For a long time I have thought I was a statistician, interested in inferences from the particular to the general. But as I have watched mathematical statistics evolve, I have had cause to wonder and to doubt. And when I have pondered about why such techniques as the spectrum analysis of time series have proved so useful, it has become clear that their “dealing with fluctuations” aspects are, in many circumstances, of lesser importance than the aspects that would already have been required to deal effectively with the simpler case of very extensive data, where fluctuations would no longer be a problem. All in all, I have come to feel that my central interest is in data analysis, which I take to include, among other things: procedures for analyzing data, techniques for interpreting the results of such procedures, ways of planning the gathering of data to make its analysis easier, more precise or more accurate, and all the machinery and results of (mathematical) statistics which apply to analyzing data.

/pdf/the-future-of-data-analysis-1d3xhzp0y1.pdf

The Future of Data Analysis

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

https://www.jaad.org/article/S0190-9622(09)00012-7/pdf

Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: Overview and guidelines of care for treatment with an emphasis on the biologics

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fourth of 6 sections of the guidelines of care for psoriasis, we discuss the use of traditional systemic medications for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety, and offer recommendations for the use of the 3 most commonly used, and approved, traditional systemic agents: methotrexate, cyclosporine, and acitretin. We will also briefly discuss the available data for the use of azathioprine, fumaric acid esters, hydroxyurea, leflunomide, mycophenolate mofetil, sulfasalazine, tacrolimus, and 6-thioguanine in psoriasis.

https://piel-l.org/blog/wp-content/uploads/2010/05/Guidelines-of-care-for-the-management.pdf

Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In the first 5 parts of the AmericanAcademy of Dermatology Psoriasis Guidelines of Care, we have presented evidence supporting the use of topical treatments, phototherapy, traditional systemic agents, and biological therapies for patients with psoriasis and psoriatic arthritis. In this sixth and final section of the Psoriasis Guidelines of Care, we will present cases to illustrate how to practically use these guidelines in specific clinical scenarios. We will describe the approach to treating patients with psoriasis across the entire spectrum of this fascinating disease from mild to moderate to severe, with and without psoriatic arthritis, based on the 5 prior published guidelines. Although specific therapeutic recommendations are given for each of the cases presented, it is important that treatment be tailored to meet individual patients' needs. In addition, we will update the prior 5 guidelines and address gaps in research and care that currently exist, while making suggestions for further studies that could be performed to help address these limitations in our knowledge base.

Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions.

Current and future management of psoriasis

Summary
Background Patients receiving long-term methotrexate for psoriasis are at risk of developing hepatic fibrosis. Repeated liver biopsy has long been regarded as the only reliable method of detecting this and it is still recommended by the American Academy of Dermatology (AAD). More recently, monitoring by serum procollagen III aminopeptide (PIIINP) measurement (Orion Diagnostica, Espoo, Finland) has been advocated as a means of significantly reducing the need for liver biopsy.

Objectives  To assess the validity of guidelines developed in Manchester for the use of PIIINP to monitor patients with psoriasis receiving long-term methotrexate; to assess the anticipated benefits to patients of introducing this change in practice, including reduction in requirement for liver biopsy; and to determine the impact of its introduction on healthcare costs.

Methods  A multicentre audit was conducted over a 24-month period to compare the healthcare costs and outcomes of two intervention groups from centres where serial PIIINP measurement was employed with those of two control groups from centres in which AAD guidelines were followed.

Results  A sevenfold reduction in the need for liver biopsy was observed in the two intervention groups (n = 166; 0·04 and 0·02 biopsies/patient/year, respectively) compared with the two control groups (n = 87; 0·26 and 0·30 biopsies/patient/year, respectively). Abnormalities of sufficient severity to influence management were identified in one in five patients biopsied in the main intervention group compared with one in 16 in the control groups. The overwhelming majority of patients surveyed expressed a preference for being monitored by methods that would minimize the need for liver biopsy. The adoption of PIIINP for monitoring would result in significant cost savings.

Conclusions  This audit has shown that patients managed by the Manchester protocol using serial PIIINP measurement and selective liver biopsy were not disadvantaged in comparison with those managed according to AAD guidelines; they were subjected to sevenfold fewer liver biopsies without evidence that important liver toxicity was missed in the process. If PIIINP monitoring were widely adopted, methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy; it would also result in significant savings to the healthcare budget.

Replacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long‐term methotrexate: a multicentre audit and health economic analysis

SUMMARY

The serum level of the aminoterminal peptide of type III procollagen (P3NP) was measured in 51 psoriatic patients on long-term, once weekly, low-dose methotrexate and in a control group of patients with extensive psoriasis who had never had systemic treatment. Serum P3NP levels were normal in all control patients, but were elevated in the majority of methotrexate-treated patients, even those with normal or non-specific liver histology. Although the highest P3NP values were found in the groups of patients with fibrosis and cirrhosis, isolated P3NP measurements did not discriminate between individuals with and without significant liver pathology.



Neither standard nor dynamic liver function tests were able to identify patients with significant liver damage and in most cases results were in the normal range.

Serum type III procollagen peptide, dynamic liver function tests and hepatic fibrosis in psoriatic patients receiving methotrexate.

In a previous study, it was shown that the serum levels of type III procollagen aminoterminal peptide (P3NP) were significantly greater in patients receiving methotrexate (MTX) treatment for psoriasis than in untreated control patients with psoriasis. Although levels were highest in patients with hepatic fibrosis and cirrhosis, serum P3NP concentrations in those patients with normal liver histology on light microscopy were also shown to be significantly higher than in controls. In the present study, liver biopsies from 22 such 'normal' patients were examined by electron microscopy, in order to determine whether P3NP levels correlated with ultrastructurally demonstrable fibrosis. Fibrosis in the perisinusoidal space of Disse was present in as many as 82% of biopsies. Although the prevalence of such fibrosis in psoriasis patients who have not received MTX is unknown, the high prevalence of Disse space fibrosis and of raised P3NP in MTX-treated patients suggests that MTX causes subtle liver damage in a majority of treated patients. However, we were unable to show a statistical correlation between P3NP and the degree of Disse space fibrosis.

Abnormalities of serum type III procollagen aminoterminal peptide in methotrexate-treated psoriatic patients with normal liver histology do not correlate with hepatic ultrastructural changes.

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Replacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long‐term methotrexate: a multicentre audit and health economic analysis

Serum type III procollagen peptide, dynamic liver function tests and hepatic fibrosis in psoriatic patients receiving methotrexate.

Abnormalities of serum type III procollagen aminoterminal peptide in methotrexate-treated psoriatic patients with normal liver histology do not correlate with hepatic ultrastructural changes.

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