3.0, respectively), and in each age group, ranging from 1.6 and 1.9, respectively, in the 50-59 years age group to 6.6 and 4.2, respectively, in the 30-39 years age group (P <<0.01). Excluding AIDS-NHL, the estimated average annual percentage increases in NHL were greatest in the 30-39 and the 60 years and older age groups among men, and these two age groups plus the 15-29 years age group among women, ranging between 2.4 and 2.9 (P < 0.05). CONCLUSIONS: As elsewhere, factors in addition to AIDS are involved in the increasing incidence of NHL in New Jersey. Because diagnostic and classification changes probably do not explain the entire increase unrelated to AIDS, other risk factors are likely responsible. Public health interventions to reduce the incidence of NHL not related to AIDS are problematic until more is known about the causes of NHL.