Diabetes and further risk of cancer: a nationwide population-based study.

BACKGROUND: Individuals with diabetes have a significantly higher risk of developing various forms of cancer, and the potential biological links between these two diseases are not completely understood. METHODS: This was a longitudinal retrospective nationwide cohort study, a study design that allows us to examine the natural course of cancer development over an extended period of time with a large sample size. Initially, 3,111,975 and 22,208,395 eligible patients aged ≥ 20 years with and without diabetes, respectively, were matched by age, sex, and the Charlson comorbidity index. Ultimately, 1,751,457 patients were selected from each group. Stratified populations for diabetic retinopathy (DR) (n = 380,822) and without DR (n = 380,822) as well as proliferative DR (PDR) (n = 141,150) and non-proliferative DR (NPDR) (n = 141,150) were analyzed in this study. The main outcome measure was the first-time diagnosis of cancer during the follow-up period. RESULTS: We observed a 20% higher risk of total cancer incidence [hazard ratios (HR), 1.20; p < 0.001] in the diabetes cohort compared to the non-diabetes cohort. The highest HR was observed for liver and pancreas cancers. Moderately increased risks were observed for oral, colon, gallbladder, reproductive (female), kidney, and brain cancer. Furthermore, there was a borderline significantly increased risk of stomach, skin, soft tissue, female breast, and urinary tract (except kidney) cancers and lymphatic and hematopoietic malignancies. The stratified analysis revealed that the total cancer incidence was significantly higher in the DR cohort compared to the non-DR cohort (HR, 1.31; p < 0.001), and there was a borderline increased risk in the PDR cohort compared to the NPDR cohort (HR, 1.13; p = 0.001). CONCLUSIONS: This study provides large-scale, nationwide, population-based evidence that diabetes is independently associated with an increased risk of subsequent development of total cancer and cancer at specific sites. Notably, this risk may further increase when DR develops.

Sodium-glucose co-transporter-2 inhibitors and the risk of venous thromboembolism: A nationwide population-based study and meta-analysis.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have off-target effects on haemoconcentration and anti-inflammation. The impact of SGLT-2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT-2i in comparison to dipeptidyl peptidase-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonists (GLP-1RA). MATERIALS AND METHODS: In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20 years or older who received SGLT-2i, DPP-4i, or GLP-1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT-2i users were compared with those of DPP-4i and GLP-1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta-analysis of relevant articles published before 23 May 2023, was conducted. RESULTS: Data from 136,530 SGLT-2i, 598,280 DPP-4i, and 5760 GLP-1RA users were analysed. SGLT-2i use was associated with a lower risk of VTE than DPP-4i (HR, 0.70; 95% CI, 0.59-0.84; p < 0·001), but not with GLP-1RA (HR, 1.39; 95% CI, 0.32-5.94; p = 0.66). Our meta-analysis further supported these findings (SGLT-2i vs. DPP-4i: HR, 0.71; 95% CI, 0.62-0.82; p < 0·001; SGLT-2i vs. GLP-1RA: HR, 0.91; 95% CI, 0.73-1.15; p = 0.43), suggesting the robustness of our retrospective analysis. CONCLUSIONS: In patients with DM, SGLT-2i was associated with a lower risk of VTE compared to DPP-4i, but not GLP-1RA.

Combined phacovitrectomy versus sequential surgery for idiopathic macular holes: systematic review and meta-analysis.

OBJECTIVE: To compare the best-corrected visual acuity (BCVA) change, idiopathic macular (IMH) closure, and complications in IMH patients receiving combined phacovitrectomy and sequential surgery (vitrectomy followed by phacoemulsification). DESIGN: Systematic review and meta-analysis. METHODS: PubMed, Ovid EMBASE, and Cochrane Library databases were searched from their inception through February 2022. Randomized, controlled trials and observational studies that presented results of BCVA change, IMH closure, and surgery-related complications were included. A random-effects meta-analysis was conducted to calculate effect estimates with 95% CIs. RESULTS: One randomized, controlled trials and 7 cohort studies with 585 patients were included. Overall, the meta-analyses of BCVA change (mean difference, -0.03; 95% CI, -0.10-0.04) and IMH closure (risk ratio = 1.04; 95% CI, 0.96-1.13) revealed no significant differences between combined phacovitrectomy and sequential surgery. The pooled risk ratios for various surgical complications such as postoperative retinal detachment, inflammation, and intraocular pressure elevation showed no significant differences between the 2 groups. CONCLUSIONS: Similar visual gain and IMH closure rates were achieved after both combined phacovitrectomy and sequential surgery, with similar complication risks. The anatomic and functional outcomes of combined surgery were not better than those of sequential surgery. These results could serve as a reference for future trials.

Risk of Subsequent Dementia or Alzheimer Disease Among Patients With Age-Related Macular Degeneration: A Systematic Review and Meta-analysis.

PURPOSE: Alzheimer disease (AD), a common form of dementia, shares several clinical and pathologic features with age-related macular degeneration (AMD). Epidemiologic reports on the association of AMD with subsequent dementia or AD are inconsistent. DESIGN: Systematic review and meta-analysis. METHODS: The Meta-analysis of Observational Studies in Epidemiology reporting guidelines were applied. The Newcastle-Ottawa Scale was used to evaluate the risk of bias in the included cohort studies that examined the association of AMD with subsequent dementia or AD. We estimated the pooled hazard ratios (HRs) of dementia or AD using random effects model meta-analysis and subgroup analysis on different follow-up periods, AMD subtype, gender, age, study design, and methods to ascertain dementia or AD. RESULTS: A total of 8 223 581 participants were included in 8 studies published during 2000-2021. The meta-analysis showed that AMD was significantly associated with subsequent dementia (pooled HR 1.22, 95% CI 1.01-1.47) or AD (pooled HR 1.21, 95% CI 1.03-1.43). Our secondary analysis revealed that the association was more noticeable in dry AMD than wet AMD. CONCLUSIONS: Patients with AMD have higher risks of developing dementia or AD, and therefore identifying related comorbidities and retinal biomarkers is much warranted for older adults with AMD in ophthalmologic practice.

Association Between Oral Metformin Use and the Development of Age-Related Macular Degeneration in Diabetic Patients: A Systematic Review and Meta-Analysis.

Purpose: Metformin is a biguanide derivative that is commonly used for the treatment of diabetes mellitus (DM). It demonstrates antioxidative, anti-inflammatory, and antiangiogenic activity within the ocular tissue and thus may be implicated in the treatment of age-related macular degeneration (AMD). However, epidemiological studies have shown conflicting results. Methods: The Ovid MEDLINE/Embase, Cochrane Library, and Web of Science databases were systematically searched from inception through August 3, 2022. Studies reporting the association between metformin use and odds of AMD were enrolled. Adjusted odds ratios (ORs) of AMD were extracted and pooled with random-effects model meta-analysis. Subgroup analyses based on AMD subtypes, ethnicity, study design, sex, and confirmation of AMD diagnosis were conducted. Results: A total of 9 observational studies with 1,446,284 participants were included in the analysis. The meta-analysis showed that metformin use was associated with a significant reduction in the odds of AMD (pooled ORs = 0.81, 95% confidence interval [CI] = 0.70-0.93). Subgroup analyses revealed that metformin use was not significantly associated with dry or wet AMD. Black (pooled ORs = 0.61, 95% CI = 0.58-0.64) and Hispanic populations (pooled ORs = 0.85, 95% CI = 0.81-0.89) demonstrated significantly lower odds of AMD. Conclusions: This systematic review and meta-analysis found that patients with DM with metformin usage were at lower odds of developing AMD. Future prospective clinical trials are needed to confirm this association.

Efficacy of atropine, orthokeratology, and combined atropine with orthokeratology for childhood myopia: A systematic review and network meta-analysis.

BACKGROUND/PURPOSE: Orthokeratology (Ortho-K), atropine eye drops and combined atropine with Ortho-K are proven to be effective ways to prevent myopic progression in many studies, but there is scarce evidence regarding the comparative efficacy of different dosages of atropine,Ortho-K, and combined atropine with Ortho-K for childhood myopia. METHODS: We performed a network meta-analysis (NMA) to assess the relative efficacy of the aforementioned interventions for myopic progression; moreover, we calculated the surface under cumulative ranking area (SUCRA) to determine the relative ranking of treatments. RESULTS: We identified 19 randomized controlled trials (3435 patients). NMA revealed that 0.01%-1% atropine, Ortho-K, and 0.01% atropine combined with Ortho-K inhibited axial elongation (AL) over one year. For refractive change, SUCRA analysis revealed that the hierarchy was high-dose (0.5%-1%), moderate-dose (0.1%-0.25%), and low-dose (0.01%-0.05%) atropine. Regarding AL, SUCRA analysis revealed the following hierarchy: Ortho-K combined with 0.01% atropine, high-dose atropine, moderate-dose atropine, Ortho-K, and low-dose atropine. CONCLUSION: In conclusion, we found that atropine (0.01%-1%), Ortho-K, and 0.01% atropine combined with Ortho-K could significantly slow down myopia progression. The atropine efficacy followed a dose-related pattern; moreover, Ortho-K and low-dose atropine showed similar efficacy. There was a synergistic effect of using 0.01% atropine combined with Ortho-K, and it showed comparable efficacy to that of high-dose atropine.

Association of Psoriasis With Incident Venous Thromboembolism and Peripheral Vascular Disease: A Systematic Review and Meta-analysis.

IMPORTANCE: Psoriasis, venous thromboembolism (VTE), and peripheral vascular disease (PVD) share similar mechanisms involving chronic inflammation. However, the associations between psoriasis and VTE or PVD are unclear. OBJECTIVE: To determine the association of psoriasis with incident VTE and PVD. DATA SOURCES: MEDLINE, Embase, Cochrane Library, Web of Science, and Cumulative Index to Nursing and Allied Health Literature were systematically searched for relevant publications from their respective inception through May 21, 2021. No restrictions on language or geographic locations were imposed. STUDY SELECTION: Two authors independently selected cohort studies that investigated the risk for incident VTE or PVD in patients with psoriasis. Any discrepancy was resolved through discussion with 2 senior authors until reaching consensus. Only 13 initially identified studies met the selection criteria for qualitative review, and only 9 of these for quantitative analysis. DATA EXTRACTION AND SYNTHESIS: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Two authors independently extracted data and assessed the risk of bias of included studies by using the Newcastle-Ottawa Scale. Disagreements were resolved by discussion with 2 other authors. A random-effects model meta-analysis was conducted to calculate the pooled hazard ratios (HRs) with the corresponding confidence intervals for incident VTE and PVD. Subgroup analyses based on arthritis status, psoriasis severity, sex, and geographic location were also performed. MAIN OUTCOMES AND MEASURES: Hazard ratios for incident VTE and PVD associated with psoriasis. RESULTS: A total of 13 cohort studies with 12 435 982 participants were included. The meta-analysis demonstrated a significantly increased risk for incident VTE (pooled HR, 1.26; 95% CI, 1.08-1.48) and PVD (pooled HR, 1.27; 95% CI, 1.16-1.40) among patients with psoriasis. Subgroup analyses illustrated increased risk for incident VTE among participants with psoriatic arthritis (pooled HR, 1.24; 95% CI, 1.01-1.53), women (pooled HR, 1.89; 95% CI, 1.36-2.61), and those in Asia (pooled HR, 2.02; 95% CI, 1.42-2.88) and Europe (pooled HR, 1.28; 95% CI, 1.06-1.53). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis found an increased risk for incident VTE and PVD among patients with psoriatic disease. Typical presentations of VTE or PVD should not be overlooked in patients with psoriasis. Risk factors, such as obesity, physical inactivity, smoking, and varicose veins, should be identified and treated in patients with psoriasis, and medications like hormone-related therapies should be prescribed with caution.

Face-Down Posture versus Non-Face-Down Posture following Large Idiopathic Macular Hole Surgery: A Systemic Review and Meta-Analysis.

Evidence regarding the effect of a face-down posture (FDP) for large idiopathic macular hole (IMH) is inconsistent. We conducted a systematic review and meta-analysis to determine whether a postoperative FDP is required for the treatment of large IMH. Eligible randomized controlled trials published before September 2021 were retrieved from the Medline, Embase, and Cochrane Library databases. The efficacy outcome was the IMH closure rate and the visual acuity improvement rate. A meta-analysis was performed using a random effects model. The "Grading of Recommendations Assessment, Development, and Evaluation" approach was implemented, and the numbers needed-to-treat (NNTs) were calculated. Seven studies comprising 640 patients were included. We performed a predefined subgroup analysis of IMH size using a cut-off point of 400 µm. Compared with non-FDP, a significant effect of FDP was found in the IMH > 400 µm group (OR = 3.34; 95% CI = 1.57-7.14; trial sequential analysis-adjusted CI = 1.20-11.58; NNTs = 7.9). After stratifying by the posturing periods, the beneficial effect of FDP lasting at least five days, but not three days was observed for large IMH. Maintaining a FDP for at least five days postoperatively is an effective strategy (certainty of evidence: "moderate") for treating large IMH.

Is 0.01% Atropine an Effective and Safe Treatment for Myopic Children? A Systemic Review and Meta-Analysis.

Several conflicting results regarding the efficacy of 0.01% atropine in slowing axial elongation remain in doubt. To solve this issue and evaluate the safety of 0.01% atropine, we conducted a systematic review and meta-analysis with the latest evidence. The review included a total of 1178 participants (myopic children). The efficacy outcomes were the mean annual progression in standardized equivalent refraction (SER) and axial length (AL). The safety outcomes included mean annual change in accommodative amplitude, photopic and mesopic pupil diameter. The results demonstrated that 0.01% atropine significantly retarded SER progression compared with the controls (weighted mean difference [WMD], 0.28 diopter (D) per year; 95% confidence interval (CI) = 0.17, 0.38; p < 0.01), and axial elongation (WMD, -0.06 mm; 95% CI = -0.09, -0.03; p < 0.01) during the 1-year period. Patients receiving 0.01% atropine showed no significant changes in accommodative amplitude (WMD, -0.45 D; 95% CI = -1.80, 0.90; p = 0.51) but showed dilated photopic pupil diameter (WMD, 0.35 mm; 95% CI = 0.02, 0.68; p = 0.04) and mesopic pupil diameter (WMD, 0.20 mm; 95% CI = 0.08, 0.32; p < 0.01). In the subgroup analysis of SER progression, myopic children with lower baseline refraction (>-3 D) and older age (>10-year-old) obtained better responses with 0.01% atropine treatment. Furthermore, the European and multi-ethnicity groups showed greater effect than the Asian groups. In conclusion, 0.01% atropine had favorable efficacy and adequate safety for childhood myopia over a 1-year period.

Effect of orthokeratology on anisometropia control: A meta-analysis.

BACKGROUND: The effectiveness of orthokeratology in retarding anisometropic progression has been investigated in several small-sample studies. This quantitative analysis aimed to elucidate the efficacy of orthokeratology for anisometropia control. METHODS: We searched PubMed, Embase, and Cochrane databases for relevant studies through September 2020. Axial length (AL) data at baseline and final follow-up were extracted, and AL elongation and difference were calculated. Methodological quality was evaluated using the risk of bias in non-randomized studies of interventions (ROBINS-I) tool. Meta-analyses were performed using a fixed-effect model based on the heterogeneity. RESULTS: A total of 10 cohort studies (nine retrospective studies; one prospective study) were included. The pooled results for the unilateral myopia group showed that the mean AL elongation difference between myopic and emmetropic eyes was -0.27 mm (95% CI, -0.31 to -0.22; p < 0.01) at the one-year follow-up (four studies) and -0.17 mm (95% CI, -0.33 to -0.02; p = 0.03) at the two-year follow-up (two studies). In the bilateral anisomyopic group, mean AL elongation difference between high and low myopic eyes was -0.06 mm (95% CI, -0.09 to -0.04; p < 0.01) at the one-year follow-up (seven studies) and -0.13 mm (95% CI, -0.21 to -0.06; p < 0.01) at the two-year followup (three studies). CONCLUSION: This study demonstrated that orthokeratology can effectively retard myopic progression and reduce anisomyopic values. However, additional wellstructured randomized controlled trials or prospective studies with longer follow-up periods are warranted to address this topic in more detail.

Application of Janus Kinase Inhibitors in Atopic Dermatitis: An Updated Systematic Review and Meta-Analysis of Clinical Trials.

Janus kinase (JAK) inhibitors are promising treatments for atopic dermatitis (AD). The aim of this study was to assess the efficacy and safety of JAK inhibitors for AD treatment via the "Grading of Recommendations Assessment, Development, and Evaluation" approach. We identified 15 randomized controlled trials comparing oral or topical JAK inhibitors against placebo to treat AD. A random-effects meta-analysis was performed, and the numbers-needed-to-treat (NNTs)/numbers-needed-to-harm (NNHs) were calculated. Patients treated with JAK inhibitors were associated with higher rates of achieving eczema area and severity index-75 (rate ratio (RR): 2.84; 95% confidence interval (CI): 2.20-3.67; I2: 38.9%; NNT = 3.97), Investigator's Global Assessment response (RR: 2.99; 95% CI: 2.26-3.95; I2: 0%; NNT = 5.72), and pruritus numerical rating scale response (RR: 2.52; 95% CI: 1.90-3.35; I2: 39.4%; NNT = 4.91) than those treated with placebo. Moreover, patients treated with JAK inhibitors had a higher risk of treatment-emergent adverse events (RR: 1.14; 95% CI: 1.02-1.28; I2: 52%; NNH = 14.80) but not adverse events leading to drug discontinuation. According to the evidence-based results, JAK inhibitors are potentially effective strategies (certainty of evidence: "moderate") for treating AD with tolerable side effects (certainty of evidence: "low"). Nevertheless, long-term follow-up is required.