Oral Medications to Treat Toenail Fungal Infection.

CLINICAL QUESTION: Which oral antifungal medication is associated with the highest clinical (ie, normal appearance of the toenail) and mycological (negative culture, microscopy, or both) cure rates vs placebo or other antifungals when used to treat fungal infections? BOTTOM LINE: Both terbinafine and azole-based medications were associated with higher clinical and mycological cure rates compared with placebo (high-quality evidence). Azoles were associated with lower cure rates than terbinafine when compared directly.

Oral antifungal medication for toenail onychomycosis.

BACKGROUND: Fungal infection of the toenails, also called onychomycosis, is a common problem that causes damage to the nail's structure and physical appearance. For those severely affected, it can interfere with normal daily activities. Treatment is taken orally or applied topically; however, traditionally topical treatments have low success rates due to the nail's physical properties. Oral treatments also appear to have shorter treatment times and better cure rates. Our review will assist those needing to make an evidence-based choice for treatment. OBJECTIVES: To assess the effects of oral antifungal treatments for toenail onychomycosis. SEARCH METHODS: We searched the following databases up to October 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We sought to identify unpublished and ongoing trials by correspondence with authors and by contacting relevant pharmaceutical companies. SELECTION CRITERIA: RCTs comparing oral antifungal treatment to placebo or another oral antifungal treatment in participants with toenail onychomycosis, confirmed by one or more positive cultures, direct microscopy of fungal elements, or histological examination of the nail. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 48 studies involving 10,200 participants. Half the studies took place in more than one centre and were conducted in outpatient dermatology settings. The participants mainly had subungual fungal infection of the toenails. Study duration ranged from 4 months to 2 years.We assessed one study as being at low risk of bias in all domains and 18 studies as being at high risk of bias in at least one domain. The most common high-risk domain was 'blinding of personnel and participants'.We found high-quality evidence that terbinafine is more effective than placebo for achieving clinical cure (risk ratio (RR) 6.00, 95% confidence interval (CI) 3.96 to 9.08, 8 studies, 1006 participants) and mycological cure (RR 4.53, 95% CI 2.47 to 8.33, 8 studies, 1006 participants). Adverse events amongst terbinafine-treated participants included gastrointestinal symptoms, infections, and headache, but there was probably no significant difference in their risk between the groups (RR 1.13, 95% CI 0.87 to 1.47, 4 studies, 399 participants, moderate-quality evidence).There was high-quality evidence that azoles were more effective than placebo for achieving clinical cure (RR 22.18, 95% CI 12.63 to 38.95, 9 studies, 3440 participants) and mycological cure (RR 5.86, 95% CI 3.23 to 10.62, 9 studies, 3440 participants). There were slightly more adverse events in the azole group (the most common being headache, flu-like symptoms, and nausea), but the difference was probably not significant (RR 1.04, 95% CI 0.97 to 1.12; 9 studies, 3441 participants, moderate-quality evidence).Terbinafine and azoles may lower the recurrence rate when compared, individually, to placebo (RR 0.05, 95% CI 0.01 to 0.38, 1 study, 35 participants; RR 0.55, 95% CI 0.29 to 1.07, 1 study, 26 participants, respectively; both low-quality evidence).There is moderate-quality evidence that terbinafine was probably more effective than azoles for achieving clinical cure (RR 0.82, 95% CI 0.72 to 0.95, 15 studies, 2168 participants) and mycological cure (RR 0.77, 95% CI 0.68 to 0.88, 17 studies, 2544 participants). There was probably no difference in the risk of adverse events (RR 1.00, 95% CI 0.86 to 1.17; 9 studies, 1762 participants, moderate-quality evidence) between the two groups, and there may be no difference in recurrence rate (RR 1.11, 95% CI 0.68 to 1.79, 5 studies, 282 participants, low-quality evidence). Common adverse events in both groups included headache, viral infection, and nausea.Moderate-quality evidence shows that azoles and griseofulvin probably had similar efficacy for achieving clinical cure (RR 0.94, 95% CI 0.45 to 1.96, 5 studies, 222 participants) and mycological cure (RR 0.87, 95% CI 0.50 to 1.51, 5 studies, 222 participants). However, the risk of adverse events was probably higher in the griseofulvin group (RR 2.41, 95% CI 1.56 to 3.73, 2 studies, 143 participants, moderate-quality evidence), with the most common being gastrointestinal disturbance and allergic reaction (in griseofulvin-treated participants) along with nausea and vomiting (in azole-treated participants). Very low-quality evidence means we are uncertain about this comparison's impact on recurrence rate (RR 4.00, 0.26 to 61.76, 1 study, 7 participants).There is low-quality evidence that terbinafine may be more effective than griseofulvin in terms of clinical cure (RR 0.32, 95% CI 0.14 to 0.72, 4 studies, 270 participants) and mycological cure (RR 0.64, 95% CI 0.46 to 0.90, 5 studies, 465 participants), and griseofulvin was associated with a higher risk of adverse events, although this was based on low-quality evidence (RR 2.09, 95% CI 1.15 to 3.82, 2 studies, 100 participants). Common adverse events included headache and stomach problems (in griseofulvin-treated participants) as well as taste loss and nausea (in terbinafine-treated participants). No studies addressed recurrence rate for this comparison.No study addressed quality of life. AUTHORS' CONCLUSIONS: We found high-quality evidence that compared to placebo, terbinafine and azoles are effective treatments for the mycological and clinical cure of onychomycosis, with moderate-quality evidence of excess harm. However, terbinafine probably leads to better cure rates than azoles with the same risk of adverse events (moderate-quality evidence).Azole and griseofulvin were shown to probably have a similar effect on cure, but more adverse events appeared to occur with the latter (moderate-quality evidence). Terbinafine may improve cure and be associated with fewer adverse effects when compared to griseofulvin (low-quality evidence).Only four comparisons assessed recurrence rate: low-quality evidence found that terbinafine or azoles may lower the recurrence rate when compared to placebo, but there may be no difference between them.Only a limited number of studies reported adverse events, and the severity of the events was not taken into account.Overall, the quality of the evidence varied widely from high to very low depending on the outcome and comparison. The main reasons to downgrade evidence were limitations in study design, such as unclear allocation concealment and randomisation as well as lack of blinding.

Women's questions about medicines in pregnancy - An analysis of calls to an Australian national medicines call centre.

BACKGROUND: For many medicines, safe use during pregnancy is not established and adherence is often poor due to safety concerns. Therefore, it is important to identify consumers' medicines information needs during pregnancy. MATERIALS AND METHODS: A retrospective, mixed methods analysis was conducted on eight years of pregnancy-related calls to an Australian national medicines call centre. The call profile of pregnancy and non-pregnancy-related questions were compared. Medicines involved in pregnancy calls were categorised by class (Anatomical Therapeutic Chemical (ATC)3 level), and Therapeutic Goods Administration pregnancy category. Questions in these calls were also themed by pregnancy stage. RESULTS: We identified 4573 pregnancy-related and 118 547 non-pregnancy-related calls. The caller profile for pregnancy-related calls was female (93.7%), asking for herself (83.0%), and while 70.1% of questions involved one medicine, 9.6% involved three or more medicines. Pregnancy enquiries were prompted more often by conflicting information, inadequate information or desire for a second opinion. For 1166 calls, where the stage of pregnancy was available, most questions concerned safety. Medication classified as 'safe' during pregnancy accounted for 34% of these questions. After antidepressants, most calls were made about over-the-counter (OTC) medicines (paracetamol, dexchlorpheniramine, codeine). Safe treatment for everyday conditions was of increasing concern as the pregnancy progressed. CONCLUSION: Pregnant women are concerned about the safety of medication use in pregnancy and a significant proportion overestimate risk. Psychotropic medication and fertility are strong drivers to seek information during preconception. Everyday illnesses and self-medication with OTC medication are a common concern throughout pregnancy, even though many medicines are safe to use.

Chewing the fat over statins: Consumer concerns about lipid-lowering medication.

BACKGROUND: The objective of this article was to explore the information needs of consumers using statins. METHODS: Calls made to a national medicines call centre in Australia were analysed. Where question narratives were available electronically (n = 1486), the main concerns were identified using a coding scheme. Subsequently, we evaluated whether these concerns were addressed in the medication leaflet. RESULTS: The most common concerns were about side effects (36%) and interactions (28%). Concerns about side effects related to musculoskeletal (27%), gastrointestinal (12%) and skin problems (5%). Concerns about interactions included other medicines (49%), complementary and alternative medicines (CAMs; 39%) and grapefruit (6%). Additional questions related to differences between treatments (12%) and dosage (8%). Most topics were mentioned in the medication leaflet, but strategies to manage these concerns were lacking. DISCUSSION: When prescribing statins, information about common side effects, when symptoms require action, and interactions with other medicines, especially CAMs, should be addressed and tailored to the patient.

Your questions about complementary medicines answered: gingko biloba.

This is the fourth article in a series providing evidence-based answers to common questions about complementary medicines from consumers and healthcare professionals.

Your questions about complementary medicines answered: fish oil.

This is the third article in a series providing evidence-based answers to common questions about complementary medicines from consumers and healthcare professionals.

Your questions about complementary medicines answered.

This is the first article in a series providing evidence-based answers to common questions about complementary medicines from consumers and healthcare professionals.

Your questions about complementary medicines answered: glucosamine.

This is the second article in a series providing evidence-based answers to common questions about complementary medicines from consumers and healthcare professionals.

A is for aphorism - the power of silence.

'All you have to do is listen' is the title of Rob Kapilow's delightful book on classical music; but he could equally have been talking about general practice consultations. Listening requires several skills including attention, echoing and body language, but begins with silence. Well timed silences, used judiciously, can allow the patient adequate space to express symptoms and concerns, while allowing the general practitioner more time for attention, comprehension and synthesis.

Treating chronic fatigue syndrome - a study into the scientific evidence for pharmacological treatments.

BACKGROUND: Chronic fatigue syndrome, or myalgic encephalomyelitis (CFS), is a severe disabling condition. Patients with CFS usually trial many different medicines, both conventional and complementary. An overview of the pharmacological treatments used by CFS patients and the available evidence underpinning the use of these treatments would be of great value to both patients and their healthcare providers. METHODS: Ninety-four CFS patients recruited into an Australian study investigating immunological biomarkers filled out a questionnaire assessing the medicines they were taking. Evidence from randomised clinical trials was sought in biomedical databases. RESULTS: The 94 CFS patients used 474 different medicines and supplements. The most commonly used medicines were antidepressants, analgesics, sedatives, and B vitamins. We identified 20 randomised controlled trials studying these medicines in CFS patients. DISCUSSION: While conventional and complementary medicines are widely used by CFS patients, the evidence for effectiveness in CFS is very limited.

Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women.

BACKGROUND: The relatively high dietary intake of soy in Asian countries has been hypothesized to, at least partly, explain the lower breast cancer incidence patterns in these countries compared with the Western world. The aim of the present study was to determine the effect of daily soy supplementation on mammographic density, one of the strongest known risk factors for breast cancer. METHODS: A double-blind, randomized, controlled trial was conducted to compare the effects of soy protein intake containing 99 mg isoflavones daily with intake of milk protein (placebo) for the duration of 1 year. Two hundred and two Dutch postmenopausal women ages 60 to 75 years were randomized. Mammographic density was assessed using a quantitative computer-assisted method on digitized mammograms. Equol producer status was assessed in plasma provided at the final visit (soy group) or after a 3-day challenge with soy after the trial was finished (placebo group). RESULTS: A total of 175 women completed the baseline visits and at least one follow-up visit and were included in the intention-to-treat analyses. For 126 women, both pre- and post-trial mammograms were available. Mammographic density decreased in both study arms, but the decrease did not differ significantly between intervention and placebo groups. Equol producer status did not modify the results. CONCLUSION: The results of this trial do not support the hypothesis that a diet high in soy protein among postmenopausal women decreases mammographic density.

Dietary phytoestrogen intake and cognitive function in older women.

BACKGROUND: Aging is associated with a decline in cognitive function; we explored the possible influence of dietary phytoestrogens on this decline. METHODS: We conducted a cross-sectional study in 301 Dutch women aged 60-75 years. Dietary isoflavone and lignan intake was assessed with a food-frequency questionnaire covering habitual diet in the year preceding enrolment. The endpoints were cognitive function measured in three domains: memory, processing capacity and speed, and executive function. Data were analyzed using linear regression models, after adjusting for confounders. RESULTS: No association between dietary isoflavone intake and cognitive function was found. High lignan intake was associated with a better performance in processing capacity and speed, and in executive function (p for trend over quartiles =.01 and.02, respectively). CONCLUSIONS: This finding calls for further research to elucidate the relatively underexplored role of lignans within the range of phytoestrogens.

What do health consumers want to know about childhood vaccination? An evaluation of data from an Australian medicines call centre.

OBJECTIVES: Immunisation is crucial to population health. This study aimed to identify the information needs and concerns of health consumers regarding childhood vaccination. METHODS: We analysed 1,342 calls concerning childhood vaccination to an Australian pharmacist-operated medicines call centre (MCC). Data were available from September 2002 until June 2010. We identified key themes and compared these for callers from high and low immunisation coverage areas. RESULTS: Most calls related to safety concerns (60.4%), with many questions about vaccine constituents (31.6%). In low immunisation areas, a higher level of concern persisted about vaccine preservatives (mercury and thiomersal) despite their removal from vaccines in 2000. Of specific vaccines, the measles, mumps and rubella vaccine raised most questions (29.9%). Common motivations to call the MCC were 'inadequate information' (54%), 'second opinion' (21%) 'conflicting information' (9%) and 'worrying symptom' (6%). CONCLUSION AND IMPLICATIONS: The consistent number of vaccine-related calls, particularly about safety, demonstrates an information gap that can contribute to vaccination hesitancy. Health professionals need to know their local immunisation rate and associated carer concerns, to proactively address these information-related barriers to vaccination.

Opioid analgesic use in Australia and The Netherlands: a cross-country comparison.

Background Increasing use of opioid analgesics (OA) has been reported worldwide. Objective To compare the use of OA in two countries in order to better understand these trends. Setting Outpatient settings in Australia and The Netherlands. Method We analysed publicly available government data on outpatient OA dispensing over 15 years (2000-2014). We compared dispensing trends for specific OA and explored medical (national clinical guidelines), contextual and policy-related factors to explain differences in use between the two countries. Main outcome measure OA prescribing in Australia and The Netherlands, absolute volume of use, preferred types of opioids and changes over time. Results The average annual increase in OA prescribing was 10% in Australia and 8% in The Netherlands between 2000 and 2014. In 2014, the total use of OA was 10.0 daily defined doses (DDD)/1000 population/day in Australia and 9.4 DDD/1000 population/day in The Netherlands. In Australia, the most commonly prescribed opioids were oxycodone and tramadol, compared to fentanyl and tramadol in The Netherlands. We found differences in prescribing guidelines, culture of prescribing and regulatory frameworks that could explain some of the observed differences. Conclusion OA prescribing has increased remarkably in both countries between 2000 and 2014 but the types of prescribed OA vary. Differences in national evidence-based guidelines influenced the types of OA used. Prescribing culture as well as regulatory policies and costs, may also contribute to the different patterns of OA use.

Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women.

BACKGROUND: Phytoestrogens have been suggested to lower cardiovascular disease risk, but existing research focused on non-Western high intake levels and on risk factors. We investigated whether habitual low phytoestrogen intake is associated with manifest cardiovascular disease risk. METHODS AND RESULTS: Between 1993 and 1997, 16,165 women 49 to 70 years old and free from cardiovascular disease were enrolled in the Dutch Prospect-EPIC cohort (European Prospective study Into Cancer and nutrition) and followed up for a median period of 75 months. At enrollment, women filled in questionnaires on chronic disease risk factors and nutrition. Intake of phytoestrogens was estimated using the food frequency questionnaire covering regular dietary intake of 178 food items in the year before enrollment. Cox regression analysis was used to estimate hazard ratios of cardiovascular disease for quartiles of phytoestrogen intake adjusted for age at intake, body mass index, smoking, physical activity, hypertension, hypercholesterolemia, use of hormone replacement therapy, menopausal status, and intake of total energy, total fiber, vegetables, fruit, and alcohol. In total, 372 women experienced a coronary event (CHD) (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9], 410 to 414, 427.5) and 147 women a cerebrovascular event (CVD) (ICD-9, 430 to 438) during follow-up. Overall, neither isoflavones nor lignans were associated with decreased cardiovascular disease risk. When stratifying for ever versus never smokers, CHD risk decreased with increasing lignan intake for ever smokers. CONCLUSIONS: Our results do not support the presence of a protective effect of higher intake of phytoestrogens in low doses on cardiovascular disease risk, although a small risk reduction with higher lignan intake cannot be excluded for smokers.

Randomized controlled trial of the effects of soy protein containing isoflavones on vascular function in postmenopausal women.

BACKGROUND: The incidence of cardiovascular disease increases after menopause, possibly because of the decline in estrogen. Soy protein, a rich source of estrogen-like isoflavones, is hypothesized to improve vascular function. OBJECTIVE: The objective of this study was to investigate whether supplementation with soy protein, a rich source of estrogen-like isoflavones, improves vascular function. DESIGN: We performed a 12-mo double-blind randomized trial to compare the effects of soy protein containing 99 mg isoflavones/d (aglycone weights) with those of milk protein (placebo) on blood pressure and endothelial function in 202 postmenopausal women aged 60-75 y. RESULTS: Changes in endothelial function during the intervention were not significantly different between the soy and the placebo groups. After the intervention, systolic blood pressure increased in the soy group significantly more than it did in the placebo group; the difference in change was 4.3 mm Hg (95% CI: 0.3, 8.4 mm Hg; P = 0.04) for systolic blood pressure, but only 2.0 mm Hg (95% CI: -0.74, 4.71 mm Hg; P = 0.15) for diastolic blood pressure. In the soy group only, systolic and diastolic blood pressure decreased and endothelial function improved in the equol producers, whereas systolic and diastolic blood pressure increased and endothelial function deteriorated in the equol nonproducers. CONCLUSIONS: The results of this trial do not support the hypothesis that soy protein containing isoflavones have beneficial effects on vascular function in older postmenopausal women. Whether certain subgroups of women (eg, equol producers) do benefit from the intervention remains to be elucidated.

Dietary phytoestrogens and plasma lipids in Dutch postmenopausal women; a cross-sectional study.

OBJECTIVE: Isoflavone supplementation in high doses is associated with plasma lipid, glucose and insulin levels. Little is known about the effects of intake within the range of western diets on these endpoints. DESIGN: We conducted a population-based cross-sectional study in 301 women aged 60-75 years. METHODS: Dietary isoflavone and lignan intake was assessed with a food frequency questionnaire covering habitual diet during the year preceding enrollment. The outcome measures were total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, Lp(a), fasting glucose and insulin levels. Data were analysed using linear regression and logistic regression models. In the analyses we adjusted for a wide range of potential confounders. RESULTS: High intake of isoflavones was associated with lower Lp(a) levels (tertile three versus tertile one: odds ratio 0.36, 95% CI 0.16; 0.80). No relation was found between blood levels and the other plasma lipids, glucose or insulin was found. CONCLUSION: The results of this study suggest that an effect of dietary phytoestrogen intake at low levels on plasma lipid levels is of limited magnitude. It is premature to advise postmenopausal women with low phytoestrogen intake to change their diet towards a phytoestrogen rich diet with the sole aim to prevent cardiovascular disease.