The impact of COVID-19 public health measures on attendance and overdose at supervised injecting facilities in Australia.

OBJECTIVES: The COVID-19 pandemic disrupted service provision of harm reduction and drug treatment services for people who inject drugs in many countries. The two supervised injecting facilities (SIFs) in Sydney and Melbourne were differentially impacted by the pandemic, requiring local procedural changes in each service. We aimed to examine the impact of pandemic responses (including restrictions on movement, known as 'lockdowns') on service use and key parameters such as client reports of drug injected and recorded overdose rates. STUDY DESIGN: Time series analysis of weekly client visits and monthly overdoses occurring at each service. METHODS: Administrative client data from the two SIFs (Sydney data from 1 January 2018 to 30 April 2022; Melbourne data from 1 July 2018 to 30 April 2022) were examined using interrupted time series analyses with lockdown dates in each state entered as interruption terms. We analysed weekly SIF visits overall and by drug type, and monthly rates of opioid overdose at each service. RESULTS: Lockdowns resulted in decreased visits to both services. The number of weekly client visits decreased during the first national lockdown for both the Sydney (trend change = -57.9; 95% CI [-109.4, -6.4]) and Melbourne SIF (near sig trend change = -54.8 [-110.8, 1.05]). Trends in visit numbers increased after lockdowns were lifted in each city; however, visits in Sydney have not returned to the numbers recorded prior to the pandemic. Visits to the Melbourne SIF related to heroin use declined at each lockdown (trend 1 = -42.7 [-81.5, -3.9]; trend 2 = -56.1 [-94.6, -17.7]; trend 3 = -33.8 [-67.4, -0.2]); heroin visits to the Sydney SIF declined during the first lockdown and remained low (trend = -55.6 [-82.8, -28.3]). Methamphetamine visits to the Sydney SIF fluctuated, surpassing heroin visits at several timepoints. Rates of monthly opioid overdoses at both services declined immediately following the start of the first lockdown (Sydney = -16.6 [-26.1, -6.8]; Melbourne = -6.4 [-8.7, -4.1]), with increasing trends recorded at the end of the final lockdown in each jurisdiction (Sydney = 2.8 [0.6, 5.0]; Melbourne = 1.3 [0.72, 3.2]). CONCLUSIONS: Public health restrictions related to the COVID-19 pandemic were associated with reduced client visits to, and overdoses in, Australian SIFs. Variations were noted in the drugs injected, likely reflecting changes in local drug markets. Shifts to other drugs during these periods were evident: methamphetamine in Sydney; co-injection of heroin and diphenhydramine in Melbourne.

Solar irradiance and ENSO affect food security in Lake Tanganyika, a major African inland fishery.

Food security in a warming world is a grave concern for rapidly growing impoverished populations. Low-latitude inland fisheries provide protein for millions of rural poor, yet the impacts of high-frequency climate oscillations on these aquatic ecosystems are unknown. Here, we present a sub-annual-to-annual resolution paleolimnological reconstruction of upwelling, productivity, and algal composition at Lake Tanganyika, one of Africa's largest landlocked fisheries. The data reveal increases in diatom production at centennial-scale solar irradiance maxima, and interannual variability in upwelling linked to La Niña. Our study shows that interactions between global climatic controls and El Niño-Southern Oscillation teleconnections exert profound influences on the foundation of Lake Tanganyika's food web. Adapting long-term management practices to account for high-frequency changes in algal production will help safeguard inland fish resources.

A rapid chair-side method for the estimation of oral bacterial colonization density.

AIMS: Caries and periodontal disease are associated with inadequate control of oral bacteria. Since conventional microbiological evaluations are impractical in dental clinics or public engagement activities, a rapid test for the quantification of oral bacteria represents a useful tool. We describe the development of a colour change test to rapidly estimate bacterial colonisation density in the mouth. METHODS AND RESULTS: Volunteers rinsed with milk or milkshake. Viability indicators were added and colour changes quantified during incubation. Using milkshake and the resazurin-based solution PrestoBlue (9% v/v), the method distinguished between samples before and after brushing within 5 min. Colour changes were quantified and viable counts were obtained using oral rinses. Measured colour changes strongly correlated with total counts of both anaerobes and streptococci (Spearman's correlation coefficient of 0·782 and 0·769, respectively, P ≤ 0·001) and with perceived changes, as determined by volunteers (n = 10) visually ranking images. CONCLUSIONS: The resazurin milkshake test can rapidly and visually quantify viable bacteria in oral samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The resazurin milkshake test could serve as a sensitive semi-quantitative method for measuring oral bacteria in human oral rinse samples.

Predicting rapid recovery from acute low back pain based on the intensity, duration and history of pain: a validation study.

BACKGROUND: Clinical prediction rules can assist clinicians to identify patients with low back pain (LBP) who are likely to recover quickly with minimal treatment; however, there is a paucity of validated instruments to assist with this task. METHOD: We performed a pre-planned external validation study to assess the generalizability of a simple 3-item clinical prediction rule developed to estimate the probability of recovery from acute LBP at certain time points. The accuracy of the rule (calibration and discrimination) was determined in a sample of 956 participants enrolled in a randomized controlled trial. RESULTS: The calibration of the rule was reasonable in the new sample with predictions of recovery typically within 5-10% of observed recovery. Discriminative performance of the rule was poor to moderate and similar to that found in the development sample. CONCLUSIONS: The results suggest that the rule can be used to provide accurate information about expected recovery from acute LBP, within the first few weeks of patients presenting to primary care. Impact analysis to determine if the rule influences clinical behaviours and patient outcomes is required.

Does magnetic resonance imaging predict future low back pain? A systematic review.

BACKGROUND AND OBJECTIVE: Magnetic resonance imaging (MRI) has the potential to identify pathology responsible for low back pain (LBP). However, the importance of findings on MRI remains controversial. We aimed to systematically review whether MRI findings of the lumbar spine predict future LBP in different samples with and without LBP. DATABASES AND DATA TREATMENT: MEDLINE, CINAHL and EMBASE databases were searched. Included were prospective cohort studies investigating the relationship between baseline MRI abnormalities of the lumbar spine and clinically important LBP outcome at follow-up. We excluded cohorts with specific diseases as the cause of their LBP. Associations between MRI findings and LBP pain outcomes were extracted from eligible studies. RESULTS: A total of 12 studies met the inclusion criteria. Six studies presented data on participants with current LBP; one included a sample with no current LBP, three included a sample with no history of LBP and two included mixed samples. Due to small sample size, poor overall quality and the heterogeneity between studies in terms of participants, MRI findings and clinical outcomes investigated, it was not possible to pool findings. No consistent associations between MRI findings and outcomes were identified. Single studies reported significant associations for Modic changes type 1 with pain, disc degeneration with disability in samples with current LBP and disc herniation with pain in a mixed sample. CONCLUSIONS: The limited number, heterogeneity and overall quality of the studies do not permit definite conclusions on the association of MRI findings of the lumbar spine with future LBP (PROSPERO: CRD42012002342).

Mitochondrial DNA damage as a biomarker for ultraviolet radiation exposure and oxidative stress.

The skin is regularly exposed to the harmful effects of sunlight, such as ultraviolet radiation (UVR), which leads to ageing effects as well as clinical precancerous lesions and skin cancer. The accumulation of mitochondrial DNA (mtDNA) damage has been strongly associated as an underlying cause of the general ageing process in tissues and mtDNA damage has been associated with cancer development in many tissues including human skin. This scenario is linked to the key roles of mitochondrial function and mtDNA both in terms of energy production and also oxidative stress production as well as a mediator of apoptosis. We and others have pioneered the use of mtDNA damage as a highly sensitive biomarker of UVR exposure and oxidative stress in human skin; furthermore, ageing-dependent mtDNA mutations can be accelerated by exposure to sunlight. In addition, this review will also highlight useful applications of mtDNA as a biomarker of UVR-induced oxidative stress including effects of antioxidants.

Patterns of physical activity in children with haemophilia.

The current widespread use of prophylaxis in developed countries has enabled greater participation in physical activity. However, there are no data available on leisure-time physical activity in Australian children with haemophilia. The data reported here were obtained from a case-crossover study nested in a prospective cohort study of 104 boys with moderate and severe haemophilia followed for one year. Each child's physical activity was assessed using a modifiable physical activity questionnaire (Kriska's MAQ) administered at baseline, and a one-week prospective activity diary at a randomly determined time. Children were aged 4-18 years. The median time spent in sport or leisure-time physical activity in the preceding year was 7.9 h/week (IQR 4.6 to 12.9). The median time spent in vigorous physical activity was 3.8 h/week (IQR 1.6 to 6.4) and in moderate and vigorous physical activity 6.4 h/week (IQR 3.7 to 10.0). The median small-screen time was 2.5 h/day (IQR 0.5 to 2.5). Forty-five per cent of all children and 61% of children over the age of 10 years played at least one competitive sport. Averaged across one week, 43% of all children met the Australian government physical activity guidelines for children and 36% met the guidelines for small-screen time. This study provides the first data regarding leisure-time physical activity in children with haemophilia living in Australia. The majority of Australian children with haemophilia are not meeting the national physical activity and small-screen time guidelines.

Feasibility of short message service to document bleeding episodes in children with haemophilia.

The increasing emphasis on home-based treatment for the management of children with haemophilia has meant that many of these children no longer regularly report to a medical facility. Consequently, it is difficult to monitor incidence of bleeding episodes. The aim of this study was to assess the feasibility of using a short message service (SMS) to monitor incidence of bleeding episodes in children with haemophilia. One hundred and four children with moderate and severe haemophilia A or B took part in a 1-year prospective study between 2008 and 2010. Children or their parents were asked to maintain a bleeds diary. They received a weekly SMS asking whether there had been a bleeding episode in the preceding week. Response rates were calculated. Children were followed for a total of 4839 person-weeks. SMS replies were received for 4201 weeks. Thus, the rate of follow-up was 86.8%. Median responses rates were 94.2% (IQR: 86.1-100%). Weekly SMS is a feasible reporting tool for documenting bleeding episodes in children with haemophilia. It is associated with high response rates and minimal expense and intrusion. The use of SMS could be extended to encourage compliance to prophylactic treatment, particularly in adolescents with haemophilia.

Thoracic discitis as a complication of self-expanding metallic stents in esophageal carcinoma.

The role of metallic stents in the palliation of esophageal cancer is well established. Self-expanding metal stents (SEMSs) are frequently used, as they provide an effective and safe method of relieving malignant dysphagia. A number of complications are associated with the use of SEMSs, including esophageal perforation. We report a case of thoracic discitis occurring in a patient with advanced esophageal malignancy, treated with SEMSs. We propose that the likely etiology in this patient was esophageal perforation by a metallic stent.

Fitness and quality of life in children with haemophilia.

Prior to the introduction of prophylactic clotting factor, children with haemophilia were discouraged from physical activity due to the risk of bleeds. Reports of children with haemophilia having lower levels of fitness and strength than their healthy peers were therefore well accepted. This study aimed to establish whether these deficits continued, and specifically, whether Australian boys with haemophilia and von Willebrand disorder had lower strength and aerobic capacity than their peers, despite widespread use of prophylaxis. Forty-four boys aged 6.1-17.0 years (mean 10.9, SD 3.2) with haemophilia A and B and von Willebrand disorder participated in the study. Fitness, strength and body mass index (BMI) measures were compared with age- and gender-matched data from a representative cohort of school children. Quality of Life was measured using the Haemo-QoL to obtain baseline measures in an Australian population. There were no statistically significant or clinically important differences in aerobic fitness or BMI between the boys with haemophilia and controls in any age category. Boys with haemophilia in Years 4, 6 and 10 had greater strength than their peers. Australian boys with bleeding disorders do not have impaired aerobic capacity or strength compared with their peers. Quality of life in Australian boys with haemophilia is comparable to their European counterparts.

Dual interventional approach of endoscopic reboring in completely stenosed rectal anastomosis using radiology guidance: a novel technique.

OBJECTIVE: Rectal stricture/stenosis is a well-recognized complication following anterior resection. Completely stenosed rectal anastomoses have been conventionally treated conservatively with permanent stoma. The surgical alternatives are either a redo low resection with its accompanying hazards or formation of a permanent colostomy. We describe a simple method of treating anastomotic stenoses using a novel technique in patients with a defunctioned bowel. METHOD: Three patients with complete stenosis of a rectal anastomosis following anterior resection underwent this novel technique with informed consent. A stenosis with no identifiable lumen was diagnosed at the time of examination under anaesthetic (EUA) or by contrast enema. Using a novel technique of combined endoscopic and radiology guidance, the anastomotic stenosis was rebored and subsequently dilated to restore bowel continuity. RESULTS: There were no complications observed following this procedure. Two of the three patients needed repeat endoscopic dilatation. All patients had restoration of the lumen in the anastomosis and subsequently underwent closure of ileostomy and made an uneventful recovery. CONCLUSION: Combined endoscopic dilatation under radiological guidance is a novel technique and appears to be a simple, safe, effective and inexpensive method for treating rectal anastomotic stenoses.

Effect of margin status on cervical intraepithelial neoplasia recurrence following LLETZ in women over 50 years.

OBJECTIVE: To establish the effect of margin status on recurrence following large loop excision of the transformation zone (LLETZ) in women over 50 years. STUDY DESIGN: Prospectively collected data of women over 50 years, who underwent LLETZ for suspected cervical intraepithelial neoplasia between 1998 and 2003, were analysed. Women were followed up for up to over 6 years. SETTING: District colposcopy service based at a gynae-oncology cancer centre. MAIN OUTCOME MEASURES: The main outcome measure included histologically detected recurrence. Any abnormal cytology on follow up was also documented. METHODS: Prospectively collected data were analysed from the colposcopy database. Recurrence was analysed using Kaplan-Meir plots and Cox regression. Fisher's exact test was used to determine the association between margins and grade. The Kruskal-Wallis and Mann-Whitney U tests were used to compare age and duration of follow up between groups. RESULTS: A total of 118 women underwent LLETZ and 92 were included in the final analysis. Margins were designated as clear (n = 62), involved (n = 22) or uncertain (n = 8). Histological recurrence occurred in 12 while abnormal cytology was demonstrated in 17 women. One woman with involved margins developed cervical cancer. Individuals with clear margins were less likely to have recurrence than those with involved margins (Hazard Ratio (HR) 0.18, 95% CI: 0.06-0.59). Involved margins were more common with high-grade than low-grade lesions (P = 0.002). CONCLUSION: The data show an association between disease recurrence and the finding of involved margins in this cohort.

Magnetic resonance imaging findings of tamoxifen-associated uterine Müllerian adenosarcoma: a case report.

Müllerian adenosarcoma of the uterus is a rare biphasic tumor, which was first described in 1974. Recent studies have suggested an association with tamoxifen therapy, but there have been few reports with detailed imaging findings. We present a case with magnetic resonance imaging (MRI) findings of this rare tumor in a woman who received long-term tamoxifen therapy for breast cancer. In addition, myometrial invasion was detected more accurately with MRI compared to ultrasound in this one single case.

The relevance of cross-cultural adaptation and clinimetrics for physical therapy instruments

BACKGROUND: Self-report outcome measures (questionnaires) are widely used by physiotherapists for measuring patient's health status or treatment outcomes. Most of these measurement tools were developed in English and their usefulness is very limited in non-English speaking countries such as Brazil. The only way to solve this problem is to properly adapt the relevant questionnaires into a target language and culture (e.g. Brazilian-Portuguese) and then test the instrument by checking its psychometric (clinimetric) characteristics. OBJECTIVES: The purpose of this paper was to present relevant issues in the process of cross-cultural adaptations and clinimetric testing for self-report outcome measurements. Advice on how to perform a cross-cultural adaptation, how to properly check the clinimetric properties, how to select a relevant questionnaire and how to evaluate the quality of an adapted questionnaire are provided. Additionally we present all Brazilian-Portuguese cross-cultural adaptations of low back pain measurements that we know of. CONCLUSIONS: There is a clear need for more effort in the field of cross-cultural adaptation and clinimetrics, without proper instruments, the management of patients from non-English speaking countries is compromised.

INTRODUÇÃO: Questionários vem sendo amplamente utilizados por fisioterapeutas para medir a condição de saúde do paciente ou dos resultados de tratamento. A maioria desses instrumentos para avaliação foi desenvolvida em inglês, sendo seu uso bastante limitado em países que não usam o inglês como língua nativa, a exemplo do Brasil. A única forma de resolver esse problema é através de uma adaptação apropriada dos questionários relevantes para um alvo lingüístico e cultural (por exemplo, português do Brasil) e então testar suas características psicométricas (clinimétricas). OBJETIVO: A finalidade deste artigo foi a apresentar os tópicos relevantes no processo das adaptações transculturais de questionários e os seus respectivos testes clinimétricos. São fornecidas propostas sobre como realizar uma adaptação transcultural, como avaliar adequadamente as propriedades clinimétricas, como selecionar um questionário relevante e como avaliar a qualidade de um questionário adaptado. Além disso, são também apresentadas as adaptações conhecidas, para português do Brasil, dos questionários para avaliação de dor lombar. CONCLUSÃO: Existe uma clara necessidade de mais esforços na área de adaptação transcultural e clinimetria. Sem os instrumentos adequados, o gerenciamento no cuidado de pacientes nos países onde o inglês não é a língua nativa torna-se comprometido.

Systematic review of tests to identify the disc, SIJ or facet joint as the source of low back pain.

Clinical practice guidelines state that the tissue source of low back pain cannot be specified in the majority of patients. However, there has been no systematic review of the accuracy of diagnostic tests used to identify the source of low back pain. The aim of this systematic review was therefore to determine the diagnostic accuracy of tests available to clinicians to identify the disc, facet joint or sacroiliac joint (SIJ) as the source of low back pain. MEDLINE, EMBASE and CINAHL were searched up to February 2006 with citation tracking of eligible studies. Eligible studies compared index tests with an appropriate reference test (discography, facet joint or SIJ blocks or medial branch blocks) in patients with low back pain. Positive likelihood ratios (+LR) > 2 or negative likelihood ratios (-LR) < 0.5 were considered informative. Forty-one studies of moderate quality were included; 28 investigated the disc, 8 the facet joint and 7 the SIJ. Various features observed on MRI (high intensity zone, endplate changes and disc degeneration) produced informative +LR (> 2) in the majority of studies increasing the probability of the disc being the low back pain source. However, heterogeneity of the data prevented pooling. +LR ranged from 1.5 to 5.9, 1.6 to 4.0, and 0.6 to 5.9 for high intensity zone, disc degeneration and endplate changes, respectively. Centralisation was the only clinical feature found to increase the likelihood of the disc as the source of pain: +LR = 2.8 (95%CI 1.4-5.3). Absence of degeneration on MRI was the only test found to reduce the likelihood of the disc as the source of pain: -LR = 0.21 (95%CI 0.12-0.35). While single manual tests of the SIJ were uninformative, their use in combination was informative with +LR of 3.2 (95%CI 2.3-4.4) and -LR of 0.29 (95%CI 0.12-0.35). None of the tests for facet joint pain were found to be informative. The results of this review demonstrate that tests do exist that change the probability of the disc or SIJ (but not the facet joint) as the source of low back pain. However, the changes in probability are usually small and at best moderate. The usefulness of these tests in clinical practice, particularly for guiding treatment selection, remains unclear.

Risk of malignancy index in the preoperative evaluation of pelvic masses.

OBJECTIVES: To assess the ability of a risk malignancy index (RMI) based on serum levels of CA 125, ultrasound findings, and menopausal status to discriminate between benign and malignant pelvic masses in a particular population. METHODS: A retrospective study was conducted of 100 women with pelvic masses admitted for laparotomy. The sensitivity and specificity of serum levels of CA 125, ultrasound findings, and menopausal status were calculated both separately and combined into a RMI to diagnose malignancy. RESULTS: The RMI was more accurate than any single criterion in diagnosing malignancy. Using a cut-off level of 200 to indicate malignancy, the RMI gave a sensitivity of 90%, specificity of 89%, positive predictive value of 96%, and negative predictive value of 78%. CONCLUSION: The RMI is able to correctly discriminate between malignant and benign pelvic masses. It is a simple scoring system that can be introduced easily into clinical practice to facilitate the selection of patients who would benefit from primary surgery.

Response of three paleo-primary production proxy measures to development of an urban estuary.

In this study we present a novel comparison of three proxy indicators of paleoproductivity, pigments, biogenic silica (BSi), and cysts of autotrophic dinoflagellates measured in cored sediments from New Bedford Harbor, Massachusetts. In addition to detailed historical reports we use palynological signals of land clearance, changes in the ratio of centric and pennate diatoms, sedimentary organic carbon and stable carbon isotopes to constrain our interpretations. Our study spans the period from prior to European settlement to approximately 1977, during which watersheds were cleared, port development occurred and much of the coastal property became industrialized. The combined effects of nutrient loading from watershed clearance and urban sewage on the estuarine ecosystem shifted not only levels of primary production, but also the nature of the production. Our proxies show that when European colonists first arrived the estuarine production was benthic-dominated, but eventually became pelagic-dominated. Importance of water column production (by diatoms and dinoflagellates) rapidly increased as soil nitrogen was released following forest clearance. Stabilization in rates of forest clearance is reflected as a decline in production. However, population increases in the urbanizing watershed brought new sources of nutrients through direct sewage discharge, apparently again stimulating primary production. We assume that early 20th century changes in sewage discharge and introduction of heavy metals into Harbor waters caused a temporary reduction in primary production. The introduction of a new sewer outfall near the core site and changes in estuarine hydrography due to construction of a hurricane barrier across the mouth of the harbor are reflected by renewed water column production, but decreases in the population of diatoms and dinoflagellates. Fossil pigments suggest renewed water column production in the latest years recorded by our sediment core.

Prediction of the position of the intraparotid portion of the facial nerve on MRI and CT.

Despite developments in imaging technology, visualisation of the intraparotid portion of the facial nerve is not possible. Three separate radiological techniques have been described to predict the position of the facial nerve: Conn's arc; a plane extending posteriorly from the outer surface of the mandibular ramus; and soft-tissue structures, including the posterior belly of the digastric muscle, the retromandibular vein and the lateral border of the masseter muscle. We investigated the reliability of these techniques in predicting the relationship of tumours to the facial nerve. Cross-sectional imaging of the parotid glands was performed prior to the removal of a parotid mass in 26 patients. Twenty patients underwent MRI, and six had CT scans. We removed 14 malignant neoplasms, nine benign lesions and three non-neoplastic lesions. The relationship of the tumour to the facial nerve was assessed radiologically by each of the three techniques, and compared with the findings at surgery. In 18 patients the tumour involved the parotid gland deep to the facial nerve. The above techniques predicted the position of the facial nerve in 69%, 58% and 46% of cases, respectively. When planning parotid surgery, it is important that the surgeon understands the advantages and limitations of the radiological assessment of the position of parotid tumours in relation to the facial nerve.

Manual examination of accessory movements--seeking R1.

Movement diagrams are used by physiotherapists to depict the behaviour of resistance through the available range of accessory and physiological joint movement. It is generally accepted that for an asymptomatic joint, the resistance first felt by the therapist (R1) occurs towards the end of range. R1 is considered to be at the transition point between the toe and linear region of a load displacement curve. The aim of this study was to more accurately define R1 from force displacement curves of accessory movement to the spine and peripheral joints using a validated instrument, the Spinal Assessment Machine (SAM). Thirty archived force displacement curves obtained using the SAM, which applied a posteroanterior force of 100N at a frequency of 0.5 Hz to L3 spinous process, were examined. In addition force displacement curves were similarly obtained from the tibiofemoral joint, glenohumeral joint and radiocarpal joint of one asymptomatic individual. In all cases resistance to a PA movement commenced at the beginning of range, the curve ascending as soon as the force was applied. While in most cases there was a low stiffness 'toe' region there was no unambiguous point where it could be said that the toe region ended. It is concluded that for spinal and peripheral accessory movements both the onset of resistance and the toe occurs at the beginning of range. Therapists should therefore depict R1 at the beginning of range not toward the end of range as is current practice.

Effect of applying different "levels of evidence" criteria on conclusions of Cochrane reviews of interventions for low back pain.

The objective of this study was to examine the consistency of conclusions of Cochrane systematic reviews when different criteria are used to determine levels of evidence. We reanalyzed the data in six Cochrane reviews of conservative treatment of low back pain by applying three additional sets of "levels of evidence" criteria. Overall agreement between the conclusions attained with the different levels of evidence criteria was only "fair" (multirater kappa coefficient 0.33; 95% CI 0.28 to 0.38). For example, the four sets of levels of evidence criteria produced four conclusions on the efficacy of back school: "strong evidence that back schools are effective," "weak evidence," "limited evidence," and "no evidence." Pairwise agreement between the four pooling systems ranged from slight to substantial (kappas ranging from 0.10 to 0.80). Different rules for determining levels of evidence in systematic reviews produce markedly different conclusions on treatment efficacy. Crown