Systematic review and narrative synthesis of surgeons’ perception of postoperative outcomes and risk

Background The accuracy with which surgeons can predict outcomes following surgery has not been explored in a systematic way. The aim of this review was to determine how accurately a surgeon's ‘gut feeling’ or perception of risk correlates with patient outcomes and available risk scoring systems. Methods A systematic review was undertaken in accordance with PRISMA guidelines. A narrative synthesis was performed in accordance with the Guidance on the Conduct of Narrative Synthesis In Systematic Reviews. Studies comparing surgeons' preoperative or postoperative assessment of patient outcomes were included. Studies that made comparisons with risk scoring tools were also included. Outcomes evaluated were postoperative mortality, general and operation‐specific morbidity and long‐term outcomes. Results Twenty‐seven studies comprising 20 898 patients undergoing general, gastrointestinal, cardiothoracic, orthopaedic, vascular, urology, endocrine and neurosurgical operations were included. Surgeons consistently overpredicted mortality rates and were outperformed by existing risk scoring tools in six of seven studies comparing area under receiver operating characteristic (ROC) curves (AUC). Surgeons' prediction of general morbidity was good, and was equivalent to, or better than, pre‐existing risk prediction models. Long‐term outcomes were poorly predicted by surgeons, with AUC values ranging from 0·51 to 0·75. Four of five studies found postoperative risk estimates to be more accurate than those made before surgery. Conclusion Surgeons consistently overestimate mortality risk and are outperformed by pre‐existing tools; prediction of longer‐term outcomes is also poor. Surgeons should consider the use of risk prediction tools when available to inform clinical decision‐making. Introduction Surgical procedures all carry associated risks. It is therefore important that surgeons are able to make accurate predictions of potential benefit and risk, including immediate mortality and morbidity, as well as long‐term outcomes, to enable balanced decision‐making and fully informed consent. Risks can also be estimated after surgery, based on additional perioperative and intraoperative data, which allows contemporary prediction of outcome. There are numerous risk prediction models that enable the surgeon to quantify risk based on measurable parameters1-5. However, there are inherent limitations in using a generalized risk prediction model, which may not include clinical data pertinent to the individual case in question, leading to variability in model accuracy6-10. As a result, risk prediction tools are generally used in tandem with the surgeon's ‘gut feeling’ of overall risk and anticipated outcome (‘clinical gestalt’). Several disparate factors influence surgeons' perception of outcome: patient factors, such as their perceived fitness, their pathology and planned procedure; setting factors, such as the experience of other members of staff; and surgeon factors, such as clinical knowledge, operative skill, previous significant surgical complications, and inclinations and attitudes11-13. Anticipating surgical risk is subject to multiple biases, which make it challenging. These include the natural tendency toward anecdotal recall and the availability heuristic (the likelihood of making a decision based on how easily the topic or examples come to mind)14, 15. Some studies16-18 support the accuracy and reproducibility of surgeons' predictions, whereas others19-22 demonstrate less favourable results. The complexity of synthesizing risk perceptions is significant and incompletely understood23, 24. The accuracy of surgeons' prediction has not been explored previously in a systematic manner. The aim of this review was thus to determine, from the available evidence, whether a surgeon's gut feeling or perception of risk correlates with postoperative outcomes, and to compare this prediction with currently available risk scoring systems, where available. Methods This systematic review was undertaken in accordance with the PRISMA guidelines25, 26. MEDLINE (via PubMed), Embase, the Cochrane Library Database, and the Cochrane Collaboration Central Register of Controlled Clinical Trials were searched with no date or language restrictions, with the last search date on 9 July 2018. The search term used was (‘Surgeons’[Mesh] OR ‘General Surgery/manpower*’ [MeSH]) AND (‘perception’ OR ‘intuition’ OR ‘predict*’ OR ‘decision making’ [mesh]). There was no restriction on publication type. This search was complemented by an exhaustive review of the bibliography of key articles, and also by using the Related Articles function in PubMed of included papers. Results were restricted to human research published in English. Inclusion and exclusion criteria All studies of patients undergoing surgery in which a preoperative or postoperative surgeon assessment (or proxy assessment) of a postoperative outcome was performed were included. This included articles that reported general risk (such as mortality) or a surgery‐specific risk (for example anastomotic leakage). Studies that made comparisons with established risk scoring tools were also included. Papers or abstracts in English, or non‐English papers with an English abstract, were included. Papers describing the risk assessment of ‘theoretical’ cases, or patient vignettes in a situation distant from clinical practice (such as a conference), were excluded, as were studies in which surgeons' assessment of risk was compared with an established risk scoring tool, without data on actual patient outcome. Data extraction and assessment of study quality Three authors independently extracted data and assessed the methodological quality of the studies, with all data extraction independently checked by the senior author. The following baseline data were extracted from each study: first author, year of publication, data collection period, geographical location, study design and type (single or multiple centres, number of surgeons involved in risk estimation, whether consecutive patients were enrolled), surgical specialty, whether other risk scoring systems were used for comparison and, if so, whether the assessor was blinded to this result. Data extracted regarding the assessment of risk included: risk outcome assessed; timing of risk estimation (preoperative or postoperative); type of risk assessment by surgeons (qualitative, quantitative, continuous scale such as a visual analogue scale (VAS), or composite score); absolute value of risk event predicted by surgeon and by scoring system; absolute value of risk occurrence rate; summary data on outcome reported, including area under the curve (AUC) of receiver operating characteristic (ROC) curves, observed : expected (O : E) or predicted : observed (P : O) ratios, or any other summary data. When data were available, AUCs were extracted with their 95 per cent confidence intervals. AUCs greater than 0·9 were considered as indicating high performance, 0·7–0·9 as moderate performance, 0·5–0·7 as low performance, and less than 0·5 as indicating risk assessment no better than chance alone27, 28. Risk predictions made by pre‐existing tools, such as the Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (POSSUM)1, Portsmouth‐POSSUM (P‐POSSUM)4 or Continuous Improvement in Cardiac Surgery Program (CICSP)5, were compared with outcome when given. Internal prediction models, where authors would derive significant predictive co‐variables from their data set and assess the accuracy of these co‐variables within the same data set, were not evaluated as they lacked validity. Study quality was assessed using the Newcastle–Ottawa (NO) score29, 30. The NO score assigns points based on: the quality of patient selection (maximum 4 points); comparability of the cohort (maximum 2 points); and outcome assessment (maximum 3 points). Studies that scored 6 points or more were considered to be of higher quality. Outcome measures The following outcome measures were defined a priori and refined during data extraction: postoperative mortality (usually defined as 30 days after surgery); postoperative general morbidity (usually defined as 30 days after surgery); postoperative procedure‐specific morbidity; and long‐term outcome (typically operation‐specific). Further comparative analyses of outcomes included comparison of preoperative and postoperative predictions, and of predictions made by consultants and surgical trainees. Narrative synthesis Given the marked heterogeneity in study design, patient population included, method of assessing risk and outcomes assessed, meta‐analysis was deemed not appropriate. A narrative synthesis was therefore performed according to the Guidance on the Conduct of Narrative Synthesis In Systematic Reviews31. Three authors systematically summarized each article using bullet points to document key aspects of each study, focusing particularly on methods used and results obtained. The validity and certainty of the results were noted (whether appropriate statistical comparisons were used and, if so, their effect size and significance). The senior author identified and grouped common themes, divided larger themes into subthemes, tabulated a combined summary of the paper, and synthesized a common rubric for each theme. Consolidated reviewers' comments can be found in Table S1 (supporting information). Results A total of 584 articles were identified from the literature search, of which 48 were retrieved for evaluation. Papers were excluded on the basis of being duplicates (1) and being irrelevant based on the title (497) and abstract (38) (Fig. 1). Twenty‐seven studies16-24, 32-49 comprising 20 898 patients met the inclusion criteria and were included in the narrative synthesis (Appendix S1, supporting information)

Angiosome specific revascularisation: does the evidence support it?

Objective To explain the angiosome concept and explore the practical application of the angiosome literature to a clinical scenario, in this case a tibial angioplasty for critical ischaemia. Methods Clinical vignette with explanation of the decisions made and subsequent clinical results based on the theory of the angiosome concept and the literature on angiosomal revascularisation; in this case the results of our group’s recent update to a systematic review and meta-analysis. Results Endovascular combined or direct angiosomal revascularisation if superior to indirect revascularisation. This was borne out in the clinical scenario, where an indirect peroneal reperfusion of the AT angiosome resulted in major amputation. Open surgery is less dependent on the angiosome concept. The presence of adequate collateralisation into a foot arch seems to be the most important factor predicting success of indirect revascularisation. The evidence for both suffers from selection bias and many of the findings in the literature are wholly due to selection bias. Conclusion The angiosome concept is useful during both open and endovascular tibial revascularisation. However, the runoff in the foot is critical to success and may not follow the ‘classic’ angiosome model in diabetes

Clinical presentation and natural history of infantile-onset ascending spastic paralysis from three families with an ALS2 founder variant.

Biallelic mutations of the alsin Rho guanine nucleotide exchange factor (ALS2) gene cause a group of overlapping autosomal recessive neurodegenerative disorders including infantile-onset ascending hereditary spastic paralysis (IAHSP), juvenile primary lateral sclerosis (JPLS), and juvenile amyotrophic lateral sclerosis (JALS/ALS2), caused by retrograde degeneration of the upper motor neurons of the pyramidal tracts. Here, we describe 11 individuals with IAHSP, aged 2-48 years, with IAHSP from three unrelated consanguineous Iranian families carrying the homozygous c.1640+1G>A founder mutation in ALS2. Three affected siblings from one family exhibit generalized dystonia which has not been previously described in families with IAHSP and has only been reported in three unrelated consanguineous families with JALS/ALS2. We report the oldest individuals with IAHSP to date and provide evidence that these patients survive well into their late 40s with preserved cognition and normal eye movements. Our study delineates the phenotypic spectrum of IAHSP and ALS2-related disorders and provides valuable insights into the natural disease course

Predicting technical success after fistuloplasty: an analysis of 176 procedures.

Background Significant stenoses in arteriovenous fistulae (AVFs) or arteriovenous grafts (AVGs) with limitation of flow and dialysis inadequacy should prompt consideration for fistuloplasty. We sought to identify fistulae, lesions, and patient-specific variables, which predict for outcomes after fistuloplasty. Methods Data were extracted retrospectively from a renal access database from 2011 to 2016 of patients undergoing fistuloplasty. Demographics, comorbidities, outcomes of intervention, and flow rates documented on preintervention and postintervention duplex were collected. Secondary analysis of factors associated with postfistuloplasty flow rates of >600 mL/min, previously shown to be predictive of not requiring future intervention, was performed. Results Of 204 attempted fistuloplasties, 176 were completed. One hundred forty (79.5%) were native AVFs and 34 (19.3%), AVGs (no data for 2). Median stenosis treated was 75%, with a majority (43.8%) in the proximal outflow vein. Flow rate on duplex after fistuloplasty was significantly better in AVFs (mean improvement 189.2 mL/min) than that in AVGs (mean improvement 51.8 mL/min; P = 0.034). Greatest flow improvement occurred for needling site stenotic lesions compared with other locations (from anastomosis to central vein) but was not significant. Brachio-brachial or brachio-axillary AVGs did significantly (P 600 mL/min. Conclusions Flow rates after fistuloplasty vary depending on the type of fistula treated and the presence of hypertension. Knowledge of this can lead to better patient selection and counseling for fistuloplasty

Construction and Development of a Cardiac Tissue-Specific and Hypoxia-Inducible Expression Vector

Purpose: Cardiovascular gene therapy is a sophisticated approach, thanks to the safety of vectors, stable transgene expression, delivery method, and different layers of the heart. To date, numerous expression vectors have been introduced in biotechnology and biopharmacy industries in relation to genetic manipulation. Despite the rapid growth of these modalities, they must be intelligently designed, addressing the cardiac-specific transgene expression and less side effects. Herein, we conducted a pilot project aiming to design a cardiac-specific hypoxia-inducible expression cassette. Methods: We explored a new approach to design an expression cassette containing cardiac specific enhancer, hypoxia response elements (HRE), cardiac specific promoter, internal ribosome entry site (IRES), and beta globin poly A sequence to elicit specific and inducible expression of the gene of interest. Enhanced green fluorescent protein (eGFP) was sub-cloned by BglII and NotI into the cassette. The specificity and inducible expression of the cassette was determined in both mouse myoblast C2C12 and mammary glandular tumor 4T1 as ‘twin’ cells. eGFP expression was evaluated by immunofluorescence microscope and flow cytometry at 520 nm emission peak. Results: Our data revealed that the designed expression cassette provided tissue specific and hypoxia inducible (O2<1%) transgene expression. Conclusion: It is suggested that cardiac-specific enhancer combined with cardiac-specific promoter are efficient for myoblast specific gene expression. As well, this is for the first time that HRE are derived from three well known hypoxia-regulated promoters. Therefore, there is no longer need to overlap PCR process for one repeated sequence just in one promoter

A systematic review and narrative synthesis of risk prediction tools used to estimate mortality, morbidity, and other outcomes following major lower limb amputation

Objective The decision to undertake a major lower limb amputation can be complex. This review evaluates the performance of risk prediction tools in estimating mortality, morbidity, and other outcomes following amputation. Methods A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The MEDLINE, Embase, and Cochrane databases were searched to identify studies reporting on risk prediction tools that predict outcomes following amputation. Outcome measures included the accuracy of the risk tool in predicting a range of post-operative complications, including mortality (both short and long term), peri-operative morbidity, need for re-amputation, and ambulation success. A narrative synthesis was performed in accordance with the Guidance on the Conduct of Narrative Synthesis In Systematic Reviews. Results The search identified 518 database records. Twelve observational studies, evaluating 13 risk prediction tools in a total cohort of 61 099 amputations, were included. One study performed external validation of an existing risk prediction tool, while all other studies developed novel tools or modified pre-existing generic calculators. Two studies conducted external validation of the novel/modified tools. Nine tools provided risk estimations for mortality, two tools provided predictions for post-operative morbidity, two for likelihood of ambulation, and one for re-amputation to the same or higher level. Most mortality prediction tools demonstrated acceptable discrimination performance with C statistic values ranging from 0.65 to 0.81. Tools estimating the risk of post-operative complications (0.65 – 0.74) and necessity for re-amputation (0.72) also performed acceptably. The Blatchford Allman Russell tool demonstrated outstanding discrimination for predicting functional mobility outcomes post-amputation (0.94). Overall, most studies were at high risk of bias with poor external validity. Conclusion This review identified several risk prediction tools that demonstrate acceptable to outstanding discrimination for objectively predicting an array of important post-operative outcomes. However, the methodological quality of some studies was poor, external validation studies are generally lacking, and there are no tools predicting other important outcomes, especially quality of life

Niemann-Pick Diseases; largest Iranian cohort with genetic analysis

Background: Niemann-Pick diseases (NPD) is an autosomal recessive inherited lysosomal lipid storage disorder which occurs due to a defect in cellular cholesterol trafficking, leading to excess lipid accumulation in multiple organ systems such as the brain, lungs, spleen and liver. SPMD1-associated disease includes classic infantile and visceral NPD type A and B respectively. Type C NPD is subacute or juvenile.Methods: Sanger sequencing of the candidate genes for NPD were performed followed by bioinformatic analysis to confirm the types of NPD and to identify novel mutations. All patients underwent full clinical assessment.Results: In this case series, we present two cases with NPD type A, six cases with NPD type B, and 11 cases with type C with various enzymatic defects identified in these cases. Within these 19 patients we present seven previously reported mutations and 10 novel mutations causing NPD.Conclusion: Our report demonstrates that NPD has a variable age of onset and can present early in life. In this study, we investigated the clinical and genetic manifestations of a large Iranian cohort. Understanding the variable presentation of NPD will allow for clinicians to have a high index of suspicion for the disease

The physiology and clinical utility of anti-Müllerian hormone in women

BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS).METHODSThis paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors.RESULTSPhysiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future.CONCLUSIONSFor the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. An international standard for AMH and improved assay validity are urgently needed to maximize the clinical utility of this very promising biomarker of ovarian function in a large array of clinical situations, both in childhood and adulthood