Diagnostic performance of a faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: an evaluation in the South West of England

Background The faecal immunochemical test (FIT) was introduced to triage patients with low-risk symptoms of possible colorectal cancer in English primary care in 2017, underpinned by little primary care evidence.Methods All healthcare providers in the South West of England (population 4 million) participated in this evaluation. 3890 patients aged ≥50 years presenting in primary care with low-risk symptoms of colorectal cancer had a FIT from 01/06/2018 to 31/12/2018. A threshold of 10 μg Hb/g faeces defined a positive test.Results Six hundred and eighteen (15.9%) patients tested positive; 458 (74.1%) had an urgent referral to specialist lower gastrointestinal (GI) services within three months. Forty-three were diagnosed with colorectal cancer within 12 months. 3272 tested negative; 324 (9.9%) had an urgent referral within three months. Eight were diagnosed with colorectal cancer within 12 months. Positive predictive value was 7.0% (95% CI 5.1–9.3%). Negative predictive value was 99.8% (CI 99.5–99.9%). Sensitivity was 84.3% (CI 71.4–93.0%), specificity 85.0% (CI 83.8–86.1%). The area under the ROC curve was 0.92 (CI 0.86–0.96). A threshold of 37 μg Hb/g faeces would identify patients with an individual 3% risk of cancer.Conclusions FIT performs exceptionally well to triage patients with low-risk symptoms of colorectal cancer in primary care; a higher threshold may be appropriate in the wake of the COVID-19 crisis.Subject terms: Digestive signs and symptoms, Diagnostic markers, Gastrointestinal cancer     

Local Anesthetic Inhibition of m1 Muscarinic Acetylcholine Signaling

Background: Local anesthetics inhibit lipid mediator signaling (lysophosphatidate, thromboxane) by acting on intracellular domains of the receptor or on the G protein. On receptors for polar agonists, the ligand-binding pocket could form an additional site of interaction, possibly resulting in superadditive inhibition. The authors therefore investigated the effects of local anesthetics on m1 muscarinic receptor functioning.

Methods: The authors expressed receptors in isolation using Xenopus oocytes. Using a two-electrode voltage clamp, the authors measured the effects of lidocaine, QX314 (permanently charged), and benzocaine (permanently uncharged) on Ca2+-activated Cl- currents elicited by methylcholine. The authors also characterized the interaction of lidocaine with [3H] quinuclydinyl benzylate ([3H]QNB) binding to m1 receptors.

Results: Lidocaine inhibited muscarinic signaling with a half-maximal inhibitory concentration (IC50 18 nm) 140-fold less than that of extracellularly administered QX314 (IC50 2.4 [mu]m). Intracellularly injected QX314 (IC50 0.96 mm) and extracellularly applied benzocaine (IC50 1.2 mm) inhibited at high concentrations only. Inhibition of muscarinic signaling by extracellularly applied QX314 and lidocaine was the result of noncompetitive antagonism. Intracellularly injected QX314 and benzocaine inhibited muscarinic and lysophosphatidate signaling at similar concentrations, suggesting an action on the common G-protein pathway. Combined administration of intracellularly injected (IC50 19 [mu]m) and extracellularly applied QX314 (IC50 49 nm) exerted superadditive inhibition. Lidocaine did not displace specific [3H]QNB binding to m1 receptors.     

High-frequency oscillatory ventilation in premature infants with respiratory failure: a preliminary report

High-frequency ventilation has been used successfully to manage life-threatening complications in premature infants with lung disease. Here we report a preliminary assessment of the efficacy and safety of high-frequency oscillatory ventilation-(HFO-A, A = active expiratory phase) when used as a primary ventilator in 11 infants of 24-34 weeks gestation who required ventilatory support. HFO-A was initiated after no more than 5.5 hr of conventional mechanical ventilation (CMV). HFO-A at 15 Hz was used for 12-203 hr following a protocol designed for rapid reduction of FI02 requirements. CO2 elimination was easily achieved in all infants. Oxygenation was satisfactory, except in one infant with congenital pneumonia. There were four deaths during HFO-A: two pulmonary (one congenital pneumonia; one pulmonary hemorrhage) and two nonpulmonary. The HFO-A protocol utilized lung volume recruitment maneuvers plus mean airway pressures (MAwP) greater than those generally used early in the course of CMV. Therefore, in a subset of infants less than or equal to 29 weeks' gestation with respiratory distress syndrome (RDS), ventilator pressures and gas exchange were compared in infants treated with either HFO-A or CMV. Maximum MAwP levels were reached earlier in six infants on HFO-A (5.2 +/- 2.5 hr; mean +/- SD) than in a comparable group of 9 CMV-treated infants (36 +/- 1 hr). This earlier use of high MAwP lowered the FI02 to less than 0.4 by 18.9 +/- 11 hr with HFO-A as compared with 64 +/- 6 hr using CMV, without any evidence of an increase in pulmonary complications. There were 17 complications in the nine CMV-treated infants; and four in the six HFO-A treated ones. We conclude that HFO-A, instituted early and used with a protocol designed for early reduction in FI02 requirements, demonstrates sufficient efficacy and safety to warrant further clinical trials in the routine management of infant RDS.     

Supported discharge service versus inpatient care evaluation (SITE): a randomised controlled trial comparing effectiveness of an intensive community care service versus inpatient treatment as usual for adolescents with severe psychiatric disorders: self-harm,functional impairment,and educational and clinical outcomes

Clinical guidelines recommend intensive community care service treatment (ICCS) to reduce adolescent psychiatric inpatient care. We have previously reported that the addition of ICCS led to a substantial decrease in hospital use and improved school re-integration. The aim of this study is to undertake a randomised controlled trial (RCT) comparing an inpatient admission followed by an early discharge supported by ICCS with usual inpatient admission (treatment as usual; TAU). In this paper, we report the impact of ICCS on self-harm and other clinical and educational outcomes. 106 patients aged 12–18 admitted for psychiatric inpatient care were randomised (1:1) to either ICCS or TAU. Six months after randomisation, we compared the two treatment arms on the number and severity of self-harm episodes, the functional impairment, severity of psychiatric symptoms, clinical improvement, reading and mathematical ability, weight, height and the use of psychological therapy and medication. At six-month follow-up, there were no differences between the two groups on most measures. Patients receiving ICCS were significantly less likely to report multiple episodes (five or more) of self-harm (OR = 0.18, 95% CI: 0.05–0.64). Patients admitted to private inpatient units spent on average 118.4 (95% CI: 28.2–208.6) fewer days in hospitals if they were in the ICCS group compared to TAU. The addition of ICCS to TAU may lower the risk of multiple self-harm and may reduce the duration of inpatient stay, especially in those patients admitted for private care. Early discharge with ICCS appears to be a viable alternative to standard inpatient treatment.

     

Universal Mindfulness Training in Schools for Adolescents: a Scoping Review and Conceptual Model of Moderators,Mediators, and Implementation Factors

Prevention Science - There is evidence that universal school-based mindfulness training (SBMT) can have positive effects for young people. However, it is unknown who benefits most from such...     

Randomized controlled trial of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: the POPMACT study

BACKGROUND: We carried out a large randomized trial of a brief form of cognitive therapy, manual-assisted cognitive behaviour therapy (MACT) versus treatment as usual (TAU) for deliberate self-harm. METHOD: Patients presenting with recurrent deliberate self-harm in five centres were randomized to either MACT or (TAU) and followed up over 1 year. MACT patients received a booklet based on cognitive behaviour therapy (CBT) principles and were offered up to five plus two booster sessions of CBT from a therapist in the first 3 months of the study. Ratings of parasuicide risk, anxiety, depression, social functioning and global function, positive and negative thinking, and quality of life were measured at baseline and after 6 and 12 months. RESULTS: Four hundred and eighty patients were randomized. Sixty per cent of the MACT group had both the booklet and CBT sessions. There were seven suicides, five in the TAU group. The main outcome measure, the proportion of those repeating deliberate self-harm in the 12 months of the study, showed no significant difference between those treated with MACT (39%) and treatment as usual (46%) (OR 0.78, 95% CI 0.53 to 1.14, P=0.20). CONCLUSION: Brief cognitive behaviour therapy is of limited efficacy in reducing self-harm repetition, but the findings taken in conjunctin with the economic evaluation (Byford et al. 2003) indicate superiority of MACT over TAU in terms of cost and effectiveness combined.     

Evaluation of an indirect fluorescent-antibody stain for detection of Pneumocystis carinii in respiratory specimens.

Two prospective studies were undertaken to evaluate a commercial indirect fluorescent-antibody (IFA) stain for the detection of Pneumocystis carinii in respiratory specimens from individuals at risk for or with the acquired immunodeficiency syndrome. The first study compared IFA with Diff-Quik (DQ; a rapid Giemsa-like stain) for detecting P. carinii in 95 induced sputa obtained from 77 asymptomatic patients who had survived one previous episode of P. carinii pneumonia and who were being treated prophylactically with aerosolized pentamidine. Only one induced sputum specimen was found to contain P. carinii; organisms were detected by both stains. The second study compared the performance of the IFA stain versus DQ, modified toluidine blue O, and Gomori methenamine silver stains for detecting P. carinii in symptomatic individuals at risk for or with acquired immunodeficiency syndrome. Of 182 specimens examined, P. carinii was detected in 105 by one or more stains; the DQ stain detected 73 (70%), the modified toluidine blue O stain detected 75 (71%), the Gomori methenamine silver stain detected 76 (72%), and the IFA stain detected 95 (90%). The IFA stain was more sensitive (P less than 0.01) than the other traditional stains for detecting P. carinii; however, a subsequent clinical evaluation revealed that a subset of IFA-positive-only specimens were from patients whose clinical symptoms resolved without specific anti-P. carinii therapy.     

Campylobacter-like organisms are uncommon pathogens in patients infected with the human immunodeficiency virus.

Over a 25-month period, we prospectively evaluated 36 patients with symptomatic human immunodeficiency virus disease (including 27 with unexplained chronic diarrhea) by flexible sigmoidoscopy for the presence of Campylobacter-like organisms. No Campylobacter-like organisms were isolated. Campylobacter-like organisms appear to be an uncommon cause of idiopathic chronic diarrhea in symptomatic human immunodeficiency virus disease.