Specific, Fair and Transparent: A Canadian Process for Funding Drugs for Rare Diseases.

In Canada, the focus on value for money and evaluating efficacy according to traditional ways has presented challenges to the funding of drugs for rare diseases (DRDs). This commentary validates and extends two worthy recommendations from the lead paper in this issue of Healthcare Papers (Sirrs et al. 2023). The paper's first recommendation, for a pan-Canadian approach for collecting evidentiary data, is critical. In the commentary, I add to this finding by suggesting that we enable patients to track and measure their response to treatment through data capture. The second recommendation is a pan-Canadian framework for funding DRDs. I extend the recommendation with an argument for public and private payer guidance as well as a fair and transparent funding framework solely for DRDs.

Pain and Operative Technologies Used in Office Hysteroscopy: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: To identify technologies associated with the least operative pain in women undergoing operative office hysteroscopic procedures. DATA SOURCES: MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials were searched until January 2021 using a combination of keywords "hysteroscop*," "endometrial ablation," "outpatient," "ambulatory," "office," and associated Medical Subject Headings. METHODS OF STUDY SELECTION: Randomized controlled trials evaluating the effect of hysteroscopic devices on pain experienced by women undergoing operative office hysteroscopy were included. Data were also collected regarding efficacy, procedural time, adverse events, and patient/clinician acceptability and/or satisfaction. TABULATION, INTEGRATION, AND RESULTS: The search returned 5347 records. Ten studies provided data for review. Two trials compared endometrial ablation using bipolar radiofrequency with thermal balloon energy, with no significant difference in pain observed (p <.05). Seven trials evaluated technologies for endometrial polypectomy, of which, 4 compared energy modalities: miniature bipolar electrode resection against resectoscopy (N = 1), morcellation (N = 2), and diode laser resection (N = 1). Two studies compared hysteroscope diameter, and one study compared methods of polyp retrieval. A significant reduction in pain was found using morcellators rather than miniature bipolar electrosurgical devices (p <.001), 22Fr rather than 26Fr resectoscopes (p <.001), and 3.5-mm fiber-optic hysteroscopes with 7Fr forceps rather than 5-mm lens-based hysteroscopes with 5Fr forceps (p <.05). One study investigating septoplasty showed significant reduction in pain when cold mini-scissors, rather than a miniature bipolar electrode, were used (p = .013). Average procedural times ranged from 5 minutes 28 seconds to 22 minutes. The incidence of adverse events was low, and data regarding efficacy and acceptability/satisfaction were limited. CONCLUSION: Pain is reduced when mechanical technologies such as morcellators and scissors are used compared with electrical devices for removing structural lesions in the office. For hysteroscopic and ablative procedures, smaller and quicker devices are less painful. Large-scale RCTs investigating patient pain and experience with modern operative devices in the office setting are urgently needed.

A Systematic Review of the Effect of Type, Pressure, and Temperature of the Distension Medium on Pain During Office Hysteroscopy.

OBJECTIVE: To identify the optimal distension medium type, pressure, and temperature to minimize pain during office hysteroscopy. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and CENTRAL were searched from inception to January 29, 2020. METHODS OF STUDY SELECTION: We included randomized controlled trials in which women undergoing office hysteroscopy were randomized to either a distension medium type, pressure, or temperature against a suitable control, where pain was an outcome. Data regarding feasibility, visualization, complications, and satisfaction were also collected. TABULATION, INTEGRATION, AND RESULTS: The literature search returned 847 studies, of which 18 were included for systematic review and 17 for meta-analysis. There was no significant difference in intraprocedural pain when comparing the use of normal saline against carbon dioxide (standardized mean difference [SMD], -0.12; 95% confidence interval [CI], -0.36 to 0.13). Subgroup analysis of high-quality studies revealed a statistically significant reduction in postprocedural pain with normal saline (SMD, -0.65; 95% CI, -1.14 to -0.16). Side effects were less frequent (Peto odds ratio, 0.29; 95% CI, 0.20-0.40) and patient satisfaction was higher (SMD, 1.39; 95% CI, 0.51-2.28) with normal saline compared with carbon dioxide. Pressures of ≤40 mm Hg reduced intraprocedural pain (SMD, -0.67; 95% CI, -1.09 to -0.26) at the expense of a higher proportion of unsatisfactory views (81%-89% at ≤40 mm Hg vs 95%-99% at ≥50 mm Hg). Postprocedural pain was reduced with lower filling pressures. Warming saline did not reduce intraprocedural pain (SMD, 0.59; 95% CI, -0.14 to 1.33). CONCLUSION: Normal saline, instilled at the lowest pressure to acquire a satisfactory view, should be used for uterine distension during office hysteroscopy to minimize pain.

Evaluating the value of intrapartum fetal scalp blood sampling to predict adverse neonatal outcomes: A UK multicentre observational study.

OBJECTIVE: To evaluate the value of fetal scalp blood sampling (FBS) as an adjunct test to cardiotocography, to predict adverse neonatal outcomes. STUDY DESIGN: A multicentre service evaluation observational study in forty-four maternity units in the UK. We collected data retrospectively on pregnant women with singleton pregnancy who received FBS in labour using a standardised data collection tool. The primary outcome was prediction of neonatal acidaemia diagnosed as umbilical cord arterial pH < 7.05, the secondary outcomes were the prediction of Apgar scores<7 at 1st and 5th minutes and admission to the neonatal intensive care unit (NICU). We evaluated the correlation between the last FBS blood gas before birth and the umbilical cord blood and adjusted for time intervals. We constructed 2 × 2 tables to calculate the sensitivity, specificity, positive (PPV) and negative predictive value (NPV) and generated receiver operating curves to report on the Area Under the Curve (AUC). RESULTS: In total, 1422 samples were included in the analysis; pH values showed no correlation (r = 0.001, p = 0.9) in samples obtained within an hour (n = 314), or within half an hour from birth (n = 115) (r=-0.003, p = 0.9). A suboptimal FBS pH value (<7.25) had a poor sensitivity (22%) and PPV (4.9%) to predict neonatal acidaemia with high specificity (87.3%) and NPV (97.4%). Similar performance was noted to predict Apgar scores <7 at 1st (sensitivity 14.5%, specificity 87.5%, PPV 23.4%, NPV 79.6%) and 5th minute (sensitivity 20.3%, specificity 87.4%, PPV 7.6%, NPV 95.6%), and admission to NICU (sensitivity 20.3%, specificity 87.5%, PPV 13.3%, NPV 92.1%). The AUC for FBS pH to predict neonatal acidaemia was 0.59 (95%CI 0.59-0.68, p = 0.3) with similar performance to predict Apgar scores<7 at 1st minute (AUC 0.55, 95%CI 0.51-0.59, p = 0.004), 5th minute (AUC 0.55, 95%CI 0.48-0.62, p = 0.13), and admission to NICU (AUC 0.58, 95%CI 0.52-0.64, p = 0.002). Forty-one neonates had acidaemia (2.8%, 41/1422) at birth. There was no significant correlation in pH values between the FBS and the umbilical cord blood in this subgroup adjusted for sampling time intervals (r = 0.03, p = 0.83). CONCLUSIONS: As an adjunct tool to cardiotocography, FBS offered limited value to predict neonatal acidaemia, low Apgar Scores and admission to NICU.

Endometrial Polyps and Abnormal Uterine Bleeding (AUB-P): What is the relationship, how are they diagnosed and how are they treated?

The diagnosis and treatment of endometrial polyps will be familiar to most gynaecologists. However, the aetiology and natural history of these focal intrauterine lesions are yet to be elucidated. This lack of clarity is also true with regard to their clinical significance; whilst endometrial polyps are highly prevalent in all types of abnormal uterine bleeding (AUB), they are also commonly found in women without AUB. These controversies will be discussed along with current thoughts on the diagnosis and treatment of endometrial polyps. Criteria for diagnosis of uterine polyps vary according to the test used, but optimal testing is not yet solidified. Recent data from randomised trials evaluating new and established surgical technologies as well as comparing treatment protocols and settings will be examined.

Effectiveness of photographs of study models for IOTN scoring.

AIM: The aim'of the present study was to investigate whether the same orthodontic information can be obtained from study models or photographs of study models in order to assess the Index of Orthodontic Treatment Need (IOTN). The study also aimed to assess inter- and intra-examiner reliability in the assessment of orthodontic treatment need. SAMPLE: Thirty sets of start and finish study models, demonstrating a range of malocclusions, were non-randomly obtained from patients treated at the University of Manchester Dental Hospital. The start models demonstrated a range of malocclusions (according to The British Standard Institute Incisor Classification 1983) of varying complexity. METHOD: Six photographic views of each set of study models were taken against a dark background. Millimetric distances were determined by using dividers to measure photographic distances and actual distances in millimeters from a ruler embedded in the image. Four examiners assessed the study models and photographs of the models in a random order and the Aesthetic and Dental Health components of the IOTN were recorded. RESULTS: There were no statistically significant differences in the IOTN scores from photographs of study models compared with IOTN scoresrom study models of the same patient. CONCLUSION: The IOTN scores derived from photographs of study models are valid and reliable measures of malocclusion.

An evaluation framework for funding drugs for rare diseases.

OBJECTIVES: For rare diseases it may be difficult to generate data from randomized trials to support funding of a drug. Enzyme replacement therapies for diseases of inherited metabolic enzyme deficiency provide an example of this dilemma. The Ontario Public Drug Programs convened the Drugs for Rare Diseases Working Group to develop a policy for assessing these drugs. METHODS: The Drugs for Rare Diseases Working Group developed terms of reference expecting that the ideal policy product would be transparent and consistent and address unique aspects of the treatment of a specific rare condition while being adaptable to other dissimilar conditions. The perspective was that of a public payer addressing requests for funding generated for a specific drug, and included respect for the principles of "accountability for reasonableness" of Daniels and Sabin. RESULTS: A seven-step framework was developed and tested by using the case study of idursulfase for mucopolysaccharidosis II (Hunter disease). Estimation of clinical effectiveness was done by using decision modeling. The model developed informed funding recommendations and ultimately led to an agreement with the manufacturer allowing funding of idursulfase in Ontario. CONCLUSIONS: This policy framework attempts to address the policy challenges of funding drugs for rare diseases. The framework will be used to assess other drugs in future and will inevitably require modification with experience. It is hoped that it may be of value to other policymakers.

Structured abstracts: do they improve citation retrieval from dental journals?

OBJECTIVES: To assess whether structured abstracts improved the sensitivity, precision and yield of retrieving clinical trials, using electronic searches, for example, MEDLINE, from dental journals. DESIGN: Retrospective, observational study. SAMPLE: Clinical trials, published in six dental journals. Three that adopted structured abstracts (BDJ, CPJ, JO) and three that remained unchanged (JDR, EJO, AJODO) between January 1995 and December 1998 (extended to December 2002 for the JO). INTERVENTION: Adoption of a structured abstract format. CONTROL: Continued use of a non-structured abstract format. METHOD: A combination of handsearching and the Cochrane Collaboration Oral Health Group's Trials Register and/or CENTRAL were used to identify randomised controlled trials (RCTs) and controlled clinical trials (CCTs) over the selected time period. MEDLINE was used to identify clinical trials in the selected journals over the same time period. RESULTS: There was no significant difference in the sensitivity or yield of clinical trial retrieval in journals with either abstract format over time. However, there was a significant increase in precision in journals that did not change their format (OR=4.96 (95% CI 1.18, 20.86) but not those that did. There was no significant difference in the sensitivity or yield of clinical trial retrieval either before or after the change in format or precision of retrieval before the change. However, in the later period, the precision of retrieval was significantly better in journals with unstructured abstracts compared to those with structured abstracts (OR=0.17 (95% CI 0.04, 0.7). CONCLUSION: The use of a structured abstract format does not improve the sensitivity, precision or yield of retrieval of clinical trials from MEDLINE.

The statins: drug interactions of significance to the dental practitioner.

UNLABELLED: This report outlines the potential for concomitant use of dentally prescribed medication to increase the risk of statin-induced myopathy. The associated signs and symptoms of statin-induced myopathy are also highlighted, as well as the need for an accurate and updated drug history for all dental patients. CLINICAL RELEVANCE: This article describes the recognized adverse interactions associated with concomitant drug therapy for patients on statins.

Mental nerve anaesthesia; a complication of sickle cell crisis during childbirth.

This report describes the case of an Afro-Caribbean lady diagnosed with sickle cell anaemia, who presented with permanent mental nerve anaesthesia as a result of a sickle cell crisis during childbirth.

Angioedema of the lips and tongue induced by angiotensin-converting enzyme inhibitor. A report of two cases.

The following case reports describe the clinical presentation, diagnosis and management of two patients who attended Liverpool University Dental Hospital with rapidly increasing swelling of the lips and tongue. Both patients were suffering from angioedema and were taking an angiotension-converting enzyme (ACE) inhibitor (ACEI). A provisional diagnosis of ACEI-induced angioedema was made. An intramuscular injection of chlorpheniramine maleate was given to both patients and they were immediately transferred to the local accident and emergency department. These cases illustrate the potential role of the general dental practitioner in the early recognition and management of this potentially life-threatening condition.