Best-practice care pathway for improving management of mastitis and breast abscess.

BACKGROUND: Surgical subspecialization has resulted in mastitis and breast abscesses being managed with unnecessary admission to hospital, prolonged inpatient stay, variable antibiotic prescribing, incision and drainage rather than percutaneous aspiration, and loss to specialist follow-up. The objective was to evaluate a best-practice algorithm with the aim of improving management of mastitis and breast abscesses across a multisite NHS Trust. The focus was on uniformity of antibiotic prescribing, ultrasound assessment, admission rates, length of hospital stay, intervention by aspiration or incision and drainage, and specialist follow-up. METHODS: Management was initially evaluated in a retrospective cohort (phase I) and subsequently compared with that in two prospective cohorts after introduction of a breast abscess and mastitis pathway. One prospective cohort was analysed immediately after introduction of the pathway (phase II), and the second was used to assess the sustainability of the quality improvements (phase III). The overall impact of the pathway was assessed by comparing data from phase I with combined data from phases II and III; results from phases II and III were compared to judge sustainability. RESULTS: Fifty-three patients were included in phase I, 61 in phase II and 80 in phase III. The management pathway and referral pro forma improved compliance with antibiotic guidelines from 34 per cent to 58·2 per cent overall (phases II and III) after implementation (P = 0·003). The improvement was maintained between phases II and III (54 and 61 per cent respectively; P = 0·684). Ultrasound assessment increased from 38 to 77·3 per cent overall (P < 0·001), in a sustained manner (75 and 79 per cent in phases II and III respectively; P = 0·894). Reductions in rates of incision and drainage (from 8 to 0·7 per cent overall; P = 0·007) were maintained (0 per cent in phase II versus 1 per cent in phase III; P = 0·381). Specialist follow-up improved consistently from 43 to 95·7 per cent overall (P < 0·001), 92 per cent in phase II and 99 per cent in phase III (P = 0·120). Rates of hospital admission and median length of stay were not significantly reduced after implementation of the pathway. CONCLUSION: A standardized approach to mastitis and breast abscess reduced undesirable practice variation, with sustained improvements in process and patient outcomes.

Reduced healthcare utilization following successful hepatitis C virus treatment in HIV-co-infected patients with mild liver disease.

New direct-acting antivirals (DAA) for hepatitis C virus (HCV) infection have achieved high cure rates in many patient groups previously considered difficult-to-treat, including those HIV/HCV co-infected. The high price of these medications is likely to limit access to treatment, at least in the short term. Early treatment priority is likely to be given to those with advanced disease, but a more detailed understanding of the potential benefits in treating those with mild disease is needed. We hypothesized that successful HCV treatment within a co-infected population with mild liver disease would lead to a reduction in the use and costs of healthcare services in the 5 years following treatment completion. We performed a retrospective cohort study of HIV/HCV-co-infected patients without evidence of fibrosis/cirrhosis who received a course of HCV therapy between 2004 and 2013. Detailed analysis of healthcare utilization up to 5 years following treatment for each patient using clinical and electronic records was used to estimate healthcare costs. Sixty-three patients were investigated, of whom 48 of 63 (76.2%) achieved sustained virological response 12 weeks following completion of therapy (SVR12). Individuals achieving SVR12 incurred lower health utilization costs (£5,000 per-patient) compared to (£10 775 per-patient) non-SVR patients in the 5 years after treatment. Healthcare utilization rates and costs in the immediate 5 years following treatment were significantly higher in co-infected patients with mild disease that failed to achieve SVR12. These data suggest additional value to achieving cure beyond the prevention of complications of disease.

Cerebral function tests reveal differences in HIV-infected subjects with and without chronic HCV co-infection.

Neurocognitive impairment (NCI) remains prevalent in HIV-infected subjects despite effective combination antiretroviral therapy (CART). In subjects without evidence of hepatic decompensation, NCI is also a feature of chronic HCV infection. The present study aimed to examine cerebral function and establish differences between HIV-HCV co-infected (HCVco) and HIV mono-infected (HIVmo) individuals. Neurologically asymptomatic subjects with chronic HCVco were eligible and underwent computerized neurocognitive testing (CogState; CogState Ltd, Melbourne, Australia), a dementia assessment [International HIV Dementia Scale (IHDS)] and memory assessment [the Prospective and Retrospective Memory Questionnaire (PRMQ)]. Historic control data were available for 45 HIVmo individuals and differences between study groups were assessed. Twenty-seven HCVco subjects were recruited. Plasma HIV RNA was <50 copies/mL in 25/27 of HCVco subjects and all HIVmo subjects and nadir CD4+ cell count (mean ± SD) was 214 ± 166 cells/µL and 180 ± 130 cells/µL, in HCVco and HIVmo subjects, respectively. No statistically significant differences in neurocognitive parameters or PRMQ scores were observed between groups. However, a trend towards poorer executive function score was observed in HCVco subjects (p 0.106). IHDS score (mean ± SD) was poorer in HCVco subjects (10.48 ± 1.25) vs. HIVmo subjects (11.51 ± 0.76), (p <0.001). In a multivariate model, increasing age and HCVco were the only factors significantly associated with poorer IHDS scores (p 0.039 and <0.001, respectively). In HIV-infected subjects stable on CART, statistically significantly poorer performance in the IHDS score was observed in subjects with HCVco, although no differences were observed after neurocognitive testing or memory assessment.

Does acute hepatitis C infection affect the central nervous system in HIV-1 infected individuals?

Central nervous system (CNS) manifestations of chronic hepatitis C virus (HCV) and chronic human immune deficiency virus-1 (HIV-1) infections have been reported, but the impact of acute HCV infection on the CNS is unknown. A total of 10 individuals with chronic stable HIV-1 with documented acute HCV (HCV-RNA polymerase chain reaction positive and HCV antibody negative, group 1) underwent cerebral proton magnetic resonance spectroscopy (MRS) using acquisition parameters to quantify myo-inositol/creatine (mI/Cr) ratio in the right basal ganglia (RBG). Two matched control groups also underwent MRS; group 2: ten with chronic HIV-1 and no evidence of HCV, and group 3: ten with no evidence of HIV or HCV. Subjects also underwent computerized neurocognitive assessments (CogState). RBG mI/Cr ratio in group 1 (acute HCV in a background of HIV) was significantly lower than that in groups 2 and 3 [2.90 (+/-0.7) vs 3.34 (+/-0.4) and 3.43 (+/-0.4), mean (SD) for group 1 vs 2 and 3 respectively, P = 0.049], with 50% of subjects in group 1 having a mI/Cr ratio below the lowest observed ratio in either of the other groups. On neurocognitive testing, significant defects in the monitoring domain were observed in group-1, compared with matched controls (P = 0.021). Acute HCV in HIV-1 infected subjects is associated with CNS involvement. Clinicians should be vigilant of early CNS involvement when assessing subjects with acute HCV.

Resonance widths in open microwave cavities studied by harmonic inversion.

From the measurement of a reflection spectrum of an open microwave cavity, the poles of the scattering matrix in the complex plane have been determined. The resonances have been extracted by means of the harmonic inversion method. By this, it became possible to resolve the resonances in a regime where the linewidths exceed the mean level spacing up to a factor of 10, a value inaccessible in experiments up to now. The obtained experimental distributions of linewidths were found to be in perfect agreement with predictions from random matrix theory when wall absorption and fluctuations caused by couplings to additional channels are considered.

Antibiotic-resistant Campylobacter: an increasing problem.

The case is described of a 27-year-old woman who presented with an acute diarrhoeal illness. She was initially poorly responsive to antibiotics and developed lymphocytic ascites. Diagnosis was difficult to establish, and peritoneal tuberculosis was considered to be the most likely cause of her symptoms. Serological tests eventually confirmed Campylobacter jejuni infection. Campylobacter is one of the most common bacterial diarrhoeal infections, and complications, except for colitis, are rare except in specific disease states--for example, patients with cirrhosis or undergoing peritoneal dialysis. Antibiotic resistance is an increasing problem, and this may potentially lead to a greater incidence of complications in the future.

Effects of load carrying on metabolic cost and hindlimb muscle dynamics in guinea fowl (Numida meleagris).

The goal of this study was to test whether the contractile patterns of two major hindlimb extensors of guinea fowl are altered by load-carrying exercise. We hypothesized that changes in contractile pattern, specifically a decrease in muscle shortening velocity or enhanced stretch activation, would result in a reduction in locomotor energy cost relative to the load carried. We also anticipated that changes in kinematics would reflect underlying changes in muscle strain. Oxygen consumption, muscle activation intensity, and fascicle strain rate were measured over a range of speeds while animals ran unloaded vs. when they carried a trunk load equal to 22% of their body mass. Our results showed that loading produced no significant (P > 0.05) changes in kinematic patterns at any speed. In vivo muscle contractile strain patterns in the iliotibialis lateralis pars postacetabularis and the medial head of the gastrocnemius showed a significant increase in active stretch early in stance (P < 0.01), but muscle fascicle shortening velocity was not significantly affected by load carrying. The rate of oxygen consumption increased by 17% (P < 0.01) during loaded conditions, equivalent to 77% of the relative increase in mass. Additionally, relative increases in EMG intensity (quantified as mean spike amplitude) indicated less than proportional recruitment, consistent with force enhancement via stretch activation, in the proximal iliotibialis lateralis pars postacetabularis; however, a greater than proportional increase in the medial gastrocnemius was observed. As a result, when averaged for the two muscles, EMG intensity increased in direct proportion to the fractional increase in load carried.

Health benefits of antiviral therapy for mild chronic hepatitis C: randomised controlled trial and economic evaluation.

OBJECTIVES: To determine whether combined therapy with interferon-alpha and ribavirin was more effective and cost-effective than no treatment for patients with mild chronic hepatitis C. DESIGN: A multicentre, randomised, controlled, non-blinded trial assessed the efficacy of combination therapy. A Markov model used these efficacy data combined with data on transition probabilities, costs and health-related quality of life (HRQoL) to assess the lifetime cost-effectiveness of the intervention. SETTING: A multicentre NHS setting. PARTICIPANTS: Treatment-naive, adult patients with histologically mild chronic hepatitis C (Ishak necroinflammatory scores <4 and fibrosis scores <3 on liver biopsy). INTERVENTIONS: Patients were randomised to receive interferon-alpha and ribavirin for 48 weeks or no treatment (control). MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients having a sustained virological response (SVR), measured at 6 months after cessation of therapy. Secondary outcome measures were: the ability of early phase kinetics to predict the eventual outcome of treating mild disease; HRQoL measured using the Short Form 36 and EuroQol (5 Dimensions) questionnaires, and the cost per quality-adjusted life-year (QALY) of interferon-alpha and ribavirin for mild disease compared with no treatment. RESULTS: In the treatment group, 32 out of 98 patients (33%) achieved an SVR. Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% versus 49%, p = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved an SVR. HRQoL fell during treatment and rose with treatment cessation. For patients having an SVR there were modest improvements in HRQoL at 6 months post-treatment. The mean cost per QALY gained was 4535 pounds sterling for 40-year-old patients with genotype non-1 and 25,188 pounds sterling for patients with genotype 1. For patients with genotype 1 aged 65, providing interferon-alpha and ribavirin for mild disease led to fewer QALYs gained, and a mean cost per QALY of 53,017 pounds sterling. The model using efficacy estimates from the literature, showed that the cost per QALY gained from providing pegylated interferon alpha-2b and ribavirin at a mild stage rather than a moderate stage was 7821 pounds sterling for patients with genotype non-1 and 28,409 pounds sterling for patients with genotype 1. CONCLUSIONS: Based on the evidence collected in this study, interferon-alpha and ribavirin treatment for mild chronic hepatitis C patients is in general cost-effective at the 30,000 pounds sterling per QALY threshold previously used by policy-makers in the NHS. For patients with chronic hepatitis C aged 65 or over with genotype 1, antiviral treatment at a mild stage does not appear cost-effective. Further research is required on the cost-effectiveness of pegylated interferon and ribavirin, in particular the intervention's long-term impact on HRQoL and health service costs requires further evaluation. Further research is also needed to develop predictive tests, based on pharmacogenomics, that can identify those cases most likely to respond to antiviral therapy. Liver biopsy before treatment no longer appears justified apart from for older patients (aged 65 or over) with genotype 1. However, further research should monitor the impact this strategy would have on costs and outcomes.

Cost effectiveness of interferon alpha or peginterferon alpha with ribavirin for histologically mild chronic hepatitis C.

BACKGROUND: For patients with mild chronic hepatitis C the cost effectiveness of antiviral therapy is unknown. AIMS: To assess whether antiviral therapy (either interferon alpha or peginterferon alpha combined with ribavirin) is cost effective at a mild stage compared with waiting and only treating those cases who progress to moderate disease. PATIENTS: Cases with mild chronic hepatitis C. METHODS: A cost effectiveness model which estimates long term costs and outcomes for patients with mild chronic hepatitis C. The model uses effectiveness and cost data from the UK mild hepatitis C randomised controlled trial, combined with estimates of disease progression and cost from observational studies. RESULTS: Antiviral treatment at a mild rather than a moderate stage improved outcomes measured by quality adjusted life years (QALYS) gained. The mean cost per QALY gained from antiviral treatment with interferon alpha-2b and ribavirin, compared with no treatment at a mild stage, was 4535 pounds sterling (7108 dollars) for patients with genotype non-1 and 25,188 pounds sterling (39,480 dollars) for patients with genotype 1. Providing peginterferon alpha-2b and ribavirin at a mild rather than a moderate stage was also associated with a gain in QALYS; the costs per QALY gained were 7821 pounds sterling (12,259 dollars) for patients with genotype non-1 and 28,409 pounds sterling (44,528 dollars) for patients with genotype 1. CONCLUSIONS: For patients with chronic hepatitis C, it is generally more cost effective to provide antiviral treatment at a mild rather than a moderate disease stage. For older patients (aged 65 years or over) with genotype 1, antiviral treatment at a mild stage is not cost effective.

An elderly lady with sudden blindness and a sore foot.

We report the case of an elderly woman presenting with group G streptococcal septicaemia associated with osteomyelitis and endophthalmitis.

Patient delay in oral cancer: a qualitative study of patients' experiences.

Up to 30% of patients delay seeking the advice of a healthcare professional after self-discovery of symptom(s) of oral cancer. Reasons for this patient delay are poorly understood. The aim of the present study was to explore patients' initial experiences and reactions to developing symptoms of oral cancer, and to identify factors influencing their decision to consult a health care professional. In-depth semi-structured interviews were conducted with 17 consecutive patients who had received a diagnosis of oral squamous cell carcinoma, but had yet to start treatment. Participants were asked about their beliefs about their symptoms over the course of the disease and their decision to seek help. The tape-recorded interviews were transcribed verbatim and analysed using 'Framework analysis'. Oral symptoms were rarely attributed to cancer and were frequently interpreted as minor oral conditions. As a result of these beliefs, patients tended to postpone seeking help or fail to be concerned over their symptoms. Prior to seeking help, patients responded to symptoms by using self-medication, changing the way they ate and disclosing their discovery of symptoms to friends or family. Problems with access to healthcare professionals and patients' social responsibilities acted as barriers to prompt help-seeking. This study has documented that an individual's interpretation of oral cancer symptoms may be misguided and this can adversely affect subsequent help-seeking behaviour.

Treatment of hepatitis C.

The combination of pegylated interferon alpha and ribavirin has improved treatment success rates in patients with hepatitis C with sustained response rates of just over 50% overall and more than 70% for those with genotypes 2 and 3. This article reviews the use of combination therapy, contraindications, factors influencing response and describes approaches to specific patient groups.

Discontinuation of pegylated interferon plus ribavirin in patients who are not responding to therapy -- patients' views of early cessation of therapy.

BACKGROUND: Current therapy for chronic hepatitis C infection involves a course of pegylated interferon and ribavirin. Patients who do not show a virological response after 12 weeks of therapy have a low probability of sustained virological response and it is therefore recommended that such patients stop treatment. AIM: To assess patients' views of early treatment cessation. METHODS: We conducted a open-labelled study in three UK centres, in which patients with biopsy-proven chronic hepatitis C requiring therapy were offered the choice of a full course of therapy with 40 kDa pegylated interferon-alpha 2a plus ribavirin (24 or 48 weeks depending on viral genotype) or early cessation if therapy had failed after 12 weeks. RESULTS: Ninety-five participants were enrolled and the majority (69%) did not wish to discontinue therapy even if it had low probability of success. In this unselected UK population, very few patients (4%) did not achieve an early virological response with the 40-kDa pegylated interferon-alpha 2a plus ribavirin and two of the four early virological non-responders decided to continue therapy. CONCLUSION: Early discontinuation of 'ineffective' anti-viral therapy may prove less popular with patients than with health care providers, and further patient-directed education regarding the cost-effectiveness of therapy will be needed if early discontinuation of unsuccessful therapy is to be accepted by patients.

Treatment of histologically mild hepatitis C virus infection with interferon and ribavirin: a multicentre randomized controlled trial.

Current guidelines advocate no treatment for patients with histologically mild hepatitis C virus (HCV) infection. This was a UK multicentre randomized controlled trial comparing alpha-interferon (3 MU thrice weekly) + ribavirin (1000-1200 mg/day) for 48 weeks with no treatment in treatment naive, adult patients with histologically mild chronic HCV infection. The aim was to compare benefits, safety and efficacy of combination therapy with alpha-interferon 2b and ribavirin for 48 weeks with no treatment (current standard management) in this patient group. In the treatment group 32 of 98 (33%) patients achieved a sustained virological response (SVR). Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% vs 49% P = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved SVR. Improvements in quality of life 24 weeks postcessation of therapy compared with baseline using the SF-36 questionnaire measures were observed in the treated group. For patients with mild HCV infection with viral genotype non-1, the results are sufficiently good to suggest that therapeutic decisions should no longer be biopsy-driven. For patients infected with genotype 1, a liver biopsy is still indicated as the low chance of SVR is outweighed by an unacceptable burden of side-effects. Patients who fail to respond by 12 weeks of therapy should have their treatment curtailed early.

Hepatitis C: How should we manage the patient?

The patient with HCV infection may present with a variety of problems and range from the asymptomatic patient with mild liver damage to a patient presenting with complications of cirrhosis or hepatocellular carcinoma. The diagnosis of hepatitis C may be a complete surprise to the patient or be an expected diagnosis in someone with known risk factors. Similarly the physician may be faced with a patient who knows very little about hepatitis C or someone who has read extensively on the subject. The initial consultation is useful for gaining information on the patient's background, physical examination may give useful clinical clues on the stage of the liver disease. The consultation gives the physician a chance to educate the patient on the current thinking on hepatitis C and to organize confirmatory and other investigations that will help decide on the next line of management, i.e. whether the patient is a candidate for combination therapy of interferon and ribavirin.