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Nevin Manimala Statistics

Posterior urethral valves and the risk of neurodevelopmental disorders in two FINNISH cohorts

J Pediatr Urol. 2021 Jun 5:S1477-5131(21)00298-9. doi: 10.1016/j.jpurol.2021.05.027. Online ahead of print.

ABSTRACT

BACKGROUND: The Posterior Urethral Valve (PUV) is a persistent membrane of the urethra, which causes obstruction in the urogenital tract in boys. To our knowledge, no comprehensive reports have been published on whether PUV is associated to neurodevelopmental disorders. Here, we analyzed a cohort of PUV patients for neurodevelopmental disorders and verified findings in an older cohort.

METHODS: In a register based study, we reviewed the hospital registries for patients treated for PUV during 1992-2013 to identify those with neurodevelopmental disorders. Primary outcome measure was any neurodevelopmental diagnosis. Secondary outcome measures were specific disorders: ASD; ADHD, intellectual disability, learning disabilities. Birth weight and gestational age were recorded, serum creatinine levels at specific timepoints were noted. We then investigated these variables to see any correlations to neurodevelopmental disorders. We replicated the strategy for verification in an older cohort of PUV-patients, who had been treated in our institute during 1970-1991.

RESULTS: We identified 87 patients treated for PUV of which thirteen (15%) had a verified diagnosis of a neurodevelopmental disorder. 2.3% of PUV patients fulfilled criteria of mild intellectual disability (F70.0/F79.0), 9% had ADHD/ADD-spectrum diagnoses (F90.0/F90.9) and 2.3% had learning disabilities (F83/F81.3). 5.7% of patients presented with difficulties in social interactions (F93.89, F94.8). Five patients presented with more than one neurodevelopmental diagnosis. We confirmed these findings in the older cohort of patients, where a verified neurodevelopmental diagnosis was detected in 14% of patients. We identified no statistically significant associations to gestational age, birth weight or creatinine levels of PUV-patients with neurodevelopmental diagnoses as compared to the PUV-patients not diagnosed for neurodevelopmental disorders. Intellectual disability/mental retardation was more prevalent in our material and this association was statistically significant.

DISCUSSION: We show, that the prevalence of intellectual disability among PUV patients exceeds the cumulative prevalence in Finland in both cohorts analyzed here. 15% of PUV-patients presented with a diagnosis of a neurodevelopmental disorder. To our knowledge, this is the first study attempting to outline neurodevelopmental disorders among boys with PUV. This study has limitations. It is register based and only diagnoses made at an institute within our hospital district are considered. The PUV-patients may be under closer surveillance than age-matched healthy children, which may lead to an overrepresentation of cases. The patient number is small and the small subsets of patients within each cohort hamper any further statistical analysis. The neurodevelopmental impacts of pediatric general anesthesia remain elusive and may have corollaries which must be kept in mind when interpretating our results. Patients with PUV require close follow-up in a multi-disciplinary manner, not forgetting neurodevelopmental aspects. Attention to intellectual disability is mandatory. Any suspicion of a developmental delay in a patient with PUV warrants further investigation and corresponding interventions.

PMID:34158248 | DOI:10.1016/j.jpurol.2021.05.027

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Effect of Adding Bevacizumab to Chemotherapy on Pathologic Response to Preoperative Systemic Therapy for Resectable Colorectal Liver Metastases: A Systematic Review and Meta-analysis

Clin Colorectal Cancer. 2021 May 24:S1533-0028(21)00048-7. doi: 10.1016/j.clcc.2021.05.006. Online ahead of print.

ABSTRACT

BACKGROUND: Liver-limited metastatic colorectal cancer is a potentially curable disease. Pathologic response (pR) to preoperative chemotherapy (CT) for colorectal liver metastases (CLM) is a surrogate endpoint for overall survival (OS). We conducted the first meta-analysis of observational studies to estimate the overall effect of bevacizumab on pR in preoperative systemic therapy for CLM.

METHODS: We systematically searched PubMed, Cochrane Library, CINAHL, Web of Science, Embase, and LILACS for studies published between January 2004 and August 2019 that compared the pR of CT plus bevacizumab to CT alone as preoperative therapy for CLM. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were pathologic major (pMaR) and minor (pMiR) response. Overall effects were expressed by odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model.

RESULTS: Of the 1,452 studies yielded by the search, 9 were eligible, totaling 1,202 patients (516 CT plus bevacizumab and 686 CT alone). The addition of bevacizumab to CT increased the pCR rate without reaching statistical significance (OR: 1.24, 95% CI 0.81 to 1.92, P = .32). However, pMaR was significantly higher (OR: 2.45, 95% CI 1.85 to 3.25, P < .001), and pMiR was significantly lower (OR: 0.41, 95% CI 0.31 to 0.54, P < .001), in the bevacizumab group. The analyses showed a low level of heterogeneity (I2 = 0% to 6%). Publication bias was not found.

CONCLUSIONS: This meta-analysis demonstrates that bevacizumab plus preoperative CT is associated with higher rates of pR in CLM. Antiangiogenics might improve the OS of CLM patients and should be evaluated in randomized clinical trials.

MICROABSTRACT: The benefit of perioperative chemotherapy for colorectal liver metastases (CLM) is uncertain, but pathologic response (pR) to preoperative chemotherapy is a strong prognostic factor. Our meta-analysis of observational studies compared the pR of bevacizumab plus chemotherapy to chemotherapy alone as preoperative systemic therapy in the management of CLM. The addition of bevacizumab was associated with significantly higher rates of pR.

PMID:34158251 | DOI:10.1016/j.clcc.2021.05.006

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Three-dimensional digital measurement of the facet joint in normal and lumbar intervertebral disc herniation aged 13-18 years

Asian J Surg. 2021 Jun 19:S1015-9584(21)00305-5. doi: 10.1016/j.asjsur.2021.05.028. Online ahead of print.

ABSTRACT

BACKGROUND: Lumbar facet joint is an important element of spinal “three-joint complex”. Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults.

OBJECTIVE: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation.

METHODS: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al.

RESULTS: 1. The left and right transverse angle of L5S1 segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L3-L5 segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm2 in male than (18.92 ± 3.71) mm2 in female. 3. In comparison between normal and ALDH group, there was significant difference in L3-4 transverse angle (P < 0.05), L4-5 facet joint height and facet joint thickness (P < 0.05), L5S1 facet joint thickness and transverse angle (P < 0.05).

CONCLUSION: When ALDH occurs in the L5S1 segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.

PMID:34158200 | DOI:10.1016/j.asjsur.2021.05.028

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Single center consecutive series cohort study of partial stomach-partitioning gastrojejunostomy for gastric outlet obstruction

Asian J Surg. 2021 Jun 19:S1015-9584(21)00326-2. doi: 10.1016/j.asjsur.2021.05.047. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVE: Gastric outlet obstruction can have a large impact on quality of life for patients with upper gastrointestinal cancer or benign obstruction. Partial stomach-partitioning gastrojejunostomy has previously shown promising outcomes compared to conventional gastrojejunostomy in terms of reduced delayed gastric emptying. The objective of the current study was to present outcomes of partial stomach-partitioning gastrojejunostomy in a single high-volume center for upper gastrointestinal cancer.

METHODS: A retrospective cohort study including all consecutive patients who underwent partial stomach-partitioning gastrojejunostomy from 2013 to 2020. The primary outcome was oral intake tolerance. A subgroup analysis was performed in all patients with manifest gastric outlet obstruction comparing partial stomach-partitioning gastrojejunostomy to conventional gastrojejunostomy.

RESULTS: Partial stomach-partitioning gastrojejunostomy was performed in 32 patients and laparoscopic technique was used in 19 patients (59%). The procedure improved oral intake tolerance defined by gastric outlet obstruction scoring system by 0.63 points on average (P = 0.041). No postoperative complications related to the procedure were observed. Recurrence of gastric outlet obstruction developed in six patients (19%), four patients (13%) required endoscopic reintervention but no patient required surgical reintervention. A comparison between partial stomach-partitioning gastrojejunostomy and conventional gastrojejunostomy showed no statistically significant differences regarding postoperative nutritional status, length of hospital stay, recurrence or reintervention.

CONCLUSION: The results of the study show that partial stomach-partitioning gastrojejunostomy can be an effective surgical treatment for patients suffering from gastric outlet obstruction and that the procedure can be safely performed with laparoscopic technique.

PMID:34158203 | DOI:10.1016/j.asjsur.2021.05.047

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Immune checkpoints and liver resection after neoadjuvant chemotherapy including bevacizumab in patients with microsatellite-stable colorectal liver metastases

HPB (Oxford). 2021 Jun 7:S1365-182X(21)00166-0. doi: 10.1016/j.hpb.2021.05.015. Online ahead of print.

ABSTRACT

BACKGROUND: The clinical value of immune checkpoint expression as prognostic biomarker in bevacizumab-pretreated patients with resected microsatellite-stable (MMS) colorectal liver metastases is unclear and was retrospectively investigated in this study.

METHODS: Expression analyses of IDO-1, PD-L1, and CTLA-4 were performed by immunohistochemistry in resected bevacizumab-pretreated colorectal liver metastases. Association of immune checkpoint expression in tumor cells and immune cells with response and clinical outcome was investigated. Expression profiles were compared with those of patients with anti-EGFR-targeted therapy and lung metastases, respectively.

RESULTS: One hundred thirty-six patients with MMS disease were investigated (79 (58.1%) male/57 (41.9%) female, median age 62.9 years (range 31.0-80.4)). High expression of IDO-1 in immune cells was associated with longer OS (not reached versus 44.8 months, HR 0.23 (95% CI 0.09, 0.55), P = 0.001). Low expression of CTLA-4 in tumor cells was associated with better histological response (26 major, 19 partial, 18 none versus 14 major, 23 partial, 30 none, P = 0.032). Expression profiles differed compared to patients with anti-EGFR-targeted therapy and patients with lung metastases.

CONCLUSION: Immune checkpoint expression was associated with response and survival. IDO-1 may serve as a novel prognostic and/or predictive biomarker in patients with MMS colorectal liver metastases.

PMID:34158230 | DOI:10.1016/j.hpb.2021.05.015

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Outcomes following the delayed management of open tibial fractures

Injury. 2021 Jun 2:S0020-1383(21)00492-7. doi: 10.1016/j.injury.2021.05.042. Online ahead of print.

ABSTRACT

AIMS: National guidelines set standards for the definitive management of open fractures within 72 h. This study aims to investigate our outcomes where this timeline was unachievable for most cases due to a split-site orthoplastic service.

PATIENTS & METHODS: 116 consecutive Gustilo-Anderson grade IIIB & IIIC open tibial fractures presenting to our major trauma centre (MTC) between September 2012 and April 2018 were reviewed. The mean follow up was 46 months (17 to 88). 110 (95%) were grade IIIB and 6 (5%) grade IIIC. The most common injury mechanism included road traffic accidents (59%) and falls (28%). Primary outcomes were recorded according to; timing of initial debridement and definitive cover, rates of superficial and deep infection, non-union and amputation. Subgroups were statistically analysed according to time to initial debridement, definitive soft-tissue cover and injury severity score (ISS).

RESULTS: The mean time to initial debridement was 11.3 h (2.9 to 38.9) and definitive soft-tissue cover 9.9 days (0 to 37). We recorded rates of: superficial infection; 42 cases (36%), deep infection; 14 cases (12%) and non-union requiring revision; 19 cases (16%). There were 20 amputations (17%) with 9 (8.6%) performed early and 11 (9.5%) delayed. Subgroup analysis showed higher rates of superficial infection (50%, p = 0.002) and amputation (26.6%, p = 0.01) for those debrided <12 h. A greater presenting ISS related to a delay to definitive cover >7 days (p = 0.05). Primary outcomes trended worse for those covered >7 days but did not reach significance.

CONCLUSION: Major trauma patients are particularly vulnerable to poor outcomes resulting from the delay in definitive management of open fractures. MTC’s need resources and a co-located orthoplastic service to achieve national standards and better outcomes. Current guidelines do not advise for the management of patients where a delay in definitive surgery is anticipated.

PMID:34158158 | DOI:10.1016/j.injury.2021.05.042

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Comparison of strength of milled and conventionally processed PMMA complete-arch implant-supported immediate interim fixed dental prostheses

J Prosthet Dent. 2021 Jun 19:S0022-3913(21)00264-X. doi: 10.1016/j.prosdent.2021.04.025. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: A typical conversion process of a complete-arch immediate loading protocol entails preparing holes in a complete denture for connection to interim copings, which reduces the strength of the prosthesis. The excellent mechanical properties of milled polymethyl methacrylate (PMMA) disks may provide interim prostheses with improved strength.

PURPOSE: The purpose of this in vitro study was to measure the flexural strength and failure load of simulated acrylic resin immediate implant-supported interim prostheses fabricated by conventional processing and computer-aided manufacturing.

MATERIAL AND METHODS: A master patient model was created with an acrylic resin base and 2 BioHorizons Internal 4.5-mm-diameter implants placed with a 21.5-mm span and multiunit abutments (MUA) tightened to place. Two groups with different prosthodontic designs were used: one represented the standard fixed prosthesis with support at each end (noncantilever, NC), and the other group represented the cantilever portion of the prosthesis (cantilever, C). Two connection designs of prosthesis blocks to MUA abutments were evaluated: one with typical holes in the prosthesis for capturing interim copings and one with a low-profile coping. For the heat-processed PMMA groups (HP/NC and HP/C), wax patterns were milled, and heat-polymerized denture base PMMA prostheses were processed. The milled PMMA groups (M/NC and M/C) were milled from a tooth-shaded PMMA disk for the prosthesis blocks. The milled low-profile groups (Mlp/NC and Mlp/C) had identical dimensions except that connection to the low-profile coping was designed with a cement space and a narrow diameter screw access hole and was milled from a PMMA disk. The failure load (N) of the cantilever prostheses was recorded, and for NC groups, the 3-point flexural strength formula (MPa) was calculated. The Weibull modulus, characteristic strength, and summary statistics were computed, and the groups were statistically analyzed with ANOVA and the post hoc Tukey test (α=.05).

RESULTS: The mean flexural strengths (MPa) were HP/NC=91.35 ±18.92; M/NC=143.94 ±36.79; Mlp/NC=117.06 ±13.86. Significant differences were found among groups (P<.001). Mean failure loads (N) and Weibull modulus (WM) of cantilever prosthesis strengths were for HP/C=512.66, WM=5.597; M/C=695.06, WM=4.875; Mlp/C=254.97, WM=1.797 (P<.001).

CONCLUSIONS: Implant fixed interim structures milled from high-density PMMA blanks had a 35% higher flexural strength for both the standard prostheses and the cantilever prostheses than heat-processed denture base PMMA. The low-profile coping design was stronger than the heat-processed material, and the failure point was relocated from the lateral walls to the cervical margin area.

PMID:34158174 | DOI:10.1016/j.prosdent.2021.04.025

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Capturing the Healthfulness of the In-store Environments of United Kingdom Supermarket Stores Over 5 Months (January-May 2019)

Am J Prev Med. 2021 Jun 20:S0749-3797(21)00269-5. doi: 10.1016/j.amepre.2021.04.012. Online ahead of print.

ABSTRACT

INTRODUCTION: Numerous environmental factors within supermarkets can influence the healthfulness of food purchases. This research aims to identify the changes in store healthfulness scores and assess the variations by store type and neighborhood deprivation using an adapted Consumer Nutrition Environment tool.

METHODS: Between January and May 2019, a total of 104 supermarkets in London were surveyed on 1-3 occasions. The adapted Consumer Nutrition Environment tool included data on 9 variables (variety, price, quality, promotions, shelf placement, store placement, nutrition information, healthier alternatives, and single fruit sale) for 11 healthy and 5 less healthy food items. An algorithm was used to create a composite score of in-store healthfulness and to assess inter-rater reliability. Longitudinal changes in overall store healthfulness and individual variables were investigated using multivariable hierarchical mixed models. Descriptive statistics were used to describe the differences by store type and neighborhood deprivation in each month. All analyses were conducted between January and July 2020.

RESULTS: The adapted Consumer Nutrition Environment tool showed acceptable inter-rater reliability. Large stores exhibited healthier environments than small stores (p<0.001), with a similar pattern for each of the 9 individual variables. Within large stores, the overall healthfulness score did not change over the study period. Promotions on more healthful items increased in February (p=0.04), and the availability of healthier alternatives for less healthy foods decreased in March (p=0.01). Within small stores, there was a trend toward increasing healthfulness (p<0.001), primarily owing to more promotions on healthy items (p<0.001). There was no difference in overall healthfulness by neighborhood deprivation.

CONCLUSIONS: The adapted Consumer Nutrition Environment tool is sensitive to longitudinal changes in environmental variables that contribute to store healthfulness. A wider application of this tool could be used to map in-store environments to identify targets for interventions to encourage healthier food purchasing.

PMID:34158196 | DOI:10.1016/j.amepre.2021.04.012

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Knowledge and perception of biosimilars in ambulatory care: a survey among Belgian community pharmacists and physicians

J Pharm Policy Pract. 2021 Jun 22;14(1):53. doi: 10.1186/s40545-021-00330-x.

ABSTRACT

BACKGROUND: With the approval of biosimilars for subcutaneously administered products, such as adalimumab, etanercept and insulin, biosimilars become increasingly available in ambulatory care. Little is known about the knowledge and attitudes of healthcare providers who are in charge of dispensing and prescribing biosimilars in this context. This study aims to assess the knowledge and perception about biosimilars among community pharmacists and physicians.

METHODS: Belgian community pharmacists (n = 177) and physicians (n = 30) were surveyed on their knowledge, experience with dispensing/prescribing biologicals including biosimilars, perception regarding interchangeability, switching and substitution and informational and educational needs. Descriptive and statistical analyses were performed.

RESULTS: Only 32% of community pharmacists and 52% of physicians had yet dispensed/prescribed a biosimilar. Approximately 35% of community pharmacists felt insufficiently trained to counsel patients with biosimilar therapy, which was significantly higher compared to their self-assessed competence to counsel patients with biological therapy in general (p = 0.023). Community pharmacists experienced questions about similarity between reference products and biosimilars (47%) and their interchangeability (42%). Over 40% of physicians found patient uncertainty about efficacy and safety challenging when prescribing biosimilars. A similar proportion of physicians would only prescribe a biosimilar in indications for which the biosimilar has been tested clinically. The majority of pharmacists (58%) was in favor of substitution of biologicals, on the condition that the prescriber would be contacted. Also over 40% of physicians was open to this approach in case of substitution. Educational support, budget for additional staff and transparency about savings were considered suitable stimuli to incentivize biosimilar use. The need for information about biologicals including biosimilars was nearly unanimous among community pharmacists. Also 67% of physicians requested more information. Both community pharmacists and physicians preferred to be informed by their respective professional associations.

CONCLUSIONS: This study showed a substantial need for targeted educational measures to increase the knowledge and confidence about both biological medicines in general and biosimilars in particular among Belgian community pharmacists and physicians. The results may inform educational and policy measures to stimulate biosimilar use in ambulatory care.

PMID:34158128 | DOI:10.1186/s40545-021-00330-x

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American psychiatry in the new millennium: a critical appraisal

Psychol Med. 2021 Jun 23:1-9. doi: 10.1017/S0033291721001975. Online ahead of print.

ABSTRACT

This article casts a critical eye over the development of American psychiatry from 1980 to the present. It notes the rapid decline of psychoanalysis that followed the publication of DSM III; the rising influence of genetics and neuroscience; the re-emphasis on the biology of mental illness; and the collapse of public psychiatry that accompanied deinstitutionalization. It argues that while genetics and neuroscience have made scientific progress, the clinical utility of their findings to date has been very limited. The fifth edition of the DSM was supposed to base itself on this new science but that proved impossible. Diagnosis remains purely phenomenological and controversial. One of the ironies of research on psychiatric genetics is that has failed to find either a Mendelian origin of schizophrenia and depression or to validate the importance of hypothesized candidate genes. Genome-wide association studies have instead uncovered risk factors for major mental illnesses, but these overlap considerably, and the genetic associations are not dispositive. Most of those who carry these genetic variants do not develop mental illness. The status of psychopharmacology since the mid-1950s is scrutinized, as is the influence of the pharmaceutical industry on contemporary psychiatry, and the implications of its recent decision to abandon work in this arena. The paper concludes with an assessment of the crisis that it contends confronts contemporary American psychiatry: its overemphasis on biology; the urgent questions that persist about diagnosis and therapeutics; concerns about the directions of future research; and its inability to reduce the excess mortality that plagues the mentally ill.

PMID:34158141 | DOI:10.1017/S0033291721001975