Not just in man's best friend: A review of Staphylococcus pseudintermedius host range and human zoonosis.

Staphylococcus pseudintermedius is one species in the commensal staphylococcal population in dogs. While it is commonly carried on healthy companion dogs it is also an opportunistic pathogen associated with a range of skin, ear, wound and other infections. While adapted to dogs, it is not restricted to them, and we have reviewed its host range, including increasing reports of human colonisation and infections. Despite its association with pet dogs, S. pseudintermedius is found widely in animals, covering companion, livestock and free-living species of birds and mammals. Human infections, typically in immunocompromised individuals, are increasingly being recognised, in part due to improved diagnosis. Colonisation, infection, and antimicrobial resistance, including frequent multidrug resistance, among S. pseudintermedius isolates represent important One Health challenges.

Diagnostic findings in sinonasal aspergillosis in dogs in the United Kingdom: 475 cases (2011-2021).

OBJECTIVES: To describe the diagnostic tests used and their comparative performance in dogs diagnosed with sinonasal aspergillosis in the United Kingdom. A secondary objective was to describe the signalment, clinical findings and common clinicopathologic abnormalities in sinonasal aspergillosis. MATERIALS AND METHODS: A multi-centre retrospective survey was performed involving 23 referral centres in the United Kingdom to identify dogs diagnosed with sinonasal aspergillosis from January 2011 to December 2021. Dogs were included if fungal plaques were seen during rhinoscopy or if ancillary testing (via histopathology, culture, cytology, serology or PCR) was positive and other differential diagnoses were excluded. RESULTS: A total of 662 cases were entered into the database across the 23 referral centres. Four hundred and seventy-five cases met the study inclusion criteria. Of these, 419 dogs had fungal plaques and compatible clinical signs. Fungal plaques were not seen in 56 dogs with turbinate destruction that had compatible clinical signs and a positive ancillary test result. Ancillary diagnostics were performed in 312 of 419 (74%) dogs with observed fungal plaques permitting calculation of sensitivity of cytology as 67%, fungal culture 59%, histopathology 47% and PCR 71%. CLINICAL SIGNIFICANCE: The sensitivities of ancillary diagnostics in this study were lower than previously reported challenging the clinical utility of such tests in sinonasal aspergillosis. Treatment and management decisions should be based on a combination of diagnostics including imaging findings, visual inspection, and ancillary testing, rather than ancillary tests alone.

HRI London 2023: The Homeopathy Research Community Reunites after a 4-Year Hiatus, Sparking Fresh Collaborations between Researchers 'Old and New'.

The Homeopathy Research Institute's (HRI) 5th international research conference took place in the heart of London, from 16th to 18th June 2023. With 230 attendees from 27 countries, HRI's conferences remain truly international. HRI London 2023 will be remembered for its inspiring blend of 'old and new', with a programme notable for the maturity of the evidence presented by experienced names drawing on decades of work, as well as the enthusiasm and skill of up-and-coming researchers who took the floor to present their new findings. In this report, we present scientific highlights from the event.

Computer controlled expansion of equine cord blood mesenchymal stromal cells on microcarriers in 3 L vertical-wheel® bioreactors.

Mesenchymal stromal cells (MSCs) are an ideal cell source for allogenic cell therapy due to their immunomodulatory and differentiation properties. Equine MSCs (eMSCs) have been found to be a promising treatment for equine joint injuries including meniscal injuries, cartilage degradation, and osteoarthritis. Although the use of eMSCs has shown efficacy in preliminary studies, challenges associated with biomanufacturing remain. To achieve the required cell numbers for clinical application, bioreactor-based processes are required. Initial studies have shown that eMSCs can be cultivated in microcarrier-based, stirred suspension bioreactor culture at the laboratory 0.1 L scale using a Vertical-Wheel® (VW) bioreactor. However, investigations regarding scale up of these processes to the required biomanufacturing scales are required. This study investigated the scale-up of a equine cord blood MSC (eCB-MSC) bioprocess in VW bioreactors at three scales. This included scale-up from the 0.1-0.5 L bioreactor, scale-up from static culture to the 3 L computer-controlled bioreactor, and scale-up into the 3 L computer-controlled bioreactor using a mock clinical trial process. Results from the various scale-up experiments demonstrated similar cell expansion at the various tested scales. The 3 L computer-controlled system resulted in a final cell densities of 1.5 × 105 cells/cm2 on average, achieving 1.5 × 109 harvested cells. Biological testing of the cells showed that cell phenotype and functionality were maintained after scale-up. These findings demonstrate the scalability of an eCB-MSC bioprocess using microcarriers in VW bioreactors to achieve clinically relevant cell numbers, a critical step to translate MSC treatments from research to clinical applications. This study also represents the first known published study expanding any cell type in the 3 L VW bioreactor.

Priorities in Chronic nonbacterial osteomyelitis (CNO) - results from an international survey and roundtable discussions.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder that predominantly affects children and young people. The pathophysiology and molecular mechanisms of CNO remain poorly understood, and diagnostic criteria and biomarkers are lacking. As a result, treatment is empiric and follows personal experience, case series and expert consensus plans. METHODS: A survey was designed to gain insight on clinician and patient experiences of diagnosing and treating CNO and to collate opinions on research priorities. A version containing 24 questions was circulated among international expert clinicians and clinical academics (27 contacted, 21 responses). An equivalent questionnaire containing 20 questions was shared to explore the experience and priorities of CNO patients and family members (93 responses). RESULTS: Responses were used to select topics for four moderated roundtable discussions at the "International Conference on CNO and autoinflammatory bone disease" (Liverpool, United Kingdom, May 25-26th, 2022). The group identified deciphering the pathophysiology of CNO to be the highest priority, followed by clinical trials, necessary outcome measures and classification criteria. Surprisingly, mental wellbeing scored behind these items. CONCLUSIONS: Agreement exists among clinicians, academics, patients and families that deciphering the pathophysiology of CNO is of highest priority to inform clinical trials that will allow for the approval of medications for the treatment of CNO by regulatory agencies.

Gathering expert consensus to inform a proposed trial in chronic nonbacterial osteomyelitis (CNO).

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and adolescents. CNO is associated with pain, bone swelling, deformity, and fractures. Its pathophysiology is characterized by increased inflammasome assembly and imbalanced expression of cytokines. Treatment is currently based on personal experience, case series and resulting expert recommendations. Randomized controlled trials (RCTs) have not been initiated because of the rarity of CNO, expired patent protection of some medications, and the absence of agreed outcome measures. An international group of fourteen CNO experts and two patient/parent representatives was assembled to generate consensus to inform and conduct future RCTs. The exercise delivered consensus inclusion and exclusion criteria, patent protected (excludes TNF inhibitors) treatments of immediate interest (biological DMARDs targeting IL-1 and IL-17), primary (improvement of pain; physician global assessment) and secondary endpoints (improved MRI; improved PedCNO score which includes physician and patient global scores) for future RCTs in CNO.

HRI Online 2022: Leading International Experts Illustrate the Positive Impact of Increased Collaboration in Homeopathy Research.

The Homeopathy Research Institute (HRI) welcomed more than 450 people from 35 countries to their first online event on June 25, 2022. The one-day programme featured an excellent line-up of international speakers and provided a unique interactive platform in keeping with the theme of the event - Key Collaborations in Homeopathy Research. Scientists from a range of different research fields gave an exceptional insight into the current status of homeopathy research. Here we give an overview of the most significant findings in both clinical and basic research presented during HRI Online 2022.

The impact of obstructive sleep apnea on exercise capacity in a cardiac rehabilitation program.

PURPOSE: Cardiac rehabilitation (CR) improves clinical outcomes in patients with cardiovascular disease (CDV). Patients with CVD often have multiple comorbidities, including obstructive sleep apnea (OSA), potentially affecting their ability to participate and achieve functional improvement during CR. We aimed to test the hypothesis that OSA reduces peak exercise capacity (EC) in patients undergoing CR and to explore if OSA treatment modifies this relationship. METHODS: Data from a retrospective cohort of CR patients was analyzed. OSA was defined as a respiratory event index > 5/h or physician diagnosis. Patients with OSA were considered "treated" if using continuous positive airway pressure regularly during the CR period. Change in METs was the primary study outcome. RESULTS: Among 312 CR patients, median age of 67 years, 103 (33%) had known OSA (30 treated, 73 untreated). Patients with OSA vs. those with no OSA were more likely to be obese and male; otherwise, groups were similar. Compared with the no OSA group, patients with OSA had lower pre-CR METs (3.3 [2.9-4.5] vs. 3.9 [3.1-5], P = .01) and lower post-CR METs (5.3 [4-7] vs. 6 [4.6-7.6], P = .04), but achieved a similar increase in METs post-CR (1.8 [0.6-2.6] vs. 2.0 [0.9-3], P = .22). Furthermore, compared to no OSA, pre-CR and post-CR METs tended to be similar in patients with treated OSA, but lower in untreated patients, with similar increases in METs across all groups, even when adjusting for covariates via multivariable regression. CONCLUSION: OSA is prevalent in patients with CVD undergoing CR. CR substantially improves exercise capacity independent of OSA status, but screening for-and treatment of-OSA may improve the absolute exercise capacity achieved through CR.

Incidence of Parkinson disease in North America.

Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.

Toxic epidermal necrolysis-like lupus.

Toxic epidermal necrosis (TEN)-like lupus is a rare condition characterized by epidermal loss and mucosal ulceration occurring in patients with acute severe flares of systemic lupus erythematosus. The clinical picture may mimic drug-induced Stevens-Johnson syndrome/TEN; however, the absence of a suitable culprit drug, and the context of acute lupus point to the correct diagnosis. In a case series of three patients, further discriminating features included a slower onset of epidermal loss, more limited mucosal ulceration and a lack of ocular involvement when compared with drug-induced TEN. Histology may show similar features, including basal layer vacuolation, apoptosis and full-thickness epidermal necrosis. Patients with TEN-like lupus may have additional features of lupus, and a lupus band on direct immunofluorescence. It is important to identify this condition correctly, so that these patients can be appropriately managed with early input from Rheumatologists and prompt treatment with high-dose combined immunosuppressant therapy.

O-serotype distribution of Escherichia coli bloodstream infection isolates in critically ill patients in The Netherlands.

OBJECTIVES: Invasive infections by extra-intestinal pathogenic Escherichia coli (ExPEC) strains are increasing. We determined O-serogroups of E. coli isolates from ICU patients having bloodstream infections (BSI) and the potential coverage of a 10-valent O-polysaccharide conjugate vaccine currently in development for the prevention of invasive ExPEC disease. METHODS: We studied E. coli BSI among patients admitted to a tertiary ICU in the Netherlands between April 2011 and November 2016. O-serogroups were determined in vitro by agglutination and whole genome sequencing. RESULTS: Among 714 ICU patients having BSI, 70 (10%) had an E. coli BSI. Among 68 (97%) isolates serogrouped, the most common serogroups were O25 (n = 11; 16%), O8 (n = 5; 7%), O2 (n = 4; 6%), O6 (n = 4; 6%), and O15 (n = 4; 6%). The theoretical coverage of a 10-valent ExPEC vaccine was 54% (n = 37). CONCLUSIONS: A multi-valent ExPEC O-polysaccharide conjugate vaccine in development could potentially aid in the prevention of E. coli BSI in Dutch ICU patients.

What is the demand for out-of-hours dermatology? A UK-based region-wide survey of dermatology demand and provision during the evenings and at weekends.

BACKGROUND: Little is known about the demand for out-of-hours (OOH) dermatology in the UK, and this can make commissioning of acute services difficult. The East Midlands region has a population of 4.5 million people, with variable access to OOH dermatology services. AIM: We sought to investigate the provision of, and demand for, OOH dermatology services across the region with a view to informing commissioning decisions for the future. METHODS: We contacted all dermatology departments in the East Midlands region to establish what level of service was commissioned at evenings and weekends. At the sites providing any form of OOH service, we recorded all requests for advice received after 17.00 h on weekdays, or at any time during weekends and bank holidays over a 3-month period from October to December 2019. RESULTS: The OOH services provided ranged from 24 h/day cover 7 days/week at one site, to no formal provision across much of the rest of the region. In total, 125 calls were received during the study period, averaging 1 call per day on weekday evenings, and 2 calls per day at weekends and on bank holidays. Of these 125 calls, 11 patients (9%) were prioritized and seen by the on-call dermatologist on the day of referral, and 9 of these had potentially life-threatening skin conditions. A further 39 (31%) were deemed to need review within 24 h and 22 (18%) within 48 h. The remaining 42% were given appointments within 7 days or dealt with by telephone advice. CONCLUSION: The demand for OOH dermatology across the East Midlands is low, but access to timely dermatology advice is essential in some situations. Commissioning of a regional dermatology OOH service incorporating digital technology may help to improve the equity of access for all patients across the region.

Expansion of immature, nucleated red blood cells by transient low-dose methotrexate immune tolerance induction in mice.

Biological treatments such as enzyme-replacement therapies (ERT) can generate anti-drug antibodies (ADA), which may reduce drug efficacy and impact patient safety and consequently led to research to mitigate ADA responses. Transient low-dose methotrexate (TLD-MTX) as a prophylactic ITI regimen, when administered concurrently with ERT, induces long-lived reduction of ADA to recombinant human alglucosidase alfa (rhGAA) in mice. In current clinical practice, a prophylactic ITI protocol that includes TLD-MTX, rituximab and intravenous immunoglobulin (optional), successfully induced lasting control of ADA to rhGAA in high-risk, cross-reactive immunological material (CRIM)-negative infantile-onset Pompe disease (IOPD) patients. More recently, evaluation of TLD-MTX demonstrated benefit in CRIM-positive IOPD patients. To more clearly understand the mechanism for the effectiveness of TLD-MTX, non-targeted transcriptional and proteomic screens were conducted and revealed up-regulation of erythropoiesis signatures. Confirmatory studies showed transiently larger spleens by weight, increased spleen cellularity and that following an initial reduction of mature red blood cells (RBCs) in the bone marrow and blood, a significant expansion of Ter-119+ CD71+ immature RBCs was observed in spleen and blood of mice. Histology sections revealed increased nucleated cells, including hematopoietic precursors, in the splenic red pulp of these mice. This study demonstrated that TLD-MTX induced a transient reduction of mature RBCs in the blood and immature RBCs in the bone marrow followed by significant enrichment of immature, nucleated RBCs in the spleen and blood during the time of immune tolerance induction, which suggested modulation of erythropoiesis may be associated with the induction of immune tolerance to rhGAA.

Electrolyte measurements differ between point-of-care and reference analysers in dogs with hypoadrenocorticism.

INTRODUCTION: Dogs treated for hypoadrenocorticism are monitored through analysis of their blood electrolytes. This is routinely performed with point-of-care analysers and doses of medications are adjusted based on the results. OBJECTIVES: To investigate the performance of two point-of-care analysers (IDEXX Catalyst Dx and IDEXX VetStat) against a reference laboratory method for the measurement of blood sodium, potassium and chloride concentrations, as well as sodium: potassium ratios, in dogs diagnosed with and treated for hypoadrenocorticism. METHODS: Forty-eight dogs were enrolled into a prospective cross-sectional study. Paired blood samples were taken and tested on two point-of-care analysers and at a reference laboratory. Statistical analysis was then performed with Bland-Altman analysis and Passing-Bablok regression. The clinical effects of inaccurate electrolyte analysis were investigated. RESULTS: In total, 329 samples were tested on the Catalyst analyser, while another 72 samples were tested on the VetStat. Passing-Bablok regression identified both proportional and constant bias for some analytes. There was poor agreement between sodium and chloride concentrations on both analysers. Both analysers tended to give higher results than the reference method for all analytes, except for potassium when measured on the VetStat. CLINICAL SIGNIFICANCE: There are inherent differences between the electrolyte concentrations measured by these two point-of-care analysers and reference laboratory methods in dogs with hypoadrenocorticism.

HRI London 2019: 10 Years of Excellence in Homeopathy Research.

The Homeopathy Research Institute's (HRI's) 4th International Research Conference took place in the heart of London from 14 to 16 June 2019. With 352 attendees from 38 countries, this was HRI's largest and most international conference to date. HRI London 2019 will be remembered for the highest quality scientific programme so far, combined with a vibrant, positive atmosphere throughout, making it the perfect way to celebrate HRI's 10th Anniversary. Here we summarise the science presented during the intense 2.5-day programme.

Treatment of acne with spironolactone: a retrospective review of 395 adult patients at Mayo Clinic, 2007-2017.

BACKGROUND: Few large studies have assessed spironolactone treatment of adult female acne. OBJECTIVES: To explore the role of spironolactone in the treatment of adult female acne. METHODS: We performed a retrospective case series assessing the efficacy of spironolactone treatment of a cohort of women evaluated at Mayo Clinic in Rochester, Minnesota, from 2007 through 2017. RESULTS: In total, 395 patients (median age, 32 years) received a median spironolactone dose of 100 mg daily. Approximately two-thirds of patients (66.1%) had a complete response; 85.1% had a complete response or a partial response greater than 50%. Median times to initial response and maximum response were 3 and 5 months. Efficacy was observed across all severity subtypes of acne, including those with papulopustular and nodulocystic acne. Patients received long-term treatment with spironolactone (median duration, 13 months) and had few adverse effects. CONCLUSIONS: Spironolactone is a safe and effective treatment of acne for women.

Clinical outcomes of patients discharged from the Rapid Access Chest Pain Clinic with non-anginal chest pain: A retrospective cohort study.

BACKGROUND: The Rapid Access Chest Pain Clinic (RACPC) has become an important means of assessing patients who present with ischaemic or ischaemia-like symptoms of recent onset. Observations have shown that up to 70% are discharged with a diagnosis of non-anginal chest pain (NACP) and accordingly "reassured". This study aims to describe the actual clinical outcomes of this cohort of patients discharged from the RACPC. METHODS: We undertook a single centre retrospective cohort study at a tertiary cardiac hospital. The outcomes of unselected patients diagnosed with NACP and discharged from the RACPC between April 2010 and March 2013 at University Hospitals of Leicester (UHL) were recorded. Re-referrals to cardiology outpatient clinic and emergency hospital admissions for cardiovascular disease within 6 months, and the mortality rate at 12 months, were determined. RESULTS: 7066 patients were seen in the UHL RACPC during the 36-month period. 3253 (46.0%) were diagnosed with NACP and discharged. 7 (0.2%) were diagnosed with coronary artery disease (CAD) and 8 (0.25%) cases of acute coronary syndrome (ACS) identified during the review period. 11 (0.3%) patients died within 12 months of discharge from RACPC. No deaths were attributable to CAD. CONCLUSIONS: Comprehensive assessment using risk-stratification criteria in a nurse practitioner-led RACPC can accurately identify patients who are at low-risk for subsequent CAD. Despite contemporary National Institute for Health and Care Excellence (NICE) guidelines that shift focus away from a clinical judgement based approach, this strategy appears to robustly predict favourable outcomes in patients diagnosed with NACP.

Homeopathy for treatment of irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) is a common, chronic disorder that leads to decreased health-related quality of life and work productivity. A previous version of this review was not able to draw firm conclusions about the effectiveness of homeopathic treatment for IBS and recommended that further high quality RCTs were conducted to explore the clinical and cost effectiveness of homeopathic treatment for IBS. Two types of homeopathic treatment were evaluated in this systematic review: 1. Clinical homeopathy where a specific remedy is prescribed for a specific condition; 2. Individualised homeopathic treatment, where a homeopathic remedy based on a person's individual symptoms is prescribed after a detailed consultation. OBJECTIVES: To assess the effectiveness and safety of homeopathic treatment for IBS. SEARCH METHODS: For this update we searched MEDLINE, CENTRAL, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), the Cochrane IBD Group Specialised Register and trials registers from inception to 31 August 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs), cohort and case-control studies that compared homeopathic treatment with placebo, other control treatments, or usual care, in adults with IBS were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. The primary outcome was global improvement in IBS as measured by an IBS symptom severity score. Secondary outcomes included quality of life, abdominal pain, stool frequency, stool consistency, and adverse events. The overall certainty of the evidence supporting the primary and secondary outcomes was assessed using the GRADE criteria. We used the Cochrane risk of bias tool to assess risk of bias. We calculated the mean difference (MD) and 95% confidence interval (CI) for continuous outcomes and the risk ratio (RR) and 95% CI for dichotomous outcomes. MAIN RESULTS: Four RCTs (307 participants) were included. Two studies compared clinical homeopathy (homeopathic remedy, asafoetida or asafoetida plus nux vomica) to placebo for IBS with constipation (IBS-C). One study compared individualised homeopathic treatment (consultation plus remedy) to usual care for the treatment of IBS in female patients. One study was a three armed RCT comparing individualised homeopathic treatment to supportive listening or usual care. The risk of bias in three studies (the two studies assessing clinical homeopathy and the study comparing individualised homeopathic treatment to usual care) was unclear on most criteria and high for selective reporting in one of the clinical homeopathy studies. The three armed study comparing individualised homeopathic treatment to usual care and supportive listening was at low risk of bias in four of the domains and high risk of bias in two (performance bias and detection bias).A meta-analysis of the studies assessing clinical homeopathy, (171 participants with IBS-C) was conducted. At short-term follow-up of two weeks, global improvement in symptoms was experienced by 73% (46/63) of asafoetida participants compared to 45% (30/66) of placebo participants (RR 1.61, 95% CI 1.18 to 2.18; 2 studies, very low certainty evidence). In the other clinical homeopathy study at two weeks, 68% (13/19) of those in the asafoetida plus nux vomica arm and 52% (12/23) of those in the placebo arm experienced a global improvement in symptoms (RR 1.31, 95% CI 0.80 to 2.15; very low certainty evidence). In the study comparing individualised homeopathic treatment to usual care (N = 20), the mean global improvement score (feeling unwell) at 12 weeks was 1.44 + 4.55 (n = 9) in the individualised homeopathic treatment arm compared to 1.41 + 1.97 (n=11) in the usual care arm (MD 0.03; 95% CI -3.16 to 3.22; very low certainty evidence).In the study comparing individualised homeopathic treatment to usual care, the mean IBS symptom severity score at 6 months was 210.44 + 112.4 (n = 16) in the individualised homeopathic treatment arm compared to 237.3 + 110.22 (n = 60) in the usual care arm (MD -26.86, 95% CI -88.59 to 34.87; low certainty evidence). The mean quality of life score (EQ-5D) at 6 months in homeopathy participants was 69.07 (SD 17.35) compared to 63.41 (SD 23.31) in usual care participants (MD 5.66, 95% CI -4.69 to 16.01; low certainty evidence).For In the study comparing individualised homeopathic treatment to supportive listening, the mean IBS symptom severity score at 6 months was 210.44 + 112.4 (n = 16) in the individualised homeopathic treatment arm compared to 262 + 120.72 (n = 18) in the supportive listening arm (MD -51.56, 95% CI -129.94 to 26.82; very low certainty evidence). The mean quality of life score at 6 months in homeopathy participants was 69.07 (SD 17.35) compared to 63.09 (SD 24.38) in supportive listening participants (MD 5.98, 95% CI -8.13 to 20.09; very low certainty evidence).None of the included studies reported on abdominal pain, stool frequency, stool consistency, or adverse events. AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain. Thus no firm conclusions regarding the effectiveness and safety of homeopathy for the treatment of IBS can be drawn. Further high quality, adequately powered RCTs are required to assess the efficacy and safety of clinical and individualised homeopathy for IBS compared to placebo or usual care.