Practice variation in surgical treatment for lumbar degenerative disc disease: exploring regional and hospital factors influencing surgical rates.

The presence of significant, unwarranted variation in treatment suggests that clinical decision making also depends on where patients live instead of what they need and prefer. Historically, high practice variation in surgical treatment for lumbar degenerative disc disease (LDDD) has been documented. This study aimed to investigate current regional variation in surgical treatment for sciatica resulting from LDDD. We conducted a retrospective, cross-sectional analysis of all Dutch adults (>18 years) between 2016 and 2019. Demographic data from Statistics Netherlands were merged with a nationwide claims database, covering over 99% of the population. Inclusion criteria comprised LDDD diagnosis codes and relevant surgical codes. Practice variation was assessed at the level of postal code areas and hospital service areas (HSAs). Multivariable logistic regression analysis was employed to identify variables associated with surgical treatment. Among the 119,148 hospital visitors with LDDD, 14,840 underwent surgical treatment. Practice variation for laminectomies and discectomies showed less than two-fold variation in both postal code and HSAs. However, instrumented fusion surgery demonstrated a five-fold variation in postal code areas and three-fold variation in HSAs. Predictors of receiving surgical treatment included opioid prescription and patient referral status. Gender differences were observed, with males more likely to undergo laminectomy or discectomy, and females more likely to receive instrumented fusion surgery. Our study revealed low variation rates for discectomies and laminectomies, while indicating a high variation rate for instrumented fusion surgery in LDDD patients. High-quality research is needed on the extent of guideline implementation and its influence on practice variation.

The diagnostic accuracy of spirometry as screening tool for adult patients with a benign subglottic stenosis.

BACKGROUND: There is a considerable diagnostic delay in the diagnosis 'benign acquired subglottic stenosis in adults' (SGS, diagnosed by the reference standard, i.e. laryngo- or bronchoscopy). Patients are frequently misdiagnosed since symptoms of this rare disease may mimic symptoms of 'asthma.' The 'Expiratory Disproportion Index' (EDI) obtained by spirometry, may be a simple instrument to detect an SGS-patient. The aim of this study was to evaluate the diagnostic accuracy of the EDI in differentiating SGS patients from asthma patients. METHODS: We calculated the EDI from spirometry results of all SGS-patients in the Leiden University Medical Center (LUMC), who had not received treatment 2 years before their spirometry examination. We compared these EDI results with the EDI results of all true asthma patients between 2011 and 2019, who underwent a bronchoscopy (exclusion of SGS by laryngo- or bronchoscopy). RESULTS: Fifty patients with SGS and 32 true asthma patients were included. Median and IQR ranges of the EDI for SGS and asthma patients were 67.10 (54.33-79.18) and 37.94 (32.41-44.63), respectively. Area under the curve (ROC) of the accuracy of the EDI at discriminating SGS and asthma patients was 0.92 (95% CI = 0.86-0.98). The best cut-off point for the EDI was > 48 (i.e. possible upper airway obstruction), with a sensitivity of 88.0%% (95%CI = 77.2-95.0%%) and specificity of 84.4% (95%CI = 69.4-94.1%). CONCLUSIONS: The EDI has a good diagnostic accuracy discriminating subglottic stenosis patients from asthma patients, when compared to the reference standard. This measurement from spirometry may potentially shorten the diagnostic delay of SGS patients. Further studies are needed to evaluate clinical reproducibility.

Pan-genome and multi-parental framework for high-resolution trait dissection in melon (Cucumis melo).

Linking genotype with phenotype is a fundamental goal in biology and requires robust data for both. Recent advances in plant-genome sequencing have expedited comparisons among multiple-related individuals. The abundance of structural genomic within-species variation that has been discovered indicates that a single reference genome cannot represent the complete sequence diversity of a species, leading to the expansion of the pan-genome concept. For high-resolution forward genetics, this unprecedented access to genomic variation should be paralleled and integrated with phenotypic characterization of genetic diversity. We developed a multi-parental framework for trait dissection in melon (Cucumis melo), leveraging a novel pan-genome constructed for this highly variable cucurbit crop. A core subset of 25 diverse founders (MelonCore25), consisting of 24 accessions from the two widely cultivated subspecies of C. melo, encompassing 12 horticultural groups, and 1 feral accession was sequenced using a combination of short- and long-read technologies, and their genomes were assembled de novo. The construction of this melon pan-genome exposed substantial variation in genome size and structure, including detection of ~300 000 structural variants and ~9 million SNPs. A half-diallel derived set of 300 F2 populations, representing all possible MelonCore25 parental combinations, was constructed as a framework for trait dissection through integration with the pan-genome. We demonstrate the potential of this unified framework for genetic analysis of various melon traits, including rind color intensity and pattern, fruit sugar content, and resistance to fungal diseases. We anticipate that utilization of this integrated resource will enhance genetic dissection of important traits and accelerate melon breeding.

Practice Variation Research in Degenerative Lumbar Disc Surgery: A Literature Review on Design Characteristics and Outcomes.

STUDY DESIGN: Literature review. OBJECTIVE: To describe whether practice variation studies on surgery in patients with lumbar degenerative disc disease used adequate study methodology to identify unwarranted variation, and to inform quality improvement in clinical practice. Secondary aim was to describe whether variation changed over time. METHODS: Literature databases were searched up to May 4th, 2021. To define whether study design was appropriate to identify unwarranted variation, we extracted data on level of aggregation, study population, and case-mix correction. To define whether studies were appropriate to achieve quality improvement, data were extracted on outcomes, explanatory variables, description of scientific basis, and given recommendations. Spearman's rho was used to determine the association between the Extreme Quotient (EQ) and year of publication. RESULTS: We identified 34 articles published between 1990 and 2020. Twenty-six articles (76%) defined the diagnosis. Prior surgery cases were excluded or adjusted for in 5 articles (15%). Twenty-three articles (68%) adjusted for case-mix. Variation in outcomes was analyzed in 7 articles (21%). Fourteen articles (41%) identified explanatory variables. Twenty-six articles (76%) described the evidence on effectiveness. Recommendations for clinical practice were given in 9 articles (26%). Extreme Quotients ranged between 1-fold and 15-fold variation and did not show a significant change over time (rho= -.33, P= .09). CONCLUSIONS: Practice variation research on surgery in patients with degenerative disc disease showed important limitations to identify unwarranted variation and to achieve quality improvement by public reporting. Despite the availability of new evidence, we could not observe a significant decrease in variation over time.

Underground heterosis for yield improvement in melon.

Heterosis, the superiority of hybrids over their parents, is a major genetic force associated with plant fitness and crop yield enhancement. We investigated root-mediated yield heterosis in melons (Cucumis melo) by characterizing a common variety grafted onto 190 hybrid rootstocks, resulting from crossing 20 diverse inbreds in a diallel-mating scheme. Hybrid rootstocks improved yield by more than 40% compared with their parents, and the best hybrid yield outperformed the reference commercial variety by 65% under both optimal and minimal irrigation treatments. To characterize the genetics of underground heterosis we conducted whole genome re-sequencing of the 20 founder lines, and showed that parental genetic distance was no predictor for the level of heterosis. Through inference of the 190 hybrid genotypes from their parental genomes, followed by genome-wide association analysis, we mapped multiple quantitative trait loci for root-mediated yield. Yield enhancement of the four best-performing hybrid rootstocks was validated in multiple experiments with four different scion varieties. Our grafting approach is complementary to the common roots genetic approach that focuses mainly on variation in root system architecture, and is a step towards discovery of candidate genes involved in root function and yield enhancement.

Functional and early weight-bearing protocol for achilles tendon ruptures: a retrospective study.

PURPOSE: Conservative treatment of achilles tendon rupture (ATR) might be favoured in centres with an early weight-bearing protocol, but no consensus exists on the clear definition of an early weight-bearing protocol. The aim of this study is to evaluate the introduction of an early weight-bearing conservative treatment protocol in patients with ATR compared to patients without this protocol. METHODS: A single-centre retrospective study was performed. All patients presenting with an ATR during a 10-year period were included. Between January 1st 2008 and December 31st 2015, all patients were included for either operative or conservative treatment without an early weight-bearing protocol (non-EWB). Between January 1st 2016 and 30th June 2019, patients were, primarily, treated conservatively with early weight-bearing protocol (EWB). A primary-outcome parameter was re-rupture, and secondary-outcome parameters were treatment-related complications. RESULTS: In the period 2008-2015, 246 patients were treated with non-EWB. In the period 2016-2019, 58 patients were treated conservatively with EWB. No significant differences were found in re-rupture rates between non-EWB (5.3%) and conservative EWB (6.9%) (p = 0.536) or conservative non-EWB (9.4%) and conservative EWB (6.9%) (p = 0.283). Pulmonary embolism (1.0%) and deep venous thrombosis (1.0%) were observed in operative non-EWB patients. In conservative EWB patients, superficial pressure ulcers (5.2%) and treatment failure (5.2%) were observed. CONCLUSION: Conservative treatment of ATR with an early weight-bearing protocol showed similar re-rupture rates and complication rates compared to conservative and operative treatments without an early weight-bearing protocol.

Biomarkers for prediction and targeted prevention of Alzheimer's and Parkinson's diseases: evaluation of drug clinical efficacy.

Neurodegenerative diseases like Parkinson's disease (PD) and Alzheimer's disease (AD) are considered disorders of multifactorial origin, inevitably progressive and having a long preclinical period. Therefore, the availability of biological markers or biomarkers (BMs) for early disease diagnosis will impact the management of AD and PD in several dimensions; it will 1) help to capture high-risk individuals before symptoms develop, a stage where prevention efforts might be expected to have their greatest impact; 2) provide a measure of disease progression that can be evaluated objectively, while clinical measures are much less accurate; 3) help to discriminate between true AD or PD and other causes of a similar clinical syndrome; 4) delineate pathophysiological processes responsible for the disease; 5) determine the clinical efficacy of novel, disease-modifying (neuroprotective) strategies. In the long run the availability of reliable BMs will significantly advance the research and therapeutics of AD and PD.

Depression and dementia.

Depression and cognitive impairment are both common conditions in old age, and frequently occur together. However, accurate figures of the co-occurrence are not available. The inter-relationship between the two clinical entities is still complex and not well understood. Clearly depression can be a psychological reaction to cognitive decline, and thus may also appear as an early symptom in dementing individuals. However, recent data suggest that depression, and in particularly late-life depression, can also be a risk factor for Alzheimer's disease (AD). The relationship between the two clinical entities should be seen in view of observations of white matter changes both in AD and in depression. Since these white matter changes are thought to frequently reflect vascular changes, the concept of "vascular depression" has been advanced. Vascular changes in the brain occur commonly in demented individuals and conversely depression is frequent co-occurrence in vascular disease. Additionally neurotransmitter loss may occur in both, particularly monoaminergic disturbances which is characteristic of depression but may occur also in AD. The same is true for hippocampal atrophy, which is characteristic of AD but has also been described in depression. Here we review the complex relationships between dementia and depression and suggest that excessive release of corticosteroids may have a neurotoxic effects.

Biomarkers for evaluation of clinical efficacy of multipotential neuroprotective drugs for Alzheimer's and Parkinson's diseases.

During the last century, the world population has shown a staggering increase in its proportion of elderly members and thus neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), respectively, are becoming an increasing burden on society. Among the diverse, significant challenges facing clinicians, is the improvement of diagnostic measures to detect early and subtle symptoms, a phase in which prevention efforts might be expected to have their greatest impact and provide a measure of disease progression that can be evaluated during the course of drug treatment. At present, clinical diagnosis of AD and PD is based on a constellation of symptoms and manifestations, although the disease originated several years earlier. Given the multiple etiological nature of AD and PD, it is reasonable to assume that the initial causative pathobiological processes may differ between the affected individuals. Therefore, the availability of biological markers or biomarkers will help not only early disease diagnosis, but also delineate the pathological mechanisms more definitively and reliably than the traditional cognitive and neurological phenotypes. In the current article, we review the literature on biochemical, genetic, and neuroimaging biomarkers and discuss their predictive value as indicative for disease vulnerability to detect individuals at risk for PD and AD, and to determine the clinical efficacy of novel, disease-modifying (neuroprotective) strategies.

[Depression precedes development of dementia].

Dementia and depression are common disorders in old age. Dementia typically manifests itself as a neurodegenerative disease that affects cognitive functions such as memory, orientation and speech. Dementia is common in old age and its frequency increases from 1% in 65 year olds up to 50% beyond 90 years. Depression usually appears as an episodic disease which extends in length from a few weeks up to many years. The core symptoms of depression include depressed mood, loss of interests and pleasure and loss of will to live. Cognitive disorders may accompany depression and are considered separate from dementia, and were thus named "pseudo-dementia", presuming that these cognitive disorders will disappear as the depressed mood will remit. Lately it has been documented that depression may precede dementia, particularly in Alzheimer's disease. Although correlation never proves causation we discuss three possibilities, not mutually exclusive: 1) Certain brain changes may manifest first as depression and later as dementia. 2) Depression and dementia have partially overlapping biological causes. 3) Certain biological changes associated with depression may lead to dementia. Dementia and depression show many common biologic features such as white matter changes in the brain, reduction of hippocampus volume, changes in the serotonergic and noradrenalinergic systems and abnormalities in the hypothalamic-pituitary-adrenal axis.

Computerized diagnosis of mild cognitive impairment.

BACKGROUND: We previously described software that we have developed for use in the evaluation of mild cognitive impairment (MCI). Our previous study included an aged nondemented population with memory complaints (n = 41) that was relatively homogenous in terms of education, clinical history, neurological examination, and Mini-Mental Status Examination (MMSE) scores. Performance patterns in the computerized tests separated the subjects into two groups, and we hypothesized that one group might have had incipient dementia. METHODS/RESULTS: In the present study we report a follow-up of 35 of the subjects 2 years later. Eight subjects who were thought to have incipient dementia at baseline could be evaluated in the follow-up, and six of them have deteriorated according to both MMSE and neurologists' evaluations and have now fulfilled clinical diagnostic criteria of dementia. The other two deteriorated only according to their computer performance. Of the 27 remaining subjects, only one now fulfilled clinical diagnostic criteria for dementia, although the present computerized examinations identified 10 subjects whose performance has deteriorated compared with the previous session. CONCLUSION: The follow-up examination thus supported our hypothesis that human-computer interaction features can contribute to the detection of incipient dementia.

[Mild cognitive impairment (MCI): characteristics, risk factors and prevention].

Mild cognitive impairment (MCI) is a term describing the individual's cognitive state, ranging from normal aging to dementia. Since the term MCI was only recently introduced, there are still controversies regarding its definition, frequency and characteristics. Despite ambiguity in the clinical definitions, MCI is strongly considered as representing enhanced risk for the development of dementia. Therefore, MCI seems to be an important target phase for clinical intervention aimed at inhibiting deterioration to dementia. Despite the controversies regarding the diagnosis of MCI and its exact definition, great progress has been achieved in identifying brain changes, genetic risk factors and prevention factors associated with MCI.