title: Time (Pink Floyd song)

text: The lyrics deal with the passage of time. Waters got the idea when he realised he was no longer preparing for anything in life, but was right in the middle of it. He has described this realisation taking place at ages 28 and 29 in various interviews. It is noted for its long introductory passage of clocks chiming and alarms ringing. The sounds were recorded in an antique store made as a quadrophonic test by engineer Alan Parsons, not specifically for the album.


title: Time (Pink Floyd song)

text: The album track also includes a reprise of the song "Breathe". It is the only song on the album to credit all four principal members for songwriting, and the last to do so in the band's discography.


title: Time (Pink Floyd song)

text: "Time" is in the key of F♯ minor. Each clock at the beginning of the song was recorded separately in an antiques store. These clock sounds are followed by a two-minute passage dominated by Nick Mason's drum solo, with rototoms and backgrounded by a "tick-tock" sound created by Roger Waters picking two muted strings on his bass. With David Gilmour singing lead on the verses and with Richard Wright singing lead on the bridges and with female singers and Gilmour providing backup vocals, the song's lyrics deal with Roger Waters' realization that life was not about preparing yourself for what happens next, but about grabbing control of your own destiny.


title: Time (Pink Floyd song)

text: According to an interview by Phil Taylor in 1994, David Gilmour had been using a Lexicon PCM-70 to store the circular delay sounds heard in "Time", which could duplicate the kind of echo he used to get from his old Binson echo unit.


title: Time (Pink Floyd song)

text: The verse chords cycle through F♯ minor, A major, E major, and F♯ minor again. During this section, Gilmour's guitar and Wright's keyboards are panned to the extreme right and left of the stereo spectrum, respectively. Gilmour sings lead during this section.


title: Time (Pink Floyd song)

text: The bridge section, with Wright singing lead, has a notably "thicker" texture, with the female backing vocalists singing multi-tracked "oohs" and "aahs" throughout, and Gilmour singing harmony with Wright in the second half. The chords of this section are D major seventh to A major ninth, which is repeated. The D major seventh, with the notes of D, F♯, A, and C♯, can be heard as an F♯ minor chord with a D in the bass, fitting the song's overall key. The second half progresses from D major seventh to C♯ minor, then B minor to E major.


title: Time (Pink Floyd song)

text: The first bridge leads to a guitar solo by Gilmour, which plays over the verse and bridge progressions. The solo is followed by another verse sung by Gilmour. When the bridge is repeated, it does not conclude on E major as before. Instead, the B minor leads to an F major chord, while Waters's bass stays on B, resulting in an unusual dissonance as a transition to the key of E minor for "Breathe (Reprise)".


title: Time (Pink Floyd song)

text: Pink Floyd performed the song live from 1972 to 1975, and after the departure of Waters, from 1987 to 1994. Waters began performing the song in his solo concerts, singing the verses himself, beginning in 1999 with In the Flesh and again with The Dark Side of the Moon Live from 2006 to 2008 (occasionally featuring guest appearances from Nick Mason) and the Us + Them Tour from 2017 to 2018. Gilmour has performed the song live on every one of his solo tours since Pink Floyd's "Pulse" tour, with the late Richard Wright sharing vocals until his death.


title: Time (Pink Floyd song)

text: In a contemporary review for "The Dark Side of the Moon", Loyd Grossman of "Rolling Stone" gave "Time" a positive review, describing the track as "a fine country-tinged rocker with a powerful guitar solo by David Gilmour".


title: Time (Pink Floyd song)

text: During live performances, the band back-projected a specially-commissioned, animated film by Ian Emes. The film was subsequently included as an extra on the "Pulse" DVD.


title: Robert Snodgrass

text: Robert Snodgrass (born 7 September 1987) is a Scottish professional footballer who plays as a winger for Heart of Midlothian.


title: Robert Snodgrass

text: Snodgrass started his senior career with Livingston. He also had a loan spell at Stirling Albion before moving to England in 2008, joining Leeds United. He helped Leeds win promotion to the Championship in 2010. In February 2012, Snodgrass was appointed captain of Leeds, but he rejected a new contract offer and moved to Norwich City later that year.


title: Robert Snodgrass

text: He left Norwich after they were relegated in 2014 and moved to Hull City. On his league debut for Hull, Snodgrass suffered a serious knee injury that sidelined him for over a year. Hull were relegated in his absence, but Snodgrass helped them gain promotion via the playoffs in 2016. Snodgrass moved to West Ham United in January 2017, and he was loaned to Aston Villa for most of the 2017–18 season. Snodgrass left West Ham in January 2021 to sign for West Bromwich Albion, and he then had a short stint with Luton Town.


title: Robert Snodgrass

text: After playing for Scotland at various youth levels including under-21s, Snodgrass received a call up to the Scotland national team side in 2009, and won his first cap in February 2011. Snodgrass retired from international football in October 2019, having made 28 appearances and scored seven goals for Scotland.


title: Robert Snodgrass

text: Born in Glasgow, Snodgrass grew up in the city's Gallowgate area; he played boys' club football for a team affiliated with Rangers alongside future international teammate James McArthur who is a month younger and lived a few blocks away. Celtic offered him an apprenticeship, along with Clyde and Livingston. He felt that he had little chance of breaking through at Parkhead, so chose Livingston, joining their setup at the same time as another East End boy who would go on to play for Scotland, Graham Dorrans.


title: Robert Snodgrass

text: Snodgrass started his career at Livingston, where he scored 15 goals in 79 league games. He caught attention by turning down a trial with Spanish giants Barcelona. Before he turned professional, he was offered a move to Blackburn Rovers, though he chose to stay with Livingston. After recovering from a broken metatarsal, he moved to Stirling Albion on loan for the remainder of the 2006–07 season on 30 January 2007 to step up his recovery from injury.


title: Robert Snodgrass

text: Snodgrass established himself as a regular first-team member during the 2005–06 season. This was a campaign of mixed fortunes, as he gained regular first-team football, yet his side were relegated to Division 1. During Livingston's first season in the second tier, he scored ten goals for Livingston in the Scottish First Division during the 2007–08 season; he was offered a new contract at Livingston, but turned it down. After failing to impress during a trial spell with Barnsley, he joined League One team Leeds United in July 2008. He left the Lions scoring 15 goals in 79 games.


title: Robert Snodgrass

text: After joining Leeds, Snodgrass came into the side for the first game of the season to make his debut against Scunthorpe United, gaining an assist after setting up Enoch Showunmi's headed goal. He scored his first goal for Leeds in the 5–2 League Cup victory over Chester City. After initially struggling to hold a regular place in the starting line-up, Snodgrass established himself after a string of impressive performances throughout November and December, which saw the young winger score four goals in seven games during a poor run of form for the Yorkshire club, culminating in the sacking of manager Gary McAllister.


title: Robert Snodgrass

text: Leeds reached the playoffs but ultimately were knocked out of the competition after losing 2–1 on aggregate to Millwall. In his first season at Leeds, he scored 11 goals and got 19 assists.


title: Robert Snodgrass

text: On the eve of the season, Snodgrass signed a new four-year contract with the club. He scored his first goals of the season with two against Watford in the League Cup second round, sending Leeds through to the third round.


title: Robert Snodgrass

text: Snodgrass scored a late winner against Milton Keynes Dons in a 1–0 win for Leeds for his first league goal of the season.


title: Robert Snodgrass

text: In May 2010, he was selected in the League One PFA Team of the Year for the 2009–10 season. Snodgrass played an instrumental part as Leeds were promoted to The Championship after finishing in second place in League One and thus earning automatic promotion. In his second season Snodgrass scored 10 goals in total and gained 14 assists.


title: Robert Snodgrass

text: On 27 July 2010, Snodgrass was believed to have suffered a serious knee injury during the pre-season game away to Norwegian team Brann after falling victim to a horrendous challenge by David Nielsen. The knee injury ruled him out of the rest of the pre-season campaign, but after two scans on the injured knee, the injury was not as serious as first feared, but kept Snodgrass out for several weeks. Manager Simon Grayson claimed that no exact timescale had been put on Snodgrass' recovery from injury. Snodgrass returned to training at the start of September 2010. To help gain match fitness after his injury, Snodgrass played 90 minutes in a closed-doors friendly against Middlesbrough. Snodgrass returned to Leeds' squad after injury when he was named on the bench the game against Doncaster Rovers, he came on as a second-half substitute replacing Ross McCormack.


title: Robert Snodgrass

text: Snodgrass came on as a second-half substitute against Sheffield United and managed to assist Leeds' late winner for Bradley Johnson, however his game ended on a sour note when he was sent off for two yellow cards. Snodgrass returned from suspension for Leeds against Ipswich Town, replacing Luciano Becchio in the starting lineup and scored his first goal of the season. He scored his second goal of the season with a curled effort against Coventry City. His performance against Coventry was welcomed as a return to form by Snodgrass. His third goal of the season came against Leicester City with a long-range effort.


title: Robert Snodgrass

text: On 1 January 2011, Snodgrass was injured in the 1–1 draw with Middlesbrough, where he was kicked once in the back as well as being stamped on the calf muscle. He scored against Cardiff City with another long range goal. On 8 January 2011, Snodgrass scored with a second half penalty in a 1–1 FA Cup draw with Arsenal. He scored his sixth goal of the season on 1 February, against Hull City. Snodgrass scored against Bristol City on 12 February. Snodgrass missed Leeds' last few games of the season after suffering a back injury.


title: Robert Snodgrass

text: In June 2011, it was reported that Leeds had put an £8 million valuation on Snodgrass and that they were looking into offering him a new contract. Snodgrass missed the League Cup match in August 2011 against Bradford City as he had been called up to the Scotland squad. He started for Leeds on the opening day of the season as they lost 3–1 against Southampton. He scored his first goal of the season on 16 August, when he scored a freekick against Hull City. Snodgrass was ruled out of action when he had an emergency operation to have his appendix removed on 31 December 2011. He returned to action for Leeds just two weeks later, scoring in a 1–1 draw against Crystal Palace on 14 January 2012. On 21 January, he scored a goal in a 3–1 win over Ipswich.


title: Robert Snodgrass

text: Snodgrass was appointed club captain by new Leeds manager Neil Warnock, ahead of his first game in charge against Portsmouth on 25 February. Warnock confirmed he had offered Snodgrass a new contract which would make him Leeds' highest-paid player. Snodgrass finished the season with 13 goals and the second highest amount of assists in The Championship, with 14. Snodgrass won both Leeds' Fans Player of the Year and Players' Player of the Year awards during the club's end of season awards ceremony on 28 April.


title: Robert Snodgrass

text: Snodgrass signed for Norwich City on a three-year contract in July 2012 for an undisclosed fee. He made his debut in the opening game of the season on 18 August 2012, a 5–0 defeat away to Fulham. Two matches later, on 1 September 2012, Snodgrass scored his first goal for the club when he scored the equaliser which saw Norwich draw 1–1 with Tottenham Hotspur. He scored his second goal on 28 November, scoring a free-kick in a 1–1 draw against Southampton.


title: Robert Snodgrass

text: Snodgrass would go on to establish himself as a regular in the first team squad. After a successful campaign in which the club finished 11th in the table, he would be voted by Norwich fans as second place in the Player of the Season that season. He narrowly missed out on the trophy, which was won by Sébastien Bassong instead.


title: Robert Snodgrass

text: Snodgrass scored his first goal of the 2013–14 season with a "free-kick from around 20 yards that looped over the wall and into the bottom-left corner of the net" in a 3–1 win over West Ham United on 9 November. He scored again on 23 February 2014 against Tottenham after a cutting through ball from Bradley Johnson, holding off the defender and placing it past goalkeeper Hugo Lloris from just inside the box. That goal turned out to be the only goal, as Norwich won 1–0.


title: Robert Snodgrass

text: On 30 June 2014, Hull City signed Snodgrass for an undisclosed fee, believed to exceed £6 million, on a three-year contract. Snodgrass dislocated a kneecap during a 1–0 win at Queens Park Rangers in August 2014. The injury, which required surgery to heal, was initially expected to keep Snodgrass out of action for several months. A month later, it was reported that he would be out of action for the entirety of the 2014–15 season. Snodgrass made his first appearance in a game since the injury in November 2015, playing in an under-21 Premier League Cup match. His first return to first-team action was in the League Cup away to Manchester City on 1 December 2015 when he came on as a replacement for Sone Aluko in the 73rd-minute. On 9 January 2016, in the third-round of the FA Cup match against Brighton & Hove Albion, he scored a penalty to take the team through the next round. On 10 December 2016 Snodgrass won a penalty in a crucial home tie against Crystal Palace. Replays showed that he dived and he later apologised.


title: Robert Snodgrass

text: On 27 January 2017, Snodgrass joined West Ham United on a three-and-a-half-year deal for a fee of £10.2 million. He made his West Ham debut on 1 February 2017, coming on as a 64th-minute substitute for Pedro Obiang, in West Ham's 0–4 home defeat by Manchester City. His first start for the club came away at Saint Mary's Stadium against Southampton, which West Ham won 1–3. In August 2017, having played 15 games for West Ham without scoring, Snodgrass was told that he was free to leave the club either permanently or on loan.


title: Robert Snodgrass

text: Snodgrass spent most of the 2017–18 season on loan at Aston Villa, after which he returned to West Ham. He scored his first two goals for West Ham in their 8–0 win against Macclesfield Town in the EFL Cup on 26 September 2018. In March 2019, Snodgrass was charged by the Football Association with allegedly abusing anti-doping officials who were visiting West Ham's training ground on 6 February 2019 to conduct out-of-competition testing. The following month, Snodgrass was fined £30,000 and given a one-match ban for the offence. In July 2019, Snodgrass signed a one-year extension to his contract which would keep him at the club until the summer of 2021, with a further 12-month option. However, Snodgrass left the club to join West Bromwich Albion on 8 January 2021.


title: Robert Snodgrass

text: On 25 August 2017, Snodgrass joined Aston Villa for the remainder of the 2017–18 season. Snodgrass impressed with his early performances for Aston Villa winning praise from manager, Steve Bruce. He scored his first goal for the club in a 4–0 win over Burton Albion on 26 September.


title: Robert Snodgrass

text: During his loan spell he scored seven goals and got 14 assists, to help Aston Villa secure a play-off place and defeat Middlesbrough in the two semi finals to reach the final, playing in the final, as Villa lost 1–0 to Fulham in the final missing out on promotion to the Premier League. His 14 assists also saw him finish joint top (with Barry Douglas) of the assists charts in the EFL Championship.


title: Robert Snodgrass

text: On 8 January 2021, Snodgrass joined West Bromwich Albion on an 18-month contract for an undisclosed fee. He made his West Brom debut on 16 January in a 3–2 win in a Black Country derby at Molineux. He was omitted from the squad for their next game, a 2–1 defeat at West Ham on 19 January. West Brom manager Sam Allardyce said that he had not played due to "an agreement between the clubs". The Premier League stated their intention to investigate the terms of the transfer with regard to a possible violation of their rules regarding one club’s influence over the policies or the performance of another club. Snodgrass had been transferred permanently by West Ham, and it is only loan deals that allow for that kind of restriction. On 31 January 2022 it was announced Snodgrass had left the club by mutual consent, having last started a game in a 3–0 home victory against Bristol City in October.


title: Robert Snodgrass

text: Snodgrass left Luton at the end of the 2021–22 season. In August 2022 he was offered a contract by Motherwell.


title: Robert Snodgrass

text: Snodgrass signed a one-year contract with Scottish Premiership club Heart of Midlothian on 6 September 2022.


title: Robert Snodgrass

text: Snodgrass played for the Scotland under-19, under-20 and under-21 teams. He was part of the squad that reached the final of the 2006 European Under-19 Championships in Poland, although Snodgrass was suspended for the final itself. Snodgrass also played for Scotland under-20 in the 2007 FIFA U-20 World Cup in Canada It was his form in this tournament that led to Barcelona showing interest in Snodgrass.


title: Robert Snodgrass

text: Leeds' involvement in the play-offs against Millwall in 2009 meant that Snodgrass was unavailable to play in a Scotland B international.


title: Robert Snodgrass

text: Snodgrass was called up to the senior Scotland squad by George Burley for the first time for their friendly against Japan in October 2009. He was forced to withdraw from the squad due to a knee injury. Snodgrass made his full international debut on 9 February 2011, coming on as a substitute against Northern Ireland in a 2011 Nations Cup match. Snodgrass was called up to the Scotland squad to face Brazil on 21 March 2011, coming on as a second-half substitute. Scotland lost the game 2–0. Snodgrass was ruled out of Scotland's Nations Cup matches against Wales and the Republic of Ireland with a back injury.


title: Robert Snodgrass

text: On 2 August 2011, Snodgrass was called up to the squad for a friendly against Denmark. He made his first start for Scotland against Denmark and also scored his first international goal in this game. On 7 June 2013, during 2014 FIFA World Cup qualifying, he scored the only goal in a 1–0 win against Croatia, inflicting their first competitive defeat at home since they lost 4–1 to England in 2008.


title: Robert Snodgrass

text: The kneecap injury that Snodgrass suffered in August 2014 caused him to miss the whole of the UEFA Euro 2016 qualifying campaign. He was recalled to the national squad for a friendly match against the Czech Republic in March 2016. In the first match of 2018 FIFA World Cup qualification, Snodgrass scored a hat-trick in a 5–1 win against Malta.


title: Robert Snodgrass

text: On 24 January 2011, an arrest warrant was issued for Snodgrass after he failed to turn up to court regarding an alleged driving offence. A spokesman for Leeds United said that the non-appearance was due to a misunderstanding and that Snodgrass was working with the judicial authorities to resolve the matter.


title: Robert Snodgrass

text: On 3 March 2017, another arrest warrant was issued for him after he failed to attend his trial for allegedly driving in Glasgow with a baby being held in the arms of a passenger. His defence lawyer said that Snodgrass' absence was due to a misunderstanding.


title: Ebru Şahin

text: Ebru Şahin Osman (born 18 May 1994) is a Turkish actress and model. She made her cinematic debut with the movie "Kan Parası" and had a brief role in the TV show "İstanbullu Gelin". She rose to prominence with her role as Reyyan Şadoğlu on the Turkish drama "Hercai".


title: Ebru Şahin

text: Şahin is a graduate of Istanbul University with a degree in Sports Sciences, after which she started taking acting lessons. She made her cinematic debut in 2016 with a role in the movie "Kan Parası". She made her television debut in 2017 with a supporting role in the TV series "Savaşçı". After being cast in other supporting roles in "İstanbullu Gelin" and "Yasak Elma" between 2017–2018, she had her first leading role in the TV series "Hercai" as Reyyan Şadoğlu. For this role, she was awarded a Golden Butterfly Award as Best Actress in 2020.


title: Jason Fox

text: Jason Fox (born 31 August 1976) often referred to by his nickname 'Foxy' is a television presenter, adventurer and a former British soldier. He is best known as the longest serving directing staff on the popular Channel 4 television series "", and the presenter of the investigative documentary series "Meet the Drug Lords: Inside the Real Narcos".


title: Jason Fox

text: Fox joined the Royal Marines Commandos in 1992 at the age of 16. In 2001, he joined the Special Boat Service and reached the rank of Sergeant. After 20 years of military service, Fox was medically discharged on 5 April 2012 having been diagnosed with Post Traumatic Stress Disorder (PTSD).


title: Jason Fox

text: Fox is one of the original presenters and directing staff on "SAS: Who Dares Wins", a reality television programme where contestants experience a gruelling training course loosely based on a condensed version of the special forces selection process. Fox stars alongside former special forces soldiers Ant Middleton, Matthew ‘Ollie’ Ollerton, Mark ‘Billy’ Billingham, and Jay Morton. The programme first broadcast in 2015 is produced by Channel 4, and aired its fifth season in February 2020. In 2019, the first season of "Celebrity SAS: Who Dares Wins" aired which also stars Fox.


title: Jason Fox

text: In 2018, Fox presented a 3 part docuseries, "Meet the Drug Lords: Inside the real Narcos". The series positioned Fox in his first investigative journalism role, spending time within drug cartels in Mexico, Columbia and Peru, meeting and talking to people living and working in those communities. Fox's interviews in the series included Popeye (Jhon Jairo Velásquez) – known as one of Pablo Escobars’ hitmen in Columbia.


title: Jason Fox

text: In 2019, Fox presented the documentary "The Final Mission: Foxy's War" which saw him return to Afghanistan where he had served in the military.


title: Jason Fox

text: In 2017, Fox co-authored the book "SAS: Who Dares Wins: Leadership Secrets from the Special Forces", with his fellow TV presenters and Special Forces soldiers Anthony Middleton, Matthew "Ollie" Ollerton and Colin Maclachlan.


title: Jason Fox

text: Fox released his own first book, "Battle Scars" in 2019 which explores his struggle with mental health after being medically discharged from his military career in 2012 having been diagnosed with PTSD. "Battle Scars" became a "Sunday Times" best-seller.


title: Jason Fox

text: His second book "Life Under Fire: How to Build Inner Strength and Thrive Under Pressure" was released October 15, 2020.


title: Jason Fox

text: Fox became the host of the podcast "Jason Fox Wild Tales" in 2018, in conjunction with the Book of Man, with whom he is a regular columnist. In each episode, Fox interviews people who have experienced a variety of adventures in their life, touching on their background, and the mental and physical challenges they have faced.


title: Jason Fox

text: Since leaving the military, Fox has had several public appearances talking about mental health, and is involved in supporting several charities. Fox is a co-founder of Rock to Recovery with fellow ex royal marine Jamie Sanderson. The pair set it up to assist returning servicemen, veterans and their families.


title: Jason Fox

text: Outside of his military career, some of Fox's bigger adventures include rowing across the Atlantic Ocean from Lagos, Portugal to Macuro, Venezuela in 2016 with four of his friends including Oliver Bailey. Known as Team Essence, their expedition took the crew 50 days over 3,308 nautical miles, and landed them a record for becoming the first team to row unsupported, crossing the Atlantic Ocean from east to west - from mainland Europe to South America, non-stop from mainland to mainland. Across the journey, Team Essence also raised money for the NSPCC.


title: Jason Fox

text: In April 2018, a team of ten adventurers including Fox, embarked on an expedition to the North Pole. They made this journey in aid of the charity Borne to raise awareness of premature birth, and also raised £750,000 for new research into its prevention.


title: Jason Fox

text: In 2019, Fox alongside Sean Johnson kayaked the length of the Yukon river over 1,980 miles in Alaska. The adventure started with a 49-mile hike from Skagway to Lake Bennet, where the kayak journey stretched from Lake Bennett to the Bering Sea, across 48 days. The expedition was unsupported, with Johnson and Fox raising awareness and funds for Royal Navy and Royal Marines Charity.


title: Jason Fox

text: Fox, with his co-star of "SAS: Who Dares Wins", Ollie Ollerton, co-founded a corporate team building, training and events company. In 2019, Fox and Ollerton went on to launch the fitness and wellbeing app Battle Ready 360 – which focuses on personalised plans for individuals looking to balance mind, body and nutrition.


title: Pharmacovigilance

text: Pharmacovigilance (PV, or PhV), also known as drug safety, is the pharmaceutical science relating to the "collection, detection, assessment, monitoring, and prevention" of adverse effects with pharmaceutical products. The etymological roots for the word "pharmacovigilance" are: (Greek for drug) and (Latin for to keep watch). As such, pharmacovigilance heavily focuses on adverse drug reactions (ADR), which are defined as any response to a drug which is noxious and unintended, including lack of efficacy (the condition that this definition only applies with the doses normally used for the prophylaxis, diagnosis or therapy of disease, or for the modification of physiological disorder function was excluded with the latest amendment of the applicable legislation). Medication errors such as overdose, and misuse and abuse of a drug as well as drug exposure during pregnancy and breastfeeding, are also of interest, even without an adverse event, because they may result in an adverse drug reaction.


title: Pharmacovigilance

text: Information received from patients and healthcare providers via pharmacovigilance agreements, as well as other sources such as the medical literature, plays a critical role in providing the data necessary for pharmacovigilance to take place. In order to market or to test a pharmaceutical product in most countries, adverse event data received by the license holder (usually a pharmaceutical company) must be submitted to the local drug regulatory authority. "(See Adverse event reporting below.)"


title: Pharmacovigilance

text: Ultimately, pharmacovigilance is concerned with identifying the hazards associated with pharmaceutical products and with minimizing the risk of any harm that may come to patients. Companies must conduct a comprehensive drug safety and pharmacovigilance audit to assess their compliance with worldwide laws, regulations, and guidance.


title: Pharmacovigilance

text: Pharmacovigilance has its own unique terminology that is important to understand. Most of the following terms are used within this article and are peculiar to drug safety, although some are used by other disciplines within the pharmaceutical sciences as well.


title: Pharmacovigilance

text: The European Medicines Agency defines terms in its Guideline on good pharmacovigilance practices (GVP):


title: Pharmacovigilance

text: The activity that is most commonly associated with pharmacovigilance (PV), and which consumes a significant number of resources for drug regulatory authorities (or similar government agencies) and drug safety departments in pharmaceutical companies, is that of adverse event reporting. Adverse event (AE) reporting involves the receipt, triage, data entry, assessment, distribution, reporting (if appropriate), and archiving of AE data and documentation. The source of AE reports may include: spontaneous reports from healthcare professionals or patients (or other intermediaries); solicited reports from patient support programs; reports from clinical or post-marketing studies; reports from literature sources; reports from the media (including social media and websites); and reports reported to drug regulatory authorities themselves. For pharmaceutical companies, AE reporting is a regulatory requirement in most countries. AE reporting also provides data to these companies and drug regulatory authorities that play a key role in assessing the risk-benefit profile of a given drug. The following are several facets of AE reporting:


title: Pharmacovigilance

text: One of the fundamental principles of adverse event reporting is the determination of what constitutes an individual case safety report. During the triage phase of a potential adverse event report, it is important to determine if the "four elements" of a valid individual case safety report are present: (1) an identifiable patient, (2) an identifiable reporter, (3) a suspect drug, and (4) an adverse event.


title: Pharmacovigilance

text: If one or more of these four elements is missing, the case is not a valid individual case safety report. Although there are no exceptions to this rule there may be circumstances that may require a judgment call. For example, the term "identifiable" may not always be clear-cut. If a physician reports that he/she has a patient X taking drug Y who experienced Z (an AE), but refuses to provide any specifics about patient X, the report is still a valid case even though the patient is not specifically identified. This is because the reporter has first-hand information about the patient and is "identifiable" (i.e. a real person) to the physician. Identifiability is important so as not only to prevent duplicate reporting of the same case, but also to permit follow-up for additional information.


title: Pharmacovigilance

text: The concept of identifiability also applies to the other three elements. Although uncommon, it is not unheard of for fictitious adverse event "cases" to be reported to a company by an anonymous individual (or on behalf of an anonymous patient, disgruntled employee, or former employee) trying to damage the company's reputation or a company's product. In these and all other situations, the source of the report should be ascertained (if possible). But anonymous reporting is also important, as whistle blower protection is not granted in all countries. In general, the drug must also be specifically named. Note that in different countries and regions of the world, drugs are sold under various tradenames. In addition, there are a large number of generics which may be mistaken for the trade product. Finally, there is the problem of counterfeit drugs producing adverse events. If at all possible, it is best to try to obtain the sample which induced the adverse event, and send it to either the European Medicines Agency, FDA or other government agency responsible for investigating AE reports.


title: Pharmacovigilance

text: If a reporter can't recall the name of the drug they were taking when they experienced an adverse event, this would not be a valid case. This concept also applies to adverse events. If a patient states that they experienced "symptoms", but cannot be more specific, such a report might technically be considered valid, but will be of very limited value to the pharmacovigilance department of the company or to drug regulatory authorities.


title: Pharmacovigilance

text: Adverse event coding is the process by which information from an AE reporter, called the "verbatim", is coded using standardized terminology from a medical coding dictionary, such as MedDRA (the most commonly used medical coding dictionary). The purpose of medical coding is to convert adverse event information into terminology that can be readily identified and analyzed. For instance, Patient 1 may report that they had experienced "a very bad headache that felt like their head was being hit by a hammer" [Verbatim 1] when taking Drug X. Or, Patient 2 may report that they had experienced a "slight, throbbing headache that occurred daily at about two in the afternoon" [Verbatim 2] while taking Drug Y. Neither Verbatim 1 nor Verbatim 2 will exactly match a code in the MedDRA coding dictionary. However, both quotes describe different manifestations of a headache. As a result, in this example both quotes would be coded as PT Headache (PT = Preferred Term in MedDRA).


title: Pharmacovigilance

text: Although somewhat intuitive, there are a set of criteria within pharmacovigilance that are used to distinguish a serious adverse event from a non-serious one. An adverse event is considered serious if it meets one or more of the following criteria:


title: Pharmacovigilance

text: Aside from death, each of these categories is subject to some interpretation. Life-threatening, as it used in the drug safety world, specifically refers to an adverse event that places the patient at an "immediate risk of death", such as cardiac or respiratory arrest. By this definition, events such as myocardial infarction, which would be hypothetically life-threatening, would not be considered life-threatening unless the patient went into cardiac arrest following the MI. Defining what constitutes hospitalization can be problematic as well. Although typically straightforward, it's possible for a hospitalization to occur even if the events being treated are not serious. By the same token, serious events may be treated without hospitalization, such as the treatment of anaphylaxis may be successfully performed with epinephrine. Significant disability and incapacity, as a concept, is also subject to debate. While permanent disability following a stroke would no doubt be serious, would "complete blindness for 30 seconds" be considered "significant disability"? For birth defects, the seriousness of the event is usually not in dispute so much as the attribution of the event to the drug. Finally, "medically significant events" is a category that includes events that may be always serious, or sometimes serious, but will not fulfill any of the other criteria. Events such as cancer might always be considered serious, whereas liver disease, depending on its CTCAE (Common Terminology Criteria for Adverse Events) grade—Grades 1 or 2 are generally considered non-serious and Grades 3-5 may be considered serious.


title: Pharmacovigilance

text: This refers to individual case safety reports that involve a serious and unlisted event (an event not described in the drug's labeling) that is considered related to the use of the drug (US FDA). (Spontaneous reports are typically considered to have a positive causality, whereas a clinical trial case will typically be assessed for causality by the clinical trial investigator and/or the license holder.) In most countries, the time frame for reporting expedited cases is 7/15 calendar days from the time a drug company receives notification (referred to as "Day 0") of such a case. Within clinical trials such a case is referred to as a SUSAR (a Suspected Unexpected Serious Adverse Reaction). If the SUSAR involves an event that is life-threatening or fatal, it may be subject to a 7-day "clock". Cases that do not involve a serious, unlisted event may be subject to non-expedited or periodic reporting.


title: Pharmacovigilance

text: Also known as AE (adverse event) or SAE (serious AE) reporting from clinical trials, safety information from clinical studies is used to establish a drug's safety profile in humans and is a key component that drug regulatory authorities consider in the decision-making as to whether to grant or deny market authorization (market approval) for a drug. AE reporting occurs when study patients (subjects, participants) experience any kind of "untoward" event during the conducting of clinical trials. Non-serious adverse events are typically captured separately at a level lower than pharmacovigilance. AE and SAE information, which may also include relevant information from the patient's medical background, are reviewed and assessed for both causality and degree of seriousness by the study investigator. This information is forwarded to a sponsoring entity (typically a pharmaceutical company or academic medical center) that is responsible for the reporting of this information, as appropriate, to drug regulatory authorities.


title: Pharmacovigilance

text: Spontaneous reports are termed spontaneous as they take place during the clinician's normal diagnostic appraisal of a patient, when the clinician is drawing the conclusion that the drug may be implicated in the causality of the event.


title: Pharmacovigilance

text: Spontaneous reporting system relies on vigilant physicians and other healthcare professionals who not only generate a suspicion of an adverse drug reaction, but also report it. It is an important source of regulatory actions such as taking a drug off the market or a label change due to safety problems. Spontaneous reporting is the core data-generating system of international pharmacovigilance, relying on healthcare professionals (and in some countries consumers) to identify and report any adverse events to their national pharmacovigilance center, health authority (such as the European Medicines Agency or FDA), or to the drug manufacturer itself. Spontaneous reports are, by definition, submitted voluntarily although under certain circumstances these reports may be encouraged, or "stimulated", by media reports or articles published in medical or scientific publications, or by product lawsuits. In many parts of the world adverse event reports are submitted electronically using a defined message standard.


title: Pharmacovigilance

text: One of the major weaknesses of spontaneous reporting is that of under-reporting, where, unlike in clinical trials, less than 100% of those adverse events occurring are reported. Further complicating the assessment of adverse events, AE reporting behavior varies greatly between countries and in relation to the seriousness of the events, but in general probably less than 10% (some studies suggest less than 5%) of all adverse events that occur are actually reported. The rule-of-thumb is that on a scale of 0 to 10, with 0 being least likely to be reported and 10 being the most likely to be reported, an uncomplicated non-serious event such as a mild headache will be closer to a "0" on this scale, whereas a life-threatening or fatal event will be closer to a "10" in terms of its likelihood of being reported. In view of this, medical personnel may not always see AE reporting as a priority, especially if the symptoms are not serious. And even if the symptoms are serious, the symptoms may not be recognized as a possible side effect of a particular drug or combination thereof. In addition, medical personnel may not feel compelled to report events that are viewed as expected. This is why reports from patients themselves are of high value. The confirmation of these events by a healthcare professional is typically considered to increase the value of these reports. Hence it is important not only for the patient to report the AE to his health care provider (who may neglect to report the AE), but also report the AE to both the biopharmaceutical company and the FDA, European Medicines Agency, ... This is especially important when one has obtained one's pharmaceutical from a compounding pharmacy.


title: Pharmacovigilance

text: As such, spontaneous reports are a crucial element in the worldwide enterprise of pharmacovigilance and form the core of the World Health Organization Database, which includes around 4.6 million reports (January 2009), growing annually by about 250,000.


title: Pharmacovigilance

text: Aggregate reporting, also known as periodic reporting, plays a key role in the safety assessment of drugs. Aggregate reporting involves the compilation of safety data for a drug over a prolonged period of time (months or years), as opposed to single-case reporting which, by definition, involves only individual AE reports. The advantage of aggregate reporting is that it provides a broader view of the safety profile of a drug. Worldwide, the most important aggregate report is the Periodic Safety Update Report (PSUR) and Development Safety Update Report (DSUR). This is a document that is submitted to drug regulatory agencies in Europe, the US and Japan (ICH countries), as well as other countries around the world. The PSUR was updated in 2012 and is now referred to in many countries as the Periodic Benefit Risk Evaluation report (PBRER). As the title suggests, the PBRER's focus is on the benefit-risk profile of the drug, which includes a review of relevant safety data compiled for a drug product since its development.


title: Pharmacovigilance

text: Some countries legally oblige spontaneous reporting by physicians. In most countries, manufacturers are required to submit, through its Qualified Person for Pharmacovigilance (QPPV), all of the reports they receive from healthcare providers to the national authority. Others have intensive, focused programmes concentrating on new drugs, or on controversial drugs, or on the prescribing habits of groups of doctors, or involving pharmacists in reporting. All of these generate potentially useful information. Such intensive schemes, however, tend to be the exception. A number of countries have reporting requirements or reporting systems specific to vaccine-related events.


title: Pharmacovigilance

text: Risk management is the discipline within pharmacovigilance that is responsible for signal detection and the monitoring of the risk-benefit profile of drugs. Other key activities within the area of risk management are that of the compilation of risk management plans (RMPs) and aggregate reports such as the Periodic Safety Update Report (PSUR), Periodic Benefit-Risk Evaluation Report (PBRER), and the Development Safety Update Report (DSUR).


title: Pharmacovigilance

text: One of the most important, and challenging, problems in pharmacovigilance is that of the determination of causality. Causality refers to the relationship of a given adverse event to a specific drug. Causality determination (or assessment) is often difficult because of the lack of clear-cut or reliable data. While one may assume that a positive temporal relationship might "prove" a positive causal relationship, this is not always the case. Indeed, a "bee sting" Adverse Event — where the AE can clearly be attributed to a specific cause — is by far the exception rather than the rule. This is due to the complexity of human physiology as well as that of disease and illnesses. By this reckoning, in order to determine causality between an adverse event and a drug, one must first exclude the possibility that there were other possible causes or contributing factors. If the patient is on a number of medications, it may be the combination of these drugs which causes the AE, and not any one individually. There have been a number of recent high-profile cases where the AE led to the death of an individual. The individuals were not overdosed with any one of the many medications they were taking, but the combination there appeared to cause the AE. Hence it is important to include in your/one's AE report, not only the drug being reported, but also all other drugs the patient was also taking.


title: Pharmacovigilance

text: For instance, if a patient were to start Drug X and then three days later were to develop an AE, one might be tempted to attribute blame Drug X. However, before that can be done, the patient's medical history would need to be reviewed to look for possible risk factors for the AE. In other words, did the AE occur with the drug or "because" of the drug? This is because a patient on any drug may develop or be diagnosed with a condition that could not have possibly been caused by the drug. This is especially true for diseases, such as cancer, which develop over an extended period of time, being diagnosed in a patient who has been taken a drug for a relatively short period of time. On the other hand, certain adverse events, such as blood clots (thrombosis), can occur with certain drugs with only short-term exposure. Nevertheless, the determination of risk factors is an important step of confirming or ruling-out a causal relationship between an event and a drug.


title: Pharmacovigilance

text: Often the only way to confirm the existence of a causal relationship of an event to a drug is to conduct an observational study where the incidence of the event in a patient population taking the drug is compared to a control group. This may be necessary to determine if the background incidence of an event is less than that found in a group taking a drug. If the incidence of an event is statistically significantly higher in the "active" group versus the placebo group (or other control group), it is possible that a causal relationship may exist to a drug, unless other confounding factors may exist.


title: Pharmacovigilance

text: The process of signal management in pharmacovigilance consists of a set of activities that aim to determine if there are new risks associated with an active substance or a medicinal product or whether known risks have changed based on a thorough analysis of individual case safety reports (ICSRs), aggregate data from active surveillance systems or scientific literature.


title: Pharmacovigilance

text: Signal detection involves a range of techniques (CIOMS VIII). The WHO defines a safety signal as: "Reported information on a possible causal relationship between an adverse event and a drug, the relationship being unknown or incompletely documented previously". Usually more than a single report is required to generate a signal, depending upon the event and quality of the information available.


title: Pharmacovigilance

text: Data mining pharmacovigilance databases is one approach that has become increasingly popular with the availability of extensive data sources and inexpensive computing resources. The data sources (databases) may be owned by a pharmaceutical company, a drug regulatory authority, or a large healthcare provider. Individual case safety reports in these safety databases are retrieved and converted into structured format, and statistical methods (usually as mathematical algorithm) are applied to calculate statistical measures of association. If the statistical measure crosses an arbitrarily set threshold, a signal is declared for a given drug associated with a given adverse event. All signals deemed worthy of investigation, require further analysis using all available data in an attempt to confirm or refute the signal. If the analysis is inconclusive, additional data may be needed such as a post-marketing observational trial.


title: Pharmacovigilance

text: Signal detection is an essential part of drug use and safety surveillance. Ideally, the goal of signal detection is to identify adverse drug reactions that were previously considered unexpected and to be able to provide guidance in the product's labelling as to how to minimize the risk of using the drug in a given patient population.


title: Pharmacovigilance

text: A risk management plan is a documented plan that describes the risks (adverse drug reactions and potential adverse reactions) associated with the use of a drug and how they are being handled (warning on drug label or on packet inserts of possible side effects which if observed should cause the patient to inform/see his physician and/or pharmacist and/or the manufacturer of the drug and/or the FDA, European Medicines Agency. The overall goal of a risk management plan is to assure a positive risk-benefit profile once the drug is (has been) marketed. The document is required to be submitted, in a specified format, with all new market authorization requests within the European Union (EU). Although not necessarily required, risk management plans may also be submitted in countries outside the EU. The risks described in a risk management plan fall into one of three categories: identified risks, potential risks, and unknown risks. Also described within a risk management plan are the measures that the Market Authorization Holder, usually a pharmaceutical company, will undertake to minimize the risks associated with the use of the drug. These measures are usually focused on the product's labeling and healthcare professionals. Indeed, the risks that are documented in a pre-authorization risk management plan will inevitably become part of the product's post-marketing labeling. Since a drug, once authorized, may be used in ways not originally studied in clinical trials, this potential "off-label use", and its associated risks, is also described within the risk management plan. Risk management plans can be very lengthy documents, running in some cases hundreds of pages and, in rare instances, up to a thousand pages long.


title: Pharmacovigilance

text: In the US, under certain circumstances, the FDA may require a company to submit a document called a Risk Evaluation and Mitigation Strategy (REMS) for a drug that has a specific risk that FDA believes requires mitigation. While not as comprehensive as a risk management plan, a Risk Evaluation and Mitigation Strategy can require a sponsor to perform certain activities or to follow a protocol, referred to as Elements to Assure Safe Use, to assure that a positive risk-benefit profile for the drug is maintained for the circumstances under which the product is marketed.


title: Pharmacovigilance

text: Pharmaceutical companies are required by law in most countries to perform clinical trials, testing new drugs on people before they are made generally available. This occurs after a drug has been pre-screened for toxicity, sometimes using animals for testing. The manufacturers or their agents usually select a representative sample of patients for whom the drug is designed – at most a few thousand – along with a comparable control group. The control group may receive a placebo and/or another drug, often a so-called "gold standard" that is "best" drug marketed for the disease.


title: Pharmacovigilance

text: Clinical trials do, in general, tell a good deal about how well a drug works. They provide information that should be reliable for larger populations with the same characteristics as the trial group – age, gender, state of health, ethnic origin, and so on though target clinical populations are typically very different from trial populations with respect to such characteristics.


title: Pharmacovigilance

text: The variables in a clinical trial are specified and controlled, but a clinical trial can never tell you the whole story of the effects of a drug in all situations. In fact, nothing could tell you the whole story, but a clinical trial must tell you enough; "enough" being determined by legislation and by contemporary judgements about the acceptable balance of benefit and harm. Ultimately, when a drug is marketed it may be used in patient populations that were not studied during clinical trials (children, the elderly, pregnant women, patients with co-morbidities not found in the clinical trial population, etc.) and a different set of warnings, precautions or contraindications (where the drug should not be used at all) for the product's labeling may be necessary in order to maintain a positive risk/benefit profile in all known populations using the drug.


title: Pharmacovigilance

text: Pharmacoepidemiology is the study of the incidence of adverse drug reactions in patient populations using drug agents.


title: Pharmacovigilance

text: Although often used interchangeably, there are subtle differences between the two disciplines. Pharmacogenetics is generally regarded as the study or clinical testing of genetic variation that gives rise to differing responses to drugs, including adverse drug reactions. It is hoped that pharmacogenetics will eventually provide information as to which genetic profiles in patients will place those patients at greatest risk, or provide the greatest benefit, for using a particular drug or drugs. Pharmacogenomics, on the other hand, is the broader application of genomic technologies to new drug discovery and further characterization of older drugs.


title: Pharmacovigilance

text: The following organizations play a key collaborative role in the global oversight of pharmacovigilance.


title: Pharmacovigilance

text: The principle of international collaboration in the field of pharmacovigilance is the basis for the WHO Programme for International Drug Monitoring, through which over 150 member nations have systems in place that encourage healthcare personnel to record and report adverse effects of drugs in their patients. These reports are assessed locally and may lead to action within the country. Since 1978, the programme has been managed by the Uppsala Monitoring Centre to which member countries send their reports to be processed, evaluated and entered into an international database called VigiBase. Membership in the WHO Programme enables a country to know if similar reports are being made elsewhere. When there are several reports of adverse reactions to a particular drug, this process may lead to the detection of a signal, and an alert about a possible hazard communicated to members countries after detailed evaluation and expert review on the biological stasis and homeostasis of the body.


title: Pharmacovigilance

text: The International Council for Harmonisation is a global organization with members from the European Union, the United States and Japan; its goal is to recommend global standards for drug companies and drug regulatory authorities around the world, with its activities overseen by the Steering Committee overseeing harmonization activities. Established in 1990, each of its six co-sponsors—the EU, the European Federation of Pharmaceutical Industries and Associations, Japan's Ministry of Health, Labor and Welfare, the Japanese Pharmaceutical Manufacturers Association, the U.S. Food and Drug Administration (FDA), and the Pharmaceutical Research and Manufacturers of America (PhRMA)—have two seats on the SC. Other parties have a significant interest in the International Council for Harmonisation and have been invited to nominate Observers to the SC; three current observers are the WHO, Health Canada, and the European Free Trade Association, with the International Federation of Pharmaceutical Manufacturers Association participating as a non-voting member of the SC.


title: Pharmacovigilance

text: The CIOMS, a part of the WHO, is globally oriented think tank that provides guidance on drug safety related topics through its Working Groups. The CIOMS prepares reports that are used as a reference for developing future drug regulatory policy and procedures, and over the years, many of CIOMS' proposed policies have been adopted. Examples of topics these reports have covered include: Current Challenges in Pharmacovigilance: Pragmatic Approaches (CIOMS V); Management of Safety Information from Clinical Trials (CIOMS VI); the Development Safety Update Report (DSUR): Harmonizing the Format and Content for Periodic Safety Reporting During Clinical Trials (CIOMS VII); and Practical Aspects of Signal Detection in Pharmacovigilance: Report of CIOMS Working Group (CIOMS VIII).


title: Pharmacovigilance

text: The International Society of Pharmacovigilance is an international non-profit scientific organization, which aims to foster pharmacovigilance both scientifically and educationally, and enhance all aspects of the safe and proper use of medicines, in all countries. It was established in 1992 as the European Society of Pharmacovigilance.


title: Pharmacovigilance

text: Society of Pharmacovigilance, India, also established in 1992, is partner member of the International Society of Pharmacovigilance. Other local societies include the Boston Society of Pharmacovigilance Physicians.


title: Pharmacovigilance

text: Drug regulatory authorities play a key role in national or regional oversight of pharmacovigilance. Some of the agencies involved are listed below (in order of 2011 spending on pharmaceuticals, from the IMS Institute for Healthcare Informatics).


title: Pharmacovigilance

text: In the U.S., with about a third of all global 2011 pharmaceutical expenditures, the drug industry is regulated by the FDA, the largest national drug regulatory authority in the world. FDA authority is exercised through enforcement of regulations derived from legislation, as published in the U.S. Code of Federal Regulations (CFR); the principal drug safety regulations are found in 21 CFR Part 312 (IND regulations) and 21 CFR Part 314 (NDA regulations). While those regulatory efforts address pre-marketing concerns, pharmaceutical manufacturers and academic/non-profit organizations such as RADAR and Public Citizen do play a role in pharmacovigilance in the US. The post-legislative rule-making process of the U.S. federal government provides for significant input from both the legislative and executive branches, which also play specific, distinct roles in determining FDA policy.


title: Pharmacovigilance

text: The "pharmerging", or emerging pharmaceutical market economies, which include Brazil, India, Russia, Argentina, Egypt, Indonesia, Mexico, Pakistan, Poland, Romania, South Africa, Thailand, Turkey, Ukraine and Vietnam, accrued one fifth of global 2011 pharmaceutical expenditures; in future, aggregated data for this set will include China as well.


title: Pharmacovigilance

text: China's economy is anticipated to pass Japan to become second in the ranking of individual countries' in pharmaceutical purchases by 2015, and so its PV regulation will become increasing important; China's regulation of PV is through its National Center for Adverse Drug Reaction Monitoring, under China's Ministry of Health.


title: Pharmacovigilance

text: As JE Sackman notes, as of April 2013 "there is no Latin American equivalent of the European Medicines Agency—no common body with the power to facilitate greater consistency across countries". For simplicity, and per sources, 17 smaller economies are discussed alongside the 4 pharmemerging large economies of Argentina, Brazil, Mexico and Venezuela—Bolivia, Chile, Colombia, Costa Rica, Cuba, Dominican Republic, Ecuador, El Salvador, Guatemala, Haiti, Honduras, Nicaragua, Panama, Paraguay, Peru, Suriname, and Uruguay. As of June 2012, 16 of this total of 21 countries have systems for immediate reporting and 9 have systems for periodic reporting of adverse events for on-market agents, while 10 and 8, respectively, have systems for immediate and periodic reporting of adverse events during clinical trials; most of these have PV requirements that rank as "high or medium...in line with international standards" ("ibid."). The WHO's Pan American Network for Drug Regulatory Harmonization seeks to assist Latin American countries in develop harmonized PV regulations.


title: Pharmacovigilance

text: Some further PV regulatory examples from the pharmerging nations are as follows. In India, the PV regulatory authority is the Indian Pharmacopoeia Commission, with a National Coordination Centre under the Pharmacovigilance Program of India, in the Ministry of Health and Family Welfare. Scientists working on pharmacovigilance share their experiences, findings, innovative ideas and researches during the annual meeting of Society of Pharmacovigilance, India. In Egypt, PV is regulated by the Egyptian Pharmacovigilance Center of the Egyptian Ministry of Health.


title: Pharmacovigilance

text: The EU5 (France, Germany, Italy, Spain, United Kingdom) accrued ~17% of global 2011 pharmaceutical expenditures. PV efforts in the EU are coordinated by the European Medicines Agency and are conducted by the national competent authorities (NCAs). The main responsibility of the European Medicines Agency is to maintain and develop the pharmacovigilance database consisting of all suspected serious adverse reactions to medicines observed in the European Community; the data processing network and management system is called EudraVigilance and contains separate but similar databases of human and veterinary reactions. The European Medicines Agency requires the individual marketing authorization holders to submit all received adverse reactions in electronic form, except in exceptional circumstances; the reporting obligations of the various stakeholders are defined by EEC legislation, namely Regulation (EC) No 726/2004, and for human medicines, European Union Directive 2001/83/EC as amended and Directive 2001/20/EC. In 2002, Heads of Medicines Agencies agreed on a mandate for an ad hoc Working Group on establishing a European risk management strategy; the Working Group considered the conduct of a high level survey of EU pharmacovigilance resources to promote the utilization of expertise and encourage collaborative working.


title: Pharmacovigilance

text: In conjunction with this oversight, individual countries maintain their distinct regulatory agencies with PV responsibility. For instance, in Spain, PV is regulated by the Agencia Española de Medicamentos y Productos Sanitarios, which can suspend or withdraw the authorization of pharmaceuticals already on-market if the evidence shows that safety (or quality or efficacy) of an agent are unsatisfactory.


title: Pharmacovigilance

text: The remaining EU and non-EU countries outside the EU5 accrued ~7% of global 2011 pharmaceutical expenditures. Regulation of those outside the EU being managed by specific governmental agencies. For instance, in Switzerland, PV "inspections" for clinical trials of medicinal products are conducted by the Swiss Agency for Therapeutic Products.


title: Pharmacovigilance

text: In Japan, with ~12% of all global 2011 pharmaceutical expenditures, PV matters are regulated by the Pharmaceuticals and Medical Devices Agency and the Ministry of Health, Labour, and Welfare.


title: Pharmacovigilance

text: In Canada, with ~2% of all global 2006 and 2011 pharmaceutical expenditures, PV is regulated by the Marketed Health Products Directorate of the Health Products and Food Branch. Canada was second, following the United States, in holding the highest total prescription drug expenditures per capita in 2011 at around 750 US dollars per person. Canada also pays such a large amount for pharmaceuticals that it was second, next to Switzerland, for the amount of money spent for a certain amount of prescription drugs (around 130 US dollars). It was also accessed that Canada was one of the top countries that increased its yearly average per capita growth on pharmaceutical expenditures the most from 2000 to 2010 with 4 percent a year (with taking inflation into account) The Marketed Health Products Directorate mainly collects adverse drug reaction reports through a network of reporting centers to analyze and issue possible warnings to the public, and currently utilizes newsletters, advisories, adverse reaction centers, as well as electronic mailing lists. However, it does not currently maintain a database or list of drugs removed from Canada as a result of safety concerns.


title: Pharmacovigilance

text: In August 2017, there was a government controversy in which a bill, known as “Vanessa’s Law”, to protect patients from potentially dangerous prescription drugs was not being fully realized by hospitals; Health Canada only required hospitals to report “unexpected” negative reactions to prescription drugs, rather than any and all adverse reactions, with the justification of managing “administrative overload”.[25]


title: Pharmacovigilance

text: The Republic of Korea, with ~1% of all global 2011 pharmaceutical expenditures, PV matters are regulated in South Korea by the Ministry Of Food And Drug Safety


title: Pharmacovigilance

text: In Kenya, PV is regulated by the Pharmacy and Poisons Board.The Pharmacy and Poisons Board provides a Pharmacovigilance Electronic Reporting System which allows for the online reporting of suspected adverse drug reactions as well as suspected poor quality of medicinal products. The Pharmacovigilance activities in Kenya are supported by the School of Pharmacy, University of Nairobi through its Master of Pharmacy in Pharmacoepidemiology & Pharmacovigilance program offered by the Department of Pharmacology and Pharmacognosy.


title: Pharmacovigilance

text: The rest of the world accrued ~7% of global 2011 pharmaceutical expenditures. Some examples of PV regulatory agencies in the rest of the world are as follows. In Iraq, PV is regulated by the Iraqi Pharmacovigilance Center of the Iraqi Ministry of Health.


title: Pharmacovigilance

text: Despite attention from the FDA and regulatory agencies of the European Union, procedures for monitoring drug concentrations and adverse effects in the environment are lacking. Pharmaceuticals, their metabolites, and related substances may enter the environment after patient excretion, after direct release to waste streams during manufacturing or administration, or via terrestrial deposits (e.g., from waste sludges or leachates). A concept combining pharmacovigilance and environmental pharmacology, intended to focus attention on this area, was introduced first as "pharmacoenvironmentology" in 2006 by Syed Ziaur Rahman and later as "ecopharmacology" with further concurrent and later terms for the same concept (ecopharmacovigilance, environmental pharmacology, ecopharmacostewardship).


title: Pharmacovigilance

text: The first of these routes to the environment, elimination through living organisms subsequent to pharmacotherapy, is suggested as the principal source of environmental contamination (apart from cases where norms for treatment of manufacturing and other wastes are violated), and ecopharmacovigilance is intended to deal specifically with this impact of pharmacological agents on the environment.


title: Pharmacovigilance

text: A medical device is an instrument, apparatus, implant, "in vitro" reagent, or similar or related article that is used to diagnose, prevent, or treat disease or other conditions, and does not achieve its purposes through chemical action within or on the body (which would make it a drug). Whereas medicinal products (also called pharmaceuticals) achieve their principal action by pharmacological, metabolic or immunological means, medical devices act by physical, mechanical, or thermal means. Medical devices vary greatly in complexity and application. Examples range from simple devices such as tongue depressors, medical thermometers, and disposable gloves to advanced devices such as medical robots, cardiac pacemakers, and neuroprosthetics. This modern concept of monitoring and safety of medical devices which is known materiovigilance was quite documented in Unani System of medicine.


title: Pharmacovigilance

text: Given the inherent difference between medicinal products and medical products, the vigilance of medical devices is also different from that of medicinal products. To reflect this difference, a classification system has been adopted in some countries to stratify the risk of failure with the different classes of devices. The classes of devices typically run on a 1-3 or 1-4 scale, with Class 1 being the least likely to cause significant harm with device failure versus Classes 3 or 4 being the most likely to cause significant harm with device failure. An example of a device in the "low risk" category would be contact lenses. An example of a device in the "high risk" category would be cardiac pacemakers.


title: Pharmacovigilance

text: Medical device reporting (MDR), which is the reporting of adverse events with medical devices, is similar to that with medicinal products, although there are differences. In contrast to reporting of medical products reports of side-effects play only a minor role with most medical devices. The vast majority of the medical device reports are related to medical device defects or failures. Other notable differences are in the obligations to report by other actors that aren't manufacturers, in the US user-facilities such as hospitals and nursing homes are legally required to report suspected medical device-related deaths to both FDA and the manufacturer, if known, and serious injuries to the manufacturer or to FDA, if the manufacturer is unknown. This is in contrast to the voluntary reporting of AEs with medicinal products. Similar obligations exist in multiple European countries. The European regulation on medical devices and the European regulation on in vitro diagnostic medical devices (IVDR) obliges other economic operators most notably importers and distributors to inform manufacturers, and in certain instances the authorities, of incidents and safety issues with medical devices that they have distributed or imported in the European market.


title: Pharmacovigilance

text: The safety of herbal medicines has become a major concern to both national health authorities and the general public. The use of herbs as traditional medicines continues to expand rapidly across the world; many people now take herbal medicines or herbal products for their health care in different national health-care settings. However, mass media reports of adverse events with herbal medicines can be incomplete and therefore misleading. Moreover, it can be difficult to identify the causes of herbal medicine-associated adverse events since the amount of data on each event is generally less than for pharmaceuticals formally regulated as drugs (since the requirements for adverse event reporting are either non-existent or are less stringent for herbal supplements and medications).


title: Pharmacovigilance

text: With the emergence of advanced artificial intelligence methods and social media big data, researchers are now using publicly posted social media data to discover unknown side effects of prescription medications. Natural language processing and machine learning methods are developed and used for identifying non-standard expressions of side effects.


title: Achy Breaky Heart

text: "Achy Breaky Heart" is a song written in 1990 by Don Von Tress. First released in 1991 by the Marcy Brothers with the title "Don't Tell My Heart", it was later recorded by Billy Ray Cyrus and released on his debut album "Some Gave All" in 1992. The song is Cyrus' debut single and signature song. It became the first single ever to achieve triple platinum status in Australia and also 1992's best-selling single in the same country. In the United States, it became a crossover hit on pop and country radio, peaking at 4 on the "Billboard" Hot 100 and topping the Hot Country Songs chart, becoming the first country single to be certified platinum since "Islands in the Stream" by Kenny Rogers and Dolly Parton in 1983. The single topped in several countries, and after being featured on "Top of the Pops" in the United Kingdom, peaked at No. 3 on the UK Singles Chart. It was Cyrus' biggest hit single in the U.S. until he was featured on "Old Town Road" by rapper Lil Nas X, which peaked at No. 1 on the "Billboard" Hot 100 27 years later.


title: Achy Breaky Heart

text: The music video for the song led to the explosion of the line dance into the mainstream. The song is considered by some as one of the worst songs of all time, featuring at No. 2 on VH1 and "Blender"s list of the "50 Most Awesomely Bad Songs Ever". However, it later became a cult classic.


title: Achy Breaky Heart

text: "Achy Breaky Heart" was written by amateur songwriter Don Von Tress from Cypress Inn, Tennessee, in 1990, according to him "just fooling around on the guitar and a drum machine".


title: Achy Breaky Heart

text: The song was initially to be recorded by the Oak Ridge Boys in the early 1990s, but the group decided against recording it after lead singer Duane Allen said that he did not like the words "achy breaky". It was then recorded in 1991 under the title "Don't Tell My Heart" by the Marcy Brothers, although their version changed some lyrics.


title: Achy Breaky Heart

text: Billy Ray Cyrus heard Von Tress's version of the song, and chose to include it on his debut album "Some Gave All" in 1992. It is written in the key of A major and has only two chords: A and E.


title: Achy Breaky Heart

text: The song reached No. 23 on CMT's 100 Greatest Videos in 2008, No. 2 on VH1's 50 Most Awesomely Bad Songs, and "Blender" magazine's 50 Worst Songs Ever. In 2002, Shelly Fabian from About.com ranked the song No. 249 on the list of the Top 500 Country Music Songs. In 2007, the song was ranked at No. 87 on VH1's 100 Greatest Songs of the '90s. A review from "Cash Box" magazine was positive, stating that "The song is good, but it [sic] his performance that will keep you wired."


title: Achy Breaky Heart

text: Despite its initially negative critical reviews, the song has become a cult classic. For his 2017 album "Set the Record Straight", Cyrus recorded an updated version of the song. Members of the Muscle Shoals Rhythm Section participated in the recording "Rolling Stone" called "more faithful to songwriter Don Von Tress’ swampy demo."


title: Achy Breaky Heart

text: Two very similar versions of the video for the song exist. Directed by Marc Ball, it was filmed during a live performance at the Paramount Arts Center in Ashland, Kentucky. The version released to country stations begins with a shot of the theater and ends with extended applause from the audience. The version released to MTV (which is the version found on Cyrus' YouTube account), begins with Cyrus exiting a limo, and the ending cheer from the audience is much shorter.


title: Achy Breaky Heart

text: Alvin and the Chipmunks covered the song in 1992 on "Chipmunks in Low Places". This version, which features speaking parts by Cyrus himself, reached No. 71 on the "Billboard" Hot Country Songs chart, becoming their first entry on any "Billboard" chart in 32 years. In the United Kingdom, this version peaked at No. 53 in late December 1992, while in Australia, it reached No. 61 in early 1993.


title: Achy Breaky Heart

text: "Weird Al" Yankovic parodied the song on his album "Alapalooza" as "Achy Breaky Song", in which he pleads with the DJ not to play Billy Ray Cyrus's "Achy Breaky Heart" anymore; he can tolerate ABBA, Village People, New Kids on the Block, even Slim Whitman and Yoko Ono, but he'll really go bonkers if he has to hear "Achy Breaky Heart" once more.


title: Achy Breaky Heart

text: In 2014, rapper Buck 22 released a hip-hop version of the song with Cyrus called "Achy Breaky 2", in which Cyrus reprised his role for the chorus. While Cyrus does never explicitly say the song is a parody, the lyrics and accompanying video clearly make several references to daughter Miley's bad-girl image at the time, with Billy Ray noting in a "Rolling Stone" article that he "[hopes] that she got to read the one critic who wrote that the video made her performance at the VMAs look like "Sesame Street"".


title: Achy Breaky Heart

text: Supporters of many UK football clubs have used chants based on the tune of the song, including West Ham United (about Dimitri Payet), Arsenal F.C. (about Mesut Özil), Newcastle United F.C., Cardiff City F.C. (about Malky Mackay), Celtic F.C. and Manchester United F.C. (about Park Ji-sung). It has also been adapted as "Don't Take Me Home", which has been sung by the supporters of several national football teams, including England, Wales, the Republic of Ireland and Sweden. The chant was particularly associated with Wales' run to the semi-finals of UEFA Euro 2016, and lent its name to "Don't Take Me Home", a documentary film about the team's performances at that tournament.


title: Achy Breaky Heart

text: Cyrus' version of the song spent five weeks at the top of the "Billboard" Hot Country Songs charts in 1992. This was the longest time spent at the top of that chart by a debut single since "Skip a Rope" by Henson Cargill in 1967, and the last until "Austin" by Blake Shelton in 2001.


title: Imphal

text: Imphal (Meitei pronunciation: /im.pʰal/; English pronunciation: ) is the capital city of the Indian state of Manipur. The metropolitan centre of the city contains the ruins of Kangla Palace (also known as Kangla Fort), the royal seat of the former Kingdom of Manipur, surrounded by a moat. Spread over parts of the districts of Imphal West and Imphal East, the former contains the majority of the city's area and population. Imphal is part of the Smart Cities Mission under the Ministry of Housing and Urban Affairs.


title: Imphal

text: Initially ruled by King Khaba, Imphal was later ruled by the Pakhangba leaders. The clan of the Ningthouja tribe originated then. The Ningthouja tribe quickly expanded and dominated the region in politics and war. Kangla Palace was built by King Khagemba and his son Khunjaoba. The palace was later destroyed by the British during the Anglo-Manipur War. During the reign of Maharaja Bhagyachandra, there were a number of Burmese invasions. However, the kingdom survived with the help of Maharaj Gambhir Singh.


title: Imphal

text: Imphal remained peaceful until 1891, when there were internal differences in the royal family. The British sent J.W. Quinton to help but the situation only grew worse and Senapati Tikendrajit was hanged. The autocratic British behavior made people angry. This resulted in the 1891 Anglo-Manipur War, which the British won.


title: Imphal

text: The Battle of Imphal took place between March and July 1944, during World War II. The Japanese had invaded Imphal to destroy Allied forces and then invade India, but they were defeated and forced to retreat. The attack made the British realise the militarily strategic position of Imphal.


title: Imphal

text: Imphal city is divided between the two districts of Imphal West and Imphal East. Census collects the information for the two parts of the city separately, with the major portion of the city being in Imphal West and the minor portion in Imphal East.


title: Imphal

text: Imphal is located at in extreme eastern India, with an average elevation of . It has a humid subtropical climate (Köppen: "Cwa") with cool, dry winters and a slightly hot monsoon season. Climate of Imphal is influenced by its high altitude. Maximum temperatures in the hottest months average about ; January is the coldest month, with average lows near , often drops to around 2 °C in the coldest nights and rarely drops below freezing point. The city receives about of rain, with June the wettest month. The highest recorded temperature was , on 22 May 2009, and the lowest temperature was on 10 January 1970.


title: Imphal

text: Imphal is the state capital as well as the headquarters of the Imphal district. The civic administration of the city is under Imphal Municipal Corporation.


title: Imphal

text: According to Census 2011, Imphal constitutes 42.13% of the total urban population in Manipur. Hence, the history of urban local governance is longer in Imphal than in other parts of the state. The British established the Town Fund Board in Imphal in 1915, which was headed by the then Political Agent Lt. Col. H.W.G. Cole and other nominated members. The Town Fund Board continued after Independence and merger with India in 1949 and it was not headed by the Chief Secretary of Manipur Administration. In 1956, the Assam Municipal Act, 1923 was extended to Manipur and the Imphal Municipal Board was formed with 12 elected members. The strength of the elected members of this Board was increased to 24 in 1961 and to 28 in 1972. Initially, the Municipal Board was established only to administer the areas in Imphal under the British Reserve, covering and 2,862 inhabitants. This was extended to in 1960, in 1970, and in 1972.


title: Imphal

text: In 1992, the Municipal Board was upgraded to a Municipal Council under the Manipur Municipality Act, 1994. In 2014, the council was upgraded to the status of Municipal Corporation. There are 27 wards under the Municipal Corporation, each with its own elected councillor. There are eight committees and five sections at the corporation to govern the administration of the city.


title: Imphal

text: There are Ward Development Committees in each ward to look after developmental activities at the ward level. The local ward councillor is the chairperson of the committee, which includes two elected and two nominated members as well. The last election to the corporation was in 2016, with INC winning 12 seats, BJP winning 10 seats, and independent candidates winning 5 seats. According to the Manipur Municipality Act, 1994, the mayor is indirectly elected by the elected councillors from amongst themselves. The first mayor of the corporation was Soram Sunil and was elected in 2016. The present mayor of Imphal Municipal Corporation is Laisangbam Lokeshwar and was elected to the position in 2017. Sujata Phaomei is the present Deputy Mayor.


title: Imphal

text: Manipur is divided into two constituencies for the purpose of Lok Sabha - Outer Manipur Parliamentary Constituency and Inner Manipur Parliamentary Constituency. Imphal city is part of the Inner Manipur Parliamentary Constituency. The last elections took place during the 2019 Indian general elections. Rajkumar Ranjan Singh from the Bharatiya Janata Party won the election with 2,63,632 votes.


title: Imphal

text: Manipur State Power Distribution Company Limited is responsible for electricity supply in the city. Public Health and Engineering Department of the Manipur Government looks after both water supply, and sewage and drainage in Imphal. Roads in the city are developed and maintained by the state Public Works Department. Imphal Municipal Corporation is responsible for Solid Waste Management. The state Department of Fire Services provides fire safety services in the city with one fire station, which is also the department headquarters.


title: Imphal

text: Imphal offers sites of religious and historical importance within and around the city. Kangla Palace (also known as Kangla Fort) is on the banks of the Imphal River. "Kangla" means "dry land" in the Meitei language. It was the palace of King Pakhangba, and has religious significance with multiple temples present within the complex. It is also significant in Manipur's history with the British. Bihu Loukon is an ancient star-shaped fort made of mud situated in Maklang, Imphal West District. It was discovered in 2013. Hiyangthang Lairembi Temple is religious site important to both the local religion, Sanamahism, and to Hinduism. The temple is noted for its annual Durga Puja festival.


title: Imphal

text: India Peace Memorial at the Red Hills is located south of Imphal. The place was the scene of action and the theater of the battle that took place between the British Army and the Japanese Forces fighting alongside the Indian National Army in World War II. Red Hill has now become a tourist attraction since the Japanese war veterans constructed a monument at the foot of this hill. The Imphal War Cemetery remembers Indian and British soldiers who fought and died in 1944 during World War II and is managed by the Commonwealth War Graves Commission.


title: Imphal

text: Imphal is also home to the largest all women run market in Asia, called the Ima Keithel (Mothers' Market). It was established in the 16th century and hosts around 5,000–6,000 women vendors who sell a variety of products.


title: Imphal

text: Imphal is connected by the National Highway to major cities like Lamka, Guwahati, Kohima, Agartala, Shillong, Dimapur, Aizawl, and Silchar.


title: Imphal

text: In October 2012, India's Cabinet Committee on Infrastructure approved an extension of the Jiribam–Silchar railway to Imphal. The extension was expected to reach the city by 2019. The total length of the railway line is 110.62 km. The revised estimated cost of construction for the railway line sits at Rs 9658 crore, with Rs 4927.54 crore being spent as of 2019.


title: Imphal

text: Khuman Lampak Main Stadium is a multi-purpose stadium in Imphal. It is used mostly for football and athletics. The stadium holds 30,000 people and was built in 1999. This stadium lies inside the Khuman Lampak Sports Complex. Imphal based professional football clubs NEROCA FC and TRAU FC of I-League play their home matches at this stadium.


title: Imphal

text: There are many schools in Imphal affiliated with the Central Board of Secondary Education and Indian Certificate of Secondary Education Board, as well as state government schools.


title: Inode

text: The inode (index node) is a data structure in a Unix-style file system that describes a file-system object such as a file or a directory. Each inode stores the attributes and disk block locations of the object's data. File-system object attributes may include metadata (times of last change, access, modification), as well as owner and permission data.


title: Inode

text: A directory is a list of inodes with their assigned names. The list includes an entry for itself, its parent, and each of its children.


title: Inode

text: There has been uncertainty on the Linux kernel mailing list about the reason for the "i" in "inode". In 2002, the question was brought to Unix pioneer Dennis Ritchie, who replied:


title: Inode

text: A 1978 paper by Ritchie and Ken Thompson bolsters the notion of "index" being the etymological origin of inodes. They wrote: Additionally, Maurice J. Bach wrote that an inode "is a contraction of the term index node and is commonly used in literature on the UNIX system".


title: Inode

text: A file system relies on data structures "about" the files, as opposed to the contents of that file. The former are called "metadata"—data that describes data. Each file is associated with an "inode", which is identified by an integer, often referred to as an "i-number" or "inode number".


title: Inode

text: Inodes store information about files and directories (folders), such as file ownership, access mode (read, write, execute permissions), and file type. On many older file system implementations, the maximum number of inodes is fixed at file system creation, limiting the maximum number of files the file system can hold. A typical allocation heuristic for inodes in a file system is one inode for every 2K bytes contained in the filesystem.


title: Inode

text: The inode number indexes a table of inodes in a known location on the device. From the inode number, the kernel's file system driver can access the inode contents, including the location of the file, thereby allowing access to the file. A file's inode number can be found using the codice_1 command. The codice_1 command prints the i-node number in the first column of the report.


title: Inode

text: Some Unix-style file systems such as ZFS, OpenZFS, ReiserFS, btrfs, and APFS omit a fixed-size inode table, but must store equivalent data in order to provide equivalent capabilities. The data may be called stat data, in reference to the codice_3 system call that provides the data to programs. Common alternatives to the fixed-size table include B-trees and the derived B+ trees.


title: Inode

text: The operating system kernel's in-memory representation of this data is called codice_4 in Linux. Systems derived from BSD use the term codice_5 (the "v" refers to the kernel's virtual file system layer).


title: Inode

text: The POSIX standard mandates file-system behavior that is strongly influenced by traditional UNIX file systems. An inode is denoted by the phrase "file serial number", defined as a "per-file system" unique identifier for a file. That file serial number, together with the device ID of the device containing the file, uniquely identify the file within the whole system.


title: Inode

text: Within a POSIX system, a file has the following attributes which may be retrieved by the codice_3 system call:


title: Inode

text: It can make sense to store very small files in the inode itself to save both space (no data block needed) and lookup time (no further disk access needed). This file system feature is called inlining. The strict separation of inode and file data thus can no longer be assumed when using modern file systems.


title: Inode

text: If the data of a file fits in the space allocated for pointers to the data, this space can conveniently be used. For example, ext2 and its successors store the data of symlinks (typically file names) in this way if the data is no more than 60 bytes ("fast symbolic links").


title: Inode

text: Ext4 has a file system option called codice_7 that allows ext4 to perform inlining if enabled during file system creation. Because an inode's size is limited, this only works for very small files.


title: Christian Death

text: Christian Death is an American rock band formed in Los Angeles County, California, in 1979 by Rozz Williams. With major line-up changes over the years, Christian Death has retained "a relentlessly confrontational stand against organized religion and conventional morality".


title: Christian Death

text: Williams was eventually joined by guitarist Rikk Agnew of the band Adolescents, James McGearty on bass guitar and George Belanger on drums. This line-up was responsible for producing the band's best known work, their 1982 debut album "Only Theatre of Pain", which was highly influential in the development of the style of music known as deathrock, as well as on the American gothic scene which also produced bands such as Kommunity FK and 45 Grave.


title: Christian Death

text: Following the release of "Only Theatre of Pain", Christian Death's line-up had fallen apart, and by the time of the band's second album, "Catastrophe Ballet" (1984), Rozz was joined by Valor Kand of tour mates Pompeii 99 on vocals and guitar. Following the release of the band's third album, "Ashes", in 1985, Williams left the band and Kand became frontperson, with no original members of the band remaining. This resulted in a divide in the band's fanbase and controversy that has continued to this day.


title: Christian Death

text: Christian Death was founded by a teenage Rozz Williams in Los Angeles, California in October 1979. Williams grew up in the eastern suburb of Pomona in a Christian family. Williams had originally called his band the Upsetters, which included guitarist Jay (a.k.a. John Albert), bassist James McGearty and drummer George Belanger. The band garnered attention after changing their name to Christian Death and adding former Adolescents guitarist Rikk Agnew. In 1981, they made their first vinyl appearance with the song "Dogs" on the L.A. scene compilation album "Hell Comes to Your House".


title: Christian Death

text: In 1982, Christian Death signed to Frontier Records, and released their debut album, "Only Theatre of Pain" that March. "Only Theatre of Pain" was released in Europe by the French label L'Invitation au Suicide, followed by the record's release in Japan.


title: Christian Death

text: Christian Death broke up amid band infighting and drug abuse. Williams assembled a new version of the band in 1983 by merging with another L.A. rock band, Pompeii 99. This lineup included guitarist Valor Kand, vocalist and keyboardist Gitane DeMone, vocalist and bassist Voxx Voltair and drummer David Glass. The new version of the band recorded their next two albums, 1984's "Catastrophe Ballet" (with bassist Constance Smith) and 1985's "Ashes" (with bassist Randy Wilde).


title: Christian Death

text: In mid-1985, Williams left Christian Death, in part due to his increasing interest in experimental music and performance art. Kand took over leadership, serving as lead singer and songwriter. Augmented by bassist Johann Schumann and guitarist and keyboardist Barry Galvin, the band recorded an EP for the Italian label Supporti Fonografici titled "The Wind Kissed Pictures", credited to "For Sin And Sacrifice Must We Die A Christian Death". The EP was later reissued in Germany and the U.S., credited to Christian Death.


title: Christian Death

text: Their first post-Williams album was 1986's "Atrocities", a concept album about the aftereffects of World War II on the European psyche, which was followed by 1987's "The Scriptures", recorded by a revamped lineup of Kand, Demone, Glass, guitarist James Beam and bassist Kota. Longtime drummer Glass left the group following the release of "The Scriptures" and returned to California, where he eventually worked with several Williams side projects.


title: Christian Death

text: The band had their biggest successes on the UK Independent Chart with the 1987–89 singles "Sick of Love", "Church of No Return" and "Zero Sex" and the 1988 album "Sex and Drugs and Jesus Christ". Following the "Zero Sex" single, Demone opted to leave the band.


title: Christian Death

text: Valor recorded the two-part "All the Love All the Hate" concept album (1989) in collaboration with Nick the Bastard, which spawned the double A-side single "We Fall Like Love"/"I Hate You".


title: Christian Death

text: During the late 1980s, while also recording as Shadow Project, Williams resurrected his own version of Christian Death, with his wife Eva O contributing guitar as well as vocals. Billing themselves as the original Christian Death, they were rejoined by first-album guitarist Agnew for a 1989 tour of Canada. The band was signed to Cleopatra Records, and released "The Iron Mask" album and "Skeleton Kiss" EP in 1992. Williams' reclamation of the Christian Death name sparked a fierce battle with Kand. However, Kand already had the rights to the name due to Williams' departure from the band and subsequent neglect of the moniker. Williams consequently billed his version of the band as "Christian Death Featuring Rozz Williams". After this, Williams' version released "The Path of Sorrows" album in 1993 and "The Rage of Angels" in 1994. A 1993 show featuring "Only Theatre of Pain"-era members Williams, Agnew and Belanger (along with bassist Casey Chaos) performing live at Los Angeles' Patriot Hall was recorded and later released in 2001 as a DVD by Cleopatra. Williams pursued other projects before committing suicide on April 1, 1998.


title: Christian Death

text: Meanwhile, Kand's Christian Death continued performing and recording, issuing the 1990 album "Insanus, Ultio, Proditio, Misercordiaque", on which Kand conducted the English Abbey Choir and the Commonwealth Chamber Orchestra. The band added bassist Maitri in 1991. Her first concert with Christian Death took place at the Contemporary Festival, held at the Anfitheatro delle Cascine in Florence, Italy on 12 July 1991. The band released the "Sexy Death God" album in 1994, the double-live set "Amen" in 1995, the Nostradamus-themed "Prophecies" in 1996, and "Pornographic Messiah" in 1998.


title: Christian Death

text: In 2000, Christian Death added drummer Will Sarginson and toured Europe with Britain's Cradle of Filth in support of the "Born Again Anti Christian" album.


title: Christian Death

text: Kand and Maitri also formed another band, black metal/deathrock act Lover of Sin, releasing the album "Christian Death Presents Lover of Sin" in 2002.


title: Christian Death

text: In 2014, the band embarked on the 30th Anniversary Catastrophe Ballet tour, beginning in Europe and continuing through the year's end in North, South and Central America.


title: Christian Death

text: In January 2015, Christian Death announced the planned release of the PledgeMusic funded album, "The Root of All Evilution". The album was digitally released on August 14, 2015, by Knife Fight Media, and on vinyl on October 16, 2015, by Season of Mist. A CD release was announced for December 18, 2015, on The End Records.


title: Christian Death

text: Christian Death's style is considered gothic rock, deathrock and art punk. According to Steve Huey of AllMusic, Christian Death's music "relied on slow, doomy, effects-laden guitar riffs and ambient horror-soundtrack synths". According to Huey, Christian Death's lyrics involve shock value and are often about topics like "blasphemy, morbidity, drug use, and sexual perversity". Necrophilia also is a topic that has been used in Christian Death's lyrics. Liz Ohanesian of "L.A. Weekly" wrote that Christian Death experiments "with dirgey guitars, tribal drums and overtly spooky imagery". According to author Liisa Ladouceur, along with "spooky guitars and keyboards", elements of genres such as post-punk and spoken word also have been used in Christian Death's music.


title: Christian Death

text: Artists that have been inspired by Christian Death include Greg Mackintosh of Paradise Lost and Jonathan Davis of Korn.


title: Deemed university

text: A deemed university or deemed-to-be-university is an accreditation granted to higher educational institutions in India by the Department of Higher Education under the Ministry of Education.


title: Deemed university

text: To quote the Ministry of Education, "An Institution of Higher Education, other than universities, working at a very high standard in specific area of study, can be declared by the Central Government on the advice of the University Grants Commission (UGC), as an Institution 'Deemed-to-be-university'. Institutions that are 'deemed-to-be-university' enjoy the academic status and privileges of a university."