Accuracy of clinical diagnosis of Parkinson disease

Accuracy of clinical diagnosis of Parkinson disease

http://tinyurl.com/jq9aakn

A systematic review and meta-analysis

Giovanni Rizzo, MDMassimiliano Copetti, PhDSimona Arcuti, PhDDavide Martino, MDAndrea Fontana, MScand Giancarlo Logroscino, MD

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Correspondence to Dr. Logroscino: giancarlo.logroscino@uniba.it

Neurology February 9, 2016 vol. 86 no. 6 566-576

ABSTRACT

Objective: To evaluate the diagnostic accuracy of clinical diagnosis of Parkinson disease (PD) reported in the last 25 years by a systematic review and meta-analysis.

Methods: We searched for articles published between 1988 and August 2014. Studies were included if reporting diagnostic parameters regarding clinical diagnosis of PD or crude data. The selected studies were subclassified based on different study setting, type of test diagnosis, and gold standard. Bayesian meta-analyses of available data were performed.

Results: We selected 20 studies, including 11 using pathologic examination as gold standard. Considering only these 11 studies, the pooled diagnostic accuracy was 80.6% (95% credible interval [CrI] 75.2%–85.3%). Accuracy was 73.8% (95% CrI 67.8%–79.6%) for clinical diagnosis performed mainly by nonexperts. Accuracy of clinical diagnosis performed by movement disorders experts rose from 79.6% (95% CrI 46%–95.1%) of initial assessment to 83.9% (95% CrI 69.7%–92.6%) of refined diagnosis after follow-up. Using UK Parkinson’s Disease Society Brain Bank Research Center criteria, the pooled diagnostic accuracy was 82.7% (95% CrI 62.6%–93%).

Conclusion: The overall validity of clinical diagnosis of PD is not satisfying. The accuracy did not significantly improve in the last 25 years, particularly in the early stages of disease, where response to dopaminergic treatment is less defined and hallmarks of alternative diagnoses such as a typical parkinsonism may not have emerged. Misclassification rate should be considered to calculate the sample size both in observational studies and randomized controlled trials. Imaging and biomarkers are urgently needed to improve the accuracy of clinical diagnosis in vivo.

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Vitamin D3 for uncontrolled childhood asthma: a pilot study

 

Vitamin D3 for uncontrolled childhood asthma: a pilot study

htttp://tinyurl.com/jzar3y7

 

Author information

  • 1Paediatric Respiratory Deparment, National Children’s Hospital, Dublin 24, Ireland.
  • 2School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland.
  • 3Asthma Research Centre, Connolly Hospital, Blanchardstown, Dublin 15, Ireland.
  • 4Biomnis Ireland, Sandyford business Estate, 3 Rock Rd, Dublin, Ireland.
  • 5Deparment of Paediatric Medicine, National Children’s Hospital, Dublin 24, Ireland.
 

Abstract

BACKGROUND:

Observational and mechanistic data suggest a role for vitamin D in childhood asthma. However, subsequent interventional trials have been inconsistent. We aimed to assess the effect of 15 weeks of vitamin D3 supplementation compared to placebo in Irish asthmatic children.

METHODS:

We conducted a double-blind, randomized, placebo-controlled trial of vitamin D supplementation (2,000IU/d) in 44 urban, Caucasian children at high latitude. Assessments were completed at baseline and after 15 weeks of supplementation. Outcome measures lung function, subjective asthma control and biochemical parameters of total vitamin D, allergy, immunity, airway inflammation and systemic inflammation. Finally, parents/gaurdians completed a weekly diary during the trial.

RESULTS:

There was no significant difference in baseline 25(OH)D levels but there was a significant increase in median 25(OH)D in the vitamin D3group (57.5 to 105nmol/L) compared to the placebo group (52.5 to 57.5nmol/L) (p <0.0001). There was no significant difference between groups regarding subjective asthma control. Compared to placebo, there was as a significant decrease in school days missed due to asthma (1 vs. 5 days, p = 0.04) and alkaline phosphatase (-3.4 vs. +16; p = 0.037) in the vitamin D3 group but there were no beneficial effects regarding several other secondary endpoints. However, there were non-significant, advantageous changes in the placebo group compared to the vitamin D3 group in subjective asthma control and lung function, particularly percentage of predicted forced expiratory volume in 1 second (+2.5 vs. -4; p = 0.06).

CONCLUSION:

Vitamin D3 supplementation led to a significant increase in serum 25(OH)D and decreased school days missed (p = 0.04) but no other advantageous changes in asthma parameters compared to placebo. The potential adverse effect of vitamin D deficiency on growth and the potential negative effect of high serum 25(OH)D on pulmonary function warrant further investigation. This article is protected by copyright. All rights reserved.

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CCBYNC Open access Research Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

CCBYNC Open access Research Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports

http://tinyurl.com/hmgdrmx

  1. arang Sharma, PhD student1 2,
  2. Louise Schow Guski, medical student1 2,
  3. Nanna Freund, medical student1 2,
  4. Peter C Gøtzsche, professor1 2

Author affiliations

  1. Correspondence to: T Sharma Nordic Cochrane Centre, Rigshospitalet, Blegdamsvej 9, Department 7811, 2100 Ø Copenhagen, Denmark ts@cochrane.dk
  • Accepted 3 December 2015

Abstract

Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.

Design Systematic review and meta-analysis.

Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.

Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website.

Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms.

Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model).

Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.

Conclusions Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.

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Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a Population-based, Aging Cohort.

Temporal Cognitive Decline Associated With Exposure to Infectious Agents in a Population-based, Aging Cohort.

http://tinyurl.com/jsgacn9

Nimgaonkar, Vishwajit L. MD, PhD; Yolken, Robert H. MD, PhD; Wang, Tianxiu MS; Chung-Chou, Ho Chang PhD; McClain, Lora BS; McDade, Eric DO; Snitz, Beth E. PhD; Ganguli, Mary MD

Abstract

Background: Numerous cross-sectional studies have related exposure to neurotropic infectious agents with cognitive dysfunction in older adults, however, the temporal sequence is uncertain.

Methods: In a representative, well-characterized, population-based aging cohort, we determined whether the temporal trajectories of multiple cognitive domains are associated with exposure to cytomegalovirus (CMV), Herpes Simplex virus, type 1 (HSV-1), Herpes Simplex virus, type 2 (HSV-2), or Toxoplasma gondii (TOX). Complex attention, executive functions, memory, language, and visuospatial function were assessed annually for 5 years among consenting individuals. Study entry IgG antibody titers indexing exposure to each infectious agent were examined in relation to slopes of subsequent temporal cognitive decline using multiple linear regressions adjusted for potential confounders.

Results: The IgG levels for HSV-2 were significantly associated with baseline cognitive domain scores (N=1022 participants). Further, the IgG levels for HSV-2, TOX, and CMV, but not HSV-1 were significantly associated with greater temporal cognitive decline that varied by type of infection.

Conclusions: Exposure to CMV, HSV-2, or TOX is associated with cognitive deterioration in older individuals, independent of general age-related variables. An increased understanding of the role of infectious agents in cognitive decline may lead to new methods for its prevention and treatment.

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Mortality Trends Among Working-Age Whites: The Untold Story

Mortality Trends Among Working-Age Whites: The Untold Story

http://tinyurl.com/grfw6rq

Abstract

Recent research has called attention to an unexpected rise in death rates among middle-aged, white Americans between 1999 and 2014. The full extent of the phenomenon may be underappreciated, however. If one assumes, based on historical trends, that mortality rates should have declined by 1.8 percent per year, then whites in 2014 had higher-than-expected mortality rates from age 19 to age 65. Furthermore, while increased substance abuse and suicides explain the elevated mortality rates for younger adults, middle-aged whites also seem to be experiencing stalled or rising mortality rates for most ailments and diseases. While a national phenomenon, middle-aged whites face much more adverse mortality trends in certain states and regions. The especially broad reach of these negative mortality trends suggests there is an urgent need for further investigation of its causes and potential remedies.

INTRODUCTION

At the end of 2015, Princeton University economists Anne Case and Angus Deaton published a startling finding: since 1999, death rates have been rising for non- Hispanic, white Americans between the ages of 45 and 54, reversing a decades-long decline.1 The authors largely attribute this reversal to rising rates of drug poisonings, suicides, and alcohol-related liver disease. They also note that over the same period, middle-aged whites reported worsening self-reported health status, greater levels of pain, increased difficulty with activities of daily living, and more mental health problems.

In January 2016, the New York Times followed up on Case and Deaton’s findings with an analysis showing that the rise in white mortality rates has not been confined to middle-aged adults but has occurred among younger adults—those 25 to 34—as well.2 The main culprit: increasing abuse of prescription opioids, such as oxycodone and hydrocodone, and heroin.

These findings have attracted substantial attention. Upon further examination, however, it becomes clear that the gap between expected and actual white mortality rates is wider than commonly recognized. Moreover, the gap is not adequately explained for the middle-aged by the common narrative of rising levels of substance abuse and suicide. And while it is a national phenomenon, the mortality crisis has struck some regions of the United States much more severely than others.

THE MORTALITY GAP

Between 1999 and 2014, mortality rates in the U.S. rose for white adults between the ages of 22 and 56, peaking at around age 30 and age 50 (Exhibit 1).3 In contrast, mortality rates for both younger and older white Americans declined over this period.

However, this perspective fails to adequately account for the well-founded presumption that, absent a health crisis, mortality rates for white Americans should have been declining during this time. In other words, white Americans are now facing a substantial “mortality gap.” Since 1968, death rates had declined by nearly 2 percent per year across most age groups as well as across races and ethnicities (Appendix Table 1).4 Other high-income countries also have experienced this broad-based decline, which for many even appeared to accelerate between 1998 and 2013 (Appendix Table 2).

Relative to this baseline of improvement, the mortality gap for white Americans becomes much more pronounced (Exhibit 2).5 It spans all the years of working life (ages 19–65) but is especially large at midlife. Compared with an expected decline of 1.8 percent annually, observed mortality rates in 2014 resulted in more than 100 excess deaths for every 100,000 middle-aged white adults.

THE CAUSES

Case and Deaton conclude that three causes of death account for the increase in midlife white mortality: accidental poisonings (mostly drug overdoses), suicides, and chronic liver diseases and cirrhosis associated with alcohol consumption. These three factors have risen in tandem, killing twice as many working-age whites in 2014 as in 1999.6

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