Overview of Cochrane Systematic Reviews of rehabilitation interventions for persons with rheumatoid arthritis: a mapping synthesis.

The aim of this paper was to provide an overview of Cochrane Systematic Reviews (CSRs), which synthesizes the quality and quantity of available evidence on the effectiveness of rehabilitation interventions in rheumatoid arthritis (RA). The World Health Organization (WHO) requested Cochrane Rehabilitation the CSRs search to develop the Package of Interventions in Rehabilitation (PIR). We searched the Cochrane Library using the terms "rheumatoid arthritis" and "rehabilitation." We screened the CSRs according to the search strategy based on the methodology developed for the WHO PIR. The search period for the data provided to WHO was between 1 September 2009 and 2019. We updated the search to 1 September 2022 for this paper. We summarized the CSRs identified after the screening process using an evidence map, grouping outcomes, and comparisons of included CSRs indicating the effect and the quality of evidence to provide a comprehensive view of current knowledge. We identified 10 CSRs, including 92 primary studies with 10,801 participants and 23 comparisons. They explored the effectiveness and/or safety of either non-pharmacological or pharmacological (for symptom control only) interventions. Outcomes were pain, muscle strength, grip/pinch strength, tender joints, swollen joints, fatigue, disease activity, radiological damage, physical function, hand function, participant adherence, clinical improvement, withdrawals, and adverse events. Our mapping synthesis indicates that physical activity and exercises in RA are effective non-pharmacological interventions for some outcomes, such as hand function, muscle strength and fatigue, without any deterioration of pain, disease activity and radiological involvement. Psychosocial interventions show a small beneficial effect on fatigue. Regarding pharmacological agents, celecoxib presents similar analgesic effects with traditional NSAIDs but fewer gastric adverse events. Current evidence supports physical activity and exercise programs for individuals with RA. However, well-designed studies will help document the exact effects of these programs on different outcomes and physiological mechanisms in RA. There were inconclusive results for some of the interventions due to low and very-low quality of evidence. Furthermore, due to the lack of CSRs on therapeutic patient education, orthoses, physical modalities and assistive devices in the search period, it was impossible to synthesise the evidence on those interventions.

Deep sequencing shows low-level oncogenic hepatitis B virus variants persists post-liver transplant despite potent anti-HBV prophylaxis.

Recent studies suggest that withdrawal of hepatitis B immune globulin (HBIG) and nucleos(t)ide analogues (NA) prophylaxis may be considered in HBV surface antigen (HBsAg)-negative liver transplant (LT) recipients with a low risk of disease recurrence. However, the frequency of occult HBV infection (OBI) and HBV variants after LT in the current era of potent NA therapy is unknown. Twelve LT recipients on prophylaxis were tested in matched plasma and peripheral blood mononuclear cells (PBMCs) for HBV quasispecies by in-house nested PCR and next-generation sequencing of amplicons. HBV covalently closed circular DNA (cccDNA) was detected in Hirt DNA isolated from PBMCs with cccDNA-specific primers and confirmed by nucleic acid hybridization and Sanger sequencing. HBV mRNA in PBMC was detected with reverse-transcriptase nested PCR. In LT recipients on immunosuppressive therapy (10/12 male; median age 57.5 [IQR: 39.8-66.5]; median follow-up post-LT 60 months; 6 pre-LT hepatocellular carcinoma [HCC]), 9 were HBsAg-. HBV DNA was detected in all plasma and PBMC tested; cccDNA and/or mRNA was detected in the PBMC of 10/12 patients. Significant HBV quasispecies diversity (ie 143-2212 nonredundant HBV species) was noted in both sites, and single nucleotide polymorphisms associated with cirrhosis and HCC were detected at varying frequencies. In conclusion, OBI and HBV variants associated with severe liver disease persist in LT recipients on prophylaxis. Although HBV control and cccDNA transcriptional silencing may occur despite immunosuppression, complete virological eradication does not occur in LT recipients with a history of HBV-related end-stage liver disease.

Tenofovir disoproxil fumarate significantly decreases serum lipoprotein levels compared with entecavir nucleos(t)ide analogue therapy in chronic hepatitis B carriers.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first-line treatments for chronic hepatitis B (CHB). Studies suggest lipid lowering effect of TDF in human immunodeficiency virus positive (HIV+) individuals, but the effect on lipids and cardiovascular disease (CVD) risk in CHB is unknown. AIM: To compare TDF vs ETV effects on lipid levels in CHB. METHODS: In this retrospective cohort study, data on serum lipids and CVD risk factors at baseline and ~1 year on TDF or ETV were collected from CHB carriers. We used propensity score matched models to assess the effect on total cholesterol (TC), LDL-C, HDL and triglycerides (TGL). RESULTS: In 348 patients, median age was 57 (IQR: 47-65 years), 63% were male, 77% were Asian, 19% were cirrhotic, 25% were HBeAg positive at baseline, and 72% received TDF vs 28% ETV. ETV-treated patients were older (median age: 60 vs 55, P<.01), had similar smoking and hypertension rates, but diabetes and dyslipidemia were more prevalent (19% vs 9%, P=.01; 14% vs 6%, P=.05, respectively). In propensity score matched models for age, gender, usage of lipid lowering agents, dyslipidemia and diabetes, TDF-treated patients were more likely to show a 20% decrease in TC (95% CI: 3%-25%), LDL-C (95% CI: 1%-25%) and HDL-C (CI: 10%-30%) levels compared with those on ETV. No change in TGL was observed in either group. CONCLUSIONS: A greater decline in TC, LDL-C and HDL was observed in CHB carriers receiving TDF compared with ETV. These data may influence anti-viral choice in CHB carriers at risk for CVD.

The incidence of hepatocellular carcinoma is reduced in patients with chronic hepatitis B on long-term nucleos(t)ide analogue therapy.

BACKGROUND: North American data are lacking on the effect of nucleos(t)ide analogues (NA) in preventing chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). AIM: To determine the incidence of HCC in NA-treated patients and compare this risk with that predicted without treatment based on the REACH-B model. METHODS: In this retrospective study, the incidence of HCC was determined in CHB patients initiated on NA from 1999 to 2012. Pre-treatment data utilised in the REACH-B model were used to predict the annual HCC risk. The standardised incidence ratio (SIR) for HCC was calculated by comparing the observed to expected number of cases, and HCC risk factors determined by Cox proportional hazards regression. RESULTS: Five hundred and forty nine initiated NA (14% lamivudine, 5% adefovir, 1.5% telbivudine, 39% entecavir, 41% tenofovir). Over a median follow-up of 3.2 years (IQR 1.9-4.6), 11 (3.2%) were diagnosed with HCC. Among 322 with data to calculate the REACH-B model, the median age at treatment initiation was 46 years (IQR 38-55), 65% were male, 32% HBeAg positive and 20% had cirrhosis. The median pre-treatment ALT was 71 U/L (IQR 41-127) and HBV DNA was 6.48 log10 copies/mL (4.95-8.04). The observed annual HCC incidence (0.9%; 95% CI 0.5-1.7) was significantly lower than predicted without treatment by the REACH-B model (SIR 0.46; 95% CI 0.23-0.82); this risk was reduced after 4 years of therapy (SIR 0.49; 95% CI 0.2-1.00). CONCLUSIONS: In this Canadian study of nucleos(t)ide analogues-treated patients with chronic hepatitis B, the incidence of HCC was lower than expected, suggesting that NA reduce the risk of chronic hepatitis B-related HCC.

Ungulate browsing maintains shrub diversity in the absence of episodic disturbance in seasonally-arid conifer forest.

Ungulates exert a strong influence on the composition and diversity of vegetation communities. However, little is known about how ungulate browsing pressure interacts with episodic disturbances such as fire and stand thinning. We assessed shrub responses to variable browsing pressure by cattle and elk in fuels treated (mechanical removal of fuels followed by prescribed burning) and non-fuels treated forest sites in northeastern Oregon, US. Seven treatment paddocks were established at each site; three with cattle exclusion and low, moderate and high elk browsing pressure, three with elk exclusion and low, moderate and high cattle browsing pressure, and one with both cattle and elk exclusion. The height, cover and number of stems of each shrub species were recorded at multiple plots within each paddock at the time of establishment and six years later. Changes in shrub species composition over the six year period were explored using multivariate analyses. Generalized Linear Mixed Models were used to determine the effect of browsing pressure on the change in shrub diversity and evenness. Vegetation composition in un-browsed paddocks changed more strongly and in different trajectories than in browsed paddocks at sites that were not fuels treated. In fuels treated sites, changes in composition were minimal for un-browsed paddocks. Shrub diversity and evenness decreased strongly in un-browsed paddocks relative to paddocks with low, moderate and high browsing pressure at non-fuels treated sites, but not at fuels treated sites. These results suggest that in the combined absence of fire, mechanical thinning and ungulate browsing, shrub diversity is reduced due to increased dominance by certain shrub species which are otherwise suppressed by ungulates and/or fuels removal. Accordingly, ungulate browsing, even at low intensities, can be used to suppress dominant shrub species and maintain diversity in the absence of episodic disturbance events.

Effect of widespread agricultural chemical use on butterfly diversity across Turkish provinces.

Although agricultural intensification is thought to pose a significant threat to species, little is known about its role in driving biodiversity loss at regional scales. I assessed the effects of a major component of agricultural intensification, agricultural chemical use, and land-cover and climatic variables on butterfly diversity across 81 provinces in Turkey, where agriculture is practiced extensively but with varying degrees of intensity. I determined butterfly species presence in each province from data on known butterfly distributions and calculated agricultural chemical use as the proportion of agricultural households that use chemical fertilizers and pesticides. I used constrained correspondence analyses and regression-based multimodel inference to determine the effect of environmental variables on species composition and richness, respectively. The variation in butterfly species composition across the provinces was largely explained (78%) by the combination of agricultural chemical use, particularly pesticides, and climatic and land-cover variables. Although overall butterfly richness was primarily explained by climatic and land-cover variables, such as the area of natural vegetation cover, threatened butterfly richness and the relative number of threatened butterfly species decreased substantially as the proportion of agricultural households using pesticides increased. These findings suggest that widespread use of agricultural chemicals, or other components of agricultural intensification that may be collinear with pesticide use, pose an imminent threat to the biodiversity of Turkey. Accordingly, policies that mitigate agricultural intensification and promote low-input farming practices are crucial for protecting threatened species from extinction in rapidly industrializing nations such as Turkey. Efectos del Uso Extensivo de Agroquímicos sobre la Diversidad de Mariposas en Provincias Turcas.

Multidisciplinary Canadian consensus recommendations for the management and treatment of hepatocellular carcinoma.

Globally, hepatocellular carcinoma (hcc) is the third most common cause of death from cancer, after lung and stomach cancer. The incidence of hcc in Canada is increasing and is expected to continue to increase over the next decade. Given the high mortality rate associated with hcc, steps are required to mitigate the impact of the disease. To address this challenging situation, a panel of 17 hcc experts, representing gastroenterologists, hepatologists, hepatobiliary surgeons, medical oncologists, pathologists, and radiologists from across Canada, convened to provide a framework that, using an evidence-based approach, will assist clinicians in optimizing the management and treatment of hcc. The recommendations, summarized here, were developed based on a rigorous methodology in a pre-specified process that was overseen by the steering committee. Specific topics were identified by the steering committee and delegated to a group of content experts within the expert panel, who then systematically reviewed the literature on that topic and drafted the related content and recommendations. The set of recommendations for each topic were reviewed and assigned a level of evidence and grade according to the levels of evidence set out by the Centre for Evidence-based Medicine, Oxford, United Kingdom. Agreement on the level of evidence for each recommendation was achieved by consensus. Consensus was defined as agreement by a two-thirds majority of the 17 members of the expert panel. Recommendations were subject to iterative review and modification by the expert panel until consensus could be achieved.

Survival after liver transplantation for hepatitis C is unchanged over two decades in Canada.

Allograft failure secondary to recurrence of hepatitis C virus (HCV) infection is the most common cause of death and retransplantation among recipients with HCV infection. It has been suggested that patients transplanted for HCV have had worse outcomes in more recent years than in previous years (the 'era effect'). A Canadian transplantation registry database was analyzed to determine the outcomes of patients transplanted over the years for HCV. The results of the present analysis of 1002 patients show that the 'era effect' was not seen in liver transplantation recipients with HCV in Canada, because no survival difference was noted based on the year of transplantation. All groups had overall two-year and five-year survival rates of 76% to 83% and 69% to 72%, respectively. The present study's national results prove continued benefit to transplantation of HCV patients.

Lamivudine for the treatment of membranous glomerulopathy secondary to chronic Hepatitis B infection.

Membranous glomerulopathy is a well-recognized extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. The authors report two cases of HBV-related nephrotic syndrome treated with lamivudine. A 46-year-old Chinese man had a hepatitis B e antigen seroconversion along with improvement in his nephrotic syndrome after lamivudine therapy. Two years after treatment was discontinued, a reactivation of HBV was successfully treated again with lamivudine. A 44-year-old Chinese woman, who was intolerant of interferon, was treated with lamivudine for 15 months without a virological response. However, two years after completing lamivudine, her nephrotic syndrome resolved. Implications for the treatment of HBV-related glomerulopathy and a review of the literature are presented.

Benzocaine-induced methemoglobinemia: a condition of which all endoscopists should be aware.

Methemoglobinemia is a rare complication that can occur with the use of benzocaine-containing compounds. Two cases of methemoglobinemia are reported, and the pathophysiology and treatment of methemoglobinemia are reviewed. Both patients received topical 20% benzocaine spray before endoscopy. Immediately following the procedure, there was a reduction in O2 saturation assessed by pulse oximetry that was refractory to O2 therapy. Dramatic peripheral and central cyanosis developed. O2 saturation measured by pulse oximetry ranged from 83% to 87% on O2 by nasal prongs and 100% O2 by a nonrebreathing mask. Both patients were mildly confused and one patient complained of a significant headache. The diagnosis of methemoglobinemia was considered and arterial blood gas sampling was performed. In both patients, the arterial blood had a chocolate brown colour. A methemoglobin level of 48% and 18% was noted in patient 1 and patient 2, respectively. Both patients were treated with methylene blue, resulting in a significant improvement with gradual normalization of their O2 saturation within 10 min to 30 min. The use of benzocaine spray may not markedly alter the patient's perception of endoscopy and thus, the routine use of these agents should be questioned. If such agents are used, the physician must be aware of this association to prevent a delay in the diagnosis and management of this rare, but potentially lethal, condition.

Facemasks and facial deposition of aerosols.

Passage of aerosol around or through a facemask can result in deposition on the face and in the eyes. The present study quantified facial and eye deposition in a model simulating drug delivery to a young child. Aerosol delivery and facial deposition of radiolabeled saline test aerosols were studied in vitro with filters and a gamma camera. A child's face facsimile, attached to a piston pump, was used to simulate the patient receiving aerosol therapy. A filter placed in the oropharynx of the face facsimile measured aerosol delivery (inhaled mass). Seven commercially available facemasks in combination with three jet nebulizers were studied for aerosol delivery to the "patient" as well as for deposition on the face and in the eyes. Inhaled mass varied from 2.24-5.96% of nebulizer charge (drug placed in the nebulizer). Facial deposition varied from 0.44-2.34% of nebulizer charge, with eye deposition at 0.09-1.78%. All facemasks leaked aerosol, with significant facial and eye deposition approaching in magnitude delivery to the lung. Factors affecting facial and eye deposition include the interactive design characteristics of the facemask and nebulizer, as well as the aerodynamic properties of the aerosol.

Effect of tubing deposition, breathing pattern, and temperature on aerosol mass distribution measured by cascade impactor.

Aerosols produced by nebulizers are often characterized on the bench using cascade impactors. We studied the effects of connecting tubing, breathing pattern, and temperature on mass-weighted aerodynamic particle size aerosol distributions (APSD) measured by cascade impaction. Our experimental setup consisted of a piston ventilator, low-flow (1.0 L/min) cascade impactor, two commercially available nebulizers that produced large and small particles, and two "T"-shaped tubes called "Tconnector(cascade)" and "Tconnector(nebulizer)" placed above the impactor and the nebulizer, respectively. Radiolabeled normal saline was nebulized using an airtank at 50 PSIG; APSD, mass balance, and Tconnector(cascade) deposition were measured with a gamma camera and radioisotope calibrator. Flow through the circuit was defined by the air tank (standing cloud, 10 L/min) with or without a piston pump, which superimposed a sinusoidal flow on the flow from the air tank (tidal volume and frequency of breathing). Experiments were performed at room temperature and in a cooled environment. With increasing tidal volume and frequency, smaller particles entered the cascade impactor (decreasing MMAD; e.g., Misty-Neb, 4.2 +/- 0.9 microm at lowest ventilation and 2.7 +/- 0.1 microm at highest, p = 0.042). These effects were reduced in magnitude for the nebulizer that produced smaller particles (AeroTech II, MMAD 1.8 +/- 0.1 to 1.3 +/- 0.1 microm; p = 0.0044). Deposition on Tconnector(cascade) increased with ventilation but was independent of cascade impactor flow. Imaging of the Tconnector(cascade) revealed a pattern of deposition unaffected by cascade impactor flow. These measurements suggest that changes in MMAD with ventilation were not artifacts of tubing deposition in the Tconnector(cascade). At lower temperatures, APSD distributions were more polydisperse. Our data suggest that, during patient inhalation, changes in particle distribution occur that are related to conditions in the tubing and may reduce the diameters of particles entering the patient. This effect is more significant for nebulizers producing large particles. Changes in ambient temperature did not affect these observations.

A case of coexisting primary biliary cirrhosis and primary sclerosing cholangitis: a new overlap of autoimmune liver diseases.

Although the etiology of AIH, PBC, and PSC remains unknown, it is apparent that these autoimmune liver diseases share many common features and can coexist in the same patient. Our patient had features of PBC and later clearly developed a picture of PSC. This case suggests that PBC, PSC, AIH, and autoimmune cholangitis are part of a spectrum of chronic autoimmune liver disease that develop in response to some yet unidentified antigen.

Increased midbrain 5-HT1A receptor number and responsiveness in cholestatic rats.

Midbrain somatodendritic 5-HT1A autoreceptors play a central inhibitory role in the regulation of serotonergic neurotransmission. Given that serotonergic neurotransmission appears to be altered in experimental cholestatic liver disease we examined alterations in midbrain 5-HT1A autoreceptor binding and physiological responses in rats with experimental cholestatic liver disease in comparison to non-cholestatic controls. Using a standard receptor binding assay cholestatic rats exhibited an increase in midbrain 5-HT1A receptor number but no change in receptor affinity compared to controls. Midbrain 5-HT1A receptor mRNA expression as determined by semiquantitative RT-PCR was similar in cholestatic and non-cholestatic animals. In addition, cholestatic rats exhibited enhanced 5-HT1A autoreceptor-mediated hypothermic and hyperphagic responses compared to non-cholestatic controls after the administration of the highly specific 5-HT1A receptor agonist LY293284. These findings indicate that experimental cholestatic liver injury is associated with enhanced 5-HT1A autoreceptor-mediated physiological responsiveness in the setting of increased midbrain 5-HT1A receptor number but not affinity.

Cystadenoma of the liver without mesenchymal stroma in a female following hormonal therapy for acne.

BACKGROUND: Liver cystadenomas are relatively rare tumours that can be difficult to diagnose; treatment entails complete surgical extirpation either by either anatomical resection or enucleation. CASE OUTLINE: A 19-year-old woman presented with acute onset of abdominal pain and was found to have a multilocular giant liver cyst.The cyst was percutaneously drained; CEA and CA 19-9 tumour markers were elevated in this cyst fluid: CEA 96 microg/L, CAI9-9 37 550 kU/L. The cyst was completely enucleated and has not recurred. Pathological examination confirmed a cystadenoma without mesenchymal stroma, and tumour oestrogen and progesterone receptors were negative. DISCUSSION: This is the fourth report of a liver cystadenoma without mesenchymal stroma in a female and the first to document elevated cyst fluid tumour markers. This case also illustrates the possible relationship between hormonal therapy and tumour growth.

Treatment options in patients with chronic hepatitis C.

Hepatitis C is a major health care problem plagued by the lack of a truly effective therapy. To date, the combination of interferon and ribavirin has provided the best chance of viral eradication. However, this therapy is expensive, has multiple side effects and works in less than half of patients. New strategies need to be developed to deal with the increasing burden of hepatitis C-related disease, and we anxiously await the arrival of new drugs such as helicase and protease inhibitors.

C1 inhibitor deficiency and angioedema of the small intestine masquerading as Crohn's disease.

A case of C1 inhibitor deficiency presenting as localized edema of the small intestine is described. A 16-year-old, previously healthy woman presented with recurrent attacks of abdominal pain and vomiting following minor abdominal trauma. Investigations including computed tomography scan and barium studies confirmed localized edema of the jejunum. At laparoscopy, Crohn's disease was suspected; however, a subsequent enteroscopy was normal. Complement levels revealed a low C4 level, and C1 inhibitor deficiency was later confirmed. Attacks of abdominal pain began after starting oral contraceptives and have not returned since stopping the birth control pill. This rare cause of abdominal pain is examined, and C1 inhibitor deficiency and angioedema are reviewed.

Familial idiopathic adulthood ductopenia: a report of five cases in three generations.

BACKGROUND/AIMS: Idiopathic adulthood ductopenia is a cholestatic liver disease of unknown etiology. Although most cases are sporadic, familial cases do occur. METHODS: We describe a series of adult-onset bile duct depletion involving five members of an extended family spanning three generations. The proband, a 49-year-old man, presented in 1989 with asymptomatic elevation of liver enzyme tests. Investigations for chronic liver disease, including endoscopic retrograde cholangiopancreatography, were negative. Findings on liver biopsy progressed from normal in 1989 to striking loss of interlobular bile ducts in 1992. Ursodeoxycholic acid has resulted in improvement of liver enzyme tests. The proband's brother required a liver transplant at age 35 for cryptogenic cirrhosis. The proband's sister, age 42, has had intermittent jaundice and elevation of liver enzyme tests since 1971. Her liver biopsy findings progressed from normal in 1975, to striking bile duct damage by 1997. The proband's 21-year-old son has elevated liver enzyme tests and a liver biopsy consistent with idiopathic adulthood ductopenia. The proband's father had a liver biopsy at age 70 for investigation of a liver mass. It revealed extensive fibrosis and striking bile duct destruction. RESULTS/CONCLUSIONS: This is the largest series of familial idiopathic adulthood ductopenia reported, and the first with multiple generations described. Genetics appears to play a role in some cases of adulthood ductopenia. Ursodeoxycholic acid may be beneficial in the treatment of this condition.