Does gabapentin provide benefit for patients with knee OA? A benefit-harm and cost-effectiveness analysis.

OBJECTIVE: Gabapentin can treat neuropathic pain syndromes and has increasingly been prescribed to treat nociplastic pain. Some patients with knee osteoarthritis (OA) suffer from both nociceptive and nociplastic pain. We examined the cost-effectiveness of adding gabapentin to knee OA care. METHOD: We used the Osteoarthritis Policy Model, a validated Monte Carlo simulation of knee OA, to examine the value of gabapentin in treating knee OA by comparing three strategies: 1) usual care, gabapentin sparing (UC-GS); 2) targeted gabapentin (TG), which provides gabapentin plus usual care for those who screen positive for nociplastic pain on the modified PainDETECT questionnaire (mPD-Q) and usual care only for those who screen negative; and 3) universal gabapentin plus usual care (UG). Outcomes included cumulative quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. We derived model inputs from published literature and national databases and varied key input parameters in sensitivity analyses. RESULTS: UC-GS dominated both gabapentin-containing strategies, as it led to lower costs and more QALYs. TG resulted in a cost increase of $689 and a cumulative QALY reduction of 0.012 QALYs. UG resulted in a further $1,868 cost increase and 0.036 QALY decrease. The results were robust to plausible changes in input parameters. The lowest TG strategy ICER of $53,000/QALY was reported when mPD-Q specificity was increased to 100% and AE rate was reduced to 0%. CONCLUSION: Incorporating gabapentin into care for patients with knee OA does not appear to offer good value.

Prostaglandin E2 receptors and their role in gastrointestinal motility - Potential therapeutic targets.

Prostaglandin E2 (PGE2) is found throughout the gastrointestinal tract in a diverse variety of functions and roles. The recent discovery of four PGE2 receptor subtypes in intestinal muscle layers as well as in the enteric plexus has led to much interest in the study of their roles in gut motility. Gut dysmotility has been implicated in functional disease processes including irritable bowel syndrome (IBS) and slow transit constipation, and lubiprostone, a PGE2 derivative, has recently been licensed to treat both conditions. The diversity of actions of PGE2 in the intestinal tract is attributed to its differing effects on its downstream receptor types, as well as their varied distribution in the gut, in both health and disease. This review aims to identify the role and distribution of PGE2 receptors in the intestinal tract, and aims to elucidate their distinct role in gut motor function, with a specific focus on functional intestinal pathologies.

Clinicopathological features and oncological outcomes of patients with young-onset rectal cancer.

BACKGROUND: The incidence of rectal cancer among adults aged less than 50 years is rising. Survival data are limited and conflicting, and the oncological benefit of standard neoadjuvant and adjuvant therapies is unclear. METHODS: Disease-specific outcomes of patients diagnosed with rectal cancer undergoing surgical resection with curative intent between 2006 and 2016 were analysed. RESULTS: A total of 797 patients with rectal cancer were identified, of whom 685 had surgery with curative intent. Seventy patients were younger than 50 years and 615 were aged 50 years or more. Clinical stage did not differ between the two age groups. Patients aged less than 50 years were more likely to have microsatellite instability (9 versus 1·6 per cent; P = 0·003) and Lynch syndrome (7 versus 0 per cent; P < 0·001). Younger patients were also more likely to receive neoadjuvant chemoradiotherapy (67 versus 53·3 per cent; P = 0·003) and adjuvant chemotherapy (41 versus 24·2 per cent; P = 0·006). Five-year overall survival was better in those under 50 years old (80 versus 72 per cent; P = 0·013). The 5-year disease-free survival rate was 81 per cent in both age groups (P = 0·711). There were no significant differences in the development of locoregional recurrence or distant metastases. CONCLUSION: Despite accessing more treatment, young patients have disease-specific outcomes comparable to those of their older counterparts.

ANTECEDENTES: La incidencia de cáncer de recto entre adultos menores de 50 años está aumentando. Los datos de supervivencia son limitados y contradictorios, y el beneficio oncológico de los tratamientos neoadyuvantes y adyuvantes estándares no está claro. MÉTODOS: Se analizaron los resultados específicos relacionados con la enfermedad en pacientes diagnosticados de cáncer de recto operados con intención curativa entre 2006 y 2016. RESULTADOS: Se identificaron un total de 797 pacientes con cáncer de recto, de los cuales 685 fueron intervenidos quirúrgicamente con intención curativa. Setenta tenían menos de 50 años y 615 tenían 50 años o más. No hubo diferencias en el estadio clínico entre los dos grupos de edad. Los pacientes menores de 50 años tenían más probabilidades de tener inestabilidad de microsatélites (9% versus 2%, P = 0,003) y síndrome de Lynch (7% versus 0%, P ≤ 0,001). La supervivencia global a los 5 años fue mayor en los pacientes de menos de 50 años (80% y 72%; P = 0,013). La supervivencia libre de enfermedad a los 5 años fue del 81% en ambos grupos de edad (P = 0,711). No hubo diferencias significativas en el desarrollo de recidiva locorregional o metástasis a distancia. Los pacientes más jóvenes tenían más probabilidades de recibir quimiorradioterapia neoadyuvante (67% versus 53%, P = 0,003) y quimioterapia adyuvante (41% versus 24%, P = 0,006). CONCLUSIÓN: A pesar de tener acceso a más tratamientos, los pacientes jóvenes han presentado resultados específicos relacionados con la enfermedad comparables a sus homólogos de mayor edad.

Trends in the treatment of rectal prolapse: a population analysis.

PURPOSE: Rectal prolapse is a common condition, with conflicting opinions on optimal surgical management. Existing literature is predominantly composed of case series, with a dearth of evidence demonstrating current, real-world practice. This study investigated recent national trends in management of rectal prolapse in the Republic of Ireland (ROI). METHODS: This population analysis used a national database to identify patients admitted in the ROI primarily for the management of rectal prolapse, as defined by the International Classification of Diseases, 10th Revision (ICD-10). Demographics, procedures, comorbidities, and outcomes were obtained for patients admitted from 2005 to 2015 inclusive. RESULTS: There were 2648 admissions with a primary diagnosis of rectal prolapse; 39.3% underwent surgical correction. The majority were treated with either a perineal resection (47.2%) or an abdominal rectopexy ± resection (45.1%). The population-adjusted rate of operative intervention increased over the study period, from 25 to 42 per million (p < 0.001), with no change in the mean age of patients over time (p = 0.229). The application of a laparoscopic approach increased over time (p = 0.001). Patients undergoing an abdominal rectopexy were younger than those undergoing a perineal procedure (64.1 ± 17.3 versus 75.2 ± 15.5 years, p < 0.001) despite having a similar Charlson Comorbidity Index (p = 0.097). The mortality rate for elective repair was 0.2%. CONCLUSIONS: Despite the popularization of ventral mesh rectopexy over the study period, perineal resection Delorme's procedure remains the most common procedure employed for the correction of rectal prolapse in the ROI, with specific approach determined by age.

Technical description of laparoscopic Morgagni hernia repair with primary closure and onlay composite mesh placement.

INTRODUCTION: Morgagni hernias rarely present in adult life and, thus, little data exist on the optimal method of surgical repair. The laparoscopic approach has grown in popularity since the first reported case in 1992. This article showcases a method for laparoscopic repair of Morgagni hernias using both primary closure and mesh reinforcement. OPERATIVE APPROACH: There were three obese women who presented in adulthood with cardiopulmonary symptoms; in all cases, the symptoms were attributable to local compressive effects of large Morgagni hernias. All three hernias were repaired laparoscopically, first by approximating the diaphragm to the fascia of the anterior abdominal wall, followed by insertion of a composite mesh, tacked to the diaphragm, to buttress the closure. All patients had excellent outcomes with symptom resolution. DISCUSSION: This case series describes a method of laparoscopic Morgagni hernia repair using primary closure reinforced with a mesh, with excellent postoperative outcomes. Others have described thoracic or open approaches. The authors feel that the method described herein is likely to reduce recurrence in a patient population who are often overweight or obese and, thus, have a high risk of this complication. Furthermore, we discuss all reported laparoscopic repair cases in the literature and highlight the paucity of evidence on the optimal approach.

Clinical utility of abdominal and pelvic ultrasound in the evaluation of right iliac fossa pain in females.

BACKGROUND: Ultrasound (US) is often the imaging modality of choice in women with acute right iliac fossa (RIF) pain, identifying the appendix in up to 99% of patients. The literature, however, lacks clear guidelines on how ultrasonography should be performed to maximise sensitivity and specificity in such patients. Many centres perform untargeted abdomino-pelvic scans, including organs such as the liver and spleen, which unlikely contribute to the presenting complaint. AIMS: We aimed to evaluate the clinical utility of unfocussed abdominal and pelvic US in women of reproductive age with acute RIF pain. METHODS: This multicentre study describes 501 women between the ages of 12 and 50, over a 3-year period from three institutions, presenting acutely with RIF pain and investigated with US abdomen and pelvis. RESULTS: 5.9% of cases confirmed appendicitis sonographically. A normal appendix was visualised in 0.2%. Over 10% identified gynaecological pathology, 41% relating to the right ovary. 10.4% incidental extra-pelvic findings were unrelated to the acute clinical presentation. 0.8% of patients had extra-pelvic findings meriting further clinical assessment. CONCLUSION: The results herein reflect findings from high volume emergency surgical departments, demonstrating that unfocussed abdominal and pelvic ultrasounds are not an appropriate use of resources in reproductive women with RIF pain. Clinically relevant extra-pelvic US findings account for less than 1%, rarely contributing to the acute presentation. The appendix was only visualised in 6% of patients, suggesting that a focussed appendiceal and pelvic US would better assist diagnosis with a higher yield and increased sensitivity and specificity.

Meta-analysis of the use of surgical sealants for suture-hole bleeding in arterial anastomoses.

BACKGROUND: Suture-hole bleeding in arterial anastomoses prolongs operating time and increases blood loss, particularly with the use of prosthetic grafts. Surgical sealants (such as fibrin) may be used as haemostatic adjuncts in vascular surgery. This is a systematic review and meta-analysis of published studies that investigated the utility of surgical sealants in arterial-to-prosthetic graft anastomoses. METHODS: A systematic review was undertaken of papers published until January 2015 on Embase, MEDLINE, PubMed, PubMed Central and Cochrane databases that analysed the use of surgical sealants as haemostatic adjuncts after arterial anastomoses. RCTs were included, with study endpoints of time to haemostasis or haemostasis at 5 min. Secondary outcomes included treatment failure, mean difference in estimated blood loss and duration of surgery. Sensitivity and subgroup analyses were performed, as well as funnel plot analysis for publication bias. RESULTS: A total of 2513 citations were reviewed; 19 RCTs comprising 1560 patients were ultimately included in the analysis. The majority of studies compared fibrin sealant with control haemostatic measures. Pooled analysis suggested that surgical sealants reduced the time to haemostasis (mean difference 243·26 (95 per cent c.i. 183·99 to 302·53) s; P < 0·001), improved haemostasis at 5 min (odds ratio 4·50, 95 per cent c.i. 2·59 to 7·81; P < 0·001), and were associated with less treatment failure, blood loss and shorter duration of surgery. CONCLUSION: Surgical sealants appear to reduce suture-hole bleeding significantly in vascular prosthetic graft anastomoses compared with standard haemostatic measures.

Systematic review and meta-analysis of the impact of tumour budding in colorectal cancer.

BACKGROUND: Tumour budding is a histological finding in epithelial cancers indicating an unfavourable phenotype. Previous studies have demonstrated that it is a negative prognostic indicator in colorectal cancer (CRC), and has been proposed as an additional factor to incorporate into staging protocols. METHODS: A systematic review of papers until March 2016 published on Embase, Medline, PubMed, PubMed Central and Cochrane databases pertaining to tumour budding in CRC was performed. Study end points were the presence of lymph node metastases, recurrence (local and distal) and 5-year cancer-related death. RESULTS: A total of 7821 patients from 34 papers were included, with a mean rate of tumour budding of 36.8±16.5%. Pooled analysis suggested that specimens exhibiting tumour budding were significantly associated with lymph node positivity (OR 4.94, 95% CI 3.96-6.17, P<0.00001), more likely to develop disease recurrence over the time period (OR 5.50, 95% CI 3.64-8.29, P<0.00001) and more likely to lead to cancer-related death at 5 years (OR 4.51, 95% CI 2.55-7.99, P<0.00001). CONCLUSIONS: Tumour budding in CRC is strongly predictive of lymph node metastases, recurrence and cancer-related death at 5 years, and its incorporation into the CRC staging algorithm will contribute to more effective risk stratification.

Open versus laparoscopic abdominal rectopexy: an examination of early postoperative outcomes.

BACKGROUND: Abdominal rectopexy is used to treat full thickness rectal prolapse and obstructed defecation syndrome, with good outcomes. Use of a laparoscopic approach may reduce morbidity. The current study assessed short-term operative outcomes for patients undergoing laparoscopic or open rectopexy. METHODS: Rectopexy cases were identified from theater logs in two tertiary referral centers. Patient demographics, intra-operative details and early postoperative outcomes were examined. RESULTS: There were 62 patients included over 10 years, a third of whom underwent laparoscopic rectopexy. Laparoscopy was associated with a longer operative time (195.9 versus 129.6 min, p = 0.003), but this did not affect postoperative outcomes, with no significant differences found for complication rates and length of stay between the two groups. Univariable analysis found no influence of laparoscopic approach on the likelihood of postoperative complications, and no factor achieved significance with multivariable analysis. This study included the first laparoscopic cases performed in the involved institutions, and a "learning curve" existed as seen with a decreasing operative duration per case over time (p = 0.002). CONCLUSIONS: Laparoscopic rectopexy has similar short-term outcomes to open rectopexy.

Multicentre study of circumferential margin positivity and outcomes following abdominoperineal excision for rectal cancer.

BACKGROUND: Rectal cancer outcomes following abdominoperineal excision (APE) have been inferior to those for anterior resection, including more positive circumferential resection margins (CRMs). An erroneously conservative interpretation of APE (rather than a radical resection termed 'extralevator') has been proposed as the cause. In this multicentre study, factors contributing to CRM positivity were examined following APE according to its original description. METHODS: Data were collected from five hospital databases up to June 2011 including small- and larger-volume units (3 hospitals had 5 or fewer and 2 hospitals had more than 5 APE procedures per year). Primary outcome measures were CRM status; secondary outcomes were local recurrence and death. RESULTS: Of 327 patients, 302 patients had complete data for analysis. Some 50·0 per cent of patients had neoadjuvant chemoradiotherapy. Histopathological examination showed that 62·9 per cent had tumour category T3 or T4 cancers, 42·1 per cent had node-positive disease and the CRM positivity rate was 13·9 per cent. Multivariable analysis showed only pathological tumour category pT4 (odds ratio 19·92, 95 per cent confidence interval 6·48 to 68·61) and node positivity (odds ratio 3·04, 1·32 to 8·05) to be risk factors for a positive circumferential margin. CRM positivity was a risk factor for local recurrence (P = 0·022) and decreased overall survival (P = 0·001). Hospital volume had no impact on the likelihood of CRM positivity (P = 0·435). CONCLUSION: In patients undergoing APE by appropriately trained surgeons using a standardized approach, margin positivity was dictated by tumour stage, but not by centre or surgeon.

Rapid plastic embedding is compatible with colorimetric detection following whole mount in situ hybridization in plant specimens.

In performing in situ hybridizations, nonisotopic nucleic acid labeling coupled with colorimetric detection offers a safer, easier and more rapid alternative to using radioactively labeled nucleic acid probes and microscopic autoradiography. Whole mount in situ hybridization is also advantageous, because many samples can be processed identically and the reduced handling of specimens greatly reduces the risk of exposing tissues to RNase(s). The thickness of whole mount specimens, however, often prevents accurate determination of sites of expression within specific tissues. Although post-hybridization embedding and sectioning is a solution to this problem, the precipitate formed following the common colorimetric detection procedure is soluble in the organic solvents used for dehydration prior to embedding. We have developed a dehydration and embedding procedure that takes advantage of the compatibility of L.R. White resin containing 10% (v/v) polyethylene glycol 400, and heat polymerized. The addition of the plasticizer allows L.R. White embedded tissues to be sectioned at 10 microm providing excellent signal contrast.

The role of a CNS in a memory clinic.

The advent of medications to treat the symptoms associated with mild to moderate Alzheimer's disease has added to the critical need for early diagnosis of dementia. Yet diagnosis and treatment of Alzheimer's disease require specialized assessment and knowledge. To address the needs of patients and families coping with Alzheimer's disease, an ambulatory care memory clinic was established in Fredericton, New Brunswick, Canada. This article describes the four components of the clinical nurse specialist role in this clinic that reflect the essential characteristics of advanced nursing practice.

Vulnerability, health and health care.

The concept of vulnerability is an important one for nurses because of its implications for health. The experience of vulnerability creates stress and anxiety which affects physiological, psychological and social functioning. Although everyone is vulnerable at different times in his or her life, some individuals are more likely to develop health problems than others. Vulnerability is affected by personal factors as well as factors within the environment. Trends in society indicate that increasing numbers of vulnerable people will create additional demands on an already over-burdened health care system. Vulnerability is an area that requires much further research and application.

Magnetic resonance imaging and single photon emission tomography in treatment-responsive and treatment-resistant schizophrenia.

BACKGROUND: Patients with schizophrenia differ from controls in several measures of brain structure and function, but it is uncertain how these relate to clinical features of the illness. We dichotomised patient groups by treatment response to test the hypothesis that treatment-resistant patients exhibit more marked biological abnormalities than treatment-responsive patients. METHOD: Twenty treatment-responsive and 20 treatment-resistant patients with schizophrenia, matched for sex, age, and illness duration, were compared by magnetic resonance imaging, single photon emission tomography, and detailed neuropsychological assessment. RESULTS: Brain-imaging variables were not statistically related to treatment response, although poorly responsive patients had lower volumes of most brain structures. Several highly significant differences emerged between patient groups on neuropsychological testing. Episodic memory functioning distinguished patient groups even after we controlled for global cognitive impairment. CONCLUSIONS: Cerebral structure and blood flow have a limited effect on treatment response in schizophrenia, but long-term episodic memory impairment is associated with, and may predict, poor prognosis.

Predicted and actual change in serum PSA following prostatectomy for BPH.

OBJECTIVE: To determine the relationship between prostatic adenoma volume and serum prostate-specific antigen (PSA) levels in patients with benign prostatic hyperplasia (BPH), and to compare the predicted change in serum PSA following prostatectomy with the actual change observed. METHODS: Transrectal ultrasound (TRUS) estimation of prostatic adenoma (transition zone) and total gland volumes were calculated in 96 patients prior to prostatectomy. BPH was confirmed histologically following transurethral prostatectomy (in 86) and open prostatectomy (in 10). Serum PSA was measured preoperatively in all patients and post-operatively in 87 patients. RESULTS: Correlation coefficients of 0.607 and 0.614 were observed between PSA and adenoma and total gland volumes, respectively. The geometric mean ratio of PSA to adenoma volume was 0.120 micrograms/L/cc with 95% CI (0.104, 0.139) and to total gland volume was 0.068 micrograms/L/cc with 95% CI (0.058, 0.078). TRUS-determined adenoma and total gland volumes correlated well (r = 0.915), as did TRUS-determined adenoma volume and resected weight (r = 0.878). The mean ratio of change in PSA to resected weight was -0.096 micrograms/L/g with 95% CI (-0.128, -0.064). Neither total gland volume nor operation type affected the relationship between change in serum PSA and resected weight. CONCLUSIONS: The adenoma should be the main determinant of serum PSA levels in patients with BPH. TRUS adenoma volume measurement is therefore the most appropriate preoperative measure when one is interpreting elevated levels of serum PSA in men thought clinically to have BPH.

Identification of human chromosome 9 specific genes using exon amplification.

We have recently developed a method, exon amplification, that is designed for isolation of exon sequences from genomic DNA. To assess the efficacy of this method we have analyzed cosmid genomic clones derived from human chromosome 9, and have cloned several products from this analysis. Approximately 63% of cosmids produced at least one product derived from functioning splice sites within the target genomic fragment, and in many cases multiple products were isolated. In addition, an easily identifiable class of false positives was produced from 56% of cosmids analyzed; these are readily eliminated from subsequent study. Sequence analysis and database searches revealed that the majority (87%) of the putative exon clones were unique, the remainder being derived from repetitive sequences. Analysis of sequence conservation by Southern blotting in addition to cDNA screening experiments suggested that most, if not all, of these unique sequences represent true exons. The results of these studies indicate that exon amplification is a rapid and reliable approach for isolation of exon sequences from mammalian genomic DNA.

Impact of previously unrecognized benign prostatic hyperplasia on the daily activities of middle-aged and elderly men.

To assess the importance of benign prostatic hyperplasia on activities of daily living, a cross-sectional survey of 1627 men aged 40-79 years (representing a 65% response rate) registered with two health centres in central Scotland was carried out, using a urinary symptom questionnaire and uroflowmetry to identify men more likely to have benign prostatic hyperplasia. The condition was defined as a prostate gland of more than 20 g in the presence of symptoms of urinary dysfunction and/or a peak flow rate of less than 15 ml s-1, without evidence of malignancy. Transrectal ultrasonography was used to measure the volume (and by inference weight) of prostate glands. A total of 410 men satisfied the criteria for benign prostatic hyperplasia. Overall, 51% of men with benign prostatic hyperplasia reported interference with at least one of a number of selected activities of daily living as a result of urinary dysfunction, compared with 28% of men who did not have this condition. In 17% of men of working age (40-64 years) with benign prostatic hyperplasia, this interference occurred most or all of the time for at least one activity of daily living compared with only 3% of men in the same age group who did not have this condition. If the criteria of unmet need for treatment of benign prostatic hyperplasia constitutes interference by urinary dysfunction most or all of the time in at least one activity of daily living, then the findings of this survey suggest that a substantial number of middle aged and elderly men living in the United Kingdom may be in need of assessment and treatment for this condition.

Relationship between prostate specific antigen, prostate volume and age in the benign prostate.

The relationship between prostate specific antigen (PSA) levels, prostate volume and age was examined in 472 men who underwent PSA assay (Hybritech), digital rectal examination (DRE) and transrectal ultrasound (TRUS) as part of a community survey of benign prostatic hyperplasia following exclusion of men with prostate cancer. The mean age of the study population was 60 years (range 40-79). The mean PSA was 2.4 ng/ml and 85% of the men had levels < 4 ng/ml. There was a modest correlation between PSA and both age and prostate volume. The mean prostate and adenoma volumes were 32 ml (SD 13.4) and 15 ml (SD 10.7) respectively. Prostate volume increased with age. Linear regression analysis revealed an independent association between PSA and age when controlling for volume. The mean ratio of PSA per unit of prostate volume was 0.072 ng/ml. This ratio also increased with age. Age and prostate volume influences PSA levels independently. The sensitivity and specificity of PSA adjusted for volume and age in the diagnosis of prostate cancer need to be evaluated in association with DRE and TRUS.