Nutraceuticals known to promote hair growth do not interfere with the inhibitory action of tamoxifen in MCF7, T47D and BT483 breast cancer cell lines.

BACKGROUND: Hair loss/thinning is a common side effect of tamoxifen in estrogen receptor (ER) positive breast cancer therapy. Some nutraceuticals known to promote hair growth are avoided during breast cancer therapy for fear of phytoestrogenic activity. However, not all botanical ingredients have similarities to estrogens, and in fact, no information exists as to the true interaction of these ingredients with tamoxifen. Therefore, this study sought to ascertain the effect of nutraceuticals (+/- estrogen/tamoxifen), on proliferation of breast cancer cells and the relative expression of ERα/ß. METHODS: Kelp, Astaxanthin, Saw Palmetto, Tocotrienols, Maca, Horsetail, Resveratrol, Curcumin and Ashwagandha were assessed on proliferation of MCF7, T47D and BT483 breast cancer cell lines +/- 17ß-estradiol and tamoxifen. Each extract was analysed by high performance liquid chromatography (HPLC) prior to use. Cellular ERα and ERß expression was assessed by qRT-PCR and western blot. Changes in the cellular localisation of ERα:ERß and their ratio following incubation with the nutraceuticals was confirmed by immunocytochemistry. RESULTS: Estradiol stimulated DNA synthesis in three different breast cancer cell lines: MCF7, T47D and BT483, which was inhibited by tamoxifen; this was mirrored by a specific ERa agonist in T47D and BT483 cells. Overall, nutraceuticals did not interfere with tamoxifen inhibition of estrogen; some even induced further inhibition when combined with tamoxifen. The ERα:ERß ratio was higher at mRNA and protein level in all cell lines. However, incubation with nutraceuticals induced a shift to higher ERß expression and a localization of ERs around the nuclear periphery. CONCLUSIONS: As ERα is the key driver of estrogen-dependent breast cancer, if nutraceuticals have a higher affinity for ERß they may offer a protective effect, particularly if they synergize and augment the actions of tamoxifen. Since ERß is the predominant ER in the hair follicle, further studies confirming whether nutraceuticals can shift the ratio towards ERß in hair follicle cells would support a role for them in hair growth. Although more research is needed to assess safety and efficacy, this promising data suggests the potential of nutraceuticals as adjuvant therapy for hair loss in breast cancer patients receiving endocrine therapy.

No evidence for enhanced processing of speech that is low-pass filtered near the edge frequency of cochlear dead regions in children.

OBJECTIVES: Cochlear dead regions (DRs) are regions in the cochlea where the inner hair cells and/or neurons are not functioning. Adults with extensive high-frequency DRs have enhanced abilities in processing sounds with frequencies just below the edge frequency, fedge, of the DR. It was assessed whether the same is true for children. DESIGN: Performance was compared for children aged 8 to 13 years with: DRs (group DR), hearing impairment but without DRs (group NODR), and normal hearing (group NH). Seven ears in each group were tested. Each ear in the DR group was matched in age and low-frequency hearing with an ear in the NODR group, and in age with an ear in the NH group, giving seven "triplets". Within each triplet, the percent correct identification of vowel-consonant-vowel stimuli was measured using stimuli that were low-pass filtered at fedge and 0.67fedge, based on the ear with a DR. For the hearing-impaired ears, stimuli were given frequency-selective amplification as prescribed by DSL 4.1. RESULTS: No significant differences in performance were found between groups for either low-pass cut-off frequency. CONCLUSION: Unlike adults, the children with DRs did not show enhanced discrimination of speech stimuli with frequencies below fedge.

Access, continuity of care and consultation quality: which best predicts urgent cancer referrals from general practice?

BACKGROUND: For some cancers, late presentation is associated with poor survival. In England, less than half of patients are diagnosed following a general practitioner-initiated urgent referral. We explore whether particular practice or practitioner characteristics are associated with use of the urgent referral system. METHODS: The study sample was 603/614 practices in the East Midlands. Logistic regression models were fitted to investigate relationships between cancer detection rate, how easy it is to book appointments quickly, in advance or with a preferred doctor, and whether patients have confidence and trust in the doctor. RESULTS: The percentage of patients who definitely have confidence and trust in the doctor was positively associated with the cancer detection rate [odds ratio = 1.08 (95% confidence interval (CI) 1.01, 1.15) per 10 percentage points]. When all four survey variables were modelled together, the percentage of patients who were able to see a preferred doctor was negatively associated with the cancer detection rate [odds ratio = 0.93 (95% CI 0.88, 0.98) per 10 percentage points]. CONCLUSIONS: Our analyses suggest that in the UK National Health Service, confidence and trust in the doctor may be more important in cancer detection than the ease of access or whether there is choice of doctor.

Culture and behaviour in the English National Health Service: overview of lessons from a large multimethod study.

BACKGROUND: Problems of quality and safety persist in health systems worldwide. We conducted a large research programme to examine culture and behaviour in the English National Health Service (NHS). METHODS: Mixed-methods study involving collection and triangulation of data from multiple sources, including interviews, surveys, ethnographic case studies, board minutes and publicly available datasets. We narratively synthesised data across the studies to produce a holistic picture and in this paper present a high-level summary. RESULTS: We found an almost universal desire to provide the best quality of care. We identified many 'bright spots' of excellent caring and practice and high-quality innovation across the NHS, but also considerable inconsistency. Consistent achievement of high-quality care was challenged by unclear goals, overlapping priorities that distracted attention, and compliance-oriented bureaucratised management. The institutional and regulatory environment was populated by multiple external bodies serving different but overlapping functions. Some organisations found it difficult to obtain valid insights into the quality of the care they provided. Poor organisational and information systems sometimes left staff struggling to deliver care effectively and disempowered them from initiating improvement. Good staff support and management were also highly variable, though they were fundamental to culture and were directly related to patient experience, safety and quality of care. CONCLUSIONS: Our results highlight the importance of clear, challenging goals for high-quality care. Organisations need to put the patient at the centre of all they do, get smart intelligence, focus on improving organisational systems, and nurture caring cultures by ensuring that staff feel valued, respected, engaged and supported.

The effects of Sophora angustifolia and other natural plant extracts on melanogenesis and melanin transfer in human skin cells.

Skin pigmentation is a multistep process of melanin synthesis by melanocytes, its transfer to recipient keratinocytes and its degradation. As dyspigmentation is a prominent marker of skin ageing, novel effective agents that modulate pigmentation safely are being sought for both clinical and cosmetic use. Here, a number of plant extracts were examined for their effect on melanogenesis (by melanin assay and Western blotting) and melanin transfer (by confocal immunomicroscopy of gp100-positive melanin granules in cocultures and by SEM analysis of filopodia), in human melanocytes and in cocultures with phototype-matched normal adult epidermal keratinocytes. Mulberry, Kiwi and Sophora extracts were assessed against isobutylmethylxanthine, hydroquinone, vitamin C and niacinamide. Compared with unstimulated control, all extracts significantly reduced melanogenesis in human melanoma cells and normal adult epidermal melanocytes. These extracts also reduced melanin transfer and reduced filopodia expression on melanocytes, similar to hydroquinone and niacinamide, indicating their effectiveness as multimode pigmentation actives.

Albuterol enantiomer levels, lung function and QTc interval in patients with acute severe asthma and COPD in the emergency department.

BACKGROUND: This observational study was designed to investigate plasma levels of albuterol enantiomers among patients with acute severe asthma or COPD presenting to the emergency department, and the relationship with extra-pulmonary cardiac effects (QTc interval) and lung function. Recent reviews have raised concerns about the safety of using large doses of ß2-agonists, especially in patients with underlying cardiovascular comorbidity. It has been demonstrated that significant extrapulmonary effects can be observed in subjects given nebulised (R/S)-albuterol at a dose of as little as 6.5 mg. METHODS: Blood samples were collected and plasma/serum levels of (R)- and (S)-albuterol enantiomers were determined by LC-MS and LC-MS/MS assay. Extra-pulmonary effects measured at presentation included ECG measurements, serum potassium level and blood sugar level, which were collected from the hospital medical records. RESULTS: High plasma levels of both enantiomers were observed in some individuals, with median (range) concentrations of 8.2 (0.6-24.8) and 20.6 (0.5-57.3) ng/mL for (R)- and (S)- albuterol respectively among acute asthma subjects, and 2.1 (0.0-16.7) to 4.1 (0.0-36.1) ng/mL for (R)- and (S)- albuterol respectively among COPD subjects. Levels were not associated with an improvement in lung function or adverse cardiac effects (prolonged QTc interval). CONCLUSIONS: High plasma concentrations of albuterol were observed in both asthma and COPD patients presenting to the emergency department. Extra-pulmonary cardiac adverse effects (prolonged QTC interval) were not associated with the plasma level of (R)- or (S)-albuterol when administered by inhaler in the emergency department setting. Long-term effect(s) of continuous high circulating albuterol enantiomer concentrations remain unknown, and further investigations are required.

Using the auditory steady state response to record response amplitude curves. A possible fast objective method for diagnosing dead regions.

OBJECTIVES: To assess a novel objective method of measuring response amplitude curves (RACs) using auditory steady state responses in adults. DESIGN: RACs were recorded in 20 normal-hearing adults. The RACs were measured by recording the changes in the amplitude of the auditory steady state response in the presence of (1) swept frequency narrowband masking noise and (2) fixed narrowband masking noise. RESULTS: The mean recorded RAC tip frequency for a 2-kHz signal was 2250 Hz for the swept masker method and 2239 Hz for the fixed masker method. The estimated repeatability coefficients, calculated using an assumed mean difference of zero, were 389 Hz for the swept method and 342 Hz for the fixed method. CONCLUSIONS: These initial results indicate that the swept- and fixed-masking methods appear to be viable and fast ways to record RACs in normal-hearing adults. Further work is needed to further optimize the accuracy of the tip frequency estimation and to establish the normative range of tip frequencies over a wide range of test frequencies in normal-hearing and hearing-impaired subjects.

Fast method for psychophysical tuning curve measurement in school-age children.

The 'fast' method for measuring psychophysical tuning curves (PTC) uses a masker that sweeps across frequency and a Békésy threshold tracking procedure. The fast-PTC procedure has been recommended as a technique for diagnosing cochlear dead regions in adults. The aim of this study was to evaluate the fast-PTC procedure in children. Twelve normal-hearing children (7-10 years old) and five adults were tested. The fast-PTCs were measured for 1000 and 4000 Hz signals using ascending and descending masker sweeps. Measurements were repeated on a separate day to assess test-retest variability. All children were able to perform the task; however it was possible to define the tip in only 87% of the fast-PTCs. Although the variability in tip frequency was higher for children, the mean difference between children and adults was not statistically significant. As expected, the difference on retest was higher for children. Studies investigating the use of the fast-PTC procedure with hearing-impaired children are warranted.

Colorectal cancer screening among underserved minority population: discrepancy between physicians' recommended, scheduled, and completed tests.

OBJECTIVE: This study examines the correlates of: (1) health care provider recommendation of CRC testing; (2) provider scheduling for recommended CRC testing using sigmoidoscopy, colonoscopy, or double-contrast barium enema; and (3) adherence to CRC scheduling among underserved minority populations. METHODS: Medical record and schedule logbook reviews and interviewer-administered surveys. SETTING: Large urban safety-net, outpatient primary care setting in Los Angeles County. PARTICIPANTS: 306 African-American and Latino patients aged 50 years and older. RESULTS: A vast majority of minority patients do not receive standard CRC testing in urban safety-net primary care settings. Of those patients who were actually scheduled for sigmoidoscopy or colonoscopy, almost half completed the procedure. Completing CRC testing was associated with marital status, co-morbid chronic physical conditions, number of risk factors for colorectal cancer, and lower perceived barriers to CRC testing. CONCLUSION: Effective interventions to reduce CRC mortality among underserved minority populations require an integrated approach that engages patients, providers, and health care systems. PRACTICE IMPLICATIONS: Designing interventions that (1) increase physician-patient communications for removing patients' perceived barriers for CRC testing and (2) promote a non-physician-based navigator system that reinforces physicians' recommendation are strongly recommended.

Correlates of complementary and alternative medicine utilization in depressed, underserved african american and Hispanic patients in primary care settings.

OBJECTIVES: This study seeks to examine the correlates of complementary and alternative medicine (CAM) use in depressed underserved minority populations receiving medical care in primary care settings. METHODS: A prospective study using interviewer-administered surveys and medical record reviews was conducted at 2 large outpatient primary care clinics providing care primarily to underserved African American and Hispanic individuals located in Los Angeles, California. A total of 2321 patients were screened for depression. Of these, 315 met the Patient Health Questionnaire-9 criteria for mild to severe depression. RESULTS: Over 57% of the sample reported using CAM sometimes or often (24%) and frequently (33%) for treatment of their depressive symptoms. Controlling for demographic characteristics, lack of health care coverage remained one of the strongest predictors of CAM use. Additionally, being moderately depressed, using psychotherapeutic prescription medications, and poorer self-reported health status were all associated with increased frequency of CAM utilization for treating depression. CONCLUSIONS: The underserved African American and Hispanic individuals meeting the diagnostic criteria for depression or subsyndromal depression use CAM extensively for symptoms of depression. CAM is used as a substitute for conventional care when access to care is not available or limited. Since CAM is used so extensively for depression, understanding domains, types, and correlates of such use is imperative. This knowledge could be used to design interventions aimed at improving care for depression.

Transforming clinical practice amongst community nurses: mentoring for COPD patient self-management.

AIMS AND OBJECTIVES: To report on the process of transforming clinical practice amongst community nurses through a mentoring programme implemented to support self-management amongst community-based sufferers of chronic obstructive pulmonary disease. BACKGROUND: The increasing incidence of and health burden from, chronic diseases has led to the emergence of more proactive, integrated chronic disease management approaches across the acute and primary care sectors. An important part of these approaches is the direct involvement of patients in their own care. Despite some difficulties with comparing the benefits of chronic disease self-management programmes, many evaluations report some benefit and all highlight the importance of health professionals in supporting self-management behaviours. In the primary care sector, community nurses are ideally situated to support these behaviours, but to do this effectively transformation of nursing practice must occur. DESIGN: Qualitative, longitudinal study informed by action research methods and involving monthly group discussions with community nurse mentors. METHODS: Community nurses from four community health centres in Tasmania were trained in motivational interviewing techniques to promote self-management amongst chronic obstructive pulmonary disease patients. Nurses' mentoring experiences were monitored during group discussions and subjected to thematic analysis. RESULTS: The paper reports the findings of the first 12 months of the project. In this phase, nurses experienced a transformation in their constructions of chronic obstructive pulmonary disease and their clinical practice. This involved a shift from a fatalistic, prescriptive, biomedical approach to a primary healthcare approach characterised by empathy, consultation, facilitation and a holistic focus. CONCLUSIONS: Community nurses face challenges in supporting chronic disease self-management. These challenges can be overcome and a transformation in clinical practice instilled. RELEVANCE TO CLINICAL PRACTICE: This study highlights that it is possible to support community nurses to take a lead role in the ongoing management of chronic disease in the community.

An integrated care pathway for menorrhagia across the primary-secondary interface: patients' experience, clinical outcomes, and service utilisation.

BACKGROUND: "Referral" characterises a significant area of interaction between primary and secondary care. Despite advantages, it can be inflexible, and may lead to duplication. OBJECTIVE: To examine the outcomes of an integrated model that lends weight to general practitioner (GP)-led evidence based care. DESIGN: A prospective, non-random comparison of two services: women attending the new (Bridges) pathway compared with those attending a consultant-led one-stop menstrual clinic (OSMC). Patients' views were examined using patient career diaries, health and clinical outcomes, and resource utilisation. Follow-up was for 8 months. SETTING: A large teaching hospital and general practices within one primary care trust (PCT). RESULTS: Between March 2002 and June 2004, 99 women in the Bridges pathway were compared with 94 women referred to the OSMC by GPs from non-participating PCTs. The patient career diary demonstrated a significant improvement in the Bridges group for patient information, fitting in at the point of arrangements made for the patient to attend hospital (ease of access) (p<0.001), choice of doctor (p = 0.020), waiting time for an appointment (p<0.001), and less "limbo" (patient experience of non-coordination between primary and secondary care) (p<0.001). At 8 months there were no significant differences between the two groups in surgical and medical treatment rates or in the use of GP clinic appointments. Significantly fewer (traditional) hospital outpatient appointments were made in the Bridges group than in the OSMC group (p<0.001). CONCLUSION: A general practice-led model of integrated care can significantly reduce outpatient attendance while improving patient experience, and maintaining the quality of care.

Alternative healthcare use in the under-served population.

OBJECTIVE: To apply the Behavioral Model for Vulnerable Populations to the examination of the correlates of alternative healthcare utilization among Hispanic and African-American adults residing in public housing. DESIGN: Cross-sectional survey of a community-based sample. SETTING: Urban public housing communities in the county of Los Angeles. PARTICIPANTS: A geographically defined random sample of 287 African-American and Latino heads of households from three urban public housing communities. RESULTS: The use of alternative health care was assessed with three indices reflecting how frequently respondents used alternative sources of health care: 1) to prevent sickness; 2) to treat sickness; and 3) to substitute for conventional health care. Multivariate analysis of data indicates that lower education, greater perceived racial discrimination, and poorer health status were associated with the use of alternative health care to prevent sickness. Furthermore, greater perceived racial discrimination, greater financial strain, and poorer health status were associated with the use of alternative health care to treat sickness. In addition, four variables were associated with increased frequency of alternative healthcare utilization as a substitute for conventional care, namely: 1) diminished belief that powerful individuals (such as healthcare professionals) control one's health; 2) greater perception of racial discrimination; 3) greater financial strain; and 4) reduced access to health care. CONCLUSION: Enabling characteristics helped explain the use of alternative health care to treat sickness as a substitute for conventional health care, but not to prevent sickness, in this population. Perceived racial discrimination was the strongest correlate for each type of alternative healthcare use, while health status was also a strong predictor. The use of alternative health care for prevention and for substitution should be examined separately in disadvantaged minority populations.

How important is personal care in general practice?

OBJECTIVES: To explore patients' perceptions of the features of personal care and how far these are shared by healthcare providers; whether a continuing relationship between a health professional and a patient is essential for personal care; and the circumstances in which a continuing relationship is important. DESIGN: Qualitative analysis of semistructured interviews using the "framework" approach. SETTING: Six general practices in Leicestershire. PARTICIPANTS: 40 patients aged > or = 18 years, 13 general practitioners, 10 practice and community nurses, and six practice administrative staff, recruited through participating practices. RESULTS: Patients' and healthcare providers' accounts cited human communication, individualised treatment or management, and whole person care as features of personal care. Personal care was described in three different contexts-a continuing relationship, a single consultation, and from the practice as a whole. The extent to which a continuing relationship was important for personal care was determined by the reason for consulting, as well as patients' consulting history and lifestyle. CONCLUSIONS: Patients, general practitioners, primary care nurses, and administrative staff hold similar views on the meaning of personal care, despite differences of emphasis reflecting their different roles. Personal care is promoted by but not always dependent on a continuing provider-patient relationship; human communication and individualised care emerged as important in making care personal whatever the context. Most respondents valued relationships in primary care and had clear ideas about when care in the context of a relationship was most valuable.

Empirical aminoglycosides for peritonitis do not affect residual renal function.

BACKGROUND: Aminoglycosides have been proven to be an efficacious treatment for peritonitis in peritoneal dialysis patients for many years. Consequently, they have been recommended in previous guidelines for the empirical treatment of peritonitis. However, with the increasing emphasis on preserving residual renal function (RRF), there has been concern about the nephrotoxic potential of these compounds. The 2000 International Society of Peritoneal Dialysis (ISPD) guidelines recommended that aminoglycosides not be used in patients with RRF, and that ceftazidime be used instead. In 1997, in response to the 1996 ISPD guidelines, we changed our peritonitis regimen from vancomycin and ciprofloxacin to cefazolin and gentamicin. The aim of this study is to compare the change in renal function occurring after treatment of peritonitis with and without gentamicin. METHODS: Using 6-monthly urine and dialysis clearance measurements, preperitonitis and postperitonitis RRF (mean of 24-hour urea and creatinine clearance) were determined for 70 peritonitis episodes treated with the aminoglycoside-based regimen (group A), 61 episodes treated without aminoglycosides (group B), and 74 control patients without peritonitis (group C). RESULTS: Group A had mean declines in estimated glomerular filtration rate and urine output of -0.08 +/- 0.50 mL/min/mon and -8.82 +/- 88.09 mL/24 h/mon compared with -0.17 +/- 0.27 mL/min/mon and -34.68 +/- 69.58 mL/24 h/mon in group B and -0.20 +/- 0.39 mL/min/mon and -14.61 +/- 77.33 mL/24 h/mon in group C, respectively. There were no significant differences between groups. CONCLUSION: In our patients, there was no evidence of an accelerated decline in RRF when using an empirical regimen containing aminoglycosides for peritonitis. Because there are few data to contradict this finding, we recommend the continued use of these drugs in peritonitis regimens, even in patients with significant RRF.

Auditory filter nonlinearity in mild/moderate hearing impairment.

Sensorineural hearing loss has frequently been shown to result in a loss of frequency selectivity. Less is known about its effects on the level dependence of selectivity that is so prominent a feature of normal hearing. The aim of the present study is to characterize such changes in nonlinearity as manifested in the auditory filter shapes of listeners with mild/moderate hearing impairment. Notched-noise masked thresholds at 2 kHz were measured over a range of stimulus levels in hearing-impaired listeners with losses of 20-50 dB. Growth-of-masking functions for different notch widths are more parallel for hearing-impaired than for normal-hearing listeners, indicating a more linear filter. Level-dependent filter shapes estimated from the data show relatively little change in shape across level. The loss of nonlinearity is also evident in the input/output functions derived from the fitted filter shapes. Reductions in nonlinearity are clearly evident even in a listener with only 20-dB hearing loss.