A Placebo-Controlled Double-Blinded Randomized Pilot Study of Combination Phytotherapy in Biochemically Recurrent Prostate Cancer.

BACKGROUND: Men with biochemical recurrence of prostate cancer following local therapies often use natural supplements in an attempt to delay metastases and/or avoid the need for more aggressive treatments with undesirable side-effects. While there is a growing body of research into phytotherapeutic agents in this cohort, with some promising results, as yet no definitive recommendations can be made. This pilot study was undertaken to assess the feasibility of a fully-powered study to examine the effects of this phytotherapeutic intervention (containing turmeric, resveratrol, green tea and broccoli sprouts) on PSA doubling time in men with biochemical recurrence with a moderate PSA rise rate. METHODS: A double blind, randomized, placebo-controlled parallel trial was conducted with 22 men with biochemically recurrent prostate cancer and a moderate rise rate (PSA doubling time of 4-15 months and no evidence of metastases from conventional imaging methods). Patients were randomized to either the active treatment arm or placebo for 12 weeks. The primary endpoints were feasibility of study recruitment and procedures, and measurement of proposed secondary endpoints (prostate symptoms, quality of life, anxiety, and depression as measured on the EORTC QLQ-C30 and PR-25, the IPSS and HADS). Data were collected to estimate PSA-log slopes and PSA-doubling times, using a mixed model, for both the pre-intervention and post-intervention periods. RESULTS: Adherence to study protocol was excellent, and the phytotherapeutic intervention was well-tolerated, with similar numbers of mild-to-moderate adverse events in the active and placebo arms. Both the intervention and data collection methods were acceptable to participants. No statistical difference between groups on clinical outcomes was expected in this pilot study. There was between-subject variation in the PSA post treatment, but on average the active treatment group experienced a non-significant increase in the log-slope of PSA (pre-treatment doubling time = 10.2 months, post-treatment doubling time = 5.5 months), and the placebo group experienced no change in the log-slope of PSA (pre-treatment doubling time = 10.8 months, post-treatment doubling time = 10.9 months). CONCLUSION: The findings suggest that a fully powered study of this combination is feasible in men with biochemically recurrent prostate cancer and a moderate PSA rise rate. Prostate 77:765-775, 2017. © 2017 Wiley Periodicals, Inc.

Phytotherapeutic interventions in the management of biochemically recurrent prostate cancer: a systematic review of randomised trials.

OBJECTIVE: To evaluate the evidence from randomised trials for the efficacy and safety of phytotherapeutic interventions in the management of biochemically recurrent (BCR) prostate cancer, indicated by prostate-specific antigen (PSA) progression, numbers progressing to/time to initiation of androgen-deprivation therapy or salvage therapy. PATIENTS AND METHODS: MEDLINE (Ovid), EMBASE (Ovid), AMED (Ovid), CINAHL (EBSCO) and the Cochrane Library databases were searched. Clinical trials investigating phytotherapeutic interventions as dietary supplements or dietary components, including multi-component herbal formulations, in men with BCR prostate cancer were located. Eight of nine authors contacted for further information responded. Methodological quality was assessed using the Cochrane Collaboration's risk of bias assessment tool. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews was followed. RESULTS: Of 23 full-text articles assessed for eligibility, five met the criteria for inclusion. Two studies were placebo controlled; two were active control trials; and one a high-/low-dose trial. The interventions were administered as isolated phytochemicals (sulphoraphane), phytotherapeutic extracts [Pomi-T (pomegranate, turmeric, green tea and broccoli sprout extract), soy, lycopene, and POMx (pomegranate extract)], or plant-derived dietary items (soy and lycopene). All studies found serum PSA levels to stabilise, decrease or rise more slowly in a significant number of men, and three studies reported stabilising or lengthening of PSA-doubling time. Studies were generally of good quality, but sample sizes were predominantly small, and durations short. CONCLUSIONS: High-quality studies in this area are lacking. Sulphoraphane, lycopene, soy isoflavones, POMx, and Pomi-T are safe and well tolerated. There is limited evidence that they can affect PSA dynamics. No recommendation can be made for the use of these agents in managing prostate cancer morbidity and mortality until high-quality, fully powered studies are available. Recommendations are made for improving reproducibility and translation of findings with regard to study population, study endpoints, design, and the reporting of phytotherapeutic interventions.

Soy and soy isoflavones in prostate cancer: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the evidence from randomized controlled trials (RCTs) on the efficacy and safety of soy/isoflavones in men with prostate cancer (PCa) or with a clinically identified risk of PCa. PATIENTS AND METHODS: MEDLINE, EMBASE, the Allied and Complementary Medicine (AMED), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Library databases were searched. We identified RCTs investigating soy/soy isoflavones as dietary supplements or dietary components for the secondary prevention or treatment of PCa in men with PCa or with a clinically identified risk of developing PCa. Studies of multi-component formulations were excluded. Six authors were contacted for further information for the meta-analyses. Methodological quality was assessed using the Cochrane Collaboration's risk-of- bias tool. The PRISMA statement for reporting systematic reviews was followed. RESULTS: Of the eight RCTs that met the inclusion criteria, six restricted recruitment to men diagnosed with PCa, while two included men with clinically identified risk of PCa. A large degree of heterogeneity was found with respect to dosages and preparations of soy/isoflavones administered. Most studies had small sample sizes and were of short duration. The risk of bias was assessed as low in all assessed studies except for one, for which the risk of bias was unclear. Meta-analyses of the two studies including men with identified risk of PCa found a significant reduction in PCa diagnosis after administration of soy/soy isoflavones (risk ratio = 0.49, 95% CI 0.26, 0.95). Meta-analyses indicated no significant differences between groups for prostate-specific antigen (PSA) levels or sex steroid endpoints (sex hormone-binding globulin [SHBG], testosterone, free testosterone, oestradiol and dihydrotestosterone). CONCLUSIONS: The results of a meta-analysis of two studies suggest there may be support for epidemiological findings of a potential role for soy/soy isoflavones in PCa risk reduction; however, a clear understanding of the impact of soy/isoflavones on PSA, total testosterone, free testosterone and SHBG levels in men with, or at identified risk of, PCa could not be derived from these data, given the limitations of sample size and study duration in individual trials. A good safety profile is shown by this meta-analysis for soy/soy isoflavones supplementation.

Fibromyalgia--should we be testing and treating for vitamin D deficiency?

AIM: This review aims to synthesise the evidence regarding any association between vitamin D deficiency and fibromyalgia, addressing whether general practitioners should be testing and treating these patients for vitamin D deficiency. METHODS: A systematic literature review was performed, using MEDLINE as the primary database, to find and critically appraise all relevant research fulfilling inclusion criteria from January 1990 until September 2010. RESULTS: There were conflicting results in the cross sectional studies obtained, with no association in studies using control groups and mixed results in larger population based studies. One adequately powered randomised controlled trial suggests fibromyalgia pain is not improved by vitamin D supplementation. DISCUSSION: The evidence for an association between fibromyalgia and vitamin D deficiency is inconclusive, with no improvement in pain on supplementation. However, patients with concurrent risk factors for deficiency should be tested and treated for vitamin D deficiency to minimise osteoporosis risk and maximise muscular strength.

Breastfeeding--evidence based guidelines for the use of medicines.

BACKGROUND: General practitioners may consider prescribing medicines for breastfeeding women during the postpartum period. Most medicines can be used safely during breastfeeding at the recommended dose, however there are exceptions that necessitate caution. OBJECTIVE: This article provides an evidence based review of medicines used for common situations and their compatibility with breastfeeding. DISCUSSION: Breastfeeding women typically use relatively few medicines, and generally these are compatible with breastfeeding. If other medicines are required, information on their safety during breastfeeding can be accessed from pharmacy departments at maternity hospitals or from online resources.

Computer reminders for Chlamydia screening in general practice: a randomized controlled trial.

BACKGROUND: Chlamydia notifications are increasing in Australia, and the use of a computer alert prompting general practitioners to test young women is a potential way to increase opportunistic chlamydia testing. The aim of this trial was to determine the effectiveness of a computer alert in general practice on chlamydia testing in young women. METHODS: In 2006, clinics (n = 68) in Melbourne, Australia were cluster randomized into 2 groups: the intervention group received a computerized alert advising the general practitioner to discuss chlamydia testing with their patient which popped up when the medical record of a 16- to 24-year-old woman was opened; the control group received no alert. The outcome was whether or not that patient received a chlamydia test at the level of a single consultation with an eligible patient. A mixed effects logistic regression model adjusting for clustering was used to assess the impact of the alert on the proportion of women tested for chlamydia during the trial period. RESULTS: Testing increased from 8.3% (95% confidence interval (CI): 6.8, 9.8) to 12.2% (95% CI: 9.1, 15.3) (P < 0.01) in the intervention group, and from 8.8% (95% CI: 6.8, 10.7) to 10.6% (95% CI: 8.5, 12.7) (P < 0.01) in the control group. Overall, the intervention group had a 27% (OR = 1.3; 95% CI: 1.1, 1.4) greater increase in testing. CONCLUSION: The results of this study suggest that alerts alone may not be sufficient to get chlamydia testing levels up sufficiently high enough to have an impact on the burden of chlamydia in the population but that they could be included as part of a more complex intervention.

Incentive payments to general practitioners aimed at increasing opportunistic testing of young women for chlamydia: a pilot cluster randomised controlled trial.

BACKGROUND: Financial incentives have been used for many years internationally to improve quality of care in general practice. The aim of this pilot study was to determine if offering general practitioners (GP) a small incentive payment per test would increase chlamydia testing in women aged 16 to 24 years, attending general practice. METHODS: General practice clinics (n = 12) across Victoria, Australia, were cluster randomized to receive either a $AUD5 payment per chlamydia test or no payment for testing 16 to 24 year old women for chlamydia. Data were collected on the number of chlamydia tests and patient consultations undertaken by each GP over two time periods: 12 month pre-trial and 6 month trial period. The impact of the intervention was assessed using a mixed effects logistic regression model, accommodating for clustering at GP level. RESULTS: Testing increased from 6.2% (95% CI: 4.2, 8.4) to 8.8% (95% CI: 4.8, 13.0) (p = 0.1) in the control group and from 11.5% (95% CI: 4.6, 18.5) to 13.4% (95% CI: 9.5, 17.5) (p = 0.4) in the intervention group. Overall, the intervention did not result in a significant increase in chlamydia testing in general practice. The odds ratio for an increase in testing in the intervention group compared to the control group was 0.9 (95% CI: 0.6, 1.2). Major barriers to increased chlamydia testing reported by GPs included a lack of time, difficulty in remembering to offer testing and a lack of patient awareness around testing. CONCLUSIONS: A small financial incentive alone did not increase chlamydia testing among young women attending general practice. It is possible small incentive payments in conjunction with reminder and feedback systems may be effective, as may higher financial incentive payments. Further research is required to determine if financial incentives can increase testing in Australian general practice, the type and level of financial scheme required and whether incentives needs to be part of a multi-faceted package. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12608000499381.

Patterns of treatment of external genital warts in Australian sexual health clinics.

BACKGROUND: External genital warts are a common sexually transmitted viral disease. We describe the patterns of treatment for initial presentations of external genital warts (EGWs) in Australian sexual health centers. METHODS: This was a retrospective audit of 489 case notes from consecutive individuals who presented with a new diagnosis of EGWs to 1 of 5 major sexual health clinics in Australia. Eligibility criteria were consecutive patients aged 18 to 45 years inclusively, presenting with first ever episode of EGWs from January 1, 2004. Exclusion criteria were patients who were immunocompromised, including HIV infection, or enrollment in a treatment study for EGWs. RESULTS: The median age at presentation of women was 23.2 years and of men 26.8 years. One quarter (n = 127) of patients had another sexually transmitted infection diagnosed at presentation. Nearly half of the patients (n = 224) presented only once for treatment. Most often, patients were treated with a monotherapy (n = 382/489; 78%), usually cryotherapy (257; 53%). Staff applied treatment in 361 (74%) cases. There was wide variation across sites, possibly reflecting local policies and budgets. We found no difference in wart resolution (n = 292; 60%) by initial treatment chosen. CONCLUSIONS: The diagnosis and treatment of genital warts constitute a sizable proportion of clinical visits to the audited sexual health services and require a large input of staff time to manage, including the application of topical treatments. Our results help complete the picture of the burden of EGWs on Australian sexual health centers before the introduction of the HPV vaccine.

Acupuncture for pelvic and back pain in pregnancy: a systematic review.

The objective of our study was to review the effectiveness of needle acupuncture in treating the common and disabling problem of pelvic and back pain in pregnancy. Two small trials on mixed pelvic/back pain and 1 large high-quality trial on pelvic pain met the inclusion criteria. Acupuncture, as an adjunct to standard treatment, was superior to standard treatment alone and physiotherapy in relieving mixed pelvic/back pain. Women with well-defined pelvic pain had greater relief of pain with a combination of acupuncture and standard treatment, compared to standard treatment alone or stabilizing exercises and standard treatment. We used a narrative synthesis due to significant clinical heterogeneity between trials. Few and minor adverse events were reported. We conclude that limited evidence supports acupuncture use in treating pregnancy-related pelvic and back pain. Additional high-quality trials are needed to test the existing promising evidence for this relatively safe and popular complementary therapy.

Expectancy after the first treatment and response to acupuncture for menopausal hot flashes.

BACKGROUND: Evidence on the impact of expectancy on acupuncture treatment response is conflicting. OBJECTIVES: This secondary analysis of a randomized sham-controlled trial on acupuncture for menopausal hot flashes investigated whether treatment expectancy score was associated with hot flash score at end-of-treatment. Secondary analyses investigated whether there were associations between other pre-specified factors and hot flash score. STUDY DESIGN: Women experiencing moderately-severe hot flashes were randomized to receive 10 sessions of real or sham acupuncture over eight weeks. Hot flash score was collected using a seven-day hot flash diary, and expectancy using the modified Credibility and Expectancy Questionnaire immediately after the first treatment. Linear mixed-effects models with random intercepts were used to identify associations between expectancy score and hot flash score at end-of-treatment. Regression was also used to identify associations between pre-specified factors of interest and hot flash score. Because there was no difference between real and sham acupuncture for the primary outcome of hot flash score, both arms were combined in the analysis. RESULTS: 285 women returned the Credibility and Expectancy Questionnaire, and 283 women completed both expectancy measures. We found no evidence for an association between expectancy and hot flash score at end-of-treatment for individual cases in either acupuncture or sham group. Hot flash scores at end-of-treatment were 8.1 (95%CI, 3.0 to 13.2; P = 0.002) points lower in regular smokers compared to those who had never smoked, equivalent to four fewer moderate hot flashes a day. CONCLUSION: In our study of acupuncture for menopausal hot flashes, higher expectancy after the first treatment did not predict better treatment outcomes. Future research may focus on other determinants of outcomes in acupuncture such as therapist attention. The relationship between smoking and hot flashes is poorly understood and needs further exploration.

GPs' decision-making when prescribing medicines for breastfeeding women: Content analysis of a survey.

BACKGROUND: Many breastfeeding women seek medical care from general practitioners (GPs) for various health problems and GPs may consider prescribing medicines in these consultations. Prescribing medicines to a breastfeeding mother may lead to untimely cessation of breastfeeding or a breastfeeding mother may be denied medicines due to the possible risk to her infant, both of which may lead to unwanted consequences. Information on factors governing GPs' decision-making and their views in such situations is limited. METHODS: GPs providing shared maternity care at the Royal Women's Hospital, Melbourne were surveyed using an anonymous postal survey to determine their knowledge, attitudes and practices on medicines and breastfeeding, in 2007/2008 (n = 640). Content analysis of their response to a question concerning decision-making about the use of medicine for a breastfeeding woman was conducted. A thematic network was constructed with basic, organising and global themes. RESULTS: 335 (52%) GPs responded to the survey, and 253 (76%) provided information on the last time they had to decide about the use of medicine for a breastfeeding woman. Conditions reported were mastitis (24%), other infections (24%) and depressive disorders (21%). The global theme that emerged was "complexity of managing risk in prescribing for breastfeeding women". The organising themes were: certainty around decision-making; uncertainty around decision-making; need for drug information to be available, consistent and reliable; joint decision-making; the vulnerable "third party" and infant feeding decision. Decision-making is a spectrum from a straight forward decision, such as treatment of mastitis, to a complicated one requiring multiple inputs and consideration. GPs use more information seeking and collaboration in decision-making when they perceive the problem to be more complex, for example, in postnatal depression. CONCLUSION: GPs feel that prescribing medicines for breastfeeding women is a contentious issue. They manage the risk of prescribing by gathering information and assessing the possible effects on the breastfed infant. Without evidence-based information, they sometimes recommend cessation of breastfeeding unnecessarily.

Genital Candida species detected in samples from women in Melbourne, Australia, before and after treatment with antibiotics.

Vulvovaginal candidiasis (VVC) remains a common cause of morbidity, with three-quarters of women affected during their lifetimes. Use of antibiotics is an acknowledged trigger for VVC, which adversely affects women's physical and emotional health. Knowledge of patterns of genital Candida species-level identification is important for management, as Candida species other than Candida albicans often fail first-line treatment. A community sample of women with no vaginal symptoms, and who were prescribed antibiotics, was recruited into this study, where the incidence of genital colonization by various Candida species was documented, as well as symptoms of VVC plus relevant associations, before and after treatment with antibiotics. Self-collected low vaginal swabs were taken prior to and 8 days after completion of antibiotic treatment, and data on various potential risk factors for VVC were collected simultaneously, with complete data being available for 233 participants. Baseline Candida species colonization was present in 21% of women (95% confidence intervals [CI], 17% to 27%), rising to 37% (95% CI, 31% to 44%) after antibiotic treatment. The primary species detected for either period was C. albicans (73%), with Candida glabrata detected in around 20%. Self-assessed proneness to VVC after antibiotic treatment and baseline colonization with Candida spp. were significantly associated with symptomatic VVC after antibiotic treatment. For microbiologically proven candidiasis, VVC symptoms had a sensitivity of 57% and a specificity of 91%. When physicians prescribe antibiotics, the history of risk of VVC is one issue that physicians should discuss with women, particularly those who are self-identified as being prone to VVC. Furthermore, we recommend that definitive microbiological diagnoses be made for women with recurrent symptoms or those failing initial treatment, to guide appropriate therapy.

Detection of Candida species by PCR in self-collected vaginal swabs of women after taking antibiotics.

Women undergoing antibiotic treatment can develop vulvovaginal candidiasis. This study evaluated polymerase chain reaction (PCR) for the detection of Candida species in comparison with the conventional laboratory culture methods in samples from women with and without symptoms of postantibiotic candidiasis. The self-collected vaginal swabs from 90 women, with no recent symptoms of vulvovaginal candidiasis (VVC), who were prescribed antibiotics for non-genital infection were evaluated 8 days after completion of antibiotics and/or at the time of developing symptoms of VVC. Broad-spectrum fungal PCR was performed on extracted DNA from each sample. Overall PCR detected four additional Canidida albicans, three Candida parapsilosis and one Candida tropicalis when compared with culture. All but one case additionally detected by PCR were found in patients with no VVC symptoms. PCR, although more sensitive than conventional culture methods, in this small number of cases, has not been able to detect Candida species in significantly more patients with symptoms suggestive of candidiasis. The results of this study may indicate that other agents including other yeast species may be responsible for symptoms of postantibiotic vulvovaginitis.

Her choice: dealing with lactobacilli, vaginitis, and antibiotics.

Vulvovaginal candidiasis is a common problem for women, yet there are many gaps in knowledge about candida's pathogenesis, immunity, and its reputed association with antibiotic use. Women often self-diagnose and self-manage the problem, yet one of the most common folk remedies used, the probiotic lactobacillus, has no biologically plausible mechanism to explain any beneficial actions and no rigorous evidence to support its effectiveness. This paper explores these issues and summaries potential areas for further research.

"Not thrush again!" Women's experience of post-antibiotic vulvovaginitis.

OBJECTIVES: To examine the frequency of post-antibiotic vulvovaginitis (PAV); describe how women prevent and treat PAV; and determine whether concern about PAV affects their decisions about taking antibiotics. DESIGN: Cross-sectional survey using a written questionnaire. SETTING AND PARTICIPANTS: Five general practice waiting rooms in north-western Melbourne, in February 2000. 1298 women aged 18-70 years were surveyed. MAIN OUTCOME MEASURES: Self-reported symptoms and management of vulvovaginitis and PAV. RESULTS: The response rate was 86%. Thirty-five per cent of women reported ever having PAV and 73% reported ever having symptoms suggestive of vulvovaginal candidiasis. Antifungal medications and lactobacillus products or yoghurt were most popular for both prevention (49%, 40%) and treatment (63%, 43%) of PAV. Other home remedies such as tea tree oil, vinegar, and dietary and clothing modification were infrequently used by the women surveyed. Twenty-three per cent of women who had taken antibiotics in the previous month had experienced symptoms of vulvovaginitis. Of women who had ever had vulvovaginitis, 35% were moderately to very concerned about developing PAV when prescribed antibiotics. Because of this concern, around a fifth of these women would not take prescribed antibiotics. CONCLUSIONS: Concern about PAV affects women's decision-making regarding antibiotic use. Many women use unproven complementary therapies to prevent or treat PAV. When prescribing antibiotics, doctors should discuss the risks of PAV and its management with patients.