Anti-cholinergic drug burden in patients with dementia increases after hospital admission: a multicentre cross-sectional study.

BACKGROUND: Anticholinergic medications are drugs that block cholinergic transmission, either as their primary therapeutic action or as a secondary effect. Patients with dementia may be particularly sensitive to the central effects of anticholinergic drugs. Anticholinergics also antagonise the effects of the main dementia treatment, cholinesterase inhibitors. Our study aimed to investigate anticholinergic prescribing for dementia patients in UK acute hospitals before and after admission. METHODS: We included 352 patients with dementia from 17 UK hospital sites in 2019. They were all inpatients on surgical, medical or Care of the Elderly wards. Information about each patient's medications were collected using a standardised form, and the anticholinergic drug burden of each patient was calculated with an evidence-based online calculator. Wilcoxon's rank test was used to look at the correlation between two subgroups upon admission and discharge. RESULTS: On admission to hospital, 37.8% of patients had an anticholinergic burden score ≥ 1 and 5.68% ≥3. On discharge, 43.2% of patients with an anticholinergic burden score ≥ 1 and 9.1% ≥3. The increase in scores was statistically significant (p = 0.001). Psychotropics were the most common group of anticholinergic medications prescribed at discharge. Of those patients taking cholinesterase inhibitors, 44.9% were also prescribed anticholinergic medications. CONCLUSIONS: Our cross-sectional, multicentre study found that people with dementia are commonly prescribed anticholinergic medications, even if concurrently taking cholinesterase inhibitors, and are significantly more likely to be discharged from hospital with a higher anticholinergic burden than on admission.

Treatment plans and outcomes in elderly patients reaching advanced chronic kidney disease.

Background: Elderly patients with advanced chronic kidney disease require accurate outcome descriptions to make treatment decisions. Methods: The PSPA [Parcours de soins des personnes âgées (Treatment pathways for elderly patients)] prospective multicentre cohort study included 573 such patients with a median age of 82 [interquartile range (IQR) 79-86] years and a median estimated glomerular filtration rate of 14 (IQR 11-17) mL/min/1.73 m2 and studied their 5-year outcomes according to the dialysis component of their treatment plans. Results: Mean follow-up for the overall cohort was 34.5 ± 21 months and the 5-year survival rate was 27%. During follow-up, 288 (50%) patients started dialysis and 237 (42%) died before dialysis. At baseline, the four possible dialysis plans were dialysis when needed (38%), stable without mention of a dialysis plan (40%) and dialysis specifically excluded by the patient's (9%) or nephrologist's decision (12%). These baseline plans were associated with death and dialysis start. Follow-up plans were those decided during the study period: dialysis when needed for 47%, stable without mention of a dialysis plan for 20% and dialysis excluded at any time for 32%. For the subgroup of patients who started dialysis, those whose follow-up plan was dialysis started under better conditions than those who had stable or no dialysis follow-up plans before starting. However, survival afterwards did not differ significantly. Conclusions: These findings indicate that nephrology care should accommodate changes over time in older patients' treatment preferences and plans concerning dialysis. These changes are associated with whether, when and how these patients initiate dialysis but are not necessarily associated with post-dialysis survival.

Digestive toxicities after palliative three-dimensional conformal radiation therapy (3D-CRT) for cervico-thoracic spinal metastases.

OBJECTIVE: The palliative treatment for cervico-thoracic spinal metastases is based on a three-dimensional conformal radiation therapy (3D-CRT). Digestive toxicities are common and cause a clinical impact frequently underestimated in patients. We performed a retrospective study of digestive side effects occurring after palliative 3D-CRT for cervico-thoracic spinal metastases. PATIENTS AND METHODS: All patients receiving palliative 3D-CRT at Jean Bernard Center from January 2013 to December 2014 for spinal metastases between the 5th cervical vertebra (C5) and the 12th thoracic vertebra (T12) were eligible. Three-dimensional conformal RT was delivered by a linear accelerator (CLINAC, Varian). Premedication to prevent digestive toxicities was not used. Adverse events ("esophagitis" and "nausea and/or vomiting") were evaluated according to the NCI-CTCae (version 4). RESULTS: From January 2013 to December 2014, 128 patients met the study criteria. The median age was 68.6 years [31.8; 88.6]. Most patients (84.4%) received 30 Gy in 10 fractions. The median overall time of treatment was 13 days [3-33]. Forty patients (31.3%) suffered from grade ≥ 2 of "esophagitis" (35 grade 2 (27.4%) and 5 grade 3 (3.9%)). Eight patients (6.3%) suffered from grade ≥ 2 of "nausea and/or vomiting" (6 grade 2 (4.7%), 1 grade 3 (0.8%), and 1 grade 4 (0.8%)). CONCLUSION: The high incidence of moderate to severe digestive toxicities after palliative 3D-CRT for cervico-thoracic spinal metastases led to consider static or dynamic intensity-modulated radiation therapy (IMRT) to reduce the dose to organ at risk (the esophagus and stomach). Dosimetric studies and implementation in the clinic should be the next steps.

Totally implantable venous access ports: a prospective long-term study of early and late complications in adult patients with cancer.

PURPOSE: Totally implantable venous access ports (TIVAP) have been widely used for many years in the management of patients suffering from cancer. The implantation and long-term use of TIVAPs are associated with mechanical, thrombotic, and infectious complications. This is the first exhaustive prospective study of all complications occurring in a whole population on long-term follow-up and therefore allows an objective assessment to be made of the safety of TIVAPs. METHODS: We carried out a prospective single-center observational study. All adult patients with cancer who had a TIVAP implanted between January 1 and December 31, 2006 were registered. Early and late complications were recorded until the removal of the device, the patient's death, or until December 31, 2013. Exhaustive data concerning patients and TIVAP was recorded at time of implantation. RESULTS: Four hundred and ninety-three TIVAPs were implanted in 483 adult cancer patients and were followed during a period from 1 to 94 months (median = 18 months) representing a global quantity of 367,359 catheter-days. Eighty-seven complications were recorded (0.237/1000 catheter-days), including 37 infections (0.101/1000 catheter-days), 17 thrombotic events (0.046/1000 catheter-days), and 9 extravasations. Out of the 87 events, 62 (71.3%) occurred during the first year after implantation. Events were therefore extremely rare after 1 year. Thromboembolic and infectious complications were rare and no risk factors for these were found. CONCLUSIONS: This study demonstrates excellent tolerability, with only occasional complications. Most of these occurred during the year following implantation. A TIVAP may also be left in place for an extremely long time.

Real-world dostarlimab use in advanced/recurrent endometrial cancer in France.

INTRODUCTION: In October 2020, the French Health Authority granted early access outside of the clinical trial setting for dostarlimab, a programmed death-1 inhibitor. Dostarlimab was approved by the European Medicines Agency (in April 2021) as monotherapy for patients with post-platinum mismatch repair deficient/microsatellite instability-high advanced/recurrent endometrial cancer, based on the results of the GARNET trial (NCT02715284). METHODS: This was a real-world descriptive analysis of patients granted cohort temporary authorization of use to receive dostarlimab between November 2020 and June 2021. Physicians could complete follow-up forms at each treatment cycle to provide clinical information, safety, and efficacy data. Safety and disease progression data were also captured through pharmacovigilance reports. RESULTS: Of 95 temporary authorization of use requests made by 80 oncologists in 59 French hospitals, 87 patients were eligible, and 80 received≥1 dose of dostarlimab. Based on treatment response assessments received (n=43), the mean (standard deviation) time from treatment initiation to response evaluation was 11 (6) weeks. The disease control rate (complete plus partial responses plus stable disease rates) was 56% (n=24/43), and the overall response rate was 35% (n=15/43); both consistent with those reported in the GARNET trial. No new safety signals were reported. DISCUSSION: The enrolment of 80 patients in an 8-month period highlights the need for access to novel treatment regimens in France for these patients post-platinum. Prospective randomized studies are ongoing to assess the efficacy and safety of dostarlimab and other checkpoint inhibitors as first-line treatment in patients with endometrial cancer.

Low performance of prognostic tools for predicting death before dialysis in older patients with advanced CKD.

INTRODUCTION: Chronic kidney disease (CKD) is a disease which is spreading worldwide, especially among older patients. Several prognostic scores have been developed to predict death in older CKD patients, but they have not been validated. We aimed to evaluate the existing risk scores for predicting death before dialysis start, identified via an in-depth review, in a cohort of elderly patients with advanced CKD. METHODS: We performed a review to identify scores predicting death, developed in and applicable to CKD patients. Each score was evaluated with an absolute risk calculation from the patients' baseline characteristics. We used a French prospective multicentre cohort of elderly patients (> 75 years) with advanced CKD [estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2], recruited from nephrological centres, with a 5-year follow-up. The outcome considered was death before initiating dialysis. Discrimination [area under curve (AUC)], calibration and Brier score were calculated for each score at its time frame. RESULTS: Our review found 6 equations predicting death before dialysis in CKD patients. Four of these (GOLDFARB, BANSAL, GRAMS 2 and 4 years) were evaluated. The validation cohort (Parcours de Soins des Personnes Âgées Parcours de Soins des Personnes Âgées, PSPA) included 573 patients, with a median age of 82 years and a median eGFR of 13 mL/min/1.73 m2. At the end of follow-up, 287 (50%) patients had started dialysis and 238 (41%) patients had died before dialysis. The four equations evaluated showed average discrimination (AUC 0.61-0.70) and, concerning calibration, a global overestimation of the risk of death. DISCUSSION: The available scores predicting death before dialysis showed low performance among older patients with advanced CKD in a French multicentre cohort, indicating the need to upgrade them or develop new scores for this population.

Incidental findings in UK healthy volunteers screened for a COVID-19 vaccine trial.

The safety of novel therapeutics and vaccines are typically assessed in early phase clinical trials involving "healthy volunteers." Abnormalities in such individuals can be difficult to interpret and may indicate previously unrecognized medical conditions. The frequency of incidental findings (IFs) in healthy volunteers who attend for clinical trial screening is unclear. To assess this, we retrospectively analyzed data for 1838 "healthy volunteers" screened for enrolment in a UK multicenter, phase I/II severe acute respiratory syndrome-coronavirus 2 (SARS-COV-2) vaccine trial. Participants were predominantly White (89.7%, 1640/1828) with a median age of 34 years (interquartile range [IQR] = 27-44). There were 27.7% of participants (510/1838) who had at least one IF detected. The likelihood of identifying evidence of a potential, new blood-borne virus infection was low (1 in 238 participants) compared with identification of an elevated alanine transaminase (ALT; 1 in 17 participants). A large proportion of participants described social habits that could impact negatively on their health; 21% consumed alcohol in excess, 10% were current smokers, 11% described recreational drug use, and only 48% had body weight in the ideal range. Our data demonstrate that screening prior to enrollment in early phase clinical trials identifies a range of IFs, which should inform discussion during the consent process. Greater clarity is needed to ensure an appropriate balance is struck between early identification of medical problems and avoidance of exclusion of volunteers due to spurious or physiological abnormalities. Debate should inform the role of the trial physician in highlighting and advising about unhealthy social habits.

Cross-sectional Survey of Medical student Attitudes to Research and Training pathways (SMART) in the UK: study protocol.

BACKGROUND: An understanding and appreciation of scientific research is a key quality of the modern clinician. Yet the Medical Schools Council has previously reported a reduction in the number of clinicians performing research. To explore the reasons for this difficulty, this multicentre, cross-sectional study aims to determine the medical student involvement and perceptions of research and research-orientated careers. It will additionally identify perceived barriers and incentives to participating in research as a student. METHODS AND ANALYSIS: This cross-sectional study of medical students at UK medical schools recognised by the General Medical Council will be administered using an online questionnaire. This will be disseminated nationally over a 2-month period through collaborative university medical school and student networks. The primary outcome is to determine the extent to which medical students are currently involved in research. Secondary outcomes include identifying the personal and demographic factors involved in incentivising and deterring medical students from becoming involved in research during medical school. This will be achieved using a selection of Likert scale, multiple-choice and free text questions. Ordinal logistic regression analysis will be performed to understand the association between specific factors and student involvement in research. This study will also characterise the proportion of medical students who are currently interested in conducting research in the future. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Medical Sciences Interdivisional Research Ethics Committee, Oxford, England. The results will be disseminated via publication in a peer-reviewed medical journal and may be presented at local, regional, national and international conferences by medical student collaborators.

Low performance of prognostic tools for predicting dialysis in elderly people with advanced CKD.

INTRODUCTION: Clinical decision-making about care plans can be difficult for very elderly people with advanced chronic kidney disease (CKD). Current guidelines propose the use of prognostic tools predicting end stage renal disease (ESRD) to assist in a patient-centered shared decision-making approach. Our objective was to evaluate the existing risk model scores predicting ESRD, from data collected for a French prospective multicenter cohort of mainly octogenarians with advanced CKD. METHODS: We performed a rapid review to identify the risk model scores predicting ESRD developed from CKD patient cohorts and evaluated them with data from a prospective multicenter French cohort of elderly (> 75 years) patients with advanced CKD (estimated glomerular filtration rate [eGFR] < 20 mL/min/1.75m2), followed up for 5 years. We evaluated these scores (in absolute risk) for discrimination, calibration and the Brier score. For scores using the same time frame, we made a joint calibration curve and compared areas under the curve (AUCs). RESULTS: The PSPA cohort included 573 patients; their mean age was 83 years and their median eGFR was 13 mL/min/1.73 m2. At the end of follow-up, 414 had died and 287 had started renal replacement therapy (RRT). Our rapid review found 12 scores that predicted renal replacement therapy. Five were evaluated: the TANGRI 4-variable, DRAWZ, MARKS, GRAMS, and LANDRAY scores. No score performed well in the PSPA cohort: AUCs ranged from 0.57 to 0.65, and Briers scores from 0.18 to 0.25. CONCLUSIONS: The low predictiveness for ESRD of the scores tested in a cohort of octogenarian patients with advanced CKD underlines the need to develop new tools for this population.

The changing sex ratios at birth during the civil war in Tajikistan: 1992-1997.

Sex ratios at birth are known to change during wars or shortly after. This study investigated changes in sex ratios during the civil war that occurred in Tajikistan after the dismantling of the Soviet Union. This civil war was particularly bloody and long lasting, and had many demographic consequences. According to vital registration data, some 27,000 persons died in excess of previous trends during the civil war period (1992-1997), and total mortality was sometimes estimated to be three times higher by independent observers. Birth rates dropped markedly during the war, and sex ratios at birth increased significantly from 104.6 before the war to 106.9 during the war, to return to baseline values afterwards. The change in sex ratio is investigated according to demographic evidence (migration, delayed marriage, spouse separation), substantiated with qualitative evidence (difficulties with food supply), and compared with patterns found in Europe during World War II, as well as with recent wars in the Middle East.

Infection and mortality of healthcare workers worldwide from COVID-19: a systematic review.

OBJECTIVES: To estimate COVID-19 infections and deaths in healthcare workers (HCWs) from a global perspective during the early phases of the pandemic. DESIGN: Systematic review. METHODS: Two parallel searches of academic bibliographic databases and grey literature were undertaken until 8 May 2020. Governments were also contacted for further information where possible. There were no restrictions on language, information sources used, publication status and types of sources of evidence. The AACODS checklist or the National Institutes of Health study quality assessment tools were used to appraise each source of evidence. OUTCOME MEASURES: Publication characteristics, country-specific data points, COVID-19-specific data, demographics of affected HCWs and public health measures employed. RESULTS: A total of 152 888 infections and 1413 deaths were reported. Infections were mainly in women (71.6%, n=14 058) and nurses (38.6%, n=10 706), but deaths were mainly in men (70.8%, n=550) and doctors (51.4%, n=525). Limited data suggested that general practitioners and mental health nurses were the highest risk specialities for deaths. There were 37.2 deaths reported per 100 infections for HCWs aged over 70 years. Europe had the highest absolute numbers of reported infections (119 628) and deaths (712), but the Eastern Mediterranean region had the highest number of reported deaths per 100 infections (5.7). CONCLUSIONS: COVID-19 infections and deaths among HCWs follow that of the general population around the world. The reasons for gender and specialty differences require further exploration, as do the low rates reported in Africa and India. Although physicians working in certain specialities may be considered high risk due to exposure to oronasal secretions, the risk to other specialities must not be underestimated. Elderly HCWs may require assigning to less risky settings such as telemedicine or administrative positions. Our pragmatic approach provides general trends, and highlights the need for universal guidelines for testing and reporting of infections in HCWs.

Results of PONDx, a prospective multicenter study of the Oncotype DX® breast cancer assay: Real-life utilization and decision impact in French clinical practice.

Adjuvant chemotherapy shows clear benefits in HER2-positive and triple-negative breast cancer (BC). Its benefits are less universal in BCs expressing hormone receptors. The 21-gene Oncotype DX® Breast Recurrence Score test was designed for HR+, HER2- early-stage BC before decision on adjuvant chemotherapy. Its validity and utility was demonstrated prospectively across multiple studies. The observational study PONDx characterized the use of Oncotype DX® Breast in routine practice in France and evaluated its decision impact. Of 882 ER-positive BC patients (67% postmenopausal), most (79%) had N0/Nmic node involvement, grade 2 tumors (68%), tumor size 1-5 cm (88%), and ductal histology (78%). BCs with histopathologically elevated recurrence risk included grade 3: 18%; N1: 21%; Ki67 > 20%: 31%. Recurrence Score results by prognostic category were: <18: 54%, 18-30: 36%; >30: 10%. Compared to recommendations before individual availability of the score, results prompted net absolute reductions in chemotherapy recommendations of 36% (total population), and 29% (grade 3 and/or Ki67 > 20% histologies). Decisions reflected prognostic implications: in the Recurrence Score <18 category, 95% of patients received recommendations of hormonal therapy only, in the >30 category, 97.5% were recommended additional chemotherapy; 95% followed the final recommendations of their physicians. The Recurrence Score provides independent predictive and prognostic information in ER + N0/N1 early BC, including high-risk subgroups. PONDx further characterizes the population where the test is beneficial in real-life use and fits current clinical needs. Oncotype DX® Breast enables relevant net reductions in chemotherapy use, sparing patients from serious toxicities. Its therapeutic implications are highly accepted by physicians and patients.

Use of Metabolic Parameters as Prognostic Factors During Concomitant Chemoradiotherapy for Locally Advanced Cervical Cancer.

OBJECTIVES: To investigate the use of metabolic parameters as early prognostic factors during concomitant chemoradiotherapy for locally advanced cervix carcinoma (LACC). MATERIALS AND METHODS: Between February 2008 and January 2012, 34 consecutive patients treated for LACC (International Federation of Gynecology and Obstetrics Staging System stage IB2-IVA) were included in a retrospective study. Treatment was standard of care: total dose of 45 Gy in 1.8 Gy per fraction with concurrent cisplatin followed by brachytherapy. 18F-FDG PET-CT modalities were performed before treatment and per-treatment (at 40 Gy). The analyzed parameters were: maximum standardized uptake value (SUVmax), SUVmax variations of the primary tumor between the 2 investigations (DSUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Survival was assessed according to early metabolic changes during chemoradiotherapy. RESULTS: Median follow-up was 16 months (range, 5.3 to 32.4 mo). Median SUVmax before treatment was 13.15 (5.9 to 31) and was 5.05 (0 to 12) per-treatment. Median DSUVmax was 63.97% (0% to 100%). Median MTV before treatment was 44.16 mL (3.392 to 252.768 mL) and was 5.44 mL (0 to 69.88 mL) per-treatment. Median TLG before treatment was 249.82 mL (13.40 to 1931.10 mL) and was 20.14 mL (0 to 349.99 mL) per-treatment. At 40 Gy, SUVmax≥6, DSUVmax≤40%, MTV≥5.6 mL, and TLG≥21.6 mL were significantly associated with overall survival and progression-free survival reduction. MTV predicted progression with a sensitivity of 80% and a specificity of 87.5% and TLG with a sensitivity of 80% and a specificity of 83.3%. CONCLUSIONS: PET-CT imaging could be useful as an early prognostic factor during treatment for LACC. MTV and TLG seem to provide better prognostic information than SUVmax and DSUVmax.