Data harmonization for collaborative research among MS registries: A case study in employment.

OBJECTIVE: To assess the feasibility of collaboration and retrospective data harmonization among three multiple sclerosis (MS) registries by investigating employment status. METHODS: We used the Maelstrom guidelines to facilitate retrospective harmonization of data from three MS registries, including the NARCOMS (North American Research Committee on MS) Registry, German MS Register (GMSR), and United Kingdom MS (UK-MS) Register. A protocol was developed based on the guidelines, and summary-level data were used to combine results. Employment status and a limited set of factors associated with employment (age, sex, education, and disability level) were harmonized. A meta-analytic approach was used to pool estimates using a weighted average of logistic regression estimates and their variances in a random effects model. RESULTS: Employment status, age, sex, education, and disability were mapped. The overall employment rate was 57% (11,143 employed out of 19,562 persons with MS) with the GMSR having the highest proportion of participants employed (66.2%), followed by the UK-MS (55.2%) and NARCOMS (43.0%) registries. As disability level increased, the odds of not being employed increased. CONCLUSION: Harmonization across registries was feasible. The Maelstrom guidelines provide a valuable roadmap for conducting high-quality harmonization projects. The pooling of data sources has the potential to be an important mechanism for conducting research in MS.

Coherent imager module with a large field of view for synthetic aperture interferometry applications.

Optical areal profilometry of large precision-engineered surfaces require high-resolution measurements over large fields of view. Synthetic Aperture Interferometry (SAI) offers an alternative to the conventional approach of stitching small fields of view (FOV) obtained with Coherent Scanning Interferometry (CSI) using high-NA objectives. In SAI, low-resolution digital holograms are recorded for different illumination and observation directions and they are added coherently to produce a high-resolution reconstruction over a large FOV. This paper describes the design, fabrication and characterization of a large FOV, compact and low-cost coherent imager (CI) as a building block of a coherent sensor array for a SAI system. The CI consists of a CMOS photodetector array with 1.12 µm pixel pitch, a square entrance pupil and a highly divergent reference beam that emerges from a pinhole milled with a focused ion beam on the cylindrical cladding at the tip of an optical fibre. In order to accurately reconstruct the digital holograms, the wavefront of the reference beam is estimated by localizing the reference source relative to the photodetector array. This is done using an optimization approach that simultaneously reconstructs plane waves that reach the aperture from 121 different illumination directions and guarantees a phase root-mean-squared (RMS) error of less than a fifth of the wavelength across the CI entrance pupil at a boundary of the FOV. The CI performance is demonstrated with a holographic reconstruction of a 0.110 m wide object placed at a distance of 0.085 m, i.e. a FOV = ±0.57 rad, the highest reported to date with a holographic camera.

Characterization of the reference wave in a compact digital holographic camera.

A hologram is a recording of the interference between an unknown object wave and a coherent reference wave. Providing the object and reference waves are sufficiently separated in some region of space and the reference beam is known, a high-fidelity reconstruction of the object wave is possible. In traditional optical holography, high-quality reconstruction is achieved by careful reillumination of the holographic plate with the exact same reference wave that was used at the recording stage. To reconstruct high-quality digital holograms the exact parameters of the reference wave must be known mathematically. This paper discusses a technique that obtains the mathematical parameters that characterize a strongly divergent reference wave that originates from a fiber source in a new compact digital holographic camera. This is a lensless design that is similar in principle to a Fourier hologram, but because of the large numerical aperture, the usual paraxial approximations cannot be applied and the Fourier relationship is inexact. To characterize the reference wave, recordings of quasi-planar object waves are made at various angles of incidence using a Dammann grating. An optimization process is then used to find the reference wave that reconstructs a stigmatic image of the object wave regardless of the angle of incidence.

Dapsone-induced methemoglobinemia in renal transplant recipients: more prevalent than previously thought.

BACKGROUND: After an outbreak of Pneumocystis pneumonia (PCP) in our nephrology unit, dapsone was used as the second-line chemoprophylactic agent. Dapsone is the most common cause of drug-induced methemoglobinemia (MHb). Its prevalence is poorly described in the renal transplant population. Because dapsone is excreted by the kidneys, we hypothesized that the rate of MHb in these patients would be higher than previously reported. We aimed to describe the demographics, risk factors, and presenting features of MHb in these renal transplant patients. METHODS: Twenty-six transplant recipients commenced on dapsone for chemoprophylaxis against PCP from February to September 2011. All patients had normal glucose-6-phosphate dehydrogenase levels before treatment. Characteristics of patients with MHb were compared with those of the rest of the cohort to determine potential risk factors. RESULTS: Twelve (46%) patients developed MHb (levels 6.4 ± 4.1%). Six (50%) of the patients with MHb were asymptomatic on presentation. Cases had a mean drop in hemoglobin of 19 ± 7%. MHb led to five admissions (median length of stay 5 days, range 1-10 days). MHb level showed a strong correlation with the length of stay (correlation coefficient 0.762, P = 0.002). CONCLUSION: This is the highest reported prevalence of MHb, to our knowledge, in patients receiving dapsone, and its use led to significant hospitalization in this population. This study raises concerns about the use of dapsone as chemoprophylaxis in renal transplant recipients.

Breast cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK, 2000-2007: a population-based study.

BACKGROUND: We investigate whether differences in breast cancer survival in six high-income countries can be explained by differences in stage at diagnosis using routine data from population-based cancer registries. METHODS: We analysed the data on 257,362 women diagnosed with breast cancer during 2000-7 and registered in 13 population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Flexible parametric hazard models were used to estimate net survival and the excess hazard of dying from breast cancer up to 3 years after diagnosis. RESULTS: Age-standardised 3-year net survival was 87-89% in the UK and Denmark, and 91-94% in the other four countries. Stage at diagnosis was relatively advanced in Denmark: only 30% of women had Tumour, Nodes, Metastasis (TNM) stage I disease, compared with 42-45% elsewhere. Women in the UK had low survival for TNM stage III-IV disease compared with other countries. CONCLUSION: International differences in breast cancer survival are partly explained by differences in stage at diagnosis, and partly by differences in stage-specific survival. Low overall survival arises if the stage distribution is adverse (e.g. Denmark) but stage-specific survival is normal; or if the stage distribution is typical but stage-specific survival is low (e.g. UK). International differences in staging diagnostics and stage-specific cancer therapies should be investigated.

A qualitative evaluation of internet information on hip and knee osteoarthritis.

BACKGROUND: Hip and knee arthritis are two of the most common conditions that result in referral to orthopaedic outpatient clinics. Many patients now use the internet to research their condition and to inform their decision about treatment options. This has implications for the process of informed consent. AIM: To assess the quality of patient information on the internet regarding hip and knee arthritis. METHODS: 'Hip arthritis' and 'Knee arthritis' were entered as search terms into a popular search engine. To adjust for temporal variation, the process was repeated one month and one year later. Of the 200 results analysed, 83 websites met the inclusion criteria. The quality of patient information presented on these websites was assessed using a validated scoring instrument by two independent observers. RESULTS: Most websites assessed were of poor quality; nearly half of all websites did not mention any risks or complications associated with surgical intervention for these conditions. CONCLUSIONS: As part of their professional obligation to provide a robust process of informed consent, clinicians should be aware of the variable quality of patient information available on the internet. As such, they should be prepared to advise their patients about quality websites where reliable information can be sought.

Penthrox enables quicker management of fractures, dislocations and more: learning lessons from expedited care of trauma patients during the COVID-19 pandemic.

INTRODUCTION: Methoxyflurane is an historical anaesthetic agent that has undergone a renaissance with the introduction of a smaller dose in a handheld 'Penthrox' device. The benefits of Penthrox include its ease of use, with disposable individual packets, and the need for less monitoring and staff, when compared with deeper sedation. The literature acknowledges its use for analgesia and in the management of anterior shoulder dislocation but in no other procedural orthopaedic circumstance. METHODS: Following institutional approval, we undertook a retrospective review of all incidences of Penthrox use to facilitate minor procedures within a 2-month period starting 24 March 2020. Time to procedure and success were recorded using the surrogate markers of patient attendance and x-Ray occurrence times. RESULTS: Some 101 Penthrox doses were given to 89 patients over 97 unique episodes between 24 March and 26 May 2020. No complications were recorded following the use of Penthrox during this period. Patient demographics were explored. Fracture manipulations and casting (n=54) had a 100% success rate in achieving adequate and safe reduction. Joint dislocations (n=34) were treated with varying success. Native elbow dislocations were reduced most successfully (4/4, 100%). Native shoulder dislocations were seen in 17 patients and successful relocation was seen in 11 cases, giving a success rate of 65%. CONCLUSIONS: This is the first study, outside anterior shoulder dislocations, to report on the efficacy of Penthrox within emergent orthopaedic scenarios. We have demonstrated Penthrox to be a safe tool for helping to manage trauma procedures in the emergency department.

Multiple sclerosis health-related quality of life utility values from the UK MS register.

Background: New interventions for multiple sclerosis (MS) commonly require a demonstration of cost-effectiveness using health-related quality of life (HRQoL) utility values. The EQ-5D is the utility measure approved for use in the UK NHS funding decision-making. There are also MS-specific utility measures - e.g., MS Impact Scale Eight Dimensions (MSIS-8D) and MSIS-8D-Patient (MSIS-8D-P). Objectives: Provide EQ-5D, MSIS-8D and MSIS-8D-P utility values from a large UK MS cohort and investigate their association with demographic/clinical characteristics. Methods: UK MS Register data from 14,385 respondents (2011 to 2019) were analysed descriptively and using multivariable linear regression, with self-report Expanded Disability Status Scale (EDSS) scores. Results: The EQ-5D and MSIS-8D were both sensitive to differences in demographic/clinical characteristics. An inconsistency found in previous studies whereby mean EQ-5D values were higher for an EDSS score of 4 rather than 3 was not observed. Similar utility values were observed between MS types at each EDSS score. Regression showed EDSS score and age were associated with utility values from all three measures. Conclusions: This study provides generic and MS-specific utility values for a large UK MS sample, with the potential for use in cost-effectiveness analyses of treatments for MS.

Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data.

BACKGROUND: Cancer survival is a key measure of the effectiveness of health-care systems. Persistent regional and international differences in survival represent many avoidable deaths. Differences in survival have prompted or guided cancer control strategies. This is the first study in a programme to investigate international survival disparities, with the aim of informing health policy to raise standards and reduce inequalities in survival. METHODS: Data from population-based cancer registries in 12 jurisdictions in six countries were provided for 2·4 million adults diagnosed with primary colorectal, lung, breast (women), or ovarian cancer during 1995-2007, with follow-up to Dec 31, 2007. Data quality control and analyses were done centrally with a common protocol, overseen by external experts. We estimated 1-year and 5-year relative survival, constructing 252 complete life tables to control for background mortality by age, sex, and calendar year. We report age-specific and age-standardised relative survival at 1 and 5 years, and 5-year survival conditional on survival to the first anniversary of diagnosis. We also examined incidence and mortality trends during 1985-2005. FINDINGS: Relative survival improved during 1995-2007 for all four cancers in all jurisdictions. Survival was persistently higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark, England, Northern Ireland, and Wales, particularly in the first year after diagnosis and for patients aged 65 years and older. International differences narrowed at all ages for breast cancer, from about 9% to 5% at 1 year and from about 14% to 8% at 5 years, but less or not at all for the other cancers. For colorectal cancer, the international range narrowed only for patients aged 65 years and older, by 2-6% at 1 year and by 2-3% at 5 years. INTERPRETATION: Up-to-date survival trends show increases but persistent differences between countries. Trends in cancer incidence and mortality are broadly consistent with these trends in survival. Data quality and changes in classification are not likely explanations. The patterns are consistent with later diagnosis or differences in treatment, particularly in Denmark and the UK, and in patients aged 65 years and older. FUNDING: Department of Health, England; and Cancer Research UK.

Advanced breast cancer incidence following population-based mammographic screening.

BACKGROUND: Breast cancer mortality is declining in many Western countries. If mammography screening contributed to decreases in mortality, then decreases in advanced breast cancer incidence should also be noticeable. PATIENTS AND METHODS: We assessed incidence trends of advanced breast cancer in areas where mammography screening is practiced for at least 7 years with 60% minimum participation and where population-based registration of advanced breast cancer existed. Through a systematic Medline search, we identified relevant published data for Australia, Italy, Norway, Switzerland, The Netherlands, U.K. and the U.S.A. Data from cancer registries in Northern Ireland, Scotland, the U.S.A. (Surveillance, Epidemiology and End Results (SEER), and Connecticut), and Tasmania (Australia) were available for the study. Criterion for advanced cancer was the tumour size, and if not available, spread to regional/distant sites. RESULTS: Age-adjusted annual percent changes (APCs) were stable or increasing in ten areas (APCs of -0.5% to 1.7%). In four areas (Firenze, the Netherlands, SEER and Connecticut) there were transient downward trends followed by increases back to pre-screening rates. CONCLUSIONS: In areas with widespread sustained mammographic screening, trends in advanced breast cancer incidence do not support a substantial role for screening in the decrease in mortality.

COVID-19 in Multiple Sclerosis: Clinically reported outcomes from the UK Multiple Sclerosis Register.

BACKGROUND: In March 2020, the United Kingdom Multiple Sclerosis Register (UKMSR) established an electronic case return form, designed collaboratively by MS neurologists, to record data about COVID-19 infections in people with MS (pwMS). OBJECTIVES: Examine how hospital admission and mortality are affected by disability, age and disease modifying treatments (DMTs) in people with Multiple Sclerosis with COVID-19. METHODS: Anonymised data were submitted by clinical teams. Regression models were tested for predictors of hospitalisation and mortality outcomes. Separate analyzes compared the first and second 'waves' of the pandemic. RESULTS: Univariable analysis found hospitalisation and mortality were associated with increasing age, male gender, comorbidities, severe disability, and progressive MS; severe disability showed the highest magnitude of association. Being on a DMT was associated with a small, lower risk. Multivariable analysis found only age and male gender were significant. Post hoc analysis demonstrated that factors were significant for hospitalisation but not mortality. In the second wave, hospitalisation and mortality were lower. Separate models of the first and second wave using age and gender found they had a more important role in the second wave. CONCLUSIONS: Features associated with poor outcome in COVID-19 are similar to other populations and being on a DMT was not found to be associated with adverse outcomes, consistent with smaller studies. Once in hospital, no factors were predictive of mortality. Reassuringly, mortality appears lower in the second wave.

Getting animated about trauma - Using video animation as part of informed consent.

INTRODUCTION: Trauma patients are often required to make an informed decision about surgery within a short space of time. Coming to terms with their injury may mean they have limited bandwidth for absorbing information, and it may be that they don't appreciate the risks and benefits of surgery discussed during consent. Current consent practice puts the emphasis on the clinician to ensure that all reasonable steps have been taken to explain risks and benefits to patients. We propose the use of video animations that patients can watch prior to surgery as a means of improving their understanding and overall experience. METHODS: The video script was written and evaluated so that a high standard was achieved using the "Discern" instrument. The experiences of a focus group of 5 patients were used to guide script content. Using GoAnimate (GoAnimate Inc., San Mateo) a video was made with voice over provided by local drama students. The video was shown to 30 consecutive patients over a 2 month period. We included any patient with an ankle fracture managed operatively who had been consented (form 1). Evaluation consisted of interview with patients consisting of 2 focussed questions and one open. Responses to the questions were collated and grouped into positive and negative descriptors. RESULTS: 68 (81%) positive descriptors were recorded from patients' interviews versus 16 (19%) negative. Positive descriptors related to improved retention, information giving, technical detail, consolidations of information given during consent. Negatives were caveats that video couldn't replace face-to-face consent, the degree of detail being off-putting and not adding anything to standard consent. CONCLUSION: The video was well received by patients with subjective improvements being made to their understanding, retention and sharing of technical detail. The face-to-face discussion between patient and doctor remains very important to them and the video should look to augment this.

Second primary cancers in patients with skin cancer: a population-based study in Northern Ireland.

Among all 14,500 incident cases of basal cell carcinoma (BCC), 6405 squamous cell carcinomas (SCC) and 1839 melanomas reported to the Northern Ireland Cancer Registry between 1993 and 2002, compared with the general population, risk of new primaries after BCC or SCC was increased by 9 and 57%, respectively. The subsequent risk of cancer, overall, was more than double after melanoma.

Beryllium-10 dating of the duration and retreat of the last pinedale glacial sequence.

Accurate terrestrial glacial chronologies are needed for comparison with the marine record to establish the dynamics of global climate change during transitions from glacial to interglacial regimes. Cosmogenic beryllium-10 measurements in the Wind River Range indicate that the last glacial maximum (marine oxygen isotope stage 2) was achieved there by 21,700 +/- 700 beryllium-10 years and lasted 5900 years. Ages of a sequence of recessional moraines and striated bedrock surfaces show that the initial deglaciation was rapid and that the entire glacial system retreated 33 kilometers to the cirque basin by 12,100 +/- 500 beryllium-10 years.

Characterisation of Interleukin-8 and monocyte chemoattractant protein-1 expression within the abdominal aortic aneurysm and their association with mural inflammation.

OBJECTIVES: Abdominal aortic aneurysms (AAAs) are characterised by chronic transmural inflammation. This study investigated the expression of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) within the AAA, and their relationship with mural inflammation. METHODS: Biopsies were obtained from 25 AAAs, 15 abdominal aortas, and 10 atherosclerotic thoracic aortas. IL-8 and MCP-1 expression was measured in homogenised specimens by ELISA. Infiltrate composition and localised expression of IL-8 and MCP-1 were determined through immunohistochemistry. RESULTS: ELISA analysis demonstrated that IL-8 and MCP-1 were raised in the AAA compared to the controls [(IL-8, AAA vs. abdominal aorta: >28-fold, P<.001; AAA vs. thoracic aorta: >28-fold, P<.001) (MCP-1, AAA vs. abdominal aorta: 9-fold, P<.001; AAA vs. thoracic aorta: 19-fold, P<.001)]. Immunohistochemistry revealed that IL-8 was localised to the inflammatory infiltrate, which consisted predominantly of CD3(+) T- and CD20(+) B-lymphocytes. MCP-1 was predominantly expressed by CD68(+) macrophages. Increasing IL-8 expression was associated with an increase in mural inflammation, and an increase in CD3(+) T-lymphocytes of CD4(+) phenotype within the infiltrate population. CONCLUSION: Pathways involving IL-8 and MCP-1 may be involved in AAA pathogenesis. IL-8 may be directly involved in the chemotaxis of T(H)-lymphocytes into the AAA wall.

Association of early life factors and brain tumour risk in a cohort study.

Using population-based linked birth and cancer registry data, we investigated whether the risk of brain tumour in childhood (n=155) was associated with perinatal risk factors. This population-based cohort showed that being born into a larger family or to a mother with a history of miscarriage may increase childhood brain tumour risk.

Outcome-based commissioning of knee arthroplasty in the NHS: system error in a national monitoring programme and the unintended consequences on achieving the Best Practice Tariff.

AIMS: Our unit was identified as a negative outlier in the national patient-reported outcome measures (PROMs) programme, which has significant funding implications. As a centre that carries out a high volume of unicompartmental knee arthroplasty (UKA), our objectives were: 1) to determine whether the PROMs programme included primary UKA when calculating the gain in Oxford Knee Score (OKS); and 2) to determine the impact of excluding primary UKA on calculated OKS gains for primary knee arthroplasty. MATERIALS AND METHODS: National PROMs data from England (2012 to 2016) were analyzed. Inclusion of UKA cases in the national PROMs programme was determined using clinical codes. Local OKS gain was calculated for UKA and TKA and compared with the published PROMs results for 2012/13. RESULTS: Use of the recommended codes for primary UKA excluded 99.6% of UKAs locally and 97% nationally from PROMs programme analysis. Inclusion of primary UKAs in PROMs analysis improved our OKS gain from 15.1 (below average) to 16.3 (above average) for 2012/13 for primary knee arthroplasty. CONCLUSION: Exclusion of UKA patients from the PROMs programme is a nationwide issue that potentially introduces bias when comparing OKS gain between centres. Where commissioning decisions are based on routinely collected data, it is imperative that the underlying methodology is appropriate to generate valid results.

Validating the portal population of the United Kingdom Multiple Sclerosis Register.

The UK Multiple Sclerosis Register (UKMSR) is a large cohort study designed to capture 'real world' information about living with multiple sclerosis (MS) in the UK from diverse sources. The primary source of data is directly from people with Multiple Sclerosis (pwMS) captured by longitudinal questionnaires via an internet portal. This population's diagnosis of MS is self-reported and therefore unverified. The second data source is clinical data which is captured from MS Specialist Treatment centres across the UK. This includes a clinically confirmed diagnosis of MS (by Macdonald criteria) for consented patients. A proportion of the internet population have also been consented at their hospital making comparisons possible. This dataset is called the 'linked dataset'. The purpose of this paper is to examine the characteristics of the three datasets: the self-reported portal data, clinical data and linked data, in order to assess the validity of the self-reported portal data. The internet (n = 11,021) and clinical (n = 3,003) populations were studied for key shared characteristics. We found them to be closely matched for mean age at diagnosis (clinical = 37.39, portal = 39.28) and gender ratio (female %, portal = 73.1, clinical = 75.2). The Two Sample Kolmogorov-Smirnov test was for the continuous variables to examine is they were drawn from the same distribution. The null hypothesis was rejected only for age at diagnosis (D = 0.078, p < 0.01). The populations therefore, were drawn from different distributions, as there are more patients with relapsing disease in the clinical cohort. In all other analyses performed, the populations were shown to be drawn from the same distribution. Our analysis has shown that the UKMSR portal population is highly analogous to the entirely clinical (validated) population. This supports the validity of the self-reported diagnosis and therefore that the portal population can be utilised as a viable and valid cohort of people with Multiple Sclerosis for study.

A novel use of QR code stickers after orthopaedic cast application.

INTRODUCTION We present a novel solution to ensure that information and contact details are always available to patients while in cast. An information sticker containing both telephone numbers and a Quick Response (QR) code is applied to the cast. When scanned with a smartphone, the QR code loads the plaster team's webpage. This contains information and videos about cast care, complications and enhancing recovery. METHODS A sticker was designed and applied to all synthetic casts fitted in our fracture clinic. On cast removal, patients completed a questionnaire about the sticker. A total of 101 patients were surveyed between November 2015 and February 2016. The questionnaire comprised ten binary choice questions. RESULTS The vast majority (97%) of patients had the sticker still on their cast when they returned to clinic for cast removal. Eighty-four per cent of all patients felt reassured by the presence of the QR code sticker. Nine per cent used the contact details on the cast to seek advice. Over half (56%) had a smartphone and a third (33%) of these scanned the QR code. Of those who scanned the code, 95% found the information useful. CONCLUSIONS This study indicates that use of a QR code reassures patients and is an effective tool in the proactive management of potential cast problems. The QR code sticker is now applied to all casts across our trust. In line with NHS England's Five Year Forward View calling for enhanced use of smartphone technology, our trust is continuing to expand its portfolio of patient information accessible via QR codes. Other branches of medicine may benefit from incorporating QR codes as portals to access such information.

Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study.

BACKGROUND: Osteoarthritis (OA) of the knee is the most prevalent joint disorder. Previous studies suggest that bromelain, a pineapple extract, may be a safer alternative/adjunctive treatment for knee OA than current conventional treatment. AIM: To assess the efficacy of bromelain in treating OA of the knee. DESIGN: Randomized, double-blind placebo-controlled trial. METHODS: Subjects (n = 47) with a confirmed diagnosis of moderate to severe knee OA were randomized to 12 weeks of bromelain 800 mg/day or placebo, with a 4-week follow-up. Knee (pain, stiffness and function) and quality-of-life symptoms were reported monthly in the WOMAC and SF36 questionnaires, respectively. Adverse events were also recorded. The primary outcome measure was the change in total WOMAC score from baseline to the end of treatment at week 12. Longitudinal models were used to evaluate outcome. RESULTS: Thirty-one patients completed the trial (14 bromelain, 17 placebo). No statistically significant differences were observed between groups for the primary outcome (coefficient 11.16, p = 0.27, 95%CI -8.86 to 31.18), nor the WOMAC subscales or SF36. Both treatment groups showed clinically relevant improvement in the WOMAC disability subscale only. Adverse events were generally mild in nature. DISCUSSION: This study suggests that bromelain is not efficacious as an adjunctive treatment of moderate to severe OA, but its limitations support the need for a follow-up study.