A scoping review on the factors associated with the lost to follow-up (LTFU) amongst patients with chronic disease in ambulatory care of high-income countries (HIC).

BACKGROUND: Despite the importance of long term follow-up care for patients with chronic disease, many patients fail to adhere to their follow-ups, which increase their risk of further health complications. Therefore, the purpose of this scoping review was to find out the factors associated with lost to follow-up (LTFU) amongst patients with chronic disease in the ambulatory care setting of high-income countries (HICs) to gain insights for better quality of care. Understanding the definition of LTFU is imperative in informing patients, health professionals and researchers for clinical and research purposes. This review also provided an overview of the terms and definitions used to describe LTFU. METHODS: The following databases: CINAHL, EMBASE, Medline, PsycINFO and Web of Science were searched for studies investigating the factors associated to LTFU from the date of inception until 07 January 2022. RESULTS: Five thousand one hundred and seven records were obtained across the databases and 3,416 articles were screened after removing the duplicates. 25 articles met the inclusion criteria, of which 17 were cohort studies, five were cross-sectional studies and three were case-control studies. A total of 32 factors were found to be associated with LTFU and they were categorised into patient factors, clinical factors and healthcare provider factors. CONCLUSION: Overall, the factors associated with LTFU were generally inconsistent across studies. However, some factors such as financial factors (i.e., no insurance coverage) and low accessibility of care were consistently associated with LTFU for both mental and physical chronic conditions. The operational definitions of LTFU also varied greatly across studies. Given the mixed findings, future research using qualitative aproaches would be pivotal in understanding LTFU for specific chronic diseases and the development of targeted interventions. Additionally, there is a need to standardise the operational definition of LTFU for research as well as clinical practice purposes.

Predicting non-sentinel lymph node metastasis in Australian breast cancer patients: are the nomograms still useful in the post-Z0011 era?

BACKGROUND: Axillary lymph node dissection (ALND) can be avoided in breast cancer patients with low-volume disease in the sentinel lymph nodes (SLNs) according to Z0011 trial. We believe that nomograms developed for predicting non-sentinel lymph node (NSLN) metastases can guide the axillary treatment in patients who do not fully match the criteria of Z0011 study. We identified risk factors and evaluated the performance of three nomograms to predict NSLN status in patients with positive SLNs. METHODS: Data from 526 breast cancer patients with positive SLNs who underwent ALND at two Australian hospitals from 2002 to 2015 were studied. Univariate and multivariate associations for NSLN metastasis were analysed. Predictive models evaluated were MD Anderson Cancer Centre (MDA), Helsinki University Hospital and Memorial Sloan Kettering Cancer Centre. RESULTS: Thirty-nine per cent of patients demonstrated NSLN metastasis. The multivariate analysis identified extranodal extension (OR 3.2, 95% CI 2.07-4.80), tumour size >2 cm (OR 2.5, 95% CI 1.66-3.89), macrometastasis (OR 1.9, 95% CI 1.09-3.47), positive SLN ratio >0.5 (OR 1.7, 95% CI 1.16-2.60) and lymphovascular invasion (OR 1.6, 95% CI 1.09-2.44) as independent predictors for NSLN metastasis. MDA nomogram showed the best discrimination (area under the curve of 0.74) and a 9% false negative rate for predicted probability of NSLN metastasis ≤10%. CONCLUSION: Our results suggest that presence of extranodal extension and tumour size >2 cm may influence the need of further axillary treatment. Conversely, ALND can be safety spared in low risk patients identified by MDA nomogram.

Pulsed electromagnetic field stimulation for acute tibial shaft fractures: a multicenter, double-blind, randomized trial.

BACKGROUND: Tibial shaft fractures are sometimes complicated by delayed union and nonunion, necessitating further surgical interventions. Pulsed electromagnetic field stimulation is an effective treatment for delayed unions and nonunions, but its efficacy in preventing healing complications in patients with acute fractures is largely untested. The purpose of this pragmatic trial was to determine whether adjuvant pulsed electromagnetic field therapy for acute tibial shaft fractures reduces the rate of surgical revision because of delayed union or nonunion. METHODS: In a double-blind randomized trial involving six metropolitan trauma hospitals, 259 participants with acute tibial shaft fractures (AO/OTA type 42) were randomized by means of external allocation to externally identical active and inactive pulsed electromagnetic field devices. Participants were instructed to wear the device for ten hours daily for twelve weeks. Management was otherwise unaltered. The primary outcome was the proportion of participants requiring a secondary surgical intervention because of delayed union or nonunion within twelve months after the injury. Secondary outcomes included surgical intervention for any reason, radiographic union at six months, and the Short Form-36 Physical Component Summary and Lower Extremity Functional Scales at twelve months. Main analyses were by intention to treat. RESULTS: Two hundred and eighteen participants (84%) completed the twelve-month follow-up. One hundred and six patients were allocated to the active device group, and 112 were allocated to the placebo group. Compliance was moderate, with 6.2 hours of average daily use. Overall, sixteen patients in the active group and fifteen in the inactive group experienced a primary outcome event (risk ratio, 1.02; 95% confidence interval, 0.95 to 1.14; p = 0.72). According to per-protocol analysis, there were six primary events (12.2%) in the active, compliant group and twenty-six primary events (15.1%) in the combined placebo and active, noncompliant group (risk ratio, 0.97; 95% confidence interval, 0.86 to 1.10; p = 0.61). No between-group differences were found with regard to surgical intervention for any reason, radiographic union, or functional measures. CONCLUSIONS: Adjuvant pulsed electromagnetic field stimulation does not prevent secondary surgical interventions for delayed union or nonunion and does not improve radiographic union or patient-reported functional outcomes in patients with acute tibial shaft fractures.

Efficacy of camptothecin and polymer-conjugated camptothecin in tumor spheroids and solid tumors.

Camptothecin (CPT) is an anti-cancer drug with low solubility in aqueous solutions, which limits its efficacy during chemotherapy. To bypass this problem, CPT was conjugated to poly(ethylene glycol) (PEG) to make CPT more hydrophilic: CM-PEG-CPT (carboxylmethylpoly(ethlyene glycol)-camptothecin), CM-PEG-GLY-CPT (carboxylmethyl-poly(ethlyene glycol)-glycine-camptothecin) and CM-PEG-SAR-CPT (carboxylmethyl-poly(ethlyene glycol)-sarcosine camptothecin) were synthesized. These conjugates differed in the amino-acid linker, which altered the hydrolysis rate of CPT from CPT-PEG. We tested the hypothesis that CPT conjugates were more effective than unconjugated CPT in effectiveness upon direct delivery to solid tumors using two systems: in vitro tumor spheroids suspended in collagen gels and in vivo solid tumors in rats. CPT was effective in spheroids, but not in flank tumors. However, when CPT was conjugated, there was improvement in the treatment of spheroids and, to a lesser extent, tumors in rats. There was no difference in therapeutic effects among the various conjugates. We conclude that conjugation of CPT to PEG enhances CPT solubility and improves effectiveness of delivery to tumors.