Abstract
Tofacitinib and baricitinib are the first orally available, small-molecule inhibitors of Janus kinase (JAK) enzymes to be approved for the treatment of RA. Tofacitinib is a selective JAK1, 3 ...inhibitor with less activity against JAK2 and TYK2 and baricitinib is a selective, oral JAK1, 2 inhibitor with moderate activity against TYK2 and significantly less activity against JAK3. Both drugs have undergone extensive phase III clinical trials in RA and demonstrated rapid improvements in disease activity, function and patient-reported outcomes as well as disease modification. Tofacitinib 5 mg bd, was approved by the Federal Drug Administration in 2012 for the treatment of RA in patients who are intolerant or unresponsive to MTX. An extended release formulation for the treatment of RA was approved by Federal Drug Administration in 2016. In 2017 the European Medicines Agency approved tofacitinib 5 mg bd in combination with MTX and baricitinib 4 mg and 2 mg once daily for the treatment of moderate to severe active RA in adult patients who are intolerant or unresponsive to one or more conventional synthetic DMARDs.
Aims
To investigate incidence, predictors and prognostic implications of longitudinal New York Heart Association (NYHA) class changes (i.e. improving or worsening vs. stable NYHA class) in heart ...failure (HF) across the ejection fraction (EF) spectrum.
Methods and results
From the Swedish HF Registry, 13 535 patients with EF and ≥2 NYHA class assessments were considered. Multivariable multinomial regressions were fitted to identify the independent predictors of NYHA change. Over a 1‐year follow‐up, 69% of patients had stable, 17% improved, and 14% worsened NYHA class. Follow‐up in specialty care predicted improving NYHA class, whereas an in‐hospital patient registration, lower EF, renal disease, lower mean arterial pressure, older age, and longer HF duration predicted worsening. The association between NYHA change and subsequent outcomes was assessed with multivariable Cox models. When adjusting for the NYHA class at baseline, improving NYHA class was independently associated with lower while worsening with higher risk of all‐cause and cardiovascular mortality, and first HF hospitalization. After adjustment for the NYHA class at follow‐up, NYHA class change did not predict morbidity/mortality. NYHA class assessment at baseline and follow‐up predicted morbidity/mortality on top of the changes. Results were consistent across the EF spectrum.
Conclusion
In a large real‐world HF population, NYHA class trajectories predicted morbidity/mortality after extensive adjustments. However, the prognostic role was entirely explained by the resulting NYHA class, i.e. the follow‐up value. Our results highlight that considering one‐time NYHA class assessment, rather than trajectories, might be the preferable approach in clinical practice and for clinical trial design.
Stable New York Heart Association (NYHA) class over time was much more frequent than an improvement or a worsening. Follow‐up NYHA class assessment, but not change in NYHA class over time, was independently associated with better prognosis. CI, confidence interval; HR, hazard ratio.
Patients undergoing breast cancer surgery frequently experience chronic postoperative pain. The primary objective of this randomized study was to determine if thoracic paravertebral block (TPVB) ...reduced the incidence of chronic pain after a modified radical mastectomy (MRM) when compared with general anesthesia (GA).
One hundred eighty women undergoing MRM were randomized to 1 of 3 study groups: group 1: standardized GA, group 2: GA with a single-injection TPVB and placebo paravertebral infusion, and group 3: GA with a continuous TPVB. Outcomes assessed postoperatively included acute postoperative pain and analgesic consumption and, at 3 and 6 months, the incidence and severity of chronic pain and physical and mental health-related quality of life (HRQOL).
There was no significant difference in the incidence of chronic pain at 3 months (P = 0.13) and 6 months (P = 0.79) after the MRM between the study groups. The relative risk of developing chronic pain (P = 0.25) was also similar between the groups. There was no difference in acute pain (P = 0.22) or postoperative analgesic consumption (P = 0.67) between the groups. Nevertheless, differences were observed in chronic pain-related secondary outcome variables. The TPVB groups reported lower chronic pain scores (P < 0.05), exhibited fewer symptoms and signs of chronic pain (P ≤ 0.01), and also experienced better physical and mental HRQOL than did the GA group. Chronic pain scores also decreased with time in all study groups (P < 0.05).
There is no significant difference in the incidence or relative risk of chronic pain at 3 and 6 months after an MRM when TPVB is used in conjunction with GA. Nevertheless, patients who receive a TPVB report less severe chronic pain, exhibit fewer symptoms and signs of chronic pain, and also experience better physical and mental HRQOL.
: Benign tumours of the hand and upper limb are frequently seen by hand surgeons. The literature in this field is relatively rich, however there are several issues which are not referenced in the ...literature or are subject to divergent opinions. These concerns complaints caused by the tumours.
The objective of this study was to investigate the distribution, symptomatology and histological analysis of benign tumours within the upper extremity.
: The study group consisted of 346 patients – 234 women (68%) and 112 men (32%) at a mean age of 53 years who were operated on in the authors’ institution between 2015–2018. The criteria of inclusion were as follows: the presence of a tumour in the upper extremity which was not a ganglion cyst or malignant tumour, and available results of histopathological examination of the resected tumour.
: Most lesions – 231 (67%) were localized in the digits, followed by the metacarpus – 46 (13.3%). The size of most of the tumours – 204 (59%) was 0.6–2 cm. The tumours were present for a mean duration of 2.6 years before surgical excision. For most patients, an unaesthetic appearance of the hand was the primary problem. Most of the tumours – 248 (72%), were symptomatic by means of pain at compression or caused mild dysfunction. In the study group, most tumours were giant-cell tumours of the tendon sheath – 96 (27.7%), lipomas – 44 (12.7%) and rheumatoid nodules – 30 (8.7%).
In clinical practice, antibiotics and/or inhaled or oral hormone preparations are the first line of treatment for chronic pharyngitis. However, this therapeutic regimen is not satisfactory enough. At ...present, medicinal plants as dietary supplements or functional foods are widely recognized for the treatment and prevention of different diseases.
This study aimed to evaluate the efficacy of the botanical lozenge made from several medicinal plant extracts in the treatment of chronic pharyngitis and its effects on patients' illness perception and adherence to treatment.
Patients with chronic pharyngitis were randomly assigned to the experimental group (n = 52) or the control group (n = 51). Patients were given botanical lozenges prepared from the extracts of medicinal plants such as
(Swingle) C. Jeffrey ex A.M.Lu and Zhi Y. Zhang Cucurbitaceae; Siraitiae fructus,
Thunb Caprifoliaceae; Lonicerae japonicae flos,
(Jacq.) A. DC Campanulaceae; Platycodon radix, and
Fisch. ex DC Fabaceae; Glycyrrhizae radix et rhizoma or placebos made of starch for 15 days. The improvement of pharyngeal symptoms and signs, illness perception, and adherence to treatment were evaluated at the end of the intervention.
The total score of pharyngeal symptoms of patients in the experimental group (3.33 ± 2.33) was significantly lower than that in the control group (5.20 ± 2.93) (
< 0.01). In comparison to the control group (3.43 ± 1.43), the total pharyngeal signs score of patients in the experimental group (2.69 ± 1.59) was considerably lower (
0.01). The improvement rates of pharyngeal itching, dry throat, pharyngeal foreign body sensation, aggravation due to excessive speaking, and congestion of pharyngeal mucosa in the experimental group were 73.81%, 67.50%, 67.57%, 65.22% and 44%, respectively, which were significantly higher than those in the control group (
0.05). In addition, patients taking botanical lozenges had better illness perception and adherence to treatment than those taking placebos (
< 0.05). Patients with low adherence to treatment showed less personal control, concerns, and understanding of chronic pharyngitis (
< 0.05).
Botanical lozenges not only aided patients in recovering from chronic pharyngitis but also improved their positive perceptions of the disease, which helped them adhere to their treatment regimen.
: https://www.chictr.org.cn/, identifier ChiCTR2200062139.
No previous study has evaluated systematically the relationship between metabolic syndrome (MetS) and prostate-related symptoms and signs in young infertile men. We studied 171 (36.5 ± 8.3-years-old) ...males of infertile couples. MetS was defined based on the National Cholesterol Education Program Third Adult Treatment Panel. All men underwent hormonal (including total testosterone (TT) and insulin), seminal (including interleukin-8 (IL-8), seminal plasma IL-8 (sIL-8)), scrotal and transrectal ultrasound evaluations. Because we have previously assessed correlations between MetS and scrotal parameters in a larger cohort of infertile men, here, we focused on transrectal features. Prostate-related symptoms were assessed using the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Prostate Symptom Score (IPSS). Twenty-two subjects fulfilled MetS criteria. In an age-adjusted logistic ordinal model, insulin levels increased as a function of MetS components (Wald = 29.5, P < 0.0001) and showed an inverse correlation with TT (adjusted r = -0.359, P< 0.0001). No association between MetS and NIH-CPSI or IPSS scores was observed. In an age-, TT-, insulin-adjusted logistic ordinal model, an increase in number of MetS components correlated negatively with normal sperm morphology (Wald = 5.59, P< 0.02) and positively with sIL-8 levels (Wald = 4.32, P < 0.05), which is a marker of prostate inflammation, with prostate total and transitional zone volume assessed using ultrasound (Wald = 17.6 and 12.5, both P < 0.0001), with arterial peak systolic velocity (Wald = 9.57, P = 0.002), with texture nonhomogeneity (hazard ratio (HR) = 1.87 (1.05-3.33), P < 0.05), with calcification size (Wald = 3.11, P< 0.05), but not with parameters of seminal vesicle size or function. In conclusion, in males of infertile couples, MetS is positively associated with prostate enlargement, biochemical (sIL8) and ultrasound-derived signs of prostate inflammation but not with prostate-related symptoms, which suggests that MetS is a trigger for a subclinical, early-onset form of benign prostatic hyperplasia.
The relationship between physical activity and lower limb veins is complex. If a sedentary lifestyle is considered to be negative on lower limb veins, specific information on physical activity ...varicose vein volume is sparse, especially the effect of high physical activity volume. The main objective of the VARISPORT study was to evaluate lower limb veins (clinically, morphologically, and haemodynamically) and chronic venous disease symptoms in subjects exposed to high physical activity volume compared with a group of non-exposed subjects.
A cross sectional study compared a group of high exercise training volume volunteers (more than eight hours of uninterrupted vigorous intensity physical activity per week for more than six months: high physical activity volume group, HPAV group) with a volunteer control group matched for age, sex, and body mass index. Clinical examination was performed to determine the Clinical, Etiological, Anatomical, Pathophysiological (CEAP) classification of each subject and the Carpentier score was used to assess symptoms related to possible chronic venous disease. Duplex ultrasonography was used to assess vein diameters and reflux in the deep and superficial veins.
One hundred and nineteen subjects were included in each group. The lower limb veins (deep and superficial) were significantly more dilated in the HPAV group. More reflux was found in the great saphenous veins and non-saphenous veins in the HPAV group. High physical activity volume was associated with a higher frequency of visible varicose veins (stage C2 of the CEAP classification), odds ratio 3.37 (95% confidence interval 1.66 – 7.25) without impact on functional discomfort (44 subjects with a Carpentier score ≥ 1 in each group).
The VARISPORT study reported an increase in the calibre of the lower limb veins without impact on functional discomfort. Further studies are needed to determine whether these athletic veins are truly pathological varicose veins or simply an adaptation to high physical activity volumes.
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