Preferred pharmaceutical-grade opioids to reduce the use of unregulated opioids: A cross-sectional analysis among people who use unregulated opioids in Vancouver, Canada.

OBJECTIVES: Many people who use drugs in the United States and Canada continue to access the contaminated unregulated drug supply, resulting in the ever-escalating overdose epidemic. In Canada, even in areas where healthcare providers are authorized to prescribe alternatives to the unregulated supply (e.g., prescribed safer supply), availability and accessibility are low. We sought to characterize the needs of people who use unregulated opioids in Vancouver, Canada by asking them whether access to any pharmaceutical opioids would reduce their use of unregulated opioids, and if so, which pharmaceutical opioids they preferred. METHODS: We analyzed data from participants who self-reported using unregulated opioids in three Vancouver-based prospective cohort studies between 2021 and 2022. We employed multivariable logistic regression to identify factors associated with reporting a preferred pharmaceutical opioid to reduce unregulated opioid use. RESULTS: Of 681 eligible participants, 504 (74.0 %) identified a preferred pharmaceutical opioid to reduce unregulated opioid use. The most commonly reported preferred opioids included: diacetylmorphine (42.9 %), fentanyl patches (11.1 %), and fentanyl powder (10.5 %). Overall, 5.6 % of participants who identified diacetylmorphine, 12.5 % of participants who identified fentanyl patches, and no participants who identified fentanyl powder as their preferred opioids reported receiving prescriptions of them. In multivariable analysis, exposure to benzodiazepines through unregulated drug use (adjusted odds ratio [AOR] = 2.57; 95 % confidence interval [CI] = 1.69-3.90), and receipt of prescribed safer supply of opioids without opioid agonist therapy (OAT; AOR = 2.66; 95 % CI = 1.12-6.36) within the past six months were significantly associated with reporting a preferred pharmaceutical opioid. CONCLUSION: Three-quarters of participants reported that receiving prescribed pharmaceutical opioids of their preference could reduce their use of unregulated opioids; however, the proportions of those actually being prescribed their preferred opioids were very low. Further, these participants were also more likely to report exposure to benzodiazepine-adulterated drugs. Our findings provide important implications for future safer supply programs.

The impact of the COVID-19 pandemic on people who use drugs in three Canadian cities: a cross-sectional analysis.

BACKGROUND: The COVID-19 pandemic had a disproportionate impact on the health and wellbeing of people who use drugs (PWUD) in Canada. However less is known about jurisdictional commonalities and differences in COVID-19 exposure and impacts of pandemic-related restrictions on competing health and social risks among PWUD living in large urban centres. METHODS: Between May 2020 and March 2021, leveraging infrastructure from ongoing cohorts of PWUD, we surveyed 1,025 participants from Vancouver (n = 640), Toronto (n = 158), and Montreal (n = 227), Canada to describe the impacts of pandemic-related restrictions on basic, health, and harm reduction needs. RESULTS: Among participants, awareness of COVID-19 protective measures was high; however, between 10 and 24% of participants in each city-specific sample reported being unable to self-isolate. Overall, 3-19% of participants reported experiencing homelessness after the onset of the pandemic, while 20-41% reported that they went hungry more often than usual. Furthermore, 8-33% of participants reported experiencing an overdose during the pandemic, though most indicated no change in overdose frequency compared the pre-pandemic period. Most participants receiving opioid agonist therapy in the past six months reported treatment continuity during the pandemic (87-93%), however, 32% and 22% of participants in Toronto and Montreal reported missing doses due to service disruptions. There were some reports of difficulty accessing supervised consumption sites in all three sites, and drug checking services in Vancouver. CONCLUSION: Findings suggest PWUD in Canada experienced difficulties meeting essential needs and accessing some harm reduction services during the COVID-19 pandemic. These findings can inform preparedness planning for future public health emergencies.

Using a cascade of care framework to identify gaps in access to medications for alcohol use disorder in British Columbia, Canada.

BACKGROUND AND AIMS: Despite the significant burden of alcohol use disorder (AUD) and availability of safe and effective medications for AUD (MAUD), population-level estimates of access and engagement in AUD-related care are limited. The aims of this study were to generate a cascade of care for AUD in British Columbia (BC), Canada, and to estimate the impacts of MAUD on health outcomes. DESIGN: This was a retrospective population-based cohort study using linked administrative health data. SETTING: British Columbia, Canada, 2015-2019. PARTICIPANTS: Using a 20% random sample of BC residents, we identified 7231 people with moderate-to-severe alcohol use disorder (PWAUD; overall prevalence = 0.7%). MEASUREMENTS: We developed a six-stage AUD cascade (from diagnosis to ≥6 months retention in MAUD) among PWAUD. We evaluated trends over time and estimated the impacts of access to MAUD on AUD-related hospitalizations, emergency department visits and death. FINDINGS: Between 2015 and 2019, linkage to AUD-related care decreased (from 80.4% to 46.5%). However, rates of MAUD initiation (11.4% to 24.1%) and retention for ≥1 (7.0% to 18.2%), ≥3 (1.2% to 4.3%) or ≥6 months (0.2% to 1.6%) increased significantly. In adjusted analyses, access to MAUD was associated with reduced odds of experiencing any AUD-related adverse outcomes, with longer retention in MAUD showing a trend to greater odds reduction: adjusted odds ratio (95% CI) ranging from 0.59 (0.48-0.71) for MAUD retention <1 month to 0.37 (0.21-0.67) for ≥6 months retention. CONCLUSIONS: Access to medications for alcohol use disorder among people with moderate-to-severe alcohol use disorder in British Colombia, Canada increased between 2015 and 2019; however, initiation and retention remained low. There was a trend between longer retention in medications for alcohol use disorder and greater reductions in the odds of experiencing alcohol use disorder-related adverse outcomes.

Opioid agonist therapy switching among individuals with prescription-type opioid use disorder: Secondary analysis of a pragmatic randomized trial.

BACKGROUND: Engagement and retention in opioid agonist therapy (OAT) remains a challenge. This study evaluated the impact of initial randomized OAT allocation on subsequent switching among people with prescription-type opioid use disorder (POUD). METHODS: Secondary analysis of a 24-week Canadian multicenter, pragmatic, randomized trial conducted between 2017 and 2020 comparing flexible take-home buprenorphine/naloxone versus supervised methadone models of care for POUD. We used Cox Proportional Hazards modeling to assess for impact of treatment assignment on time to OAT switching, adjusting for important confounders. For clinical correlates, we analyzed data from baseline questionnaires on demographic, substance use, and health factors as well as urine drug screen. RESULTS: Of 272 randomized participants, 210 initiated OAT within 14 days per trial protocol, of whom 103 participants were randomized to buprenorphine/naloxone and 107 to methadone. Within 24-week follow-up, 41 (20.5%) of all participants switched OAT with 25 (24.3%, median 27 days, 88.4 per 100 person-years) and 16 participants (15.0%, median 53.5 days, 46.1 per 100 person-years) switching from buprenorphine/naloxone and methadone arms, respectively. In adjusted analysis, allocation to buprenorphine/naloxone was associated with significantly higher risk of switching (aHR = 2.31, 95% CI 1.22 - 4.38). CONCLUSIONS: OAT switching was common in this sample of individuals with POUD, with individuals randomly allocated to buprenorphine/naloxone being more than twice as likely to switch versus methadone. This may reflect a stepped care approach in OUD management. More research is needed to evaluate overall retention and outcomes with the different observed risks of switching between methadone and buprenorphine/naloxone.

Discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain with and without opioid use disorder in British Columbia, Canada: A retrospective cohort study.

BACKGROUND: The overdose crisis in North America has prompted system-level efforts to restrict opioid prescribing for chronic pain. However, little is known about how discontinuing or tapering prescribed opioids for chronic pain shapes overdose risk, including possible differential effects among people with and without concurrent opioid use disorder (OUD). We examined associations between discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain, stratified by diagnosed OUD and prescribed opioid agonist therapy (OAT) status. METHODS AND FINDINGS: For this retrospective cohort study, we used a 20% random sample of residents in the provincial health insurance client roster in British Columbia (BC), Canada, contained in the BC Provincial Overdose Cohort. The study sample included persons aged 14 to 74 years on long-term opioid therapy for pain (≥90 days with ≥90% of days on therapy) between October 2014 and June 2018 (n = 14,037). At baseline, 7,256 (51.7%) persons were female, the median age was 55 years (quartile 1-3: 47-63), 227 (1.6%) persons had been diagnosed with OUD (in the past 3 years) and recently (i.e., in the past 90 days) been prescribed OAT, and 483 (3.4%) had been diagnosed with OUD but not recently prescribed OAT. The median follow-up duration per person was 3.7 years (quartile 1-3: 2.6-4.0). Marginal structural Cox regression with inverse probability of treatment weighting (IPTW) was used to estimate the effect of prescribed opioid treatment for pain status (discontinuation versus tapered therapy versus continued therapy [reference]) on risk of overdose (fatal or nonfatal), stratified by the following groups: people without diagnosed OUD, people with diagnosed OUD receiving OAT, and people with diagnosed OUD not receiving OAT. In marginal structural models with IPTW adjusted for a range of demographic, prescription, comorbidity, and social-structural exposures, discontinuing opioids (i.e., ≥7-day gap[s] in therapy) was associated with increased overdose risk among people without OUD (adjusted hazard ratio [AHR] = 1.44; 95% confidence interval [CI] 1.12, 1.83; p = 0.004), people with OUD not receiving OAT (AHR = 3.18; 95% CI 1.87, 5.40; p < 0.001), and people with OUD receiving OAT (AHR = 2.52; 95% CI 1.68, 3.78; p < 0.001). Opioid tapering (i.e., ≥2 sequential decreases of ≥5% in average daily morphine milligram equivalents) was associated with decreased overdose risk among people with OUD not receiving OAT (AHR = 0.31; 95% CI 0.14, 0.67; p = 0.003). The main study limitations are that the outcome measure did not capture overdose events that did not result in a healthcare encounter or death, medication dispensation may not reflect medication adherence, residual confounding may have influenced findings, and findings may not be generalizable to persons on opioid therapy in other settings. CONCLUSIONS: Discontinuing prescribed opioids was associated with increased overdose risk, particularly among people with OUD. Prescribed opioid tapering was associated with reduced overdose risk among people with OUD not receiving OAT. These findings highlight the need to avoid abrupt discontinuation of opioids for pain. Enhanced guidance is needed to support prescribers in implementing opioid therapy tapering strategies with consideration of OUD and OAT status.

Impact of fentanyl use on initiation and discontinuation of methadone and buprenorphine/naloxone among people with prescription-type opioid use disorder: secondary analysis of a Canadian treatment trial.

BACKGROUND AND AIMS: Fentanyl is primarily responsible for the current phase of the overdose epidemic in North America. Despite the benefits of treatment with medications for opioid use disorder (MOUD), there are limited data on the association between fentanyl, MOUD type and treatment engagement. The objectives of this analysis were to measure the impact of baseline fentanyl exposure on initiation and discontinuation of MOUD among individuals with prescription-type opioid use disorder (POUD). DESIGN, SETTING AND PARTICIPANTS: Secondary analysis of a Canadian multi-site randomized pragmatic trial conducted between 2017 and 2020. Of the 269 randomized participants, 65.4% were male, 67.3% self-identified as white and 55.4% had a positive fentanyl urine drug test (UDT) at baseline. Fentanyl-exposed participants were more likely to be younger, to self-identify as non-white, to be unemployed or homeless and to be currently using stimulants than non-fentanyl-exposed participants. INTERVENTIONS: Flexible take-home dosing buprenorphine/naloxone or supervised methadone models of care for 24 weeks. MEASUREMENTS: Outcomes were (1) MOUD initiation and (2) time to (a) assigned and (b) overall MOUD discontinuation. Independent variables were baseline fentanyl UDT (predictor) and assigned MOUD (effect modifier). FINDINGS: Overall, 209 participants (77.7%) initiated MOUD. In unadjusted analyses, fentanyl exposure was associated with reduced likelihood of treatment initiation [odds ratio (OR) = 0.18, 95% confidence interval (CI) = 0.08-0.36] and shorter median times in assigned [20 versus 168 days, hazard ratio (HR) = 3.61, 95% CI = 2.52-5.17] and any MOUD (27 versus 168 days, HR = 3.32, 95% CI = 2.30-4.80). The negative effects were no longer statistically significant in adjusted models, and no interaction between fentanyl and MOUD was observed for any of the outcomes (all P > 0.05). CONCLUSIONS: Both buprenorphine/naloxone and methadone may be appropriate treatment options for people with prescription-type opioid use disorder regardless of fentanyl exposure. Other characteristics of fentanyl-exposed individuals appear to be driving the association with poorer treatment outcomes.

Prevalence and correlates of intentional substance use to reduce illicit opioid use in a Canadian setting.

Background: While preliminary evidence has begun to document intentional use of one substance to reduce the use of another, the phenomenon of drug substitution among people who use illicit opioids remains understudied. Therefore, we sought to estimate the prevalence and correlates of intentional substance use to reduce illicit opioid use among persons who use drugs (PWUD). Methods: We analysed data from three prospective cohorts of PWUD in Vancouver, Canada, using multivariable generalized estimating equations (GEE). Results: Between June 2012 and June 2016, 1527 participants were recruited and contributed 4991 interviews. Of those, 336 (22%) illicit opioid-using participants self-reported substitution to reduce illicit opioid use at least once during study period contributing 467 (9.4%) interviews. Among those interviews, substances substituted for opioids were alcohol (15 participants, 3.2%), stimulants (235, 50.3%), cannabis (129, 27.6%), benzodiazepines (21, 4.5%), and others (20, 4.3%). In multivariable GEE model adjusted for socio-demographic factors, reporting substitution to reduce illicit opioid use was positively associated with greater likelihood of daily cannabis use (Adjusted Odds Ratio = 1.56, 95% Confidence Interval: 1.24-1.96]. Conclusions: While daily cannabis use was associated with reporting opioid substitution attempts, additional study is needed to examine potential of cannabis/cannabinoids to reduce illicit opioid use.

Longitudinal Analysis of Influenza A(H5) Sero-Surveillance in Myanmar Ducks, 2006-2019.

Between 2006 and 2019, serological surveys in unvaccinated domestic ducks reared outdoors in Myanmar were performed, using a haemagglutination inhibition (HI) test, to confirm H5 avian influenza virus circulation and assess temporal and spatial distribution. Positive test results occurred every year that samples were collected. The annual proportion of positive farms ranged from 7.1% to 77.2%. The results revealed silent/sub-clinical influenza A (H5) virus circulation, even in years and States/Regions with no highly pathogenic avian influenza (HPAI) outbreaks reported. Further analysis of the 2018/19 results revealed considerable differences in seroconversion rates between four targeted States/Regions and between years, and showed seroconversion before and during the sampling period. By the end of the trial, a high proportion of farms were seronegative, leaving birds vulnerable to infection when sold. Positive results likely indicate infection with Gs/GD/96-lineage H5Nx HPAI viruses rather than other H5 subtype low-pathogenicity avian influenza viruses. The findings suggested persistent, but intermittent, circulation of Gs/GD/96-lineage H5Nx HPAI viruses in domestic ducks, despite the veterinary services' outbreak detection and control efforts. The role of wild birds in transmission remains unclear but there is potential for spill-over in both directions. The findings of this study assist the national authorities in the design of appropriate, holistic avian influenza control programs.

Comparison of Target Enrichment Platforms for Circulating Tumor DNA Detection.

Cancer-related mortality of solid tumors remains the major cause of death worldwide. Circulating tumor DNA (ctDNA) released from cancer cells harbors specific somatic mutations. Sequencing ctDNA opens opportunities to non-invasive population screening and lays foundations for personalized therapy. In this study, two commercially available platforms, Roche's Avenio ctDNA Expanded panel and QIAgen's QIAseq Human Comprehensive Cancer  panel were compared for (1) panel coverage of clinically relevant variants; (2) target enrichment specificity and sequencing performance; (3) the sensitivity; (4) concordance and (5) sequencing coverage using the same human blood sample with ultra-deep next-generation sequencing. Our finding suggests that Avenio detected somatic mutations in common cancers in over 70% of patients while QIAseq covered nearly 90% with a higher average number of variants per patient (Avenio: 3; QIAseq: 8 variants per patient). Both panels demonstrated similar on-target rate and percentage of reads mapped. However, Avenio had more uniform sequencing coverage across regions with different GC content. Avenio had a higher sensitivity and concordance compared with QIAseq at the same sequencing depth. This study identifies a unique niche for the application of each of the panel and allows the scientific community to make an informed decision on the technologies to meet research or application needs.

Retroperitoneal Knee Pain: An Unusual Case Report and Review of an Ancient Schwannoma.

Schwannomas are nerve sheath tumors that occur in Schwann cells. They are usually benign, but malignant transformation can occur. Symptomatology depends on the involvement of the surrounding tissues or the mass effect of the tumor. We describe a case of a 28-year-old man who initially presented with right iliac fossa pain associated with radiating pain over the anterior and lateral aspect of his right knee. Following subsequent investigations, we found a retroperitoneal schwannoma of the right lateral femoral cutaneous nerve. The key to our diagnosis was the referred pain to his right knee, which gave us a clue of possible neuropathic pain. Our patient highlights the need to consider a unified diagnosis when faced with an incongruent set of symptoms. Magnetic resonance imaging is the diagnostic modality of choice for the diagnosis of schwannomas. Treatment is directed towards symptomatic control. Surgery, radiation, and, in rare instances, chemotherapy are the major treatment modalities employed.

Bronchiectasis in yellow nail syndrome.

BACKGROUND AND OBJECTIVE: Yellow nail syndrome (YNS) is a rare and poorly described disease process. In this case-control study, clinical features and findings on HRCT were compared with idiopathic bronchiectasis (IBx). METHODS: A review of all patients attending an adult bronchiectasis clinic between 2007 and 2013 identified 25 YNS patients. IBx patients were matched in a 2:1 ratio for age, duration of symptoms and gender. RESULTS: Median age of onset was 53 years. There were 12 male and 23 Caucasian YNS patients. Respiratory manifestations included chronic productive cough (100%), chronic rhinosinusitis (88%), pleural effusions (20%) and lymphoedema (12%). Chest symptoms preceded yellow nails in the majority (68%). Abnormal nails persisted at follow-up in 23 of 25 patients but improved in 14. In both disorders, there was symmetrical, predominantly lower lobe bronchiectasis on HRCT. Extent (P = 0.04), severity (P = 0.03) and bronchial wall thickness (P = 0.05) scores were lower in YNS, with less upper and middle lobe disease. Multivariate analysis showed an independent association with increased mucus plugging in YNS. There was a similar prevalence of Pseudomonas aeruginosa infection and mild lung function abnormalities. CONCLUSION: Bronchiectasis in YNS is less severe than IBx but is associated with increased mucus plugging, onset is in middle age and there is no female predominance. Treatment targeted at improved secretion clearance may improve both chest and nail symptoms, with consideration of long-term macrolide antibiotics.

Evaluating the diagnostic sensitivity of computed diffusion-weighted MR imaging in the detection of breast cancer.

PURPOSE: To evaluate the diagnostic sensitivity of computed diffusion-weighted (DW)-MR imaging for the detection of breast cancer. MATERIALS AND METHODS: Local research ethics approval was obtained. A total of 61 women (median 48 years) underwent dynamic contrast enhanced (DCE)- and DW-MR between January 2011 and March 2012, including 27 with breast cancer on core biopsy and 34 normal cases. Standard ADC maps using all four b values (0, 350, 700, 1150) were used to generate computed DW-MR images at b = 1500 s/mm(2) and b = 2000 s/mm(2) . Four image sets were read sequentially by two readers: acquired b = 1150 s/mm(2) , computed b = 1500 s/mm(2) and b = 2000 s/mm(2) , and DCE-MR at an early time point. Cancer detection was rated using a five-point scale; image quality and background suppression were rated using a four-point scale. The diagnostic sensitivity for breast cancer detection was compared using the McNemar test and inter-reader agreement with a Kappa value. RESULTS: Computed DW-MR resulted in higher overall diagnostic sensitivity with b = 2000 s/mm(2) having a mean diagnostic sensitivity of 76% (range 49.8-93.7%) and b = 1500 s/mm(2) having a mean diagnostic sensitivity of 70.3% (range 32-97.7%) compared with 44.4% (range 25.5-64.7%) for acquired b = 1150 s/mm(2) (both p = 0.0001). Computed DW-MR images produced better image quality and background suppression (mean scores for both readers: 2.55 and 2.9 for b 1500 s/mm(2) ; 2.55 and 3.15 for b 2000 s/mm(2) , respectively) than the acquired b value 1150 s/mm(2) images (mean scores for both readers: 2.4 and 2.45, respectively). CONCLUSION: Computed DW-MR imaging has the potential to improve the diagnostic sensitivity of breast cancer detection compared to acquired DW-MR. J. Magn. Reson. Imaging 2016;44:130-137.

Silastic injection for vocal fold medialization resulting in a false-positive finding on F18 FDG-PET/CT.

A false-positive uptake of F18-fluorodeoxyglucose (FDG) on positron-emission tomography/computed tomography (PET/CT) can result in confusion and misinterpretation of scans. Such uptakes have been previously described after injection of polytetrafluoroethylene (Teflon) into the vocal folds. Similarly, vocal fold injection of silicone elastomer (Silastic) can result not only in a false-positive FDG uptake on PET/CT, but also in chronic inflammation. We report a case of increased FDG uptake in a vocal fold after Silastic injection that was misinterpreted as a malignancy in a 70-year-old woman who had metastatic carcinoma of the stomach.

99mTc-HDP SPECT-CT Aids Localization of Joint Injections in Degenerative Joint Disease of the Foot and Ankle.

BACKGROUND: Pain relating to degenerative joint disease within the foot and ankle can be difficult to localize with clinical examination alone due to the complex anatomy of the joints. The aim of this study was to determine whether single-photon emission computed tomography combined with conventional computed tomography (SPECT-CT) could be used to localize the site of degenerative joint disease for intra-articular injection and thereby improve the clinical success of the procedure. METHODS: A prospective study was performed involving 203 patients who had undergone triple-phase (99m)Tc-hydroxymethylene diphosphonate bone scans with SPECT-CT of the foot and ankle for degenerative joint disease. Fifty-two patients went on to have joint injections for degenerative joint disease, with clinical follow-up. Correlation with the clinical diagnosis and the outcome of intra-articular injections with 0.5% bupivacaine and 80 mg of Depo-Medrone was performed. A successful outcome was determined by an improvement in the visual analog pain score of at least 50%. RESULTS: In 19 (37%) patients, the site of degenerative joint disease determined by SPECT-CT differed from the initial clinical assessment and resulted in a change in management. Overall, 46 (88%) patients showed an improvement in symptoms. CONCLUSION: The study demonstrated a high clinical success rate for SPECT-CT-guided joint injections. The technique was useful in localizing degenerative joint disease of the ankle, hindfoot, and midfoot as an adjunct to clinical examination. LEVEL OF EVIDENCE: Level IV, case series.

The value of combined assessment of vertebral fractures with 99mTc MDP scintigraphy and MRI in selecting and planning percutaneous vertebroplasty.

BACKGROUND: Percutaneous vertebroplasty is a minimally invasive radiological procedure intended for relieving painful vertebral fractures. Suitability depends largely on fracture age, with acute osteoporotic fractures being most appropriate. Selection and planning usually involves either Tc MDP scintigraphy or MRI. There is evidence indicating that either modality is predictive of response to vertebroplasty, but there is limited evidence promoting their combined use. AIM: The aim of the study was to establish the degree of concordance between MRI and Tc MDP scintigraphy in vertebral fracture assessment. MATERIALS AND METHODS: Our institution routinely uses both MRI and Tc MDP scintigraphy in vertebroplasty planning. This retrospective analysis included 39 patients, with a total of 73 vertebral fractures, all treated with vertebroplasty. The fractures were classified according to fracture age, aetiology and intermodality concordance. RESULTS: The overall concordance between MRI and Tc MDP scintigraphy was 63%. Almost twice as many fractures classified as 'acute/ subacute' on MRI were so classified on Tc MDP scintigraphy. CONCLUSION: Using MRI without Tc MDP scintigraphy, 48.2% of the potentially suitable vertebroplasty targets (37% of the total vertebral lesions) would likely have been overlooked. Clearly, Tc MDP scintigraphy and MRI provide different but complementary information on vertebral fractures, and these results support the use of dual-modality assessment in vertebroplasty selection and planning.

The Role of PET/CT in Advanced Malignant Melanoma.

Positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose demonstrates a high sensitivity and specificity for detecting both locoregional and distant metastases in patients presenting with AJCC stages III and IV disease. PET/CT also plays an important role in the detection of recurrence particularly in high-risk group patients, and this should be the modality of choice in investigating patients for suspected recurrence. The role of PET/CT in response assessment and follow-up still has to be defined, and cost-effectiveness analysis is required to strengthen its role.

In vitro selection of protein-binding DNA aptamers as ligands for biosensing applications.

Aptamers are single-stranded functional nucleic acids that possess cognate ligand recognition capability. These functional nucleic acids have been used for biosensing of a variety of ligands. Aptamers are isolated by "in vitro selection" or SELEX from random-sequence nucleic acid pools. For example, DNA aptamers that recognize a protein can be generated by applying a DNA library to an affinity column containing the protein target and retrieving the bound sequences after wash. These sequences are amplified and used for a new round of binding and amplification. The identity of enriched sequences are subsequently revealed by cloning and sequencing. The binding of individual aptamers to the protein can be confirmed by techniques such as gel mobility shift. This chapter will provide a detailed protocol for isolating protein-binding DNA aptamers.