Time intervals in the care pathway to cancer diagnosis during the COVID-19 pandemic: A large retrospective study from a high-volume center.

Despite extensive research on cancer care during the COVID-19 pandemic, evidence on the impact on prediagnostic time intervals is lacking. To better understand how COVID-19 changed the pathway to diagnosis of cancer, we examined the length of intervals from symptom onset to diagnosis for 13 common cancer types with known clinical stage over 1-year nonpandemic period (March 2019 to March 2020; N = 844) and three biannual COVID periods (March 2020 to September 2021; N = 1172). We analyzed the patient interval (from first symptoms to presentation to a physician), the primary care/emergency department interval (from presentation with relevant symptoms to a primary care or emergency department physician to referral to a hospital-based diagnosis center) and the hospital interval (from referral to diagnosis). Compared to nonpandemic data, there were significant changes across COVID periods. The pandemic mostly impacted patient intervals for cancers diagnosed over the first 6 months after onset in March 2020. Overall median patient intervals were longest in the early COVID period (39 [IQR 22-64] days) and shortest in the nonpandemic period (20 [IQR 13-30] days; Kruskal-Wallis test [χ2 ], P < .0001). Differences in clinical stage between periods were relevant, with cancers from the mid-period (September 2020 to March 2021) showing the most advanced stage. A shift to later stage was plausibly a result of delayed intervals in the early COVID period. Since intervals are eventually relevant to prognosis, our results provide a baseline against which the impact of improvement strategies to minimize the negative outcomes of COVID-19-associated cancer delays can be assessed and implemented.

Time intervals in the pathway to emergency cancer diagnosis.

Aim: Evidence on time-based metrics for cancers diagnosed through emergency presentation is lacking. We examined the duration of intervals from first symptoms to cancer diagnosis in the emergency versus primary care (PC) presentation route. Methods: Retrospective study of outpatients diagnosed with 15 solid cancers over 5 years. The outcome was the length of prediagnostic intervals by diagnostic route. Results: Median intervals in emergency presenters (n = 3167) were shorter than in PC presenters (n = 2215). However, intervals in emergency presenters with three or more prior PC consultations were similar to PC but remarkably longer than in those with one or two and no consultations. Conclusion: As we provide new interval measures for the emergency diagnostic pathway, results highlight the contribution of prior consultations to interval lengths.

Tumour markers with clinically controlled cut-offs for suspected cancer.

BACKGROUND: Due to insufficient scientific evidence, panels of tumour markers (TMs) are currently not recommended for use in suspected cancer. However, recent well-designed studies have revealed a potential clinical value in lung cancer. We analysed the diagnostic accuracy of a panel of 11 circulating TMs with clinically controlled thresholds in the differentiation of cancer from nonmalignant diseases. METHODS: We prospectively recruited 4776 consecutive patients presenting with focal or nonspecific symptoms suggestive of cancer who underwent testing for 11 serum TMs before diagnosis was known. The study abided by 2015 STARD guidelines. Tumour markers included, among others, carbohydrate antigen 19-9, carcinoembryonic antigen, alpha-fetoprotein, squamous cell carcinoma-associated antigen, prostate-specific antigen (males), neuron-specific enolase, progastrin-releasing peptide and carbohydrate antigen 125. Thresholds were adjusted for the presence of kidney failure, liver disease, effusions and dermatological disorders. Results showing ≥1 TMs with concentrations above threshold were considered positive. RESULTS: Benign diseases were diagnosed in 3281 (68.7%) patients and cancer in 1495 (31.3%), with epithelial cancers in 1214 (77% at stage IV). When applying criteria for controlled thresholds, overall specificity was 98%. Overall sensitivity of the panel in epithelial cancers was 72.2%, positive predictive value 93% and negative predictive value 90.5%. The area under the receiver operating characteristic curve was 0.920 (95% confidence interval, 0.902-0.924). CONCLUSIONS: By using clinically controlled cut-offs, the combined panel demonstrated an excellent ability to discriminate epithelial cancers from nonmalignant diseases. However, its use in clinical practice would need formal validation through a multicentre controlled trial assessing a panel-guided strategy vs. standard diagnosis.

The impact of Covid-19 on patients with suspected cancer: An analysis of ED presentation and referrals to a quick diagnosis unit.

PURPOSE: Patients evaluated in the emergency department (ED) who have concerning symptoms suggestive of a cancer diagnosis are mostly referred to the quick diagnosis unit of our tertiary hospital. This study analyzed the impact of the Covid-19 pandemic on the volume, disease patterns, and accessibility to essential investigations of patients with suspected cancer referred by the ED to this unit. METHODS: Trends in referrals were analyzed from January 1 to July 8, 2020 and the corresponding dates of 2019. Only non-Covid-19 conditions were evaluated. Three time-based cohorts were defined: prepandemic (January 1-February 19), pandemic (February 19-April 22), and postpandemic (April 22-July 8). Along with descriptive statistics, linear regression was used to test for time trends with weekly referrals as the dependent variable. RESULTS: There were 384, 193, and 450 patients referred during the prepandemic, pandemic, and postpandemic periods, respectively. Following an increasing rate, referrals decreased to unprecedented levels in the pandemic period (average weekly slope: -2.1 cases), then increasing again until near normalization. Waiting times to most diagnostic procedures including radiology, endoscopic, nuclear medicine, and biopsy/cytology during the pandemic period were significantly delayed and time-to-diagnosis was considerably longer (19.72 ± 10.37 days vs. 8.33 ± 3.94 days in prepandemic and 13.49 ± 6.45 days in postpandemic period; P < 0.001 in both). Compared to other cohorts, pandemic cohort patients were more likely to have unintentional weight loss and fever of unknown origin as referral indications while anemia and lymphadenopathy were less common. Patients from the pandemic cohort had a significantly lower rate of malignancies and higher of benign gastrointestinal disorders (40.93% vs. 19.53% and 20.89% in prepandemic and postpandemic periods, respectively; P < 0.001 in both), most notably irritable bowel disease, and of mental and behavioral disorders (15.54% vs. 3.39% and 6.00% in prepandemic and postpandemic periods, respectively; P < 0.001 in both). CONCLUSIONS: As our hospital switched its traditional care to one focused on Covid-19 patients, recognized indicators of healthcare quality of quick diagnosis units were severely disrupted. The clinical patterns of presentation and diagnosis of the pandemic period suggested that mass media-generated mental and behavioral responses with distressing symptoms played a significant role in most of these patients.

Glycemic variability: prognostic impact on acute ischemic stroke and the impact of corrective treatment for hyperglycemia. The GLIAS-III translational study.

INTRODUCTION: Glycemic variability (GV) represents the amplitude of oscillations in glucose levels over time and is associated with higher mortality in critically ill patients. Our aim is to evaluate the impact of GV on acute ischemic stroke (IS) outcomes in humans and explore the impact of two different insulin administration routes on GV in an animal model. METHODS: This translational study consists of two studies conducted in parallel: The first study is an observational, multicenter, prospective clinical study in which 340 patients with acute IS will be subcutaneously implanted a sensor to continuously monitor blood glucose levels for 96 h. The second study is a basic experimental study using an animal model (rats) with permanent occlusion of the middle cerebral artery and induced hyperglycemia (through an intraperitoneal injection of nicotinamide and streptozotocin). The animal study will include the following 6 groups (10 animals per group): sham; hyperglycemia without IS; IS without hyperglycemia; IS and hyperglycemia without treatment; IS and hyperglycemia and intravenous insulin; and IS and hyperglycemia and subcutaneous insulin. The endpoint for the first study is mortality at 3 months, while the endpoints for the animal model study are GV, functional recovery and biomarkers. DISCUSSION: The GLIAS-III study will be the first translational approach analyzing the prognostic influence of GV, evaluated by the use of subcutaneous glucose monitors, in acute stroke. Trial registration https://www.clinicaltrials.gov (NCT04001049).

Efficacy and safety of once-monthly efpeglenatide in patients with type 2 diabetes: Results of a phase 2 placebo-controlled, 16-week randomized dose-finding study.

AIMS: To determine the optimal dose(s) of once-monthly administration of efpeglenatide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D) inadequately controlled on metformin. MATERIALS AND METHODS: In this phase 2, randomized, placebo-controlled, double-blind trial (NCT02081118), patients were randomized 1:1:1:1 to subcutaneous efpeglenatide (8, 12 or 16 mg once monthly; n = 158) or placebo (n = 51). The 16-week treatment period included a 4-week titration phase with once-weekly efpeglenatide 4 mg, followed by one dose of efpeglenatide 8 mg once monthly and two doses of the assigned once-monthly dose. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to week 17. RESULTS: All efpeglenatide doses significantly reduced HbA1c versus placebo (P < 0.0001 for all). Overall, the least squares mean difference in HbA1c reductions between efpeglenatide and placebo was -7.7 mmol/mol (-0.71%; baseline to week 17). At week 17, a significantly greater proportion of efpeglenatide patients had an HbA1c level <53 mmol/mol (<7%) versus placebo (48.7% vs. 30.6%; P = 0.0320). Significant body weight loss occurred across all efpeglenatide doses (placebo-corrected reduction -2.0 kg [efpeglenatide overall]; P = 0.0003). The safety profile was consistent with GLP-1RAs, with gastrointestinal (GI) disorders being the most common treatment-emergent adverse events. Fluctuations in effects on glucose levels and rates of GI events occurred between peak and trough efpeglenatide concentrations. CONCLUSIONS: Efpeglenatide once monthly (following once-weekly titration) has significant benefits with regard to HbA1c and weight reduction versus placebo in patients with T2D. Further studies are needed to evaluate the long-term efficacy and safety of efpeglenatide once monthly.

[Effectiveness of intravenous sedation with midazolam-diphenhydramine in patients who are going to perform an magnetic resonance]. / Efectividad de la sedación intravenosa con midazolam- difenhidramina en pacientes a quienes se va a realizar una resonancia magnética (RM).

INTRODUCTION: The requirement of the anesthesiologist for patient care outside the surgical area is constantly increasing. It is an activity that encompasses the different degrees of monitoring, sedation, and anesthesia. OBJECTIVE: To compare the safety and efficacy of midazolam midazolam-diphenhydramine against magnetic resonance with level of sedation on the Ramsay scale. MATERIALS AND METHODS: We performed a study in the Instituto Mexicano del Seguro Social Obregon, Sonora, of patients scheduled for cranial magnetic resonance imaging with sedation, during October and December 2013, comparing two groups: midazolam/diphenhydramine against midazolam groups. RESULTS: We included 68 patients, 34 in the experimental group (midazolam-diphenhydramine) versus 34 controls (midazolam). The Ramsay scale showed, in the experimental group, an increased sedation effect resulting in one Ramsay 1, at 10 minutes 2.8 2.8 20 minutes and 30 minutes 2.0. In the control group the basal Ramsay was 1, 2.1 to 10 minutes, 20 minutes and 2.1 to 2.0 at 30 minutes (p = 0.0001). The analysis of heart rate, respiratory, and baseline oxygen saturation, at 10, 20 and 30 minutes, was p = 0.0001 for both groups. CONCLUSION: The combination of diphenhydramine with intravenous midazolam is safe, with the degree of sedation being better compared with use of midazolam alone, resulting in less failure of sedation during magnetic resonance imaging.

Elderly patients treated with psychotropic medicines admitted to hospital: associated characteristics and inappropriate use.

PURPOSE: The purpose of this study is to describe the characteristics of older patients treated with psychotropic medicines and the associated factors and to assess their inappropriate use. METHODS: An observational, prospective study was carried out in 672 elderly patients admitted to seven hospitals for a year. A comparison of sociodemographic characteristics, geriatric variables, multimorbidity and the number of prescribed medicines taken in the preceding month before hospitalization between patients treated with psychotropics and those not treated was performed. To assess factors associated with psychotropics, multivariate logistic regression analyses were performed. Inappropriate use was assessed using the Beers and the STOPP criteria. RESULTS: A total of 57.5 % patients (median [Q1-Q3] age 81.7 [78.2-86.1], 65.7 % female) were treated with psychotropics (44.2 % anxiolytics, 22.6 % antidepressants and 10.8 % antipsychotics). Independent factors associated with the use of psychotropics were female gender (OR = 2.3; CI 95 %,1.6-3.5), some degree of disability on admission (slight [OR = 2.2; 1.2-4.2], moderate [OR = 3.2, 1.6-6.6], severe [OR = 3.4; 1.4-8] and very severe [OR = 5.1; 2.0-12.8]) and polypharmacy (5-9 medicines [OR = 3.0; 1.3-6.9] and ≥10 medicines [OR = 6.0; 2.7-13.6]). The associated factors varied depending on the different types of psychotropics. In patients treated with psychotropics, the percentage of those with at least one Beers (61.6 %) or at least one STOPP (71.4 %) criteria was significantly higher in comparison with those not treated with psychotropics (30.7 and 47.7 %, respectively, p < 0.001). CONCLUSIONS: Psychotropics are widely used in the elderly population and often their use is inappropriate. Female gender, a poor functional status and polypharmacy, are the characteristics linked to their use. Interventional strategies should be focused on patients with these characteristics.

Factors Associated with Hospitalization among Emergency Department Patients Referred for Quick Investigation of Iron-Deficiency Anemia.

BACKGROUND: Although patients with anemia are frequently seen in emergency departments (EDs), studies on patients presenting there with symptomatic chronic anemia--usually iron-deficiency anemia (IDA) caused by occult gastrointestinal bleeding--are lacking. Awareness of predictors of hospitalization could direct the ED triage to the appropriate diagnostic setting. OBJECTIVE: Based on initial observations that some patients with IDA were hospitalized after ED referral and initial evaluation at a quick diagnosis unit (QDU), a new cost-effective alternative to hospitalization for diagnostic workup, this study aimed to determine the patient factors associated with hospitalization after the first QDU visit. METHODS: An 8-year prospective cohort study of patients with IDA referred from the ED to the QDU of a third-level university hospital was conducted. Patients with a baseline hemoglobin level of <9 g/dL in the ED, proven iron deficiency, and no overt bleeding were included. The primary outcome was hospitalization after the initial QDU assessment. RESULTS: Two hundred eighty-four (7.7%) of 3692 patients were hospitalized. Inter-rater agreement of appropriateness of admissions was 90.6% (κ = 0.82). Overall, 90% of study patients presented to the ED with symptomatic anemia, and 87% were transfused there. On multivariate analysis, age ≥ 65 years, living alone, a post-transfusion hemoglobin level of <9 g/dL, higher age-adjusted overall comorbidity, heart failure, and poor physical health-related quality of life at first QDU visit independently predicted hospitalization. CONCLUSION: While these predictors do not necessarily reflect the need for hospitalization, they are easily evaluated during the initial ED visit and can guide the triage of similar IDA patients to the suitable setting for timely investigation.

Prevalence of sarcopenia in patients attending outpatient geriatric clinics: the ELLI study.

OBJECTIVES: the aim of this study is to know the prevalence of sarcopenia in geriatric outpatient clinics using the EGWSOP (European Working Group on Sarcopenia in Older People) diagnostic criteria that include muscle mass, muscle strength and physical performance. METHODS: subjects over 69 years old, able to walk without help and who attended five geriatric outpatient clinics were recruited. Body composition was assessed using bioimpedance analysis (BIA), grip strength using a JAMAR dynamometer and physical performance by the 4 m gait speed. Sarcopenia was diagnosed using the EGWSOP criteria (gait speed <0.8 m/s; grip strength <30 kg in men or <20 kg in women, and muscle mass index (MMI) <8.31 kg/m(2) in men or <6.68 kg/m(2) in women). RESULTS: two hundred and ninety-eight subjects were included (median age 83.2 years, 63.1% women). 19.1% had sarcopenia (12.7% men, 22.9% women); 20.1% had low muscle mass; 68.8% had low gait speed and 81.2% low grip strength. Only 21.9% of the subjects with low grip strength and 19.5% of those with low gait speed had sarcopenia. No correlations between muscle mass and either muscle strength or gait speed were detected. CONCLUSIONS: sarcopenia is present in one out of five subjects attending geriatric outpatient clinics.

Inappropriate prescribing to the oldest old patients admitted to hospital: prevalence, most frequently used medicines, and associated factors.

BACKGROUND: Scientific evidence on treatments of chronic diseases in patients 85 years old or older is very limited, as is available information on inappropriate prescription (IP) and its associated factors. The study aimed to describe medicine prescription, potentially inappropriate medicines (PIM) and potentially prescribing omissions (PPO) and their associated factors on this population. METHODS: In the context of an observational, prospective and multicentric study carried out in elderly patients admitted to seven Spanish hospitals for a year, a sub-analysis of those aged 85 years and over was performed. To assess PIMs, the Beers and STOPP criteria were used, and to assess PPOs, the START and the ACOVE-3 criteria were used. To assess factors associated with IP, a multivariate logistic regression analysis was performed. Patients were selected randomly every week on consecutive days from the hospitalization lists. RESULTS: A total of 336 patients were included in the sub-analysis with a median (Q1-Q3) age of 88 (86-90) years. The median medicines taken during the month prior to admission was 10 (7-13). Forty-seven point two per cent of patients had at least one Beers-listed PIM, 63.3% at least one STOPP-listed PIM, 53.6% at least one START-listed PPO, and 59.4% at least one ACOVE-3-listed PPO. Use of benzodiazepines in patients who are prone to falls (18.3%) and omission of calcium and vitamin D supplements in patients with osteoporosis (13.3%) were the most common PIM and PPO, respectively. The main factor associated with the Beers-listed and the STOPP-listed PIM was consumption of 10 or more medicines (OR = 5.7, 95% CI 1.8-17.9 and OR = 13.4, 95% CI 4.0-44.0, respectively). The main factors associated with the START-listed PPO was a non-community dwelling origin (OR 2.3, 95% CI 1.0-5.0), and multimorbidity (OR1.8, 95% CI 1.0-3.1). CONCLUSIONS: Prescribed medicines and PIM and PPO prevalence were high among patients 85 years and over. Benzodiazepine use in those who are prone to falls and omission of calcium and vitamin D in those with osteoporosis were the most frequent PIM and PPO, respectively. Factors associated with PIM and PPO differed with polypharmacy being the most important factor associated with PIM.

Escape and lipodystrophy in acromegaly during pegvisomant therapy, a retrospective multicentre Spanish study.

BACKGROUND: Pegvisomant is an effective treatment for acromegaly. OBJECTIVE: To investigate escape (loss of biochemical control in patients previously controlled) and lipodystrophy in acromegalic patients treated with pegvisomant and to evaluate possible associations with clinical features. PATIENTS AND METHODS: Multicentre retrospective study involving 19 Spanish centres. RESULTS: Ninety-seven patients were included (59% women, mean age at diagnosis 42 ± 13 years, 80% macroadenomas); mean follow-up on pegvisomant was 5 ± 2·5 years, and 89 (92%) achieved normal IGF-1. Escape was reported in 30/89 (34%) of responders, after a mean treatment duration of 25 ± 21 months. The mean initial dose of pegvisomant was 11 ± 5 mg/day, and mean dose at escape was 14 ± 7 mg/day. Most patients (26/30, 87%) achieved control with dose increase (57%), additional medical treatment (3%) or both (27%). Mean new dose that controlled IGF-1 after escape was 20 ± 7 mg/day. Treatments associated were somatostatin analogues (SSA in 47%), cabergoline (CAB in 47%) and both (6%). Lipodystrophy was observed in 15 patients (13 females), mild in six, moderate in six, severe in three and persistent in four. Among patients with lipodystrophy, three escaped and three were nonresponders to pegvisomant. Four patients discontinued the drug, and four had dose reductions because of lipodystrophy. It tended to be more frequent in females (P = 0·06) and in patients treated with triple association SSA+CAB+PEG (P = 0·018). No relationship between escape and clinical variables was found, except prior CAB (P = 0·04) and metformin treatment (0·02) and grade of lipodystrophy (P = 0·02). CONCLUSIONS: A significant proportion of patients treated with pegvisomant escaped (34%); however, the majority (87%) was easily controlled with either dose increase, further medical treatment or both. Lipodystrophy developed in 15%, mostly females, and influenced the response to treatment.

Diagnosing unexplained fever: can quick diagnosis units replace inpatient hospitalization?

BACKGROUND: Outpatient quick diagnosis units (QDUs) have become an increasingly recognized alternative to hospitalization for the diagnosis of a number of potentially serious diseases. No study has prospectively evaluated the usefulness of QDU for the diagnosis of unexplained fever. MATERIALS AND METHODS: We prospectively assessed patients referred to QDU due to fever of uncertain nature (FUN), defined as a temperature > 38 °C during at least 1 week and no diagnosis after a previous evaluation. We also evaluated consecutive patients with FUN who were hospitalized during the same period. QDU and hospital costs were analysed by micro-costing techniques. RESULTS: We evaluated 176 QDU patients and 168 controls. QDU patients were younger and required fewer investigations than controls. QDU patients had higher prevalence of viral infections (36% vs. 8%, P < 0·001) and lower prevalence of bacterial infections (6% vs. 46%, P < 0·001) and malignancies (2% vs. 14%, P < 0·001). While time-to-diagnosis of QDU patients was longer than length-of-stay of controls (25·82 vs.12·89 days, P < 0·001), 56% of QDU patients only required up to two visits. Cost per QDU patient was €644·59, while it was €4404·64 per hospitalized patient. CONCLUSIONS: QDU patients with FUN were younger and had less serious diseases than controls including more viral and less bacterial infections and fewer malignancies. Mainly owing to untimely diagnostic reports, time-to-diagnosis was longer in QDU patients. Cost-savings in QDU were substantial. Using objective tools to evaluate the condition severity and general health status of FUN patients could help decide the most appropriate setting for their diagnostic study.

Primary care referrals of patients with potentially serious diseases to the emergency department or a quick diagnosis unit: a cross-sectional retrospective study.

BACKGROUND: In Spain, primary healthcare (PHC) referrals for diagnostic procedures are subject to long waiting-times, and physicians and patients often use the emergency department (ED) as a shortcut. We aimed to determine whether patients evaluated at a hospital outpatient quick diagnosis unit (QDU) who were referred to ED from 12 PHC centers could have been directly referred to QDU, thus avoiding ED visits. As a secondary objective, we determined the proportion of QDU patients who might have been evaluated in a less rapid, non-QDU setting. METHODS: We carried out a cross-sectional retrospective cohort study of patients with potentially serious conditions attended by the QDU from December 2007 to December 2012. We established 2 groups of patients: 1) patients referred from PHC to QDU (PHC-QDU group) and 2) patients referred from PHC to ED, then to QDU (PHC-ED-QDU group). Two observers assessed the appropriateness/inappropriateness of each referral using a scoring system. The interobserver agreement was assessed by calculating the kappa index. Multivariate logistic regression analysis was performed to identify the factors associated with the dependent variable 'ED referral'. RESULTS: We evaluated 1186 PHC-QDU and 1004 PHC-ED-QDU patients and estimated that 93.1% of PHC-ED-QDU patients might have been directly referred to QDU. In contrast, 96% of PHC-QDU patients were found to be appropriately referred to QDU first. The agreement for PHC-QDU referrals (PHC-QDU group) was rated as excellent (Ï°=0.81), while it was rated as good for PHC-ED referrals (PHC-ED-QDU group) (Ï°=0.75). The mean waiting-time for the first QDU visit was longer in PHC-QDU (4.8 days) than in PHC-ED-QDU (2.6 days) patients (P=.001). On multivariate analysis, anemia (OR 2.87, 95% CI 1.49-4.55, P<.001), rectorrhagia (OR 2.18, 95% CI 1.10-3.77, P=.01) and febrile syndrome (OR 2.53, 95% CI 1.33-4.12, P=.002) were independent factors associated with ED referral. Nearly one-fifth of all QDU patients were found who might have been evaluated in a less rapid, non-QDU setting. CONCLUSIONS: Most PHC-ED-QDU patients might have been directly referred to QDU from PHC, avoiding the inconvenience of the ED visit. A stricter definition of QDU evaluation criteria may be needed to improve and hasten PHC referrals.

The painful effects of the financial crisis on Spanish health care.

Spain has an advanced, integrated health care system that has achieved remarkable results, including substantially improved health outcomes, over a relatively short time. Measures introduced by central and regional governments to combat the financial crisis may be severely affecting the health sector, with proposed changes potentially threatening the principles of equity and social cohesion underlying the welfare state. This article examines recent developments in Spanish health care, focusing on the austerity measures introduced since 2010. In Spain, as in other countries, evaluation of health care changes is difficult due to the paucity of data and because the effects of measures often lag well behind their introduction, meaning the full effects of changes on access to care or health outcomes only become apparent years later. However, some effects are already clear. With exceptions, Spain has not used the crisis as an opportunity to increase efficiency and quality, rationalize and reorganize health services, increase productivity, and regain public trust. We argue that immediate health care cuts may not be the best long-term answer and suggest evidence-driven interventions that involve the portfolio of free services and the private sector, while ensuring that the most vulnerable are protected.

Clinical characterisation of patients diagnosed with cancer following emergency self-referral.

BACKGROUND: Despite their frequency and potential impact on prognosis, cancers diagnosed via self-referral to the emergency department are poorly documented. We conducted a detailed analysis of cancer patients diagnosed following emergency self-referral and compared them with those diagnosed following emergency referral from primary care. Given the challenges associated with measuring intervals in the emergency self-referral pathway, we also aimed to provide a definition of the diagnostic interval for these cancers. METHODS: A retrospective observational analysis was performed on patients diagnosed with 13 cancers, either following emergency self-referral or emergency referral from primary care. We analysed demographics, tumour stage, clinical data (including 28 presenting symptoms categorised by body systems), and diagnostic intervals by cancer site, then testing for differences between pathways. RESULTS: Out of 3624 patients, 37 % were diagnosed following emergency self-referral and 63 % via emergency referral from primary care. Emergency self-referrals were associated with a higher likelihood of being diagnosed with cancers manifesting with localising symptoms (e.g., breast and endometrial cancer), whereas the likelihood of being diagnosed with cancers featuring nonspecific symptoms and abdominal pain (e.g., pancreatic and ovarian cancer) was higher among patients referred from primary care. Diagnostic intervals in self-referred patients were half as long as those in patients referred from primary care, with most significant differences for pancreatic cancer (28 [95 % CI -34 to -23] days shorter, respectively). CONCLUSION: These findings enrich the best available evidence on cancer diagnosis through emergency self-referral and showed that, compared with the emergency referral pathway from primary care, these patients had a significantly increased likelihood of presenting with symptoms that are strongly predictive of cancer. Since the starting point for the diagnostic interval in these patients is their emergency presentation, comparing it with that of those referred from primary care as an emergency is likely to result in biased data.

Time to Diagnosis and Presenting Symptoms of Patients Diagnosed With Cancer Through Emergency and Nonemergency Routes: A Large Retrospective Study From a High-Volume Center.

PURPOSE: The symptoms with which a patient with cancer presents and the route taken to diagnosis (emergency v nonemergency) may affect the speed with which the diagnosis of cancer is made, thereby affecting outcomes. We examined time to diagnosis by symptom for cancers diagnosed through emergency and nonemergency routes (NERs). METHODS: We performed a retrospective review of patients diagnosed with 10 solid cancers at Hospital Clínic of Barcelona between March 2013 and June 2023. Cancers were diagnosed through emergency presentation and admission (inpatient emergency route [IER]), emergency presentation and outpatient referral (outpatient emergency route [OER]), and primary care presentation and outpatient referral (NER). We assessed the effect of diagnostic routes on intervals to diagnosis for 19 cancer symptoms. RESULTS: A total of 5,174 and 1,607 patients were diagnosed with cancer through emergency routes and NERs, respectively. Over 85% of patients presenting with alarm (localizing) symptoms such as hematuria through emergency routes were diagnosed with the expected cancer, whereas those with nonlocalizing symptoms such as abdominal pain had a more heterogeneous cancer-site composition. Median intervals were shorter for alarm than nonlocalizing symptoms and tended to be shorter in IERs than OERs. However, for most symptoms, intervals in both routes were invariably shorter than in the NER. For example, diagnostic intervals for hematuria and abdominal pain were 3 and 5 days shorter in IERs than OERs, but they were 5-8 and 17-22 days shorter than in the NER, respectively. CONCLUSION: For patients with alarm symptoms, intervals were shorter than for those with nonlocalizing symptoms and, for most symptoms, intervals were shorter when patients were evaluated by emergency routes rather than NERs.

An Open-Label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism.

CONTEXT: Hypoparathyroidism is a rare disorder characterized by a deficiency in parathyroid hormone (PTH) resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). OBJECTIVE: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. DESIGN: Open-label, phase 2 study. PARTICIPANTS: Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12, and C2, n = 16). INTERVENTION: Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). MAIN OUTCOMES: Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (s-CTX and P1NP), bone mineral density (BMD), and adverse events (AEs). RESULTS: After 3 months, ≥ 88% patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. CONCLUSION: Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range, while normalizing uCa excretion and producing a balanced resumption of bone turnover.

Clinical and subclinical arteriosclerotic disease in octagenarians with hip fracture. A case-control study.

BACKGROUND AND OBJECTIVES: Evaluate clinical and subclinical arteriosclerotic disease in older patients with hip fracture compared with patients without fracture in order to increase knowledge about the relation between both diseases in older individuals. PATIENTS AND METHODS: Age- and sex-matched case-control study of octogenarians with and without recent hip fracture. Vascular risk factors, subclinical vascular diseases (assessed by carotid plaques, carotid intima media thickness and arterial stiffness) as well as cardiovascular diseases were analyzed. Univariate and multivariate logistic models were used to estimate odds ratios (OR) with their 95% confidence intervals (CI) to assess the association of the arteriosclerosis and hip fracture. RESULTS: We analyzed 95 patients per group with a median age of 82 [79-87] years of whom 77.9% were female. Patients in both groups have elevated rates of vascular disease (25%) without differences between them. Patients with hip fracture had higher subclinical arteriosclerotic alterations with higher percentage of carotid plaques (OR 3.25 [1.06-9.97]) compared with the control group. CONCLUSIONS: Older patients with hip fracture had significantly higher presence of subclinical alterations but not increase on rate of cardiovascular arteriosclerotic disease compared with those without hip fracture.

Natural history and surgical outcomes of Rathke's cleft cysts: a Spanish multicenter study.

Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be required. However, their natural progression is not yet well understood, and the outcomes of surgery are uncertain. The objective of this study is to evaluate the natural history of Rathke's cleft cysts in patients who are clinically monitored without treatment, and to determine the outcomes of surgery and the incidence of recurrences over time. Design and patients: National multicentric study of patients diagnosed of Rathke's cleft cyst (RCC- Spain) from 2000 onwards and followed in 15 tertiary centers of Spain. A total of 177 patients diagnosed of RCC followed for 67.3 months (6-215) and 88 patients who underwent surgery, (81 patients underwent immediate surgery after diagnosis and 7 later for subsequent growth) followed for 68.8 months (3-235). Results: The cyst size remained stable or decreased in 73.5% (133) of the patients. Only 44 patients (24.3%) experienced a cyst increase and 9 of them (5.1%) experienced an increase greater than 3 mm. In most of the patients who underwent surgery headaches and visual alterations improved, recurrence was observed in 8 (9.1%) after a median time of 96 months, and no predictors of recurrence were discovered. Conclusions: Rathke's cleft cysts without initial compressive symptoms have a low probability of growth, so conservative management is recommended. Patients who undergo transsphenoidal surgery experience rapid clinical improvement, and recurrences are infrequent. However, they can occur after a long period of time, although no predictors of recurrence have been identified.