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Multimillion dollar drug trafficking ring run out of Fitzroy public housing flat
A14 year old girl visited a multimillion dollar drug trafficking ring operating out of an 11th floor Fitzroy public housing flat more than 70 times to either collect heroin for her mother or pay off her debts, a court has heard.
The mastermind who ran van cleef & arpels necklace knock off the drug trafficking ring, Thi Nho Em Le, 49, was jailed for 11 years with a minimum of eight years after she pleaded guilty in the County Court to one count of trafficking a commercial quantity of heroin, but appealed her sentence.
Court of Appeal Justices Robert Redlich and David Beach said Le (known as Chi fake van cleef and arpels necklace Tu), Khi Sin Mong, Thanh Hai Pham, and Thi Nho Le (known as Chi Ba) had all been involved in trafficking heroin and were arrested in August 2010 after a nine month police investigation.
Mong is Chi Tu's defacto partner, Chi Ba is her older sister, and Pham is Chi Ba's husband.
The appeal judges said Chi Tu was the principal of the heroin trafficking business involving her partner Mong, her brother Muoi Van Le and his wife Nga Thi.
Her sister, Chi Ba, ran a separate heroin trafficking business with her husband Pham and Mong.
Mong was a senior member of his defacto's heroin trafficking enterprise, sourcing and arranging the purchase of heroin from suppliers for both syndicates.
Chi Tu would give Mong money to buy the heroin. Chi Tu and her sister would then dilute the heroin and re package it into smaller amounts for sale.
Chi Tu primarily sold heroin in pre packaged amounts of 1.7 grams (blue package) or 3.5 grams (yellow package) and kept records of her sales out of the Fitzroy flat she lived in with Mong.
Her younger brother Muoi and his wife Nga, who also lived in the flat, assisted by selling heroin, receiving money, and recording sales.
Chi Tu also used her Brunswick property, occupied by her children and grandchildren, and her sister Sau Thi Le's house in St Albans, to store and prepare drugs.
The appeal judges said Chi Tu had many regular customers at the Fitzroy flat, with her 'shop' opening from 8am to 10pm.
"One customer would send her 14 year old daughter 'W' to the appellant's flat to buy heroin for her," the judges said.
"The appellant (Chi Tu) supplied W with heroin on ten occasions, on one occasion advising her to 'stash it in her bum.' W was observed attending the appellant's flat on 62 other occasions to either collect heroin or deliver money for her mother."
Chi Tu, Chi Ba, Pham and Mong would use code words to refer to heroin and to discuss its quantity and quality.
Customers wanting to purchase heroin were told to use terms such as being 'bored' and wanting to 'have fun', and were invited to come over for 'chit chat', or play Xap Xam, Tu Sac van cleef and arpels necklace knock off or cards. Money was often referred to as paper and was generally spoken about in multiples of 100 or 1000, depending on the context.
The police were referred to as 'big brother' and 'paternal grandfathers'.
The appeal judges said the amount of heroin sold was estimated to be more than 11 kilograms.
Police carried out raids in August 2010 and seized more than $2 million in cash, Crown Casino chips and jewellery.
Mong was jailed for 11 years and six with a minimum of eight years and six months, while Chi Ba was jailed for 12 years with a minimum of nine years.
Chi Tu appealed against her sentence but Justices Redlich and Beach rejected the appeal, saying the sentencing judge had carefully considered each sentence imposed on the different family members.
A14 year old girl visited a multimillion dollar drug trafficking ring operating out of an 11th floor Fitzroy public housing flat more than 70 times to either collect heroin for her mother or pay off her debts, a court has heard.
The mastermind who ran van cleef & arpels necklace knock off the drug trafficking ring, Thi Nho Em Le, 49, was jailed for 11 years with a minimum of eight years after she pleaded guilty in the County Court to one count of trafficking a commercial quantity of heroin, but appealed her sentence.
Court of Appeal Justices Robert Redlich and David Beach said Le (known as Chi fake van cleef and arpels necklace Tu), Khi Sin Mong, Thanh Hai Pham, and Thi Nho Le (known as Chi Ba) had all been involved in trafficking heroin and were arrested in August 2010 after a nine month police investigation.
Mong is Chi Tu's defacto partner, Chi Ba is her older sister, and Pham is Chi Ba's husband.
The appeal judges said Chi Tu was the principal of the heroin trafficking business involving her partner Mong, her brother Muoi Van Le and his wife Nga Thi.
Her sister, Chi Ba, ran a separate heroin trafficking business with her husband Pham and Mong.
Mong was a senior member of his defacto's heroin trafficking enterprise, sourcing and arranging the purchase of heroin from suppliers for both syndicates.
Chi Tu would give Mong money to buy the heroin. Chi Tu and her sister would then dilute the heroin and re package it into smaller amounts for sale.
Chi Tu primarily sold heroin in pre packaged amounts of 1.7 grams (blue package) or 3.5 grams (yellow package) and kept records of her sales out of the Fitzroy flat she lived in with Mong.
Her younger brother Muoi and his wife Nga, who also lived in the flat, assisted by selling heroin, receiving money, and recording sales.
Chi Tu also used her Brunswick property, occupied by her children and grandchildren, and her sister Sau Thi Le's house in St Albans, to store and prepare drugs.
The appeal judges said Chi Tu had many regular customers at the Fitzroy flat, with her 'shop' opening from 8am to 10pm.
"One customer would send her 14 year old daughter 'W' to the appellant's flat to buy heroin for her," the judges said.
"The appellant (Chi Tu) supplied W with heroin on ten occasions, on one occasion advising her to 'stash it in her bum.' W was observed attending the appellant's flat on 62 other occasions to either collect heroin or deliver money for her mother."
Chi Tu, Chi Ba, Pham and Mong would use code words to refer to heroin and to discuss its quantity and quality.
Customers wanting to purchase heroin were told to use terms such as being 'bored' and wanting to 'have fun', and were invited to come over for 'chit chat', or play Xap Xam, Tu Sac van cleef and arpels necklace knock off or cards. Money was often referred to as paper and was generally spoken about in multiples of 100 or 1000, depending on the context.
The police were referred to as 'big brother' and 'paternal grandfathers'.
The appeal judges said the amount of heroin sold was estimated to be more than 11 kilograms.
Police carried out raids in August 2010 and seized more than $2 million in cash, Crown Casino chips and jewellery.
Mong was jailed for 11 years and six with a minimum of eight years and six months, while Chi Ba was jailed for 12 years with a minimum of nine years.
Chi Tu appealed against her sentence but Justices Redlich and Beach rejected the appeal, saying the sentencing judge had carefully considered each sentence imposed on the different family members.
NDP passes motion to ban microbeads from personal products
The NDP successfully passed a motion in the House of Commons Tuesday fake vca necklace that could lead to the banning of microbeads from personal products.
The ban is good news for University of Waterloo researchers who found the microbeads throughout the Great Lakes along with other plastic debris.
Opposition MP and environment critic Megan Leslie's motion, which called for microbeads to be added to the list of toxic substances, received all party support Tuesday afternoon
Before the motion passed, Colin Carrie, parliamentary secretary to the Minister of the Environment, said the government will "prioritize" microbeads for assessment.
Microbeads are commonly used in personal products such face wash.
In December, UW's Philippe Van Cappellen and a team of researchers looked into what scientists actually knew about plastic debris in the Great Lakes, and found there was minimal research on the freshwater lakes, especially compared to the ocean.
Microbeads aren't the only problem, Van Cappellen said, but they are a big problem.
"The main issue is that they're very small and move very far from the source area," he told QMI Agency. "And they're also ingested by wildlife, which can have an effect on fish and van cleef pendant replica shellfish."
The research found the highest concentration of debris was in Lake Erie it had more debris than Lake Geneva, which has more than three times the van cleef arpels necklace replica surrounding population density.
The lack of knowledge of plastic debris in the Great Lakes is a big part of the problem, he said, adding his team has been advocating for more research on plastic's impact as well as for more regulation of things such as microbeads.
The NDP successfully passed a motion in the House of Commons Tuesday fake vca necklace that could lead to the banning of microbeads from personal products.
The ban is good news for University of Waterloo researchers who found the microbeads throughout the Great Lakes along with other plastic debris.
Opposition MP and environment critic Megan Leslie's motion, which called for microbeads to be added to the list of toxic substances, received all party support Tuesday afternoon
Before the motion passed, Colin Carrie, parliamentary secretary to the Minister of the Environment, said the government will "prioritize" microbeads for assessment.
Microbeads are commonly used in personal products such face wash.
In December, UW's Philippe Van Cappellen and a team of researchers looked into what scientists actually knew about plastic debris in the Great Lakes, and found there was minimal research on the freshwater lakes, especially compared to the ocean.
Microbeads aren't the only problem, Van Cappellen said, but they are a big problem.
"The main issue is that they're very small and move very far from the source area," he told QMI Agency. "And they're also ingested by wildlife, which can have an effect on fish and van cleef pendant replica shellfish."
The research found the highest concentration of debris was in Lake Erie it had more debris than Lake Geneva, which has more than three times the van cleef arpels necklace replica surrounding population density.
The lack of knowledge of plastic debris in the Great Lakes is a big part of the problem, he said, adding his team has been advocating for more research on plastic's impact as well as for more regulation of things such as microbeads.
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Moylan Obituary
Moylan, James (Jim) Age 84, of Brooklyn Center, left us peacefully on June 21st. He was preceded in death by son James Jr., brothers Harry, Joe Bob, sister Dorothy. He is survived by his wife of 65 years Bobbye; brother Dick Moylan; daughters Michelle Smith, Patricia Givogre and Katie Swedburg; grandsons Dana Smith and Jeremiah DeBolt; granddaughters Lori Gore, Mercia Givogre, Amy Moylan, Magdalene (Rob) Welp, Colleen DeBolt and Jessica Miller; 17 great grandchildren and two great great grandchildren. Jim left Mpls South High School in 1949 to join the Navy. He was stationed in Tennessee where he met Bobbye. They knew each other four months and then eloped to Mississippi to be married. After leaving the Navy in 1953 he joined Clover Leaf Creamery where he worked for the next 35 years. During this time he was imitation van cleef earrings very active in Teamster Local 471. He served on the Board of the Clover Leaf Credit Union for many years until it joined with Firstel Credit Union. Jim was the co founder of the Minnesota Frogman and taught many people to scuba dive. He was also the co founder of the Third Wheel, Inc side car club. Always looking for adventure, he even raced in the demolition derby a few times. Lions Club. He loved the Lions. He held fake van cleef and arpels necklace many offices and he felt honored to receive many awards for his hard work. Jim and his wife, Bobbye, loved to travel and van cleef and arpels necklace imitation preferred the more primitive places. Their last trip was a cruise around the world. Service Saturday, July 9th at Evans Nordby in Brooklyn Center. Memorials to Minnesota Lions Eye Bank.
Moylan, James (Jim) Age 84, of Brooklyn Center, left us peacefully on June 21st. He was preceded in death by son James Jr., brothers Harry, Joe Bob, sister Dorothy. He is survived by his wife of 65 years Bobbye; brother Dick Moylan; daughters Michelle Smith, Patricia Givogre and Katie Swedburg; grandsons Dana Smith and Jeremiah DeBolt; granddaughters Lori Gore, Mercia Givogre, Amy Moylan, Magdalene (Rob) Welp, Colleen DeBolt and Jessica Miller; 17 great grandchildren and two great great grandchildren. Jim left Mpls South High School in 1949 to join the Navy. He was stationed in Tennessee where he met Bobbye. They knew each other four months and then eloped to Mississippi to be married. After leaving the Navy in 1953 he joined Clover Leaf Creamery where he worked for the next 35 years. During this time he was imitation van cleef earrings very active in Teamster Local 471. He served on the Board of the Clover Leaf Credit Union for many years until it joined with Firstel Credit Union. Jim was the co founder of the Minnesota Frogman and taught many people to scuba dive. He was also the co founder of the Third Wheel, Inc side car club. Always looking for adventure, he even raced in the demolition derby a few times. Lions Club. He loved the Lions. He held fake van cleef and arpels necklace many offices and he felt honored to receive many awards for his hard work. Jim and his wife, Bobbye, loved to travel and van cleef and arpels necklace imitation preferred the more primitive places. Their last trip was a cruise around the world. Service Saturday, July 9th at Evans Nordby in Brooklyn Center. Memorials to Minnesota Lions Eye Bank.
Morey Amsterdam's former family home is listed
The longtime family home of "The Dick Van Dyke Show" actor Morey (Jeff Elson )
The longtime family home of "The Dick Van Dyke Show" actor Morey Amsterdam has come on the market at $6,495,000.
The Beverly Hills Midcentury classic, with many of the original features and dcor from the time of the comedian's purchase nearly a half century ago, has a '60s vibe.
The single story house was a place where guests could feel at home.
" Ronald Reagan would stop by to visit, and Dad would tell him jokes standing in the kitchen," van cleef and arpels necklace imitation said son Gregory Amsterdam, who lived there through his college years and beyond. "There were people popping in and out all the time."
The Amsterdams often entertained at home, throwing dinner parties in the formal dining room for 10 to 15 guests. Other times the area around the kidney shaped swimming pool in the backyard was used for parties of 50 to 60, Amsterdam said.
"My father loved the sun," Amsterdam said, to the point where he would walk backward on a golf course to face it. The senior Amsterdam sometimes wrote jokes while lounging in the pool area. "If there was any hint of sun, he would be out there getting a suntan."
The family made additions to the house during their ownership, changing the footprint from a T shape to replica van cleef pendant necklace a J by adding what they called a play room with large picture windows, a television, a card table and a desk, where the comic also worked on material.
The 5,854 square foot house has walls of glass that open to the backyard, a living room with a fireplace and a step down van cleef and arpels bracelet imitation bar, a breakfast room, a den with a fireplace, four bedrooms and 4 1/2 bathrooms. There is a three car garage and large motorcourt.
Morey Amsterdam, who died in 1996 at age 87, played fellow office worker Buddy Sorrell on "The Dick Van Dyke Show" (1961 66). The gregarious actor was in show business for more than seven decades years.
Jade Mills of Coldwell Banker Beverly Hills South and Gloria Benveniste of Coldwell Banker's Marina del Rey office have the listing.
The longtime family home of "The Dick Van Dyke Show" actor Morey (Jeff Elson )
The longtime family home of "The Dick Van Dyke Show" actor Morey Amsterdam has come on the market at $6,495,000.
The Beverly Hills Midcentury classic, with many of the original features and dcor from the time of the comedian's purchase nearly a half century ago, has a '60s vibe.
The single story house was a place where guests could feel at home.
" Ronald Reagan would stop by to visit, and Dad would tell him jokes standing in the kitchen," van cleef and arpels necklace imitation said son Gregory Amsterdam, who lived there through his college years and beyond. "There were people popping in and out all the time."
The Amsterdams often entertained at home, throwing dinner parties in the formal dining room for 10 to 15 guests. Other times the area around the kidney shaped swimming pool in the backyard was used for parties of 50 to 60, Amsterdam said.
"My father loved the sun," Amsterdam said, to the point where he would walk backward on a golf course to face it. The senior Amsterdam sometimes wrote jokes while lounging in the pool area. "If there was any hint of sun, he would be out there getting a suntan."
The family made additions to the house during their ownership, changing the footprint from a T shape to replica van cleef pendant necklace a J by adding what they called a play room with large picture windows, a television, a card table and a desk, where the comic also worked on material.
The 5,854 square foot house has walls of glass that open to the backyard, a living room with a fireplace and a step down van cleef and arpels bracelet imitation bar, a breakfast room, a den with a fireplace, four bedrooms and 4 1/2 bathrooms. There is a three car garage and large motorcourt.
Morey Amsterdam, who died in 1996 at age 87, played fellow office worker Buddy Sorrell on "The Dick Van Dyke Show" (1961 66). The gregarious actor was in show business for more than seven decades years.
Jade Mills of Coldwell Banker Beverly Hills South and Gloria Benveniste of Coldwell Banker's Marina del Rey office have the listing.
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Jose Mourinho one point off top four
Manchester United 2 0 Watford: Juan Mata and Anthony Martial fire Jose Mourinho's side within one point of the Premier League top four
Man United news: All the latest from Old TraffordManchester United beat Watford at Old Trafford to stay a point behind fake van cleef and arpels gold bracelet fourth placed LiverpoolJuan Mata turned home a low Anthony Martial cross from the left to open scoring after 32 minutesMartial doubled the lead on the hour mark, finishing at the near post after Zlatan Ibrahimovicset him clearRead: Man United forward Anthony Martial proved a point to Jose MourinhoBy
Yesterday, Martial was a surprise starter and justified Mourinho's decision with a man of the match performance, helping create the first goal for Juan Mata and scoring the second himself.
On his day, there replica van cleef and arpels clover bracelet are few more explosive players in the Premier League.
For all the criticism directed his way, it is worth noting that the former Monaco winger has been involved in more Premier replica van cleef white gold bracelet League goals for United than any other player since his sensational goalscoring debut against Liverpool 17 months ago.
Watford's Craig Cathcart will not want to face him again in a hurry. Martial terrorised the former United defender and, notably, did his fair share of tracking back as well.
Mkhitaryan goes down under pressure from Watford central defender Prodl during the first half at Old Trafford
A standing ovation when he left the field 10 minutes from time was well deserved.
Martial was the pick of an irrepressible United attack whose only failing was not to make more of the multiple chances they created, particularly in the first half.
For 30 minutes, it was a painfully familiar story for United.
Mourinho has bemoaned United's finishing in nine league draws this season against the likes of Stoke, Burnley, West Ham and Hull as well as some outstanding goalkeeping performances and this game was going the same way with Heurelho Gomes on top form.
But in the end Watford simply had no answer to United's attacking verve as Mourinho's side got around them with Martial on the left and Antonio Valencia on the right. Henrikh Mkhitaryan again impressed in a more central No.10 role with Mata a ready source of creativity.
Was it United's best first half under Mourinho?
'Not just under me,' came the reply.
'It was very good. I think it is the kind of football that if, instead of being a Mourinho team it is somebody else's team, you would say art. Because it is my team, you just say it's very good, but that is fine.
'They play very well, and the fans understood. They got behind them and pushed them. It was amazing.
'We have an amazing record of being unbeaten but we should have more victories and with more victories we would be in a better position but it is what it is.'
United are now unbeaten in 16 Premier League games, but it was vital that they extended that run with a win on Saturday to keep the pressure on the rest of the top six before breaking off for four games in the cup competitions, starting with Thursday's Europa League tie against Saint Etienne at Old Trafford.
M'Baye Niang, the Watford striker on loan from Milan, is challenged by Manchester United defender Eric Bailly
Gomes did his best to frustrate them in the first half, clawing away Paul Pogba' s 30 yard drive and keeping out another effort by the Frenchman from Valencia's cross.
He also saved a header at point blank range from Zlatan Ibrahimovic who failed to beat him with two volleys, the second after controlling an excellent pass from Pogba on his chest.
Mata had a goal ruled out when referee Bobby Madley ordered a freekick to be retaken before the little Spaniard finally beat Watford's Brazilian goalkeeper in the 32nd minute.
Mata helped start the move, playing a one two with Mkhitaryan who slid the ball wide to Martial. He steered it across goal where Ibrahimovic dummied and Mata flicked in with the inside of his left boot.
Watford went closest to an equaliser eight minutes after the restart when Mauro Zarate's 25 yard freekick brought a fine one handed save from David de Gea.
But United made sure of victory with a second goal on the hour mark.
The excellent Ander Herrera won back possession midway inside the opposition half and fed Pogba. The ball was transferred quickly between Mkihitaryan and Ibrahimovic to Martial who advanced on goal and looked like he was going to cross before cleverly drilling a shot just inside Gomes' near post.
Manchester United 2 0 Watford: Juan Mata and Anthony Martial fire Jose Mourinho's side within one point of the Premier League top four
Man United news: All the latest from Old TraffordManchester United beat Watford at Old Trafford to stay a point behind fake van cleef and arpels gold bracelet fourth placed LiverpoolJuan Mata turned home a low Anthony Martial cross from the left to open scoring after 32 minutesMartial doubled the lead on the hour mark, finishing at the near post after Zlatan Ibrahimovicset him clearRead: Man United forward Anthony Martial proved a point to Jose MourinhoBy
Yesterday, Martial was a surprise starter and justified Mourinho's decision with a man of the match performance, helping create the first goal for Juan Mata and scoring the second himself.
On his day, there replica van cleef and arpels clover bracelet are few more explosive players in the Premier League.
For all the criticism directed his way, it is worth noting that the former Monaco winger has been involved in more Premier replica van cleef white gold bracelet League goals for United than any other player since his sensational goalscoring debut against Liverpool 17 months ago.
Watford's Craig Cathcart will not want to face him again in a hurry. Martial terrorised the former United defender and, notably, did his fair share of tracking back as well.
Mkhitaryan goes down under pressure from Watford central defender Prodl during the first half at Old Trafford
A standing ovation when he left the field 10 minutes from time was well deserved.
Martial was the pick of an irrepressible United attack whose only failing was not to make more of the multiple chances they created, particularly in the first half.
For 30 minutes, it was a painfully familiar story for United.
Mourinho has bemoaned United's finishing in nine league draws this season against the likes of Stoke, Burnley, West Ham and Hull as well as some outstanding goalkeeping performances and this game was going the same way with Heurelho Gomes on top form.
But in the end Watford simply had no answer to United's attacking verve as Mourinho's side got around them with Martial on the left and Antonio Valencia on the right. Henrikh Mkhitaryan again impressed in a more central No.10 role with Mata a ready source of creativity.
Was it United's best first half under Mourinho?
'Not just under me,' came the reply.
'It was very good. I think it is the kind of football that if, instead of being a Mourinho team it is somebody else's team, you would say art. Because it is my team, you just say it's very good, but that is fine.
'They play very well, and the fans understood. They got behind them and pushed them. It was amazing.
'We have an amazing record of being unbeaten but we should have more victories and with more victories we would be in a better position but it is what it is.'
United are now unbeaten in 16 Premier League games, but it was vital that they extended that run with a win on Saturday to keep the pressure on the rest of the top six before breaking off for four games in the cup competitions, starting with Thursday's Europa League tie against Saint Etienne at Old Trafford.
M'Baye Niang, the Watford striker on loan from Milan, is challenged by Manchester United defender Eric Bailly
Gomes did his best to frustrate them in the first half, clawing away Paul Pogba' s 30 yard drive and keeping out another effort by the Frenchman from Valencia's cross.
He also saved a header at point blank range from Zlatan Ibrahimovic who failed to beat him with two volleys, the second after controlling an excellent pass from Pogba on his chest.
Mata had a goal ruled out when referee Bobby Madley ordered a freekick to be retaken before the little Spaniard finally beat Watford's Brazilian goalkeeper in the 32nd minute.
Mata helped start the move, playing a one two with Mkhitaryan who slid the ball wide to Martial. He steered it across goal where Ibrahimovic dummied and Mata flicked in with the inside of his left boot.
Watford went closest to an equaliser eight minutes after the restart when Mauro Zarate's 25 yard freekick brought a fine one handed save from David de Gea.
But United made sure of victory with a second goal on the hour mark.
The excellent Ander Herrera won back possession midway inside the opposition half and fed Pogba. The ball was transferred quickly between Mkihitaryan and Ibrahimovic to Martial who advanced on goal and looked like he was going to cross before cleverly drilling a shot just inside Gomes' near post.
Methotrexate use and risk of lung disease in psoriasis
AbstractObjective To evaluate the relative risk of pulmonary disease among patients with psoriasis, psoriatic arthritis, and inflammatory bowel disease treated with methotrexate.Study selection Double blind randomised controlled trials of methotrexate versus placebo or active comparator agents in adults with psoriatic arthritis, psoriasis, or inflammatory bowel disease. Heterogeneity across the studies was not significant (I2=0%), allowing combination of trial results. 504 respiratory adverse events were documented in 1630 participants. Methotrexate was not associated with an increased risk of adverse respiratory events (relative risk 1.03, 95% confidence interval 0.90 to 1.17), respiratory infections (1.02, 0.88 to 1.19), or non infectious respiratory events (1.07, 0.58 to 1.96). No pulmonary deaths occurred.Conclusions Findings suggested that there was no increased risk of lung disease in methotrexate treated patients with non malignant inflammatory diseases. Given the limitations of the study, however, we cannot exclude a small but clinically important risk.IntroductionMethotrexate is an effective treatment for malignant as well as several non malignant inflammatory diseases.1 It is recommended as a first line disease modifying treatment for rheumatoid arthritis,2 3 psoriatic arthritis, and psoriasis,4 5 6 and for both the induction and maintenance of remission in Crohn's disease.7 Methotrexate may be used as monotherapy or in combination with other drugs, including oral agents and newer biologicals.2 3 4 5 6 7 In some disorders methotrexate is not only disease altering but also life saving.8 9Methotrexate has been implicated as a cause of serious lung toxicity.1 2 3 6 The prevalence of methotrexate related interstitial lung disease remains unknown but has been reported to be as high as 11.6% in rheumatoid arthritis.10 Studies of methotrexate induced lung disease among rheumatoid arthritis populations are confounded by the propensity to develop pulmonary infections and pulmonary manifestations of rheumatoid arthritis itself, concomitant drug use, and a higher rate of pulmonary fatalities.11 12 13 Distinguishing between rheumatoid arthritis related and methotrexate related interstitial lung disease is difficult if not impossible since the clinical and histological features overlap.14 15 16 Aside from case reports, all previous studies of methotrexate related interstitial lung disease have been in rheumatoid arthritis.A recent meta analysis of clinical trials of rheumatoid arthritis reported a small but significant increase in infectious respiratory complications but no increase in non infectious events among participants treated with methotrexate.17 Studies of clinical trials among diseases without pulmonary manifestations provide an opportunity to evaluate this problem more clearly.We performed a meta analysis of randomised controlled trials of 12 weeks or greater duration to evaluate if methotrexate fake bracelet alhambra van cleef is associated with an increased risk of lung disease in adults with psoriasis, psoriatic arthritis, and inflammatory bowel disease.MethodsData sources and searchesWe carried out a systematic literature search with no date limits using PubMed, the Cochrane central register of controlled trials, and Embase. The search was performed to 9 January 2014 (see supplementary file for keywords used in search strategy). We also searched for previously published meta analyses and systematic literature reviews. The reference lists of relevant articles were also reviewed.The inclusion criteria for study selection were: double blind randomised controlled trials; patients with psoriasis, psoriatic arthritis, or inflammatory bowel disease; studies in English; studies consisting of a minimum of two arms, at least one receiving methotrexate and at least one not receiving methotrexate; studies including only adults (18 years); trials of 12 weeks or more duration; studies of 50 patients or more; and studies reporting respiratory side effects for methotrexate and comparator groups separately. In the case of multiple publications of one randomised controlled trial we included the publication most relevant to our inclusion criteria, in terms of detailed reporting of respiratory side effects. If the results of a study were reported at multiple time points, we included the publication of greatest duration provided it remained a double blind randomised controlled trial and fully reported respiratory adverse events. If required we reviewed previous publications of the same trial to fully assess the trial protocol and risk of bias. This approach was taken to avoid including participants more than once in the meta analysis.We selected relevant articles using a two step approach. Firstly, we screened the titles and abstracts of identified references to exclude articles that did not deal with the topic of interest. Secondly, we reviewed the full text of relevant articles. Adverse events were extracted as both total respiratory adverse events and individual adverse events in each category reported in any individual trial. The terminology used to describe respiratory adverse events varied widely in the included studies; to overcome the lack of standardisation in terminology used, we classified adverse events into two subgroups: infectious adverse events and non infectious adverse events.Data synthesis and analysisWe meta analysed data using RevMan Version 5.1 software,18 expressed as relative risk for dichotomous variables. Throughout we used random effects meta analysis using the Mantel Haenszel method. Results are expressed as relative risks with 95% confidence intervals. Discrepancies were resolved by discussion and consensus. A risk of bias graph and summary were generated. We generated funnel plots to assess for publication bias.Sensitivity analysisWe performed sensitivity analysis to assess the effect of trial size (ResultsLiterature searchFrom the literature search 3188 citations were identified: 2968 from PubMed, 162 from the Cochrane central register of controlled trials, and 58 from Embase. Of the 3188 studies, only seven articles met the predefined inclusion criteria and were included in the knock off van cleef & arpels bracelet meta analysis (fig 1).Fig 1 Flow of studies through reviewStudy characteristicsThe seven included studies comprised 1640 patients, 818 of whom received methotrexate and 812 comparator treatments (table 1). The study durations ranged from 16 to 52 weeks and the number of patients from 76 to 478. The studies reported a total of 946 patient years of exposure. Five studies involved placebo comparators only, one a monoclonal antibody alone, and one placebo and monoclonal antibody comparator groups.20 21 22 23 24 25 26Table 1 Characteristics of studies included in meta analysisView this table:View popupView inlineFindingsOverall, 504 respiratory adverse events were documented (table 2). Although the I2 index was low (0%), the type and number of respiratory adverse events reported varied considerably between the studies so we chose a random effects model for our analyses. Overall, methotrexate was not associated with an increased risk of total adverse respiratory events compared with comparator agents (relative risk 1.03, 95% confidence interval 0.90 to 1.17, I2=0%, fig 2). In addition we found no increased risk in infectious respiratory events (1.02, 0.88 to 1.19, I2=0%) nor non infectious replica van cleef and arpels clover bracelet respiratory adverse events (1.07, 0.58 to 1.96, I2=0%) (see supplementary figures 1 and 2). No pulmonary deaths occurred. A single case of pneumonitis was reported in a patient treated with methotrexate in one study, but no definitive diagnostic features or additional information were reported.20Risk of bias in included studiesA risk of bias graph, risk of bias summary, and funnel plot suggested a low risk of bias (see supplementary figures 3 5). Three of the studies provided inadequate information to assess the risk of selection bias.Sensitivity analysisAdditional subgroup analyses showed no effect of study size, disease under study, comparator treatment, study drop out rate, use of folic acid supplementation, or difference between methotrexate naive patients and those who had previously received methotrexate (table 3). Two additional studies with fewer than 50 patients were identified; they reported no additional respiratory adverse events and their inclusion did not change the results of the analyses (relative risk 1.03, 95% confidence interval 0.90 to 1.17, I2=0%) (see supplementary figure 6).
AbstractObjective To evaluate the relative risk of pulmonary disease among patients with psoriasis, psoriatic arthritis, and inflammatory bowel disease treated with methotrexate.Study selection Double blind randomised controlled trials of methotrexate versus placebo or active comparator agents in adults with psoriatic arthritis, psoriasis, or inflammatory bowel disease. Heterogeneity across the studies was not significant (I2=0%), allowing combination of trial results. 504 respiratory adverse events were documented in 1630 participants. Methotrexate was not associated with an increased risk of adverse respiratory events (relative risk 1.03, 95% confidence interval 0.90 to 1.17), respiratory infections (1.02, 0.88 to 1.19), or non infectious respiratory events (1.07, 0.58 to 1.96). No pulmonary deaths occurred.Conclusions Findings suggested that there was no increased risk of lung disease in methotrexate treated patients with non malignant inflammatory diseases. Given the limitations of the study, however, we cannot exclude a small but clinically important risk.IntroductionMethotrexate is an effective treatment for malignant as well as several non malignant inflammatory diseases.1 It is recommended as a first line disease modifying treatment for rheumatoid arthritis,2 3 psoriatic arthritis, and psoriasis,4 5 6 and for both the induction and maintenance of remission in Crohn's disease.7 Methotrexate may be used as monotherapy or in combination with other drugs, including oral agents and newer biologicals.2 3 4 5 6 7 In some disorders methotrexate is not only disease altering but also life saving.8 9Methotrexate has been implicated as a cause of serious lung toxicity.1 2 3 6 The prevalence of methotrexate related interstitial lung disease remains unknown but has been reported to be as high as 11.6% in rheumatoid arthritis.10 Studies of methotrexate induced lung disease among rheumatoid arthritis populations are confounded by the propensity to develop pulmonary infections and pulmonary manifestations of rheumatoid arthritis itself, concomitant drug use, and a higher rate of pulmonary fatalities.11 12 13 Distinguishing between rheumatoid arthritis related and methotrexate related interstitial lung disease is difficult if not impossible since the clinical and histological features overlap.14 15 16 Aside from case reports, all previous studies of methotrexate related interstitial lung disease have been in rheumatoid arthritis.A recent meta analysis of clinical trials of rheumatoid arthritis reported a small but significant increase in infectious respiratory complications but no increase in non infectious events among participants treated with methotrexate.17 Studies of clinical trials among diseases without pulmonary manifestations provide an opportunity to evaluate this problem more clearly.We performed a meta analysis of randomised controlled trials of 12 weeks or greater duration to evaluate if methotrexate fake bracelet alhambra van cleef is associated with an increased risk of lung disease in adults with psoriasis, psoriatic arthritis, and inflammatory bowel disease.MethodsData sources and searchesWe carried out a systematic literature search with no date limits using PubMed, the Cochrane central register of controlled trials, and Embase. The search was performed to 9 January 2014 (see supplementary file for keywords used in search strategy). We also searched for previously published meta analyses and systematic literature reviews. The reference lists of relevant articles were also reviewed.The inclusion criteria for study selection were: double blind randomised controlled trials; patients with psoriasis, psoriatic arthritis, or inflammatory bowel disease; studies in English; studies consisting of a minimum of two arms, at least one receiving methotrexate and at least one not receiving methotrexate; studies including only adults (18 years); trials of 12 weeks or more duration; studies of 50 patients or more; and studies reporting respiratory side effects for methotrexate and comparator groups separately. In the case of multiple publications of one randomised controlled trial we included the publication most relevant to our inclusion criteria, in terms of detailed reporting of respiratory side effects. If the results of a study were reported at multiple time points, we included the publication of greatest duration provided it remained a double blind randomised controlled trial and fully reported respiratory adverse events. If required we reviewed previous publications of the same trial to fully assess the trial protocol and risk of bias. This approach was taken to avoid including participants more than once in the meta analysis.We selected relevant articles using a two step approach. Firstly, we screened the titles and abstracts of identified references to exclude articles that did not deal with the topic of interest. Secondly, we reviewed the full text of relevant articles. Adverse events were extracted as both total respiratory adverse events and individual adverse events in each category reported in any individual trial. The terminology used to describe respiratory adverse events varied widely in the included studies; to overcome the lack of standardisation in terminology used, we classified adverse events into two subgroups: infectious adverse events and non infectious adverse events.Data synthesis and analysisWe meta analysed data using RevMan Version 5.1 software,18 expressed as relative risk for dichotomous variables. Throughout we used random effects meta analysis using the Mantel Haenszel method. Results are expressed as relative risks with 95% confidence intervals. Discrepancies were resolved by discussion and consensus. A risk of bias graph and summary were generated. We generated funnel plots to assess for publication bias.Sensitivity analysisWe performed sensitivity analysis to assess the effect of trial size (ResultsLiterature searchFrom the literature search 3188 citations were identified: 2968 from PubMed, 162 from the Cochrane central register of controlled trials, and 58 from Embase. Of the 3188 studies, only seven articles met the predefined inclusion criteria and were included in the knock off van cleef & arpels bracelet meta analysis (fig 1).Fig 1 Flow of studies through reviewStudy characteristicsThe seven included studies comprised 1640 patients, 818 of whom received methotrexate and 812 comparator treatments (table 1). The study durations ranged from 16 to 52 weeks and the number of patients from 76 to 478. The studies reported a total of 946 patient years of exposure. Five studies involved placebo comparators only, one a monoclonal antibody alone, and one placebo and monoclonal antibody comparator groups.20 21 22 23 24 25 26Table 1 Characteristics of studies included in meta analysisView this table:View popupView inlineFindingsOverall, 504 respiratory adverse events were documented (table 2). Although the I2 index was low (0%), the type and number of respiratory adverse events reported varied considerably between the studies so we chose a random effects model for our analyses. Overall, methotrexate was not associated with an increased risk of total adverse respiratory events compared with comparator agents (relative risk 1.03, 95% confidence interval 0.90 to 1.17, I2=0%, fig 2). In addition we found no increased risk in infectious respiratory events (1.02, 0.88 to 1.19, I2=0%) nor non infectious replica van cleef and arpels clover bracelet respiratory adverse events (1.07, 0.58 to 1.96, I2=0%) (see supplementary figures 1 and 2). No pulmonary deaths occurred. A single case of pneumonitis was reported in a patient treated with methotrexate in one study, but no definitive diagnostic features or additional information were reported.20Risk of bias in included studiesA risk of bias graph, risk of bias summary, and funnel plot suggested a low risk of bias (see supplementary figures 3 5). Three of the studies provided inadequate information to assess the risk of selection bias.Sensitivity analysisAdditional subgroup analyses showed no effect of study size, disease under study, comparator treatment, study drop out rate, use of folic acid supplementation, or difference between methotrexate naive patients and those who had previously received methotrexate (table 3). Two additional studies with fewer than 50 patients were identified; they reported no additional respiratory adverse events and their inclusion did not change the results of the analyses (relative risk 1.03, 95% confidence interval 0.90 to 1.17, I2=0%) (see supplementary figure 6).