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.

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.

Retention of potential to differentiate in long-term cultures of tooth germs.

When tooth germs derived from 14-day mouse embryos were cultured on gelatin sponges in vitro for 37 days, they lost their characteristic morphology, appearing as a layer of undifferentiated epithelium on the sponge surface, with the mesenchymal cells scattered throughout the interstices. These cultures were then transplanted subcutaneously into isologous, newborn recipients and, over a period of 56 days, developed into incisor teeth that were almost perfect in shape and structure.

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.

Doppler color flow mapping of epicardial coronary arteries: initial observations.

OBJECTIVES: We addressed the hypothesis that blood flow could be imaged by Doppler color flow mapping of the coronary arteries and characteristic patterns described in normal and diseased vessels. BACKGROUND: Echocardiographic imaging of the epicardial coronary arteries has been suggested as a useful adjunct to their intraoperative evaluation. Addition of Doppler color flow mapping could potentially enhance this evaluation by displaying the flow disturbance produced by anatomic lesions whose physiologic significance may otherwise be uncertain. In experimental models, such displays could also potentially provide insights into the pathophysiology of coronary blood flow and stenosis. METHODS: Epicardial coronary arteries were examined with a high resolution 7-MHz linear phased-array transducer both in vivo and in vitro. 1) The coronary arteries were studied in the beating hearts of 10 open chest dogs in which experimental stenoses were also created; the maximal extent of the arterial tree in which flow could be seen in the most ideal setting was also examined in four additional excised perfused canine hearts. 2) Six excised human coronary arteries were perfused in a pulsatile manner to determine whether abnormal flow patterns could be prospectively identified and subsequently correlated with pathologic evidence of stenosis. RESULTS: All normal coronary artery segments studied showed homogeneous flow without evidence of flow disturbance. In the excised heart, flow could be visualized to the distal extent of the epicardial vessels; in the open chest model, visualization of the proximal 5 to 6 cm was comparable, although surrounding structures limited access to the terminal portions of the vessels. The stenotic lesions created in the canine hearts (n = 9) showed recognizable alterations in the flow pattern: localized aliasing, proximal blood flow acceleration, distal flow disturbance and recirculatory flow. In the excised human arteries, these features identified 12 lesions, all of which corresponded to areas of > or = 50% lumen narrowing by pathologic examination. CONCLUSION: Blood flow in the epicardial coronary arteries can be imaged by Doppler color flow mapping and characteristic flow patterns described in normal and diseased vessels.

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.

Disseminated strongyloidiasis in AIDS: uncommon but important.

Disseminated Strongyloides stercoralis infection is a rare and severe but treatable complication of AIDS. We present a case where this infection was successfully treated and review the available literature. Cases may present many years after they have left an area endemic for Strongyloides infection, emphasizing the need for a full travel history. Symptoms are typically gastrointestinal and pulmonary, with infiltrates often seen on chest radiography. Diagnosis requires stool examination and biopsy of affected sites. Treatment with repeated courses of thiabendazole (25 mg/kg twice daily for 5 days) was successful in our case, but maintenance regimens have not yet been defined. The relative rarity of this complication of AIDS suggests that, where both infections are present, disseminated strongyloidiasis only arises either when HIV-induced immunodeficiency is profound or, possibly, when it is accompanied by impaired granulopoiesis.

Relation between coffee drinking and blood pressure: analysis of 6,321 subjects in the Paris region.

The possible link between coffee drinking and blood pressure (BP) was studied in a cross-sectional epidemiologic survey of 6,321 adults in the Paris region. Systolic and diastolic BP levels were higher among the 5,430 coffee drinkers than among the 891 nondrinkers (p less than 0.001 and p less than 0.01). BP levels adjusted for age by covariance analysis increased gradually from the non-coffee consumption category (125.6/79.8 +/- 15.0/10.5 mm Hg [mean +/- standard deviation]) to the highest consumption category (greater than or equal to 5 cups/day) (128.1/80.6 +/- 15.6/10.2 mm Hg) (p less than 0.001 for systolic BP and p less than 0.002 for diastolic BP). The positive association between coffee consumption and systolic, but not diastolic, BP remained significant in a multivariate analysis after controlling for age, sex, body mass index, alcohol consumption, tobacco consumption and socioeconomic category (p less than 0.02 for systolic BP and p = 0.16 for diastolic BP). It is concluded that coffee consumption is a significant but not strong contributor to the variation in BP levels.

Endothelium modulation of the effects of nitroglycerin on blood vessels from dogs with pacing-induced heart failure.

1. The relaxant actions of nitroglycerin (previously considered to be an endothelium-independent relaxing agent) and acetylcholine (an endothelium-dependent relaxing agent) were compared on 4 vascular preparations (dorsal pedal artery, saphenous vein, left anterior descending coronary artery and circumflex coronary artery) from dogs with and without pacing-induced congestive heart failure (CHF). 2. Responses of the coronary arteries to acetylcholine were unaltered in endothelium-intact rings from dogs with and without heart failure. Similarly no such changes were observed in the peripheral vessels. The maximum relaxation produced by acetylcholine was always greater in the coronary vessels compared to the peripheral vessels. 3. Before heart failure, the coronary vessels were more sensitive and reactive to nitroglycerin compared to the peripheral vessels. 4. Removal of the endothelium in both the control (dogs without CHF) and experimental (dogs with CHF) rings enhanced the relaxant effects of nitroglycerin, such that the EC50 for nitroglycerin became significantly lower in all denuded rings, with the exception of the saphenous vein and the left anterior descending coronary artery, before the development of CHF. 5. When CHF was maximally developed, vascular sensitivity to nitroglycerin was increased in peripheral vessels with an intact endothelium, but not in the coronary vessels. 6. These findings indicate that relaxation produced by nitroglycerin cannot be considered as entirely endothelium-independent but should be considered endothelium-modulated.

Short report: prednisolone withdrawal followed by lymphoblastoid interferon in the therapy of adult patients with presumed childhood-acquired chronic hepatitis B virus infection.

Eighteen patients with presumed childhood acquisition of chronic hepatitis B virus infection were initially entered into this randomized controlled trial. Twelve were treated with prednisolone for 4 weeks followed, after a 2-week gap, by thrice weekly lymphoblastoid alpha-interferon for 12 weeks. Two of these had previously acted as untreated controls. Three of the 12 patients (25%) [who were initially hepatitis B virus (HBV) surface antigen (HBsAg), 'e' antigen (HBeAg) and HBV-DNA positive] became HBeAg and HBV-DNA negative during therapy and remained so after 12 months post-therapy follow-up. One of these also lost HBsAg. A further two patients lost HBeAg and HBV-DNA during therapy but relapsed 6 and 9 months later. Two additional patients were HBV-DNA negative but HBeAg positive at the end of follow-up. None of the eight untreated control patients seroconverted during an identical follow-up period. Two further patients were HBsAg and HBeAg positive but HBV-DNA negative at the start of therapy. These were omitted from the final analysis: both subsequently lost HBeAg. The treatment response was associated with a rise in aspartate aminotransferase, peaking 2-6 weeks after prednisolone withdrawal, loss of HBV-DNA 0-8 weeks later and subsequent normalization of liver function tests. Treatment was well tolerated.

Severe haemolysis and renal failure in a patient with paroxysmal nocturnal haemoglobinuria.

Transfusion of about 60 ml of ABO incompatible plasma in 4 units of pooled platelets precipitated severe haemolysis, unmasking the emergence of paroxysmal nocturnal haemoglobinuria (PNH), in a patient with aplastic anaemia. In vitro tests showed that her red cells were lysed by both ABO compatible and incompatible plasma from normal donors. The behaviour of this case and the in vitro results suggest that it might be hazardous to relax the longstanding recommendation on transfusing patients with PNH by restricting the washing of blood components to those containing ABO incompatible plasma.

Histological and immunohistochemical study of hepatitis B virus in human immunodeficiency virus infection.

Because the risk factors for human immunodeficiency virus (HIV) infection and hepatitis B (HBV) are similar and therefore coinfection is not uncommon, a detailed histological and immunohistochemical study of chronic hepatitis B infection in a group of 20 HIV positive Caucasian males (who did not have AIDS) and 30 HIV negative controls were undertaken. Using both the conventional histological classification and the Knodell histological activity index it was shown that HIV negative patients were more likely to have active disease and also more scarring than HIV positive patients. Hepatitis B surface antigen (HBsAg) expression was not significantly different between the two groups but expression of hepatitis Be antigen (HBeAg) and HBV-DNA polymerase was greater in those who were HIV positive. HIV positive patients are therefore more likely to have immunohistochemical markers of active viral replication, although histologically, liver disease is less severe. These findings have important implications for assessing the biopsy specimens in this group of patients and for treatment strategies aimed at improving their immune function.

Adverse effects of drugs used in the management of opportunistic infections associated with HIV infection.

Pneumocystis carinii pneumonia (PCP) is one of the most common AIDS-defining diagnoses. First-line therapy is cotrimoxazole (trimethoprim-sulfamethoxazole), despite a high incidence of toxic effects, and a greater incidence of hypersensitivity reactions among HIV-positive patients compared with the seronegative population. Alternative agents such as intravenous pentamidine, or clindamycin with primaquine, and trimethoprim with dapsone, also have a wide range of serious adverse effects, but remain treatment options. Atovaquone appears promising for the treatment of both PCP and toxoplasmosis, and has a lower reported incidence of toxicity than the alternative agents. The most toxic antifungal drugs are reserved for serious infections, such as cryptococcal meningitis. Liposomal amphotericin B has less renal toxicity than standard formulations, and exemplifies that new formulations of existing drugs, although often expensive, may have a better adverse effect profile. There are 2 different drugs currently available for cytomegalovirus (CMV) infections, ganciclovir and foscarnet. Both have a high incidence of serious adverse effects; ganciclovir mainly causes bone marrow toxicity and foscarnet leads to renal toxicity. The drugs used for mycobacterial infection (including mycobacteria as well as tuberculosis) have a wide range of adverse effects, particularly skin rashes and drug-induced hepatitis. Some of these compounds are quite new, such as rifabutin and clarithromycin, and it is important to be ever vigilant for previously unreported adverse effects.

Computer-assisted evaluation of antibiotic regimen coverage and cost.

Evaluation of the cost-effectiveness of antibiotic regimens has become an essential part of drug selection for pharmacists and physicians. However, these evaluations can be complicated, time-consuming, and, if the data used are not based on local conditions, misleading. The computer program Dare to Compare 98 was developed to provide an analysis of empiric antibiotic regimens. The Infectious Disease Challenge portion of the program lists the commonly identified pathogens in specific infectious diseases. The Antibiogram Susceptibility Reports section generates susceptibility reports based on local antibiogram data or data from institutions nationwide that have similar demographic profiles. Susceptibility information is combined with cost data in the Quality/Cost Index section. Comparison of the quality and cost index values allows the user to determine which regimens provide the optimal microbiologic activity and cost values for treatment of a particular infectious disease based on local data. Thus Dare to Compare 98 can help pharmacists and physicians evaluate antibiotic regimens and their suitability for inclusion in formularies and disease-management algorithms.

Therapy of chronic viral hepatitis.

Chronic infection with hepatitis B virus (HBV), the delta agent (HDV) or hepatitis C virus (HCV) carries high risks of chronic liver disease which can result in cirrhosis and hepatocellular carcinoma. Many antiviral agents have been tried to inhibit viral replication and thereby limit infectivity and the risks of eventual serious liver disease. Interferon offers a 30-40% chance of viral clearance to the hepatitis B carrier, offers a good chance of clinical response in parenterally acquired chronic non-A non-B hepatitis and may be of benefit for some patients with chronic delta infection.

The effect of vitamin A on hamster cheek pouch mucosa in organ culture.

Vitamin A was added to the medium of neonatal hamster cheek pouch mucosa maintained in organ culture. The epithelium of the treated explants showed a reduction in keratinization and down-growth into the underlying connective tissue. The cytological and morphological changes in the epithelium were consistent with glandular metaplasia.