Clinical outcome and prognostic factors for Asian patients in Phase I clinical trials.

BACKGROUND: Patient selection is key in Phase I studies, and prognosis can be difficult to estimate in heavily pre-treated patients. Previous prognostic models like the Royal Marsden Hospital (RMH) score or using the neutrophil-lymphocyte ratio (NLR) have not been validated in current novel therapies nor in the Asian Phase I population. METHODS: We conducted a retrospective review of 414 patients with solid tumours participating in Phase I studies at our centre between October 2013 and December 2020. RESULTS: The RMH model showed poorer prognosis with increasing scores [RMH score 1, HR 1.28 (95% CI: 0.96-1.70); RMH score 2, HR 2.27 (95% CI: 1.62-3.17); RMH score 3, HR 4.14 (95% CI: 2.62-6.53)]. NLR did not improve the AUC of the model. Poorer ECOG status (ECOG 1 vs. 0: HR = 1.59 (95% CI = 1.24-2.04), P < 0.001) and primary tumour site (GI vs. breast cancer: HR = 3.06, 95% CI = 2.16-4.35, P < 0.001) were prognostic. CONCLUSIONS: We developed a NCIS prognostic score with excellent prognostic ability for both short-term and longer-term survival (iAUC: 0.71 [95% CI 0.65-0.76]), and validated the RMH model in the largest Asian study to date.

Clinical Presentation of Immune-Related Endocrine Adverse Events during Immune Checkpoint Inhibitor Treatment.

The exact clinical course and factors associated with persistent endocrine immune-related adverse events (irAEs) are not well-established. Elucidation of these information will aid irAEs screening and follow-up planning for patients on immunotherapy. We analysed the clinical course of endocrine irAEs including thyroid and pituitary dysfunction and insulin-dependent diabetes mellitus (IDDM), identified factors associated with persistent thyroid dysfunction, and determined the association between endocrine irAEs and survival parameters. This retrospective observational study enrolled patients with metastatic cancer who underwent anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 treatment and developed endocrine irAE at the National University Cancer Institute, Singapore, between June 2015 and December 2020. Sixty-six patients with endocrine irAE were evaluated, with a median follow-up time of 15.7 months. The median time to onset of thyroid dysfunction, pituitary dysfunction, and IDDM was 1.8 months (range: 0.3-15.8 months), 6.8 months (range: 1.5-27.3 months), and 7.8 months (range: 1.4-9.1 months), respectively. Positive thyroperoxidase antibodies (TPOAb) and/ or thyroglobulin antibodies (TgAb) status at the time of thyroid dysfunction was associated with persistent thyroid dysfunction (OR 11.6, 95% CI 1.3-570.8, p = 0.02; OR 8.8, 95% CI 1.3-106.9, p = 0.01, respectively). All patients with pituitary irAE had central hypocortisolism. All patients with IDDM had grade 4 irAE. Patients with endocrine irAE had longer median survival times. Endocrine irAEs were associated with non-progressive disease. The screening and follow-up approach for endocrine irAEs should be tailored according to each endocrinopathy's clinical course. Early screening is imperative given its wide median time to onset.

Evaluating the Initiation of Sodium/Glucose Cotransporter 2 Inhibitors within 2 Weeks of an Acute Hospital Admission: A Systematic Review and Meta-Analysis of Nine Clinical Trials.

OBJECTIVE: Recent studies have increasingly shown the benefits of using sodium/glucose cotransporter 2 inhibitor (SGLT2i). However, there are concerns regarding the initiation of SGLT2i during acute hospital admissions due to the potential increased risk of complications. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of SGLT2i initiation within 2 weeks of an acute hospital admission. METHODS: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched for articles published from inception up to 27 March 2021 that evaluated the efficacy and/or safety of SGLT2i initiation within 2 weeks of an acute hospital admission. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. The protocol was registered with PROSPERO (CRD42021245492). RESULTS: Nine clinical trials were included with a combined cohort of 1,758 patients. Patients receiving SGLT2i had a mean increase in 24-h urine volume of +487.55 mL (95% CI 126.86-848.25; p = 0.008) compared to those not started on SGLT2i. Patients with heart failure treated with SGLT2i had a 27% relative risk reduction in rehospitalizations for heart failure, compared to controls (risk ratio 0.73; p = 0.005). There were no differences in other efficacy and safety outcomes examined. CONCLUSION: There was no increased harm with initiation of SGLT2i within 2 weeks of an acute hospital admission, and its use reduced the relative risk of rehospitalizations for heart failure in patients with heart failure. It was also associated with increased urine output. However, current evidence pool is limited, especially in specific population subtypes.

Polypharmacy in Palliative Care: Two Deprescribing Tools Compared with a Clinical Review.

Background: Lack of guidance is highlighted as a barrier to deprescribing in palliative care. Two deprescribing tools exist, but with inclusion and exclusion criteria that limit utility. The tools have not previously been compared directly or used in an unselected palliative population. Objective: To compare the OncPal and STOPPFrail deprescribing tools to an expert review in an unselected palliative population. Secondary aims included a description of medicines incorrectly classified by both tools. Design: Fifty palliative inpatients were retrospectively reviewed by an expert panel, and both tools were independently applied to the patients. Positive and negative predictive values (PPV and NPV) were calculated per patient using the expert review as the gold standard. Results: The median number of medicines per patient was 11, with 19% of medicines deemed inappropriate. The PPV and NPV were 75% (interquartile range 50-100) and 91% (interquartile range 84-100), respectively, for OncPal, and 100% (interquartile range 50-100) and 90% (interquartile range 78-100), respectively, for STOPPFrail. There was no statistically significant difference between the tools (PPV p = 0.42 and NPV p = 0.07). The main medicines incorrectly ceased by OncPal were antianginals for stable coronary artery disease, and haloperidol for nausea by STOPPFrail. Conclusion: There was no significant difference between the tools. Both tools performed well in an unselected population. Some minor amendments could improve the PPV of both tools.

Introduction of the Pill Pruner to acute medical care: a simple medication guide to control polypharmacy.

AIM: To assess the effect of a simple medication guide (the Pill Pruner) on the number of regular medications taken by older patients following medical admission. METHODS: In July 2009, following introduction of the Pill Pruner, we audited 500 consecutive older patients, recording the number of regular medications being taken on admission and discharge. Safety data included 90-day mortality and readmission rates. Medication numbers were compared to a similar audit undertaken in September 2008 and to a repeat audit in December 2009. RESULTS: The mean number of medications on admission (± SD) was 6.3 ± 3 versus 6.5 ± 3 at discharge (P = 0.13). Number of discharge medications was decreased compared to September 2008 (7.7 ± 4; P = 0.001) but similar to that for the repeat audit. No change in mortality or readmission rate was seen. CONCLUSION: Use of the Pill Pruner reduced the number of regular medications prescribed to older patients without affecting safety.

Evaluating the outcomes of elderly patients receiving Canterbury District Health Board funded care at the end of life.

AIMS: To identify the frequency of readmission into the hospital and interventions received by patients who are known to be terminally ill under the SupportCare End-of-life Fund (SC-EOL), a 90 days fund made available to patients who are terminally ill and requires hospital level care in Canterbury. The secondary objective is to determine the survival time after allocation to the SC-EOL funding. METHOD: List of patients aged 65 years and older approved on the SC-EOL fund between March to May 2010 is obtained from the coordination centre which handles the services of all SC-EOL funded patients. Using hospital electronic database and medical records, data on demographics, sources of referral, survival, readmissions and associated interventions were recorded. RESULTS: 60 patients were identified. The average age was 80.6 years. 75% had a diagnosis of cancer as their terminal illness. Three of the 60 patients were readmitted to hospital. Two of these were deemed to have been potentially avoidable. These patients underwent routine blood tests and X-rays and received intravenous fluid. The median survival time was 19 days. CONCLUSION: The subgroup of patients who has terminal illness under the SC-EOL fund has a low rate of readmission to hospital and inappropriate interventions.

Clinical presentation and endoscopic features of primary gastric Burkitt lymphoma in childhood, presenting as a protein-losing enteropathy: a case report.

INTRODUCTION: Burkitt lymphoma and B cell lymphomas in childhood may arise in many atypical locations, which on rare occasions can include gastric mucosa. A case of primary gastric Burkitt lymphoma is described in a child presenting as a protein-losing enteropathy, including the direct monitoring of the disease response by sequential endoscopic biopsy and molecular analysis. CASE PRESENTATION: We report a 9-year-old boy who presented with gross oedema, ascites and respiratory distress caused by a protein-losing enteropathy. Initial imaging investigations were non-diagnostic but gastroduodenal endoscopy revealed massive involvement of the gastric mucosa with a primary Burkitt lymphoma. His subsequent clinical progress and disease response were monitored directly by endoscopy and he remains in clinical remission 4 years after initial diagnosis. CONCLUSIONS: This is the first case report of primary Burkitt lymphoma presenting as a protein-losing enteropathy. The clinical course and progress of the patient were monitored by sequential endoscopic biopsy, histology and molecular analysis by fluorescence in situ hybridisation.

Maxillary molar intrusion with fixed appliances and mini-implant anchorage studied in three dimensions.

The intrusion of an overerupted maxillary molar using traditional orthodontic treatment is a real challenge. The aim of this study was to investigate the envelope of intrusive movements of a maxillary molar in cases using mini-implants as anchorage with partial or full-mouth fixed edgewise appliances. The cusp tips of the pretreatment and postintrusion dental casts were recorded by a three-dimensional (3D) digitizer. The 3D data of the serial dental casts were analyzed to distinguish the direction and magnitude of individual tooth movement. The mean intrusive movement of the maxillary first molars was three to four mm, with a maximum of over eight mm. For the adjacent maxillary second molars and second premolars, the amount of intrusion was two mm and 1-2 mm, respectively. This study demonstrated that significant true intrusion of maxillary molars could be obtained in a well-controlled manner by using fixed appliances with titanium mini-implants as bony anchorage.