Should I Take Aspirin? (SITA): RCT of a decision aid for cancer chemoprevention.

Background Australian guidelines recommend that all people aged 50-70 years old consider taking low-dose aspirin to reduce the risk of colorectal cancer (CRC). Aim To determine the effect of a consultation with a researcher in general practice using a decision aid about taking low-dose aspirin to prevent CRC on informed decision-making and low-dose aspirin uptake compared to a general CRC prevention brochure. Design and Setting Individually randomised controlled trial in six general practices in Victoria, Australia, from October 2020 to March 2021. Method Patients aged 50-70 years attending a general practitioner (GP) were recruited consecutively. The intervention was a consultation using a decision aid to discuss taking aspirin to reduce CRC risk; control consultations discussed reducing CRC risk generally. The self-reported co-primary outcomes were informed choices about taking aspirin at one month and low-dose aspirin uptake at six months. Results 261 participants (86% of eligible patients) were randomised into trial arms (129 intervention, 132 control). 17.7% (20/113) of intervention and 7.6% (9/118) control participants reported making an informed choice at one month, an estimated 9.1% (95% CI 0.29% to 18.5) between-arm difference in proportions [odds ratio (OR) 2.47 (97.5% CI:0.94 to 6.52) p=0.074]. The proportions of individuals who reported using aspirin at six months were: 10.2% (12/118) intervention vs 13.8% (16/116) control (estimated between-arm difference: -4.0% (95% CI: -13.5 to 5.5); [OR= 0.68 (97.5% CI:0.27 to 1.70), p= 0.692]. Conclusion The decision aid improved informed decision-making; but has little effect on long-term regular use of aspirin to reduce CRC risk.

Should I take aspirin? A qualitative study on the implementation of a decision aid on taking aspirin for bowel cancer prevention.

OBJECTIVES: Australian guidelines recommend 50-70 years consider taking aspirin to reduce their bowel cancer risk. We trialled a decision aid in general practice to facilitate the implementation of these guidelines into clinical practice. This publication reports on the qualitative results from the process evaluation of the trial. We aimed to explore general practitioners' (GPs) and their patients' approach to shared decision-making (SDM) about taking aspirin to prevent bowel cancer and how the decision aids were used in practice. METHODS: Semistructured interviews were conducted with 17 participants who received the decision aid and 12 GPs who participated in the trial between June and November 2021. The interviews were coded inductively, and emerging themes were mapped onto the Revised Programme Theory for SDM. RESULTS: The study highlighted the dynamics of SDM for taking aspirin to prevent bowel cancer. Some participants discussed the decision aid with their GPs as advised prior to taking aspirin, others either took aspirin or dismissed it outright without discussing it with their GPs. Notably, participants' trust in their GPs, and participants' diverse worldviews played pivotal roles in their decisions. Although the decision aid supported SDM for some, it was not always prioritised in a consultation. This was likely impacted during the trial period as the COVID-19 pandemic was the focus for general practice. CONCLUSION: In summary, this study illustrated the complexities of SDM through using a decision aid in general practice to implement the guidelines for low-dose aspirin to prevent bowel cancer. While the decision aid prompted some participants to speak to their GPs, they were also heavily influenced by their unwavering trust in the GPs and their different worldviews. In the face of the COVID-19 pandemic, SDM was not highly prioritised. This study provides insights into the implementation of guidelines into clinical practice and highlights the need for ongoing support and prioritisation of cancer prevention in general practice consultations. TRIAL REGISTRATION NUMBER: ACTRN12620001003965.

The effect of time before diagnosis and treatment on colorectal cancer outcomes: systematic review and dose-response meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate existing evidence on the relationship between diagnostic and treatment intervals and outcomes for colorectal cancer. METHODS: Four databases were searched for English language articles assessing the role of time before initial treatment in colorectal cancer on any outcome, including stage and survival. Two reviewers independently screened articles for inclusion and data were synthesised narratively. A dose-response meta-analysis was performed to examine the association between treatment interval and survival. RESULTS: One hundred and thirty papers were included in the systematic review, eight were included in the meta-analysis. Forty-five different intervals were considered in the time from first symptom to treatment. The most common finding was of no association between the length of intervals on any outcome. The dose-response meta-analysis showed a U-shaped association between the treatment interval and overall survival with the nadir at 45 days. CONCLUSION: The review found inconsistent, but mostly a lack of, association between interval length and colorectal cancer outcomes, but study design and quality were heterogeneous. Meta-analysis suggests survival becomes increasingly poorer for those commencing treatment more than 45 days after diagnosis. REGISTRATION: This review was registered, and the protocol is available, in PROSPERO, the international database of systematic reviews, with the registration ID CRD42021255864.

Failure to follow up abnormal test results associated with cervical cancer in primary and ambulatory care: a systematic review.

BACKGROUND: Cervical cancer is a preventable and treatable form of cancer yet continues to be the fourth most common cancer among women globally. Primary care is the first point of contact most patients have with health services and is where most cancer prevention and early detection occur. Inadequate follow-up of abnormal test results for cervical abnormalities in primary care can lead to suboptimal patient outcomes including higher mortality and decreased quality of life. AIMS: To explore the magnitude of and factors associated with, inadequate follow-up of test results for cervical abnormalities in primary and ambulatory care. METHODS: MEDLINE, Embase, Cochrane Library and CINAHL were searched for peer-reviewed literature from 2000-2022, excluding case-studies, grey literature, and systematic reviews. Studies were included if they reported on patients aged ≥ 18 years with no previous cancer diagnosis, in a primary care/ambulatory setting. Risk of bias was assessed using the Joanna Briggs Institute Critical appraisal checklists, appropriate to the study design. A segregated methodology was used to perform a narrative synthesis, maintaining the distinction between quantitative and qualitative research. RESULTS: We included 27 publications reporting on 26 studies in our review; all were conducted in high-income countries. They included 265,041 participants from a variety of ambulatory settings such as family medicine, primary care, women's services, and colposcopy clinics. Rates of inadequate follow-up ranged from 4 to 75%. Studies reported 41 different factors associated with inadequate follow-up. Personal factors associated with inadequate follow-up included younger age, lower education, and socioeconomic status. Psychological factors were reported by only 3/26 studies and 2/3 found no significant association. System protective factors included the presence of a regular primary care provider and direct notification of abnormal test results. DISCUSSION: This review describes inadequate follow-up of abnormal cervical abnormalities in primary care. Prevalence varied and the evidence about causal factors is unclear. Most interventions evaluated were effective in decreasing inadequate follow-up. Examples of effective interventions were appointment reminders via telephone, direct notification of laboratory results, and HPV self-sampling. Even though rates of cervical cancer have decreased over the years, there is a lack of information on factors affecting follow-up in primary care and ambulatory settings, particularly in low and middle-income countries. This information is crucial if we are to achieve WHO's interim targets by 2030, and hope to avert 62 million cervical cancer deaths by 2120. TRIAL REGISTRATION: PROSPERO ID CRD42021250136.

Self-Collection Cervical Screening in the Asia-Pacific Region: A Scoping Review of Implementation Evidence.

PURPOSE: Although cervical cancer is a disease of inequity, it can be eliminated as a public health problem through vaccination, screening, and treatment. Human papillomavirus vaginal self-collection cervical screening is a high-performance test that can increase reach of screening. This review describes the different contexts and models of care used to pilot or implement self-collection within the Asia-Pacific, measures the extent that implementation outcome measures are reported and, where available, summarizes key implementation findings. METHODS: A scoping review was conducted by searching five databases of the peer-reviewed literature on June 20, 2022. Two researchers assessed eligibility and extracted data independently to the model of care used and the Conceptual Framework for Implementation Outcomes. A mixed-method consolidation of findings (quantitative: count and frequencies; qualitative: content analysis) was undertaken to narratively report findings. RESULTS: Fifty-seven articles, comprising 50 unique studies from 11 countries and two special autonomous regions, were included; 82% were conducted in trials. The implementation of self-collection was conducted in low- (2%), lower-middle- (32%), upper-middle- (32%), and high-income (35%) settings, with 10 different delivery models used; 80% delivered through practitioner-supported models with diversity in how samples were processed, and treatment was offered. Acceptability (73%) and appropriateness (64%) measures were most reported, followed by adoption (57%), feasibility (48%), and fidelity (38%). Only 7% of articles reported implementation cost or penetration measures. No articles reported sustainability measures. CONCLUSION: The literature confirms that self-collection cervical screening has been implemented within the Asia-Pacific region, with evidence demonstrating that it is acceptable and appropriate from the user's perspective. Well-designed, high-quality implementation trials and real-world evaluations of self-collection that report the breadth of implementation outcomes can support the progression toward the elimination of cervical cancer.

A systematic review of methodological considerations in time to diagnosis and treatment in colorectal cancer research.

Research focusing on timely diagnosis and treatment of colorectal cancer is necessary to improve outcomes for people with cancer. Previous attempts to consolidate research on time to diagnosis and treatment have noted varied methodological approaches and quality, limiting the comparability of findings. This systematic review was conducted to comprehensively assess the scope of methodological issues in this field and provide recommendations for future research. Eligible articles had to assess the role of any interval up to treatment, on any outcome in colorectal cancer, in English, with no limits on publication time. Four databases were searched (Ovid Medline, EMBASE, EMCARE and PsycInfo). Papers were screened by two independent reviewers using a two-stage process of title and abstract followed by full text review. In total, 130 papers were included and had data extracted on specific methodological and statistical features. Several methodological problems were identified across the evidence base. Common issues included arbitrary categorisation of intervals (n = 107, 83%), no adjustment for potential confounders (n = 65, 50%), and lack of justification for included covariates where there was adjustment (n = 40 of 65 papers that performed an adjusted analysis, 62%). Many articles introduced epidemiological biases such as immortal time bias (n = 37 of 80 papers that used survival as an outcome, 46%) and confounding by indication (n = 73, 56%), as well as other biases arising from inclusion of factors outside of their temporal sequence. However, determination of the full extent of these problems was hampered by insufficient reporting. Recommendations include avoiding artificial categorisation of intervals, ensuring bias has not been introduced due to out-of-sequence use of key events and increased use of theoretical frameworks to detect and reduce bias. The development of reporting guidelines and domain-specific risk of bias tools may aid in ensuring future research can reliably contribute to recommendations regarding optimal timing and strengthen the evidence base.

The SCRIPT trial: study protocol for a randomised controlled trial of a polygenic risk score to tailor colorectal cancer screening in primary care.

BACKGROUND: Polygenic risk scores (PRSs) can predict the risk of colorectal cancer (CRC) and target screening more precisely than current guidelines using age and family history alone. Primary care, as a far-reaching point of healthcare and routine provider of cancer screening and risk information, may be an ideal location for their widespread implementation. METHODS: This trial aims to determine whether the SCRIPT intervention results in more risk-appropriate CRC screening after 12 months in individuals attending general practice, compared with standard cancer risk reduction information. The SCRIPT intervention consists of a CRC PRS, tailored risk-specific screening recommendations and a risk report for participants and their GP, delivered in general practice. Patients aged between 45 and 70 inclusive, attending their GP, will be approached for participation. For those over 50, only those overdue for CRC screening will be eligible to participate. Two hundred and seventy-four participants will be randomised to the intervention or control arms, stratified by general practice, using a computer-generated allocation sequence. The primary outcome is risk-appropriate CRC screening after 12 months. For those in the intervention arm, risk-appropriate screening is defined using PRS-derived risk; for those in the control arm, it is defined using family history and national screening guidelines. Timing, type and results of the previous screening are considered in both arms. Objective health service data will capture screening behaviour. Secondary outcomes include cancer-specific worry, risk perception, predictors of CRC screening behaviour, screening intentions and health service use at 1, 6 and 12 months post-intervention delivery. DISCUSSION: This trial aims to determine whether a PRS-derived personalised CRC risk estimate delivered in primary care increases risk-appropriate CRC screening. A future population risk-stratified CRC screening programme could incorporate risk assessment within primary care while encouraging adherence to targeted screening recommendations. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry ACTRN12621000092897p. Registered on 1 February 2021.

Health care system factors influencing primary healthcare workers' engagement in national cancer screening programs: a qualitative study.

OBJECTIVE: This study aimed to explore factors across the environment, organisation and care team levels of the health care system that influence the engagement of primary healthcare workers (PHCWs) in Australia's national cancer screening programs. METHODS: A cross-sectional qualitative study involving semi-structured interviews with PHCWs - general practitioners (n=10), practices nurses (n=10), and practice managers (n=10) from settings across Australia. Transcripts were analysed using the Framework Method. RESULTS: Two environment-level factors were found to influence several organisation and care team level factors. Firstly, the financial structure of primary health care, impacting on practitioner: time, practice culture, screening knowledge and opportunistic conversations. Secondly, the structure of screening programs had flow-on effects for: access to patient screening records, recall and reminder systems, and sense of program ownership. CONCLUSIONS: Encouraging more effective PHCW engagement in the screening programs requires the consideration and mitigation of overarching financial and structural barriers. Up-to-date and easy-to-use recall and reminder systems, whole-of-practice approaches which optimise the role of each PHCW and the identification of a 'champion' to drive implementation should be considered. IMPLICATIONS FOR PUBLIC HEALTH: This study offers insights into what elements practice and practitioner targeted initiatives in Australia should incorporate, potentially leading to improved engagement of PHCWs and increased cancer screening participation rates.

Commentary: Pivoting during a pandemic: developing a new recruitment model for a randomised controlled trial in response to COVID-19.

BACKGROUND: Many non-COVID-19 trials were disrupted in 2020 and either struggled to recruit participants or stopped recruiting altogether. In December 2019, just before the pandemic, we were awarded a grant to conduct a randomised controlled trial, the Should I Take Aspirin? (SITA) trial, in Victoria, the Australian state most heavily affected by COVID-19 during 2020. MAIN BODY: We originally modelled the SITA trial recruitment method on previous trials where participants were approached and recruited in general practice waiting rooms. COVID-19 changed the way general practices worked, with a significant increase in telehealth consultations and restrictions on in person waiting room attendance. This prompted us to adapt our recruitment methods to this new environment to reduce potential risk to participants and staff, whilst minimising any recruitment bias. We designed a novel teletrial model, which involved calling participants prior to their general practitioner appointments to check their eligibility. We delivered the trial both virtually and face-to-face with similar overall recruitment rates to our previous studies. CONCLUSION: We developed an effective teletrial model which allowed us to complete recruitment at a high rate. The teletrial model is now being used in our other primary care trials as we continue to face the impacts of the COVID-19 pandemic.

An RCT of a decision aid to support informed choices about taking aspirin to prevent colorectal cancer and other chronic diseases: a study protocol for the SITA (Should I Take Aspirin?) trial.

BACKGROUND: Australian guidelines recommend that all people aged 50-70 years old actively consider taking daily low-dose aspirin (100-300 mg per day) for 2.5 to 5 years to reduce their risk of colorectal cancer (CRC). Despite the change of national CRC prevention guidelines, there has been no active implementation of the guidelines into clinical practice. We aim to test the efficacy of a health consultation and decision aid, using a novel expected frequency tree (EFT) to present the benefits and harms of low dose aspirin prior to a general practice consultation with patients aged 50-70 years, on informed decision-making and uptake of aspirin. METHODS: Approximately five to seven general practices in Victoria, Australia, will be recruited to participate. Patients 50-70 years old, attending an appointment with their general practitioner (GP) for any reason, will be invited to participate in the trial. Two hundred fifty-eight eligible participants will be randomly allocated 1:1 to intervention or active control arms using a computer-generated allocation sequence stratified by general practice, sex, and mode of trial delivery (face-to-face or teletrial). There are two co-primary outcomes: informed decision-making at 1-month post randomisation, measured by the Multi-dimensional Measure of Informed Choice (MMIC), and self-reported daily use of aspirin at 6 months. Secondary outcomes include decisional conflict at 1-month and other behavioural changes to reduce CRC risk at both time points. DISCUSSION: This trial will test the efficacy of novel methods for implementing national guidelines to support informed decision-making about taking aspirin in 50-70-year-olds to reduce the risk of CRC and other chronic diseases. TRIAL REGISTRATION: The Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620001003965 . Registered on 10 October 2020.

Brain cancer patient and support persons' experiences of psychosocial care: a mapping of research outputs.

BACKGROUND: People with brain cancer and their support persons (SPs) are critical sources of information on the components of care that contribute to psychosocial outcomes. AIMS: To determine the proportion of studies that examined (1) at least one of 14 nominated components of psychosocial cancer care and (2) more than one component of care. METHODS: Medline, The Cochrane Library, PsycINFO and Embase were electronically searched for publications from January 1999 to December 2019. Publications that met the inclusion criteria were coded according to the number and type of psychosocial care components assessed from 14 listed components, and whether patient and/or SPs' views about care were elicited. RESULTS: Of the 113 included publications, 61 publications included patient-reported data only (54%), 27 included both patient and SP-reported data (24%) and 25 included SP-reported data only (22%). Most assessed a single component of care (77% of patient-reported and 71% of SP-reported). No publications assessed all 14 components. The "Psychosocial" component was the most frequently assessed component of care for patient-reported (n = 80/88, 91%) and SP-reported publications (n = 46/52, 88%). CONCLUSIONS: Publications reporting on psychosocial care in brain cancer present a relatively narrow view of patient and support person experiences. The inclusion of both patient and support person perspectives and the assessment of multiple components of care are required in future research to optimize psychosocial outcomes in brain cancer.

Psychosocial well-being of brain cancer patients and support persons: A mapping review of study types over time.

INTRODUCTION: This review examined the: (1) number of publications exploring psychosocial outcomes of adults with brain cancer and/or support persons between 1999 and 2019 and whether there has been a change in the type of research over time; and (2) proportion of intervention studies meeting Cochrane Effective Practice and Organisation of Care (EPOC) research design criteria. METHODS: Embase, The Cochrane Library, Medline and PsycINFO databases were electronically searched January 1999 to December 2019. Articles were examined against inclusion/exclusion criteria and coded into measurement, descriptive or intervention categories. Intervention studies were assessed against the EPOC design criteria. RESULTS: 220 eligible publications were identified. The number of total publications significantly increased by an average of 1 each year (95%CI = 0.7-1.3; p < 0.001). There was no significant change in the proportion of publications by study type across three time periods. Descriptive research represented the majority within each time period. Of the 17 intervention studies, only 7(41%) met EPOC design criteria. CONCLUSIONS: Published literature on brain cancer psychosocial outcomes has increased significantly. However, descriptive research dominates research output. To increase high-level knowledge that can guide psychosocial care of people with brain cancer, there is a need to undertake methodologically rigorous intervention trials.

Australian GPs' perceptions of barriers and enablers to best practice palliative care: a qualitative study.

BACKGROUND: General Practitioners (GPs) often play an important role in caring for people at the end of life. While some international studies suggest that GPs experience a number of barriers to providing palliative care, little is known about views and experiences of GPs in Australia. This study explored Australian GPs' perceptions of barriers and enablers to the provision of palliative care and provides new insights into how to implement best practice care at the end of life. METHODS: This was a qualitative study using 25 semi-structured phone interviews conducted with GPs practising in metropolitan and non-metropolitan New South Wales, Australia. Data were analysed using qualitative content analysis. RESULTS: GPs reported difficulties with palliative care provision due to i) the complex and often emotional nature of doctor-family-interaction; ii) a lack of evidence to guide care; and iii) the need to negotiate roles and responsibilities within the healthcare team. GPs listed a number of strategies to help deal with their workload and to improve communication processes between healthcare providers. These included appropriate scheduling of appointments, locally tailored mentoring and further education, and palliative care guidelines which more clearly outline the roles and responsibilities within multidisciplinary teams. GPs also noted the importance of online platforms to facilitate their communication with patients, their families and other healthcare providers, and to provide centralised access to locally tailored information on palliative care services. GPs suggested that non-government organisations could play an important role by raising awareness of the key role of GPs in palliative care provision and implementing an "official visitor" program, i.e. supporting volunteers to provide peer support or respite to people with palliative care needs and their families. CONCLUSIONS: This study offers new insights into strategies to overcome well documented barriers to palliative care provision in general practice and help implement optimal care at the end of life. The results suggest that researchers and policy makers should adopt a comprehensive approach to improving the provision of palliative care which tackles the array of barriers and enablers identified in this study.

General practitioners' perceptions of best practice care at the end of life: a qualitative study.

BACKGROUND: GPs can play a central role in palliative care delivery. However, little is known about their views on what constitutes best practice care at the end of life. AIM: To explore, in a sample of Australian GPs, their perceptions of best practice palliative care and their ideal role in its delivery. DESIGN & SETTING: A qualitative interview study of 25 GPs practising in metropolitan and non-metropolitan locations in New South Wales, Australia. METHOD: Semi-structured telephone interviews were conducted. Data were analysed using qualitative content analysis. RESULTS: Participants had a mean age of 51 years, and had practised between 3 and 38 years (mean 19 years). Best practice palliative care was perceived to be proactive and responsive to a wide range of patient and family needs. Many participants indicated a need for relational continuity, which involves GPs establishing a care pathway from diagnosis to palliation, coordinating care across the pathway, and collaborating with other healthcare providers. A number of participants perceived palliative care as a natural extension of primary care and indicated that best practice palliative care mainly requires experiential knowledge and good communication skills, rather than specialised medical knowledge. Participants listed a number of communication strategies to offer patients and their families choice and ongoing negotiation about the recommended treatments. CONCLUSION: This study provides novel in-depth insights into GPs' perceptions of best practice palliative care. Future research should further investigate the identified features of care, and whether they can maximise the outcomes of patients and their families.

Methodological quality of teaching communication skills to undergraduate medical students: a mapping review.

BACKGROUND: Patient-clinician communication training is a core component of the undergraduate medical program. As with all areas of medicine, the best available evidence for teaching these skills should be incorporated into training programs. Examining the volume, type and design-quality of publications in this field can help to determine whether research is following a natural scientific progression to inform interactional skills training. This study aimed to review: (i) whether the proportion of publications examining teaching interactional skills to undergraduate medical students by study type, across three time-periods (2007-2008, 2011-2012, 2015-2016), changed over time (i.e. measurement, descriptive or interventions studies); and (ii) the proportion of intervention studies meeting Cochrane Effective Practice and Organisation of Care (EPOC) research design criteria. METHODS: Medline, PubMed, PsycInfo and the Cochrane Database were searched for studies published in English from 2007 to 2016. Title and abstract reviews were performed for the included years. Articles were examined against the inclusion/exclusion criteria and those included were coded into descriptive, measurement or intervention categories. RESULTS: A total of 243 relevant publications were identified. Fifty-two were published from 2007 to 2008, 75 from 2011 to 2012 and 116 from 2015 to 2016. Most identified studies were descriptive (63%), followed by measurement studies (22%) and intervention studies (15%). The proportion of descriptive studies increased significantly over time. However, the proportion of intervention studies did not change and the proportion of measures studies significantly decreased. Of the 37 intervention studies identified within the three time-periods, only 16 (43%) met EPOC study design criteria. CONCLUSIONS: The largest proportion of identified studies were descriptive, however, descriptive research is not sufficient to ensure communication skills training can effectively improve interactions between clinicians and patients. A more rigorous approach to research in this area is needed to inform education strategies.

Vascular risk associated with meniscal repair using Rapidloc versus FasT-Fix: comparison of two all-inside meniscal devices.

Eight fresh-frozen cadaver legs (average age 72 years) were used to evaluate the risk to the popliteal artery related to the use of two all-inside meniscal repair devices, the Mitek RapidLoc (12.5 mumudegrees) and the Smith & Nephew FasT-Fix (curved). The lumen of the femoral artery was injected with barium. Anteroposterior (AP) and lateral radiographs were obtained to ensure visualization of the popliteal artery and its anatomic location. Both devices were inserted into the posterior horn of the lateral meniscus up to the hub of the needle under direct arthroscopic visualization. The distance between the needle and the artery was measured on the radiographs using calipers. The average distance from the needle to the popliteal artery was 0.5 mm (0.5 +/- 0.8 mm, range: 0-2 mm) on the lateral radiograph and 6.0 mm (6.0 +/- 6.2 mm, range: 0-19 mm) on the AP radiograph using the FasT-Fix system without the penetration limiter. None of the RapidLoc needles were within 20 mm of the popliteal artery on either of the radiographs. The FasT-Fix device came within 3 mm of the artery on both AP and lateral radiographs in 43% of the specimens. The risk to the popliteal artery was significantly greater using the FasT-Fix device compared to the RapidLoc device (P < .05). Although both instruments appear safe when used properly, the RapidLoc device seems to be safer with less risk to the popliteal artery than the current FasT-Fix meniscal repair device. When using the FasT-Fix device, the penetration limiter must be used to avoid the complications found in this study.