Utilising systematic reviews to assess potential overtreatment and claim for better evidence-based research: an analysis of anticancer drugs versus supportive care in advanced esophageal cancer.

BACKGROUND: Highlighting the identified gaps in evidence-based research concerning advanced esophageal cancer (EC) treatment and care, this review evaluates the efficacy and safety of anticancer drugs compared to supportive care for advanced EC patients, aiming to assess the appropriateness of usual treatments and identify the gaps that need to be filled with primary research. METHODS: We searched (May 2022) MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Epistemonikos, and trial registries (ClinicalTrials.gov and PROSPERO) for randomised controlled trials (RCTs) comparing anticancer drugs (chemotherapy, immunotherapy, or biological/targeted therapy) with supportive care in advanced EC. The results were summarised using GRADE summary of finding tables. RESULTS: We included 15 RCTs. Most studies did not have a special focus on EC, did not detail the treatment lines in all patients, and did not evaluate all outcomes. Anticancer drugs may result in a slight increase in overall survival (OS) (HR 0.78; 95% CI 0.71, 0.86; MD 0.83 months) and better progression-free survival (PFS) (HR 0.56 95% CI 0.49, 0.64, MD 0.68 months), but also may increase toxicity (RR 1.37; 95% CI 1.13, 1.65), without a significant improvement in quality of life. The certainty of evidence was low or very low due to indirectness of results and lack of specific focus on EC in some studies. CONCLUSION: RCTs on advanced EC lack specificity, detailed treatment line information, and evaluation of all relevant outcomes. Moreover, when they find any benefit, this is negligible. Therefore, the certainty to justify anticancer drug treatments instead of supportive care in advanced EC is low or very low, and this information should be actively shared with affected patients. More and better RCTs should be conducted to assess whether any old or new proposed treatment for advanced EC patients provides a better balance of benefits and harms than the supportive care. SYSTEMATIC REVIEW REGISTRATION: The study protocol was registered in OSF ( https://doi.org/10.17605/OSF.IO/7CHX6 ) on 2022-03-29.

[Controversy and boundary in the diagnose and treatment of thyroid cancer].

In recent years, the incidence of thyroid cancer has rapidly increased, whereas the mortality rate has not risen correspondingly. Therefore, scholars at home and abroad have proposed the view of overdiagnosis in thyroid cancer, sparking intense debates about the phenomenon of overdiagnosis and overtreatment. A historical review and discussion of the primary reasons for the increase in thyroid cancer incidence and the improvement in treatment outcomes are beneficial. It helps clarify that the real increase in thyroid cancer is primarily due to the higher incidence rate, rather than overdiagnosis. Additionally, it allows us to reevaluate which factors guarantee favorable efficacy in thyroid cancer.

Diabetes mellitus in older persons with neurocognitive disorder: overtreatment prevalence and associated structural brain MRI findings.

BACKGROUND: Tight diabetes control is often applied in older persons with neurocognitive disorder resulting in increased hypoglycemic episodes but little is known about the pattern of brain injury in these overtreated patients. This study aims to: (a) quantify the prevalence of diabetes overtreatment in cognitively impaired older adults in a clinical population followed in an academic memory clinic (b) identify risk factors contributing to overtreatment; and (c) explore the association between diabetes overtreatment and specific brain region volume changes. METHODS: Retrospective study of older patients with type 2 diabetes and cognitive impairment who were diagnosed in a memory clinic from 2013 to 2020. Patients were classified into vulnerable and dependent according to their health profile. Overtreatment was defined when glycated hemoglobin was under 7% for vulnerable and 7.6% for dependent patients. Characteristics associated to overtreatment were examined in multivariable analysis. Grey matter volume in defined brain regions was measured from MRI using voxel-based morphometry and compared in patients over- vs. adequately treated. RESULTS: Among 161 patients included (median age 76.8 years, range 60.8-93.3 years, 32.9% women), 29.8% were considered as adequately treated, 54.0% as overtreated, and 16.2% as undertreated. In multivariable analyses, no association was observed between diabetes overtreatment and age or the severity of cognitive impairment. Among patients with neuroimaging data (N = 71), associations between overtreatment and grey matter loss were observed in several brain regions. Specifically, significant reductions in grey matter were found in the caudate (adj ß coeff: -0.217, 95%CI: [-0.416 to -0.018], p = .033), the precentral gyri (adj ßcoeff:-0.277, 95%CI: [-0.482 to -0.073], p = .009), the superior frontal gyri (adj ßcoeff: -0.244, 95%CI: [-0.458 to -0.030], p = .026), the calcarine cortex (adj ßcoeff:-0.193, 95%CI: [-0.386 to -0.001], p = .049), the superior occipital gyri (adj ßcoeff: -0.291, 95%CI: [-0.521 to -0.061], p = .014) and the inferior occipital gyri (adj ßcoeff: -0.236, 95%CI: [-0.456 to - 0.015], p = .036). CONCLUSION: A significant proportion of older patients with diabetes and neurocognitive disorder were subjected to excessively intensive treatment. The association identified with volume loss in several specific brain regions highlights the need to further investigate the potential cerebral damages associated with overtreatment and related hypoglycemia in larger sample.

Ductal carcinoma in situ of the breast: finding the balance between overtreatment and undertreatment.

Ductal carcinoma in situ (DCIS) accounts for 15-25% of all breast cancer diagnoses. Its prognosis is excellent overall, the main risk being the occurrence of local breast events, as most cases of DCIS do not progress to invasive cancer. Systematic screening has greatly increased the incidence of this non-obligate precursor of invasion, lending urgency to the need to identify DCIS that is prone to invasive progression and distinguish it from non-invasion-prone DCIS, as the latter can be overdiagnosed and therefore overtreated. Treatment strategies, including surgery, radiotherapy, and optional endocrine therapy, decrease the risk of local events, but have no effect on survival outcomes. Active surveillance is being evaluated as a possible new option for low-risk DCIS. Considerable efforts to decipher the biology of DCIS have led to a better understanding of the factors that determine its variable natural history. Given this variability, shared decision making regarding optimal, personalised treatment strategies is the most appropriate course of action. Well designed, risk-based de-escalation studies remain a major need in this field.

Clinical inertia in thyrotropin suppressive therapy for low-risk differentiated thyroid cancer: A real-world experience at an endocrine center in Bangkok.

The management of low-risk differentiated thyroid cancer (DTC) has evolved over time toward treatment de-escalation. However, overtreatment with supraphysiological dose of levothyroxine (LT4) continues to be observed despite current clinical guideline. This study aimed to assess the actual thyrotropin suppressive therapy for low-risk DTC patients at an endocrine center in Bangkok. This retrospective study included patients with low-risk DTC who were regularly follow-up for at least 18 months at Theptarin Hospital between 2016 and 2022. The serum thyroid stimulating hormone (TSH) levels were stratified as TSH < 0.1 mIU/L; TSH 0.1 to 0.5 mIU/L; TSH 0.5 to 2.0 mIU/L; and TSH > 2.0 mIU/L. The initial risk stratification (IRS) and dynamic risk stratification were determined at 12 months of follow-up after completing the initial treatment and at the last visit. The clinical factors associated with overtreatment with LT4 were analyzed. A total of 102 patients (83.3% female, age at diagnosis 41.8 ±â€…13.6 years, mean tumor size 1.6 ±â€…1.0 cm) were evaluated with a mean follow-up of 5.9 years. The IRS classified 92.2% of patients after the initial treatment and 93.1% of patients at the last follow-up visit into the excellent response category. The mean LT4 daily dosage at the last follow-up was 121.3 ±â€…44.8 µg/day. Serum TSH levels were in an appropriate target range according to IRS in only 8.8% (9/102) of the patients and then improved to 19.6% (20/102) at the last follow-up visit. Further analysis showed that treating physicians with ≥10 years of practice was associated with severe TSH suppression therapy (TSH < 0.1 mIU/L). Despite the current clinical guideline recommendations and scientific evidences, less than one-fifth of low-risk DTC patients achieved the appropriate serum TSH target. While the proportion of an optimum LT4 suppressive had improved during the study period, further efforts are needed to overcome this clinical inertia.

The overtreatment of papillary thyroid microcarcinoma in the community.

INTRODUCTION: Total thyroidectomy is the traditional primary approach for papillary thyroid cancer. However, recent evidence supports conservative management for low-risk tumors like papillary thyroid microcarcinomas (PTMCs). This study explores the adoption of these practices in our community, using a cancer database to analyze treatment strategies. METHODS: A retrospective review of a 1433-patient institutional database identified 258 â€‹PTMC cases. Outcomes, including 30-day mortality, reoperation rate, postoperative hypocalcemia, and recurrent laryngeal nerve (RLN) injury, were assessed. RESULTS: Of PTMC patients, 63.4% underwent total thyroidectomy, with higher rates of RLN injury (8.8% vs. 2.3%) and hypocalcemia (12.4% vs. 0.0%) compared to lobectomy. Non-endocrine surgeons had higher postoperative radioactive iodine administration rates (28.6% vs. 6.1%). Subgroup analysis revealed a shift in total thyroidectomy rates based on tumor size and surgery period. CONCLUSION: Our community favors total thyroidectomy for PTMC, despite associated complications. Enhanced awareness and adherence to PTMC best practice guidelines are warranted.

Avoiding Locoregional Overtreatment in Older Adults With Early-Stage Breast Cancer.

Advances in the treatment of older women with early-stage breast cancer, particularly opportunities for de-escalation of therapy, have afforded patients and providers opportunity to individualize care. As the majority of women ≥65 have estrogen receptor-positive, HER2-negative disease, locoregional therapy (surgery and/or radiation) may be tailored based on a patient's physiologic age to avoid either over- or undertreatment. To determine who would derive benefit from more or less intensive therapy, an accurate assessment of an older patient's physiologic age and incorporation of patient-specific values are paramount. While there now exist well-validated geriatric assessment tools whose use is encouraged by the American Society of Clinical Oncology when considering systemic therapy, these instruments have not been widely integrated into the locoregional breast cancer care model. This review aims to highlight the importance of assessing frailty and the concepts of and over- and undertreatment, in the context of trial data supporting opportunities for safe deescalation of locoregional therapy, when treating older women with early-stage breast cancer.

Magnetic resonance imaging targeted biopsy in biopsy-naïve patients and the risk of overtreatment in prostate cancer: a grading issue.

OBJECTIVE: To evaluate the impact of applying the 2014 and 2019 International Society of Urological Pathology (ISUP) recommendations on grade group distribution and concordance with radical prostatectomy (RP). MATERIALS AND METHODS: Overall, 655 biopsy-naïve patients diagnosed by magnetic resonance imaging (MRI) targeted and systematic biopsies for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database from 2016 and 2022. Clinically significant prostate cancer was detected in 249 patients, of whom 69 underwent RP. Wilcoxon signed rank and McNemar's tests were used to compare the ISUP grade group distribution and concordance with RP after applying the 2014 (i.e., highest grade) and 2019 (i.e., global grade) ISUP recommendations, respectively. RESULTS: Compared to the 2014 ISUP recommendations, the 2019 ISUP recommendations were associated with a significant decrease in ISUP Grade Group 4 (range of difference from -13% to -5%) and an increase in ISUP Grade Group 2 (range of difference from +6% to +11%) in MRI targeted biopsy only, MRI targeted with perilesional biopsies, and MRI targeted with systematic biopsies (all P < 0.01). In patients who underwent RP, a significant decrease in downgrading was observed with all biopsy strategies (range of difference from -19% to -12%; P ≤ 0.008), along with an increase in concordance with RP specimen (range of difference from +12% to +13%; P ≤ 0.02). The use of the 2019 ISUP recommendation was associated with RP specimen a lower treatment burden. CONCLUSIONS: The use of the 2019 ISUP recommendations mitigates the grade migration induced by MRI targeted biopsy and improves the concordance with the final RP specimen.

Open vs. minimally invasive sublay incisional hernia repair. Is there a risk of overtreatment? EVEREG registry analysis.

INTRODUCTION: Incisional hernia (IH) is a very common surgical procedure. Registries provide real world data. The objective is to analyze the open and minimally invasive (MIS) sublay technique (with or without associated components separation [CS]) in IH cases from the EVEREG registry and to evaluate the evolution over time of the techniques. METHODS: All patients in EVEREG from July 2012 to December 2021 were included. The characteristics of the patients, IH, surgical technique, complications and mortality in the first 30 days were collected. We analyzed Group 1 (open sublay vs MIS sublay, without CS), Group 2 (open sublay vs MIS sublay, with CS) and Group 3 where the evolution of open and MIS techniques was evaluated over time. RESULTS: 4867 IH were repaired using a sublay technique. Group 1: 3739 (77%) open surgery, mostly midline hernias combined (P = .016) and 55 (1%) MIS, mostly lateral hernias (LH) (P = .000). Group 2: 1049 (21.5%) open surgery and 24 (0.5%) MIS. A meaningful difference (P = .006) was observed in terms of transverse diameters (5.9 (SD 2.1) cm for the MIS technique and 10.11 (SD 4.8) for the open technique). The LH MIS associated more CS (P = .002). There was an increase in the use of the sublay technique over time (with or without CS). CONCLUSION: Increased use of the sublay technique (open and MIS) over time. For some type of hernia (LH) the MIS sublay technique with associated CS may have represented an overtreatment.

Does the Academy of Breastfeeding Medicine's Clinical Protocol #36 'The Mastitis Spectrum' promote overtreatment and risk worsened outcomes for breastfeeding families? Commentary.

BACKGROUND: In 2022 the Academy of Breastfeeding Medicine (ABM) published Clinical Protocol #36: The Mastitis Spectrum, which aims to update clinical approaches to management of benign lactation-related breast inflammation. The protocol has been timely because of the exponential increase in knowledge about the human milk microbiome over the past decade. This Commentary aims to continue respectful debate amongst clinicians and researchers within the Academy of Breastfeeding Medicine and more broadly, confident that we share a fundamental commitment to promote breastfeeding and support the well-being of lactating women, their infants and their families. ANALYSIS: Although Clinical Protocol #36 offers advances, it does not fulfil the principles of best practice implementation science for translation of evidence into clinical guidelines. Clinical Protocol #36 inaccurately represents studies; misrepresents theoretical models as proven aetiologies; does not consistently attribute sources; does not reliably apply the SORT taxonomy; and relies upon single case reports. As a result, various recommendations in Clinical Protocol #36 lack an evidence-base or credible underlying theoretical model. This includes recommendations to use 'lymphatic drainage' massage, therapeutic ultrasound, and oral lecithin. Similarly, based on a contestable theoretical model which is presented as fact, Clinical Protocol #36 makes the recommendation to either reduce frequency of milk removal or to maintain current frequency of milk removal during an episode of breast inflammation. Although Clinical Protocol #36 limits this advice to cases of 'hyperlactation', the diagnosis 'hyperlactation' itself is undefinable. As a result, this recommendation may put breastfeeding women who present with breast inflammation at risk of worsened inflammation and decreased breast milk production. CONCLUSION: Clinical Protocol #36 offers some advances in the management of breast inflammation. However, Clinical Protocol #36 also exposes clinicians to two international trends in healthcare which undermine health system sustainability: overdiagnosis, including by over-definition, which increases risk of overtreatment; and antibiotic over-use, which worsens the crisis of global antimicrobial resistance. Clinical Protocol #36 also recommends unnecessary or ineffective interventions which may be accessed by affluent patients within advanced economies but are difficult to access for the global majority. The Academy of Breastfeeding Medicine may benefit from a review of processes for development of Clinical Protocols.

Evidencing general acceptability of open-label placebo use for tackling overtreatment in primary care: a mixed methods study.

BACKGROUND: Overtreatment poses a challenge to healthcare systems due to harmful consequences of avoidable side-effects and costs. This study presents the first account for examining the feasibility of placebo use for reducing overtreatment in primary care, including whether public attitudes support the use of different placebo types in place of inappropriate prescriptions of antibiotics, antidepressants, or analgesics. METHODS: We used a multi-study, mixed-methods design, including patient and public (PPI) consultations, focus groups (Study 1) and two pre-registered online experiments (Studies 2 and 3). RESULTS: Study 1 (N = 16) explored everyday conceptions and practicalities of potential placebo use in the context of respiratory infections. Findings highlighted the importance of trusting doctor-patient relationships and safety-netting. Study 2 employed a randomised experiment with a representative UK sample (N = 980), investigating attitudes towards 5 different treatment options for respiratory infections: (1) blinded + pure placebo, (2) open-label + pure placebo, (3) open-label + impure placebo, (4) antibiotic treatment, and (5) no treatment. Study 2 also examined how attitudes varied based on wording and individual differences. Findings indicated general support (ηp2 = .149, large effect size) for replacing inappropriate antibiotics with open-label + impure placebos, although personal placebo acceptability was lower. Also, older people, individuals suffering from chronic illness or those showing higher levels of health anxiety appeared less amenable to placebo use. Study 3 (N = 1177) compared attitudes towards treatment options across three clinical scenarios: respiratory infection, depression and pain. Findings suggested significant differences in the acceptability of placebo options based on the clinical context. In the infection scenario, options for open-label + pure placebos, open-label + impure placebos and no treatment were rated significantly more acceptable (ηp2 = .116, medium effect size) compared to the depression and pain scenarios. Again, general support for placebos was higher than placebo acceptability for personal use. CONCLUSIONS: Findings from PPI and three studies indicate general support for combatting overprescribing in primary care through clinical placebo use. This is an indicator for wider UK public support for a novel, behavioural strategy to target a long-standing healthcare challenge. General acceptability appears to be highest for the use of open-label + impure placebos in the context of antibiotic overprescribing.

Reducing hypoglycemia from overtreatment of type 2 diabetes in older adults: The HypoPrevent study.

BACKGROUND: Hypoglycemia from overtreatment is a serious but underrecognized complication among older adults with type 2 diabetes. However, diabetes treatment is seldom deintensified. We assessed the effectiveness of a Clinical Decision Support (CDS) tool and shared decision-making (SDM) in decreasing the number of patients at risk for hypoglycemia and reducing the impact of non-severe hypoglycemic events. METHODS: HypoPrevent was a pre-post, single arm study at a five-site primary care practice. We identified at-risk patients (≥65 years-old, with type 2 diabetes, treated with insulin or sulfonylureas, and HbA1c < 7.0%). During three clinic visits over 6 months, clinicians used the CDS tool and SDM to assess hypoglycemic risk, set individualized HbA1c goals, and adjust use of hypoglycemic agents. We assessed the number of patients setting individualized HbA1c goals or modifying medication use, changes in the population at risk for hypoglycemia, and changes in impact of non-severe hypoglycemic events using a validated patient-reported outcome tool (TRIM-HYPO). RESULTS: We enrolled 94 patients (mean age-74; mean HbA1c (±SD)-6.36% ± 0.43), of whom 94% set an individualized HbA1c goal at either the baseline or first follow-up visit. Ninety patients completed the study. Insulin or sulfonylurea use was decreased or eliminated in 20%. An HbA1c level before and after goal setting was obtained in 53% (N = 50). Among these patients, the mean HbA1c increased 0.53% (p < 0.0001) and the number of patients at-risk decreased by 46% (p < 0.0001). Statistically significant reductions in the impact of hypoglycemia during daily activities occurred in both the total score and each functional domain of TRIM-HYPO. CONCLUSIONS: In a population of older patients at risk for hypoglycemia, the use of a CDS tool and SDM reduced the population at risk and decreased the use of insulin and sulfonylureas. Using a patient-reported outcome tool, we demonstrated significant reductions in the impact of hypoglycemia on daily life.

Overtreatment of malaria in the Nigerian healthcare setting: prescription practice, rationale and consequences.

Nigeria is one of the countries in the world with the highest burden of malaria, accounting for a quarter of all cases in Africa. According to the Centers for Disease Control and Prevention, microscopic examination remains the gold standard for laboratory confirmation of malaria. However, the policy and practice of presumptive treatment of malaria for all febrile illnesses has been widely advocated in sub-Saharan Africa. Presumptive management of fevers and/or other symptoms of malaria results in over-diagnosis, and consequently overtreatment. This article discusses the overtreatment of malaria as practiced in Nigeria and other African regions against standard treatment guidelines, highlights a wide range of its associated effects on patients and proffers possible solutions to curb the unethical practice of malaria overtreatment.

Effects of overtreatment with different attachment positions on maxillary anchorage enhancement with clear aligners: a finite element analysis study.

BACKGROUND: The effect of attachment positions on anchorage has not been fully explored. The aim of the present study is to analyze the effect of overtreatment with different anchorage positions on maxillary anchorage enhancement with clear aligners in extraction cases. METHODS: Models of the maxilla and maxillary dentition were constructed and imported into SOLIDWORKS software to create periodontal ligament (PDL), clear aligners, and attachments. Attachment positions on second premolars included: without attachment (WOA), buccal attachment (BA), and bucco-palatal attachment (BPA). Overtreatment degrees were divided into five groups (0°, 1°, 2°, 3°, 4°) and added on the second premolars. The calculation and analysis of the displacement trends and stress were performed using ANSYS software. RESULTS: Distal tipping and extrusion of the canines, and mesial tipping and intrusion of the posterior teeth occurred during retraction. A strong anchorage was achieved in cases of overtreatment of 2.8° with BA and 2.4° with BPA. Moreover, the BPA showed the best in achieving bodily control of the second premolars. When the overtreatment was performed, the canines and first molars also showed reduced tipping trends with second premolars attachments. And the stress on the PDL and the alveolar bone was significantly relieved and more evenly distributed in the BPA group. CONCLUSIONS: Overtreatment is an effective means for anchorage enhancement. However, the biomechanical effect of overtreatment differs across attachment positions. The BPA design performs at its best for stronger overtreatment effects with fewer adverse effects.