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Vol 7 (October 30, 2022) /
Hand-assisted laparoscopic nephrectomy for a kidney transplant: surgical technique—tips and tricks—how we do it?
Surgical Technique
Jorge Adrian Romero1^, Jorge Meza1^, Antonio Marmolejo1^, Roberto Bathory1^, Ana Paula Ruiz-Funes1^, Jorge Farell1^, Alfonso Bandin2^
1Department of Surgery, Hospital Central Sur de Alta Especialidad, PEMEX, México City, México; 2Department of Transplantation, Hospital Central Sur de Alta Especialidad, PEMEX, México City, México
^ORCID: Jorge Adrian Romero, 0000-0002-3557-2186; Jorge Meza, 0000-0002-2179-5565; Antonio Marmolejo, 0000-0002-3967-8471; Roberto Bathory, 0000-0002-6887-8288; Ana Paula Ruiz-Funes, 0000-0001-9888-7460; Jorge Farell, 0000-0002-3369-565X; Alfonso Bandin, 0000-0002-7474-3734.
Correspondence to: Jorge Adrian Romero. Anillo Periférico, #4091, Fuentes del Pedregal, Tlalpan, 14140 Ciudad de México, México. Email: adrianromsa93@gmail.com.
Abstract: Kidney transplant is considered the best therapy for patients with chronic kidney disease in renal replacement therapy or dialysis stage, which has better survival and quality of life with lower morbidity and lower long-term expenses, resulting in overall cost saving for the health care system compared to other therapies. In a living donor kidney transplant patient, the safety must remain as maximal priority because it is performed on a healthy patient who accepts the risks of major surgery for the benefit of the recipient. The process of donation should be as least traumatic, painful, and uncomfortable as possible to the potential donor. Over the years several approaches have been described, currently there is no gold standard to perform a nephrectomy on potential donors. Hand-assisted laparoscopic nephrectomy encompasses the benefits of the minimally invasive approach reducing the operative time and learning curve in comparison with the totally laparoscopic procedure. This technique has shown excellent results, both for the donor and the recipient. This work presents the technical description of the hand-assisted laparoscopic nephrectomy focused on the anatomical aspects, tips and tricks. Furthermore, the equipment preference card, patient's workup, post-operative management, and narrated technique video are added so that the reader can follow them visually.
Keywords: Nephrectomy; hand-assisted; laparoscopic; renal donor; kidney transplant
Received: 19 June 2022; Accepted: 02 August 2022; Published: 30 October 2022.
doi: 10.21037/ales-22-31
Video 1 Narrated hand-assisted left laparoscopic nephrectomy for kidney transplant.
The laparoscopic donor nephrectomy was first introduced in 1995 by Ratner. It is now carried out by three different approaches: laparoscopic transperitoneal donor nephrectomy (LDN), laparoscopic hand-assisted transperitoneal donor nephrectomy (HALDN), and laparoscopic retroperitoneal donor nephrectomy (LRDN). At present, there is no substantial evidence to support the use of one laparoscopic approach in preference to the other; however, there is some evidence suggesting that HALDN represents the most cost-effective method of donor surgery achieving similar clinical benefits of pure laparoscopic approaches with less operative time (1).
In the potential living donor nephrectomy for transplant, the safety must remain as maximal priority because it is performed on a healthy patient who accepts the risks of major surgery for the benefit of the recipient. The process of donation should be as least traumatic, painful, and uncomfortable as possible to the donor (2,3).
It is essential to maintain the mortality and morbidity of live donors as low as possible. A study shows that the mortality rate must be almost 0%, at the time that we need to preserve the kidney in optimal condition for transplantation (4).
HALDN encompasses the benefits of the minimally invasive approach reducing the operative time and learning curve in comparison with the totally laparoscopic procedure.
Hand assisted laparoscopic surgeries are at least as safe as totally laparoscopic procedures, in terms of time for return to normal activity are also comparable and require fewer trocars (5).
Hand-assisted laparoscopic surgery tends to decrease operation time and conversion rate compared to conventional laparoscopy for colorectal surgery (6).
We have noticed that being able to insert a hand into the surgical field resembles an open approach, which facilitates traction and makes the procedure easier for residents with less experience, taking into account that the kidney has to be taken out through a small incision anyway.
This technique has shown excellent results, both for the donor and the recipient.
Compared to classic laparoscopic nephrectomy, HALDN reduces the operative time (2.02 vs. 3.12 h) and warm ischemic time (1.23 vs. 3.9 min) (7,8). HALDN has a relatively short learning curve reflected by the rapid decrease in difficulty scores and operative times by fourth surgery (9), nevertheless there is a need for more trials to compare this specific results.
Patient selection and workup
Almost all donors eligible for an open surgical procedure can undergo hand-assisted laparoscopic surgery. All patients must undergo a complete history and physical examination, as well as an assessment by the nephrologist and the complete protocol for the potential living donor (10).
Radiological evaluation is necessary to characterize vascular anatomy and detect anomalies. We prefer a CT scan with arterial, venous, and excretory phases (11). Due to the anatomical and surgical advantages, the left kidney would be the first option for the transplant.
The final decision is made based on renal function and the number of renal arteries that should be taken into account for the reconstruction during bench surgery and implant to the recipient.
Preoperative preparation
The patient must have blood typed and screened before the procedure. Before surgery, a prophylactic antibiotic is administered, usually second-generation cephalosporin. All the materials needed for surgery are listed in (Table 1).
Equipment preference card
30-degree 10 mm laparoscope lens
5 mm Maryland dissector
5 mm Grasper
5 mm scissors
5 mm suction irrigation system
5 mm harmonic scalpel or Ligasure
Hand-access device (Gelport)
Large or medium Hem-o-Lok
Linear endoscopic stapler with vascular loads
Trocars: two 12 mm and one 5 mm
Sutures: long absorbable suture for fascial closure and 3-0 absorbable suture for skin closure
Regarding ethical considerations, no formal ethics approval was required by the research committee: "Comité de Investigacion del Hospital Central Sur de Alta Especialidad PEMEX", due to the absence of experimental treatments and the adequate protection of patient's personal data. Written informed consent was obtained for the publication of the video presented in this manuscript. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
We will describe in the first place the surgical technique for the left HALDN; later, we will talk about the adjustments that should be considered for the right HALDN.
All patients must undergo general anesthesia with endotracheal intubation, and a Foley catheter is inserted. While in a supine position, the patient skin is marked for the trocar incision access. The anatomical landmarks are left midclavicular line, 2 cm below the last costal arch for the camera port, and 2 cm above the anterior superior iliac crest for the working port (Figure 1).
Figure 1 Trocar location for left kidney.
The patient is placed in a lateral decubitus position, with the operative side upwards. The kidney rest is positioned beneath the contralateral iliac crest and raised, then the table is flexed. Appropriate measures should be taken to avoid the patient's injury, the pressure sites must be cradled on bean bags.
Additional security may be obtained by using padded straps (Figure 2).
Figure 2 Patient position on surgical room.
Trocar and Hand access device placement
The initial midline incision should be 10 cm long, at the umbilicus, in order to introduce the hand access device (Gelport). It is also possible to place the access device through a Pfannenstiel incision. Through the hand access device (Gelport), a 12 mm trocar is inserted, and pneumoperitoneum is created by insufflation of CO2 up to 12 mmHg of intraabdominal pressure.
The laparoscope is inserted through this port, and a diagnostic laparoscopy is performed, looking for adhesions and adequate position of abdominal content. After that, the rest of the ports are inserted under direct vision. Two 12 mm ports are placed using the already made skin marks however, the position should be reassessed under direct vision because gravity and reposition changes.
Hand retraction
At this point, the surgeon introduces his left-hand without losing pneumoperitoneum and, with the right hand, handle a laparoscopic instrument. The intra-abdominal hand is used to retract the left colon medially; this retraction allows a clear view of the avascular dissection plane of Toldt. Using the harmonic scalpel, an incision must be done in this plane from the iliac vessels to the splenic flexure; dissection must be continued until releasing the splenic angle. This maneuver exposes the retroperitoneal space from the psoas caudally to the Gerota's fascia cranially.
A plane of dissection is developed between the tail of the pancreas and Gerota's fascia; this will allow medial traction of the pancreas, together with the descending colon, obtaining a better view of the Gerota's fascia.
Following the edge of the upper pole, the dissection between the Gerota's fascia and the tail of the pancreas must be carried out with caution to avoid injuring the pancreas.
To continue the caudal dissection, the ureter should be identified medially to the psoas muscle alongside the gonadal vein; both structures are carefully dissected from the psoas and surrounding fat. The gonadal vein is followed up to the renal vein and the ureter until the lower pole of the kidney. All attachments on the medial side need to be released from the level of the renal hilum.
The lower pole of the kidney should be freed from lateral to medial.
The next step is to incise bottom-up the Gerota's fascia and release the renal capsule from it.
Safety triangle
There is no consensus regarding its anatomical landmarks but it has previously been described by various authors as the "golden triangle", which contains the proximal irrigation of the ureter this is why dissection at this level should be protected and avoided reducing urological complications (12,13).
In our technique we describe the "safety triangle" which is between the lower pole of the kidney, tracing a horizontal line until crossing the gonadal vein and following the gonadal vein on its way to the confluence with the renal vein. As can be seen in Figure 3.
Figure 3 Safety triangle. Triangle limits: renal vein, lower pole of the kidney, and gonadal vessels.
Care must be taken to leave perihilar fat intact due to its relevance for irrigation. A plane between the upper pole of the kidney and adrenal must be developed to maintain the gland intact.
At this moment, the kidney can be mobilized anteriorly and medially to allow posterior dissection of the hilum, which is completed when both the renal vein and artery are adequately identified and circumferentially freed. The artery runs posterior to the vein and must be dissected up to its aortic origin; if there are more than one artery, they must be dissected and respected, because there is no intrarenal anastomosis.
Once the ureter, gonadal vein, renal artery, and renal vein are adequately dissected. The ureter and gonadal vein are secured each one with one Hem-o-Lok, as proximal to the psoas muscle as possible, and cut with laparoscopic scissors. The renal artery is clipped with two Hem-o-Lok proximal to the aorta and cut with laparoscopic scissors. The last structure must be the renal vein, some authors prefer to secure this vessel with a laparoscopic linear stapler. We prefer the use of Hem-o-Lok in most left nephrectomies, after skeletonization of the renal vein.
The entire specimen is then removed through the hand port and handed to the reception team for cold perfusion with preservation solution; we use Organ preservation solution 1,000 cc with 5,000 IU heparin. The pressure of pneumoperitoneum is decreased for evaluation of adequate hemostasis. Then trocars are removed under direct vision, and finally, the hand-assisted device is taken out. An example of this technique is shown in Video 1 so you can follow these steps visually.
The midline hand port fascia is closed with a long-term absorbable suture in a continuous fashion with small bites technique (4:1). The rest of the ports are closed with long term absorbable suture in a figure of eight fashion (14). Skin is closed with subdermal stitches of a 3-0 absorbable suture.
Right nephrectomy
In case of right nephrectomy, the marks for the trocar incision points are the right midclavicular line, 2 cm below the costal arch, for the working port (10 mm). We place the camera port (10 mm) 2 cm above and medial to the anterior superior iliac crest, and a third port (5 mm) is marked in the subxiphoid region to place a hepatic retractor (Figure 4).
Figure 4 Trocar location for right kidney.
The approach begins with the dissection of Toldt's line, which is performed from cephalic to caudal. In a similar way that in the left nephrectomy, the left hand is the intra-abdominal hand that helps with medial retraction of the colon. An adequate release of the hepatic flexure must be performed, being careful not to apply too much traction avoiding bleeding from the subhepatic adhesions. The section of the hepatic triangular ligament must be done to free the right hepatic lobe from the abdominal wall. This facilitates the cephalic traction of the liver with a hepatic retractor introduced through the subxiphoid port, improving the hepatic's angle of the colon exposure, as well as the superior renal pole and the inferior vena cava (IVC) exposures.
We continue the dissection from lateral to medial in the avascular plane between the Gerota's fascia and the mesentery of the colon, which can be distinguished by a pale yellow color of the fascia and a darker yellow color of the mesentery. This dissection will continue until the medial portion of the kidney is exposed. Unlike left nephrectomy, in a right nephrectomy, medial mobilization of the duodenum must be performed with the Kocher maneuver. This allows adequate exposure of the renal vein and IVC, facilitating dissection of the vascular structures.
The right ureter may be located in the same position as on the left side, medially to the psoas muscle. The renal vein is identified by dissecting its emergence from the infrahepatic vena cava; an adequate dissection will offer a correct exposure of the ureter. As said before it is essential to preserve the periureteral tissue during its dissection, mainly between the lower pole of the kidney and the ureter (safety triangle), to prevent devascularization. The path is followed to the bifurcation of the iliac vessels, the site where the section will be made, similar to the contralateral side.
Renal dissection can be continued from lateral to medial, circumferentially, medializing the kidney with the intrabdominal hand, releasing the posterior adhesions with an energy device.
When the renal hilum is completely dissected circumferentially and prepared for cutting, the artery can be clipped with Hem-o-Locks. In addition, we prefer to secure the renal vein with Hem-o-Locks similar to the left nephrectomy. In case of using a laparoscopic stapler to secure the vein, the camera and the working port must be exchanged, allowing an adequate position of the stapler through the port of the right lower quadrant, obtaining a better orientation towards the renal vein—IVC junction. A 30 mm endo-stapler with a vascular cartridge must be fired as close as possible to the IVC, trying to preserve as much length as possible of the renal vein. Sometimes it is necessary to take a little bite of the IVC; for this, it is crucial to maintain a traction of the renal specimen laterally with the dominant hand. With this maneuver, better exposure and length of the renal vein is obtained during stapling.
Post-operative management
Most patients begin ambulation in the first 24 hours. On postoperative day 1, clear liquids are started, then progress to a soft diet. Finally, the patient is discharged after a 2-day in-hospital stay. The follow up as an outpatient must be on days 15, 30 and then 3–6 months, with complete blood count (CBC) and serum creatinine, a normalization of the glomerulation filtration rate is expected in the first six months. However, this is achieved in rare cases. Finally, annual monitoring is carried out if possible by the 1rst care provider.
Tips, tricks, and pitfalls
The patient's position must be optimal. Measures should be taken to avoid the patient's injury and additional security may be obtained by using padded straps;
Prior to trocar placement, we recommend assessing the site once the patient is already in the final position, to ensure surgeon ergonomics;
Always respect the safety triangle formed between the lower pole of the kidney, Gonadal vein, and Renal vein this step will maintain perihilar fat intact. This is important due to its relevance for irrigation;
Try to preserve as much length as possible of the renal vein, this is relevant for the future renal transplant;
Consider anatomical variants such as retro-aortic or posterior renal veins;
Carefully dissect and ligate accessory veins that may drain into the renal vein such as accessory lumbar or gonadal veins;
Ensure that gonadal vein dissection is complete and does not include the gonadal artery, avoiding compromising gonadal irrigation.
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://ales.amegroups.com/article/view/10.21037/ales-22-31/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Regarding ethical considerations, no formal ethics approval was required by the research committee: "Comité de Investigacion del Hospital Central Sur de Alta Especialidad PEMEX", due to the absence of experimental treatments and the adequate protection of patient's personal data. Written informed consent was obtained for the publication of the video presented in this manuscript. This study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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Cite this article as: Romero JA, Meza J, Marmolejo A, Bathory R, Ruiz-Funes AP, Farell J, Bandin A. Hand-assisted laparoscopic nephrectomy for a kidney transplant: surgical technique—tips and tricks—how we do it? Ann Laparosc Endosc Surg 2022;7:38.
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Q: Entering to a Collection Discord.js v13 I recently updated to v13, and I had some commands where i transform Objects to arrays using .array(), but now it gives my an error saying that .array() isn't a function
How can I enter to the information in a Collection now?
msg.array()[0].embeds[0]

This is an example of what I used to do
TypeError: mensajes.array is not a function

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If you need to convert a collection to an array of values similar to the old method, use Array.from(<Collection>.values())
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        public static extern bool CredFree([In] IntPtr cred);
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}


text:
Lindsey Graham, Rand Paul Rivalry on Foreign Aid Grows
By Niels Lesniewski
Posted October 10, 2012 at 6:40pm
A deepening rivalry over foreign policy between Sen. Lindsey Graham and fellow Republican Sen. Rand Paul burst onto the national stage this week when the South Carolina hawk decided to defend an incumbent Democrat against the Kentuckian's attacks.
After Paul launched TV ads through his political action committee against three Democratic Senators who are up for reelection this year, Graham leapt into action Tuesday and joined Sen. Joe Manchin (D-W.Va.) on a campaign conference call to dispute the ads' contention that Manchin's support for foreign aid to Libya, Egypt and Pakistan is not in the country's best interest.
On that call, Graham may have made the understatement of the year.
"Rand Paul's a good man. I like working with him on entitlement reform, but he has a little different worldview than I do," Graham said.
But Paul was more direct in his response and questioned Graham's campaign priorities during an interview with Roll Call. Paul said that while he had well-documented differences with the GOP on some policy issues, he would not take the step of supporting Democrats.
Paul was not swayed by the suggestion that Graham entering the fray in West Virginia doesn't matter because Manchin is a safe bet to prevail in his rematch with businessman John Raese.
"I think that's the mental gymnastics to justify why he's supporting a Democrat in the race," Paul said.
Though he has not yet signaled an intent to go after GOP candidates, RAND PAC would have no shortage of targets on the GOP side — 30 Republicans voted against the Paul proposal. And Paul took the extra step Wednesday of writing an op-ed for CNN that blasted GOP presidential nominee Mitt Romney's call to arm Syrian rebels who have been fighting a civil war against the regime of President Bashar Assad, even as Paul argued Romney should be elected president.
Like Paul, Graham has been out stumping for Republicans. He joined Manchin's conference call from the road in North Carolina, where he was campaigning for Romney.
"I very much would like to have a Republican president, and I would very much like to have a Republican-controlled Senate," Graham said, "but when it comes to foreign policy and matters of war and national security, I really do try to be bipartisan, and I respect Joe a lot."
Graham praised Manchin for taking a serious look at the language Paul proposed before deciding to cast a no vote, accusing Paul of promoting a foreign policy that would help al-Qaida by proposing to require America turn off the aid spigot when terrorists attack embassies abroad. The vote on the Paul proposal came in a late-night session shortly before the Senate recessed for the elections.
Graham has long criticized Paul for proposing a budget resolution that would dramatically slash Pentagon and foreign assistance spending, saying it undermines America's role in the world.
Foreign aid, Graham said, "is designed to create leverage so we influence the world and not have the world just run us over, and at the end of the day, I believe America should be involved in our national security. We shouldn't turn over decisions of where we go and what we do to terrorists."
At the moment, the votes in favor of the sort of engaged foreign policy championed by the likes of Graham and Sen. John McCain (R-Ariz.) have the clear majority in the Senate. Paul, however, believes public opinion is swinging in his direction given the debt situation at home.
"The discussion on foreign policy … within the Republican Party, I think will continue," Paul said.
While Paul only mustered 10 votes for his measure to strip foreign aid from Libya, Egypt and Pakistan until they meet his conditions, Graham rallied 90 votes for a resolution against allowing an Iranian nuclear weapons program to proceed.
Graham called Paul out on that subject last week in an interview with Roll Call, noting that he was the only one to vote against his resolution, which said that containment was not an option for dealing with an Iranian nuclear weapon.
"When they hear you say if they get a nuclear weapon, we're not going to use force, that's exactly what they want to hear," he said.
Such accusations do not faze Paul, who is also actively opposing intervention in Syria. In his CNN op-ed, Paul wrote, "In North Africa and the Middle East, our problem has not been a lack of intervention. In the past 10 years we have fought two full wars there, and bombed or sent troops into several others. … both parties rush headlong into more places they don't understand, exemplified Monday by Romney urging action to arm Syrian rebels and topple President Bashar al-Assad."
In an apparent reference to the uptick in violence against American troops in Afghanistan from Afghan security forces, Paul added, "We've been 10 years in Afghanistan and we can't identify friend from foe. Do you think we can, with certainty, identify friend and foe in Syria?"
Because Paul and Graham are both Republican Senators from Southern states, they could be in the Senate together a long time. After all, Graham succeeded Strom Thurmond, who represented South Carolina in the Senate for 48 years.
The two could continue to trade barbs on international relations and national defense for as long as they stay on the national stage, and if this week is any indication, both seem ready, willing and able to defend their positions.
Steven T. Dennis contributed to this report.

redpajama_set_name: RedPajamaCommonCrawl


I want help a woman or couple who is only seeking a donor in order to conceive. I'm open to staying in contact or remaining anonymous until 18. I'm 31, white, college educated with a stable job and no health problems.


Giant spider is invading the town and you must get it to be in their favor.
Raise your scare factor with this Halloween spiders that come with a plush hairy look and posable legs.
Get your spooky looks on and be creative with decorating your house with Halloween props and spiders.


No flowers here, but with Echeverias, who needs flowers?
We wish a Happy Thanksgiving to all who are celebrating this holiday. We give thanks, not for the excess accumulation of things which has come to signify our culture, but for the gifts of life and love and hope for all of you, wherever you my live.
Another plant which has been blooming like mad is Gibbaeum dispar. I especially appreciate the neat little clumps with their bright flowers at this time of year.
Tomorrow is Thanksgiving Day here in the U.S., so I'll be taking a day off. We'll be having a small simple meal, including a small "free range" turkey, with our younger son, Naiche. No big huge over-consumption here. And on Friday we'll be assiduously avoiding the madness which has come to be called "Black Friday" for the day the stores break into the black financially. Huge sales. Huge crowds. Yuk!
Like I said, the Fenestrarias are flowering. So I went out to the greenhouse and took a couple of photos today.
Another mesemb that's sending out its flowers, good old "Baby Toes". They can have yellow or white flowers.
Now, to be honest. This is an older photo. I didn't have time to photograph the plants today, but tomorrow - both the white and yellow flowered ones.
And another "to be honest". We tend to forget to water these plants when they need it in the winter because most of our other plants don't especially want to be watered. We're trying to do better and they like us for it.
I just don't know how people resist them!
Another Lithops with a white center to the flower is Lithops olivicea, which has been flowering the last couple of days. I think this photo catches the "shimmery" vitality of these little flowers.
Finally, I'm back...with more Lithops. This time it's Lithops helmuthii which is flowering. And what flowers! These photos don't do them justice. They literally shimmer in the sun light. Note the distinctive white centers to the flowers.
I went to the OCSS meeting tonight. Good turnout, but a pretty disorganized meeting. We must do better than this. But, the end result is that I'm bushed!!!
My apologies. I've been very busy redoing our nursery web pages. This is something I do myself and I learn as I go. Even through all my muddling, I think the end result will be well worth it. I do have some new photos and will get them up as soon as I have time. Thanks for your patience.
These vary a lot in color depending on the light. The plant is characterized by two distinct forms of leaves, the outer ones longer than the inner ones.
Now generally considered to be swallowed up in the Parodia genus, this is a really outstanding plant. Unlike some of the Lobivias, the plant itself is a beaut, even when it's not flowering.
This is Echeveria 'Lola' and it's another one of my favorites. It makes a very impressive display - all year long.
It's been a long time since I've mentioned that my wife of 41 years - Lynn-Marie Kara - is an artist. This is her latest work, a portrayal of Lithops dorotheae, and - for a short time - she is offering laser prints of this and some of her other works for a special price of $35.00. I don't usually get this "commercial" in my blog, but - hey - I'm proud of her work.
Ah yes! This helps me remember that Summer will come again!
These are the lovely flowers of Escobaria missouriensis var. asperispina. Another plant which is quite hardy if protected from too much moisture.
To end the day with a little humor, this is Osita, our now grown up Belgian Tervuren on the back of Ladybug, our miniature horse out at a neighborhood coffee shop. She's grown up now and doesn't quite fit on Ladybug's back, but they're still the closest of friends.
Today was another sunny Fall day so I spent most of the time up on the ladder putting up new gutters or going to the hardware store to get materials. I did venture into the greenhouses a couple of time and the Lithops are going wild with flowers. Have to get the camera out tomorrow!
I don't have time to pull out a photo from the archives, so I'll have to be photo-less tonight. Later.
I guess this is my favorite Gymnocalycium. The flowers are large and impressive, the body of the plant is classically beautiful, and it flowers dependably every year. Some find it hard to grow but we've never had any problems. However, it does need a potting mix with extra good drainage.


Great neighborhood friendly feel of a store. Really great service. Amazing hot food selection for a gas station. Nice new pumps are fast.
Thankful for the store being downtown! We go to the place at least once a day if not twice... thankful for all the folks who work there. They are very nice and helpful. And we love them all very much!!!
This store is wonderful. I have been ordering products on amazon because I live in a small town with a small town grocery store. But now that I have found this place I don't have to go threw amazon. The staff is great too. You don't have to look around forever to find char siu sauce, they will show you exactley where it is. And the prices are great too.
This store is the best for getting your groceries. Overall, I highly recommend this place! They have the best choices of everything here! The staff are very smiling and seem to enjoy working there.


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GMAT, one of the most dreaded exams among the MBA and MS aspirants, is no longer one such exam. There was a deep sigh of relief when I came out of the Pearson centre with a 690. Though not a very great score, it definitely made a lot of difference to me when compared with my previous score. I said it is no longer dreadful because we still have a few very good coaching centres such as Wizako(4GMAT), which boost your confidence and prepare you to face the long battle of GMAT.
The brilliant quant and verbal material that Wizako offers is no match with what is being offered by others. I gained a lot of confidence by working out the problems in the workbook and constantly pestering the real fundoo tutors at the centre. Thanks to Baskar and Shreyas who were instrumental in improving my quant. Special thanks to Subashree madam for verbal. I have gone through a lot of forums and books but never came across a robust methodology such as hers.
My special thanks to Shreyas, who constantly boosted my confidence every time I took Powerprep and Gprep (690, 690, 710 and 680). It makes a lot of difference when your tutors are genuinely interested in your performance and Wizako definitely has a brilliant set of tutors who produce many 700s (read 700 and above) everyday.


Discuss with your pals, your monetary advisor, your accountant, your family attorney and anyone else you belief who may know of an elder law specialist in your neighborhood. In any other case, it could be the state, an elder law attorney, a probate lawyer , your state's department of revenue, and/or the IRS that will obtain the biggest chunk of your assets. Draft a living will or other advance directives , including a durable energy of attorney and long term planning paperwork.
After graduating from Colby College in Waterville, Maine in 2000, Beth labored as a staff assistant and occasion planner within the discipline of upper training for 4 years earlier than attending law college at Roger Williams College Faculty of Law in Bristol, RI ('07).
The questions beneath will enable you to to get the information you need before making a last decision to hire a specific Elder Law attorney. The AARP () and the state bar affiliation () provide neutral attorney suggestions. You will also wish to inquire concerning the attorney's certifications and memberships with skilled elder law organizations.
For example, when planning an estate, an elder law attorney would think about the well being of the person or couple, the potential for nursing dwelling care and the needs and considerations of the person or couple if that occasion were to occur.
August 15, 2016, U.S. – Eight Reed Smith LLP lawyers claimed the highest spot in in Finest Lawyers' newest annual round of recognition, incomes 2017 Lawyer of the Yr" honors from the publication in their respective metropolitan areas. In addition to The New York Occasions, The Wall Avenue Journal, The Los Angeles Instances, The Washington Submit, and The Chicago Tribune, Greatest Lawyers partners with main enterprise and common publications around the world, from Les Echos in France, to the Australian Financial Assessment, Enterprise Day in South Africa, and Handelsblatt in Germany.
Revealed since 1983, Best Lawyers lists attorneys in 140 specialties, representing all 50 states, who've been chosen by an exhaustive survey in which hundreds of the nation's prime lawyers confidentially evaluate their skilled friends.
The twenty third Version of The Best Lawyers in America© (2017) consists of 54,905 attorneys in one hundred forty follow areas, protecting all 50 states and the District of Columbia, and inclusion in this 12 months's publication relies on more than 7.3 million detailed evaluations of lawyers by different lawyers.
Lawyers usually are not permitted to pay any price to take part in or be acknowledged by Greatest Lawyers. The listing accounts for greater than 5.5 million peer reviews from lawyers to seek out the Greatest Lawyer honorees. Our lists of excellent attorneys are compiled by conducting exhaustive peer overview surveys in which tens of hundreds of leading lawyers confidentially evaluate their skilled peers.
Welcome to , a free and useful resource to assist law school applicants, college students, and graduates. U.S. News plays an important role in providing not solely New York law school rankings however rankings for all law schools all through the United States. On the 2017 record, U.S. Information's high 25 best law faculties include three New York law colleges. Another great feature is you can examine a number of of your high New York law school decisions with another law college within the nation, like Stanford or Yale.
Be certain to take a look at which of the highest law colleges in New York make the lower this 12 months. Acceptance Price: That is the New York law faculty admissions proportion of scholars who apply. For these severe about finding the best law schools in New York, purchasing this 12 months-lengthy membership from U.S. News could possibly be an awesome thought and useful useful resource.
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Carnegie News
Multimedia (video and audio)
Printed Publications
Carnegie Legacy Project
- Any -Animal GeneticsAstronomy/CosmologyAwardsClimate ChangeDevelopmental BiologyEarth/Planetary ScienceEcologyEventsGrantsHigh Pressure PhysicsMaterials SciencePlant GeneticsScience EducationTrustees
Scientific Area
- Any -AstronomyEarth & Planetary ScienceGenetics & Developmental BiologyGlobal EcologyMatter at Extreme StatesPlant ScienceScience Education
Can we address climate change without sacrificing water quality?
Washington, DC—Strategies for limiting climate change must take into account their potential impact on water quality through nutrient overload, according to a new study from Carnegie's...
Predicting how forests in the western United States will respond to changing climate
Washington, DC— On the mountain slopes of the western United States, climate can play a major role in determining which tree communities will thrive in the harshest conditions, according to new...
Heather Meyer Receives Twelfth Postdoctoral Innovation and Excellence Award
Heather Meyer, a postdoctoral fellow in David Ehrhardt's Plant Biology lab since 2016, has been awarded Carnegie's twelfth Postdoctoral Innovation and Excellence Award. These prizes are...
Carnegie's Andrew Steele part of $9 million NASA astrobiology grant-winning team
Washington, DC—Carnegie's Andrew Steele is a member of the Earth First Origins project, led by Rensselaer Polytechnic Institute's Karyn Rogers, which has been awarded a $9 million...
Winslow Briggs, who discovered how plant seedlings grow toward light, dies at 90
Washington, DC— Carnegie's Winslow Briggs, a giant in the field of plant biology who explained how seedlings grow toward light, died on February 11 at Stanford University Medical Center....
What can Curiosity tell us about how a Martian mountain formed?
Washington, DC—The density of rock layers on the terrain that climbs from the base of Mars' Gale Crater to Mount Sharp is less dense than expected, according to the latest report on the...
China not "walking the walk" on methane emissions
Washington, DC—Chinese regulations on coal mining have not curbed the nation's growing methane emissions as intended, says new research from a team led by Carnegie's Scot...
Pasadena, CA— "Can moons have moons?" This simple question—asked by the four-year old son of Carnegie's Juna Kollmeier—started it all. Not long after this...
Worms help Carnegie and Stanford biologists investigate how plant-derived neurological drugs work
Stanford, CA—For millennia, humanity has used medicinal plants and plant-based compounds to treat a variety of neurological ailments including epilepsy, mania, migraines, and bipolar disorder....
Discovered: The Most-Distant Solar System Object Ever Observed
Washington, DC— A team of astronomers has discovered the most-distant body ever observed in our Solar System. It is the first known Solar System object that has been detected at a...
Pasadena, CA— Miguel Roth, director of Carnegie's Las Campanas Observatory in Chile from 1990 to 2014 and the current representative of the Giant Magellan Telescope Organization (GMTO) in...
Calibrating cosmic mile markers
Pasadena, CA—New work from the Carnegie Supernova Project provides the best-yet calibrations for using type Ia supernovae to measure cosmic distances, which has implications for our...
Could algae that are "poor-providers" help corals come back after bleaching?
Stanford, CA—How much of the ability of a coral reef to withstand stressful conditions is influenced by the type of algae that the corals hosts? Corals are marine invertebrates from the phylum...
How microbial interactions shape our lives
Baltimore, MD—The interactions that take place between the species of microbes living in the gastrointestinal system often have large and unpredicted effects on health, according to new work...
Newly discovered supernova complicates origin story theories
Pasadena, CA—A supernova discovered by an international group of astronomers including Carnegie's Tom Holoien and Maria Drout, and led by University of Hawaii's Ben Shappee,...
Carnegie's Anna Michalak's work guides North American carbon assessment
Washington, DC—Carnegie's Anna Michalak was a major contributor to the U.S. Global Change Research Program's Second State of the Carbon Cycle Report released last Friday, which...
Cold Super-Earth found orbiting second-closest star system to our own
Washington, DC—An international team including five Carnegie astronomers has discovered a frozen Super-Earth orbiting Barnard's star, the closest single star to our own Sun. The Planet...
How Invading Jumping Genes are Thwarted
Baltimore, MD—Since Carnegie Institution's Barbara McClintock received her Nobel Prize on her discovery of jumping genes in 1983, we have learned that almost half of our DNA is made up of...
Naturally occurring "batteries" fueled organic carbon synthesis on Mars
Washington, DC—Mars' organic carbon may have originated from a series of electrochemical reactions between briny liquids and volcanic minerals, according to new analyses of three Martian...
Unprecedented atlas of coral reefs released
Washington, DC—Today, Paul G. Allen Philanthropies and a consortium of partners, including Carnegie, unveiled the Allen Coral Atlas, a pioneering effort that uses high-resolution satellite...
Massive star's unusual death heralds the birth of compact neutron star binary
Pasadena, CA—Carnegie's Anthony Piro was part of a Caltech-led team of astronomers who observed the peculiar death of a massive star that exploded in a surprisingly faint and rapidly...
Steven Farber Awarded $3.3-Million NIH Grant To Identify New Pharmaceuticals To Fight Cardiovascular Disease
Carnegie's Department of Embryology scientist Steven Farber and team have been awarded a 5-year $3.3-million NIH grant to identify novel pharmaceuticals for combating a host of diseases...
To find life elsewhere, astrobiology must be integral to all NASA missions
Washington, DC—NASA should incorporate astrobiology into all stages of future exploratory missions, according to a new report from the National Academies of Sciences, Engineering, and Medicine...
Carnegie's Devaki Bhaya named California Academy of Sciences Fellow
Palo Alto, CA—Carnegie's Devaki Bhaya has been named a Fellow of the California Academy of Sciences. She is one of 14 new members selected as "partners and collaborators in the...
Former Geophysical Laboratory postdoc Sarah Stewart selected a 2018 MacArthur Fellow
Sarah Stewart was awarded a prestigious MacArthur fellowship for: "Advancing new theories of how celestial collisions give birth to planets and their natural satellites, such as the Earth...


Not that long ago, a home's energy efficiency was rated on an ascending scale — the higher the number, the better. Those days are done, and the goal now is to see how low you can go.
Energy usage measured in gigajoules is now the measuring stick, with Net Zero being the ultimate achievement. A net zero home is one designed, modelled and built to produce as much energy as it uses annually. That future is closer than you think, energy efficiency specialist Mehmet Ferdiner told a Waterloo Institute for Sustainable Energy seminar recently.
Japan had 20,000 net zero homes as of 2014. California is requiring that all new homes be net zero ready by 2020. Canada proposes that by 2030, all new buildings should be net zero ready. (A net zero ready home is airtight enough that with the addition of solar panels to generate power, it will be net zero).
Europe is requiring that all new buildings be net zero by 2021.
A few net zero home pilot projects have been done in Canada. One builder has reduced the incremental cost down to about $15,000 extra, with an eight-to 10-year payback, Ferdiner said.


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Гю́нзероде () — коммуна в Германии, в земле Тюрингия.

Входит в состав района Кифхойзер. Подчиняется управлению Киффхойзер. Население составляет 172 человека (на 31 декабря 2010 года). Занимает площадь 8,52 км². Официальный код — 16 0 65 027.

Примечания

Ссылки

Города Тюрингии

redpajama_set_name: RedPajamaWikipedia


Tortilla is perfect for a healthy make-ahead lunch.
THIS is a perfect healthy lunch packed full of protein-rich eggs, vegetables and potatoes. The tortilla can be made ahead and kept in the fridge.
Serve with some fresh green dressed salad. Also great in lunchboxes for lunch on-the-go.
This is also a twist on the classic Spanish dish and is a really speedy meal – ideal for a quick but tasty family dinner.
1 Preheat the oven to 200C, and bring a pan of salted water to the boil. Fill another dish with iced water, large enough to fir the asparagus.
2 Drop the asparagus into the boiling water, bring back to the boil then cook for two to three minutes. Remove the asparagus from the boiling water with a slotted spoon, then plunge into the iced water to preserve the bright colour of the asparagus.
3 Meanwhile, in a non-stick pan fry the sliced courgettes in the butter then add the garlic and cook over a medium heat for around 6-7 minutes until almost sticky.
4 Using the same boiling water used to cook the asparagus, parboil the potatoes and cut into cubes, then add the potatoes and the onion to the pan and cook until softened.
5 Place the asparagus into the pan, season the beaten eggs with salt and pepper and then add to the pan.
6 When the eggs have just set around the edges, transfer to the preheated oven for around six to eight minutes or until the tortilla is set.
7 When cooked turn out onto a plate.
8 Cut the tortilla into slices then serve with some dressed salad leaves.


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Buy the whole series
Jim Henson's Beneath the Dark Crystal
Jim Henson's Beneath the Dark Crystal #11
V.11 - Jim Henson's Beneath the Dark Crystal
Jim Henson & Adam Smith & Alexandria Huntington & Laura Langston
Buy the whole series for $51.91
( 9 Volumes )
Publisher's summary Archaia
Thurma and the other Firelings are under attack from an enemy more powerful than they could have imagined. With the ability to control water, The Fire That Stays could wipe out their entire race in a single attack, and only Thurma and her flame stand between the Firelings and total destruction.
Volume : 11/12 - Jim Henson's Beneath the Dark Crystal #11
Jim Henson Adam Smith Alexandria Huntington Laura Langston
This digital comic is available in english version. The following reading modes are available with the izneo reader:
In the same series. 9 volumes
See the whole series
Jim Henson's Beneath the Dark Crystal- Volume 11 - Jim Henson's Beneath the Dark Crystal #11 - Jim Henson - to read online on izneo or download on your iOS and Android tablet or smartphone.
The Glass Castle, home of the Firelings and their final protection, is under siege—and Thurma cannot defend it alone. But as her former rival, Nita, and the rest of her people come together, Thurma realizes that she has never been alone, and that working together is the only way to defeat The Fire That Stays.
V.8 - Jim Henson's Beneath the Dark Crystal
Buy the whole series for $51.91 ( 9 Volumes )
In the same series. 1 special issue
Jim Henson's Beneath the Dark Crystal Vol. 3
The stunning conclusion to the new sequel to the Dark Crystal film as two kingdoms must put aside their differences to combat a new enemy that threatens them all!
THE NEW SEQUEL TO THE HIT DARK CRYSTAL FILM CONCLUDES! Thurma and Kensho have discovered shocking truths and must return to their homelands, but they may not be welcomed back to Thra and Mithra as heroes. But when a new enemy more powerful than they could have imagined makes their move, these two kingdoms will have to find a way to join forces for the final battle that will change their very destinies. Writer Adam Smith (Jim Henson's Labyrinth) and rising-star artist Alexandria Huntington conclude their epic as Kensho and Thurma are faced with the ultimate decision! Collects Jim Henson's Beneath The Dark Crystal #9-12.
V.1 - Jim Henson's Labyrinth: Masquerade
All is not as it seems with the guests of Jareth's famous Masquerade, as one participant slowly awakens to the reality of her topsy-turvy existence in the Goblin Kingdom when Sarah shatters the glass mirrors during her escape. But as this mysterious participant puts together the pieces, her discoveries threaten to unravel everything!
Jim Henson's The Storyteller: Ghosts
V.12 - Jim Henson's The Dark Crystal: Age of Resistance
Jim Henson's The Dark Crystal: Age of Resistance: The Ballad of Hup & Barfinnious
C.4 - Jim Henson's The Storyteller: Ghosts
Jim Henson's Down at Fraggle Rock
V.9 - Jim Henson's The Dark Crystal: Age of Resistance
C.32 - Saban's Go Go Power Rangers


BACKGROUND: Psoriasis is a debilitating chronic inflammatory autoimmune disease affecting approximately 7.4 million adults in the United States. Plaque psoriasis is the most common form, affecting 80% to 90% of patients.
OBJECTIVES: To describe the impact and challenges that psoriasis presents for various stakeholders, and to provide nondermatologist healthcare decision makers with information to enhance their contributions to drug and pharmacy benefit design discussions.
DISCUSSION: Psoriasis carries an increased risk for early mortality and an increased prevalence of comorbidities, including psoriatic arthritis, cardiovascular disease, and diabetes. It is also associated with anxiety, depression, and social isolation, and can negatively impact patients' relationships, productivity, and careers. The physical, psychologic, social, and economic impact of psoriasis, plus the associated stigma, result in cumulative impairment over a patient's lifetime. The current treatments for moderate-to-severe psoriasis include topical therapy, phototherapy, and systemic drugs (nonbiologic and biologic); however, patient satisfaction remains low, combination therapy and treatment switching are common, and many patients remain untreated or undertreated. Clinicians should consider the patient holistically, and should select treatment based on a range of factors, including disease severity (with physical and psychosocial manifestations), susceptibility to cumulative life-course impairment (considering personality, behavior, and cognition), comorbidities, concomitant medication, and patient preference. It is estimated that the total annual direct cost of treating psoriasis in the United States in 2015 exceeded $12.2 billion.
CONCLUSION: Psoriasis is a complex disease, and appropriate management is correspondingly complex. Newer psoriasis treatments provide improved efficacy and safety versus traditional treatments, but challenges remain in ensuring patients access to these medications. An improved understanding of the barriers to appropriate treatment is needed, as well as clear and accessible information for payers and clinicians on current treatment options, to ensure that decision makers can control costs while providing patients with optimal care.
In light of the increasing prevalence and burden of psoriasis and the rapidly changing treatment landscape of the disease, the purpose of this article is to provide an overview of the key aspects of moderate-to-severe psoriasis, including the methods by which it is assessed, current treatment options, and unmet treatment needs. The impact of psoriasis on patients, clinicians, payers, and employers will also be discussed.
In the clinical practice setting, formal measures are often not used, relying instead on subjective assessments, particularly patient satisfaction, to drive treatment decision-making. The paucity of objective clinical outcomes, and the major limitation of risk adjustment, are significant hurdles to assessing the quality of the management of patients with psoriasis in the clinical setting.
Various options are available for the treatment of psoriasis, including topical agents, phototherapies and photochemotherapy, and systemic nonbiologic drugs, such as methotrexate (MTX) and cyclosporine (both immunosuppressive drugs), acitretin (a second-generation retinoid), and apremilast (an oral small-molecule inhibitor of phosphodiesterase-4), as noted in Table 1.
In addition, several systemic biologic therapies are currently approved (as of March 2016) by the US Food and Drug Administration (FDA) for the treatment of chronic, moderate-to-severe plaque psoriasis, including infliximab, etanercept, adalimumab, ustekinumab, secukinumab, and ixekizumab (Table 1).
In a survey conducted in the United States, Canada, France, Germany, Italy, Spain, and the United Kingdom, dermatologists reported that among patients with moderate-to-severe psoriasis, approximately 75%, 20%, and 20% of patients were receiving topical therapy, conventional oral therapy, and biologics, respectively.15 The American Academy of Dermatology has developed algorithms identifying recommended treatment options for psoriasis,19 and several drugs are currently under investigation for the treatment of psoriasis.
The efficacy of conventional systemic agents (ie, MTX and cyclosporine) and of biologic agents has been widely documented.13,20 A systematic review and meta-analysis of 48 randomized controlled trials of therapies approved for the treatment of moderate-to-severe psoriasis reported biologics to have higher efficacy than conventional systemic agents, with infliximab having the highest efficacy, followed by adalimumab and ustekinumab.20 Newer agents (ie, secukinumab, ixekizumab, and apremilast) were not included in this systematic review, because it was conducted before their availability.
Taken together, the potential for low satisfaction with psoriasis treatment, the rates of untreated and undertreated patients, frequent treatment switching, and the widespread use of combination therapy in the attempt to try to achieve a satisfactory response represent unmet treatment needs in patients with psoriasis of all severities.
Treatment should reflect the severity of disease, as is recommended by current treatment guidelines19 rather than being initiated using a stepwise approach. Treatment decisions are often difficult for physicians, because many medical management policies require a step-edit approach as a condition for reimbursement, requiring that the patient's disease fails to respond adequately to topical and/or conventional systemic therapies before being able to prescribe biologics.54 This may limit clinicians' ability to aggressively treat patients with moderate-to-severe disease, despite the recommended treatment guidelines.
As a consequence of the links between the cost of care, patient case mix, and the severity of disease, the inclusion of financial considerations in clinician performance ratings raises concerns among dermatologists that a dermatologist who manages patients with severe psoriasis could receive a lower rating than another clinician who only manages patients with mild psoriasis or who undertreats patients with moderate-to-severe psoriasis.
Most biologic therapies, and some of the newer nonbiologic agents, are effective in multiple autoimmune (and nonautoimmune) diseases, but have different dosage regimens across indications, which can present a challenge to payers.66 Payer formulary strategy and utilization management for FDA-approved specialty drugs are frequently based on a collective therapeutic review for all indicated autoimmune diseases. Such reviews are often based on the autoimmune disease with the largest patient population, which is rheumatoid arthritis.66 This strategy may result in a formulary that may limit or even preclude access to some treatment options for patients with other conditions, such as moderate-to-severe psoriasis.
Decision makers have to face difficult choices in sharing limited resources not just between competing treatments within a disease but between different disease states, and it is critical that all stakeholders have an informed understanding of this.
The high incidence of undertreatment of moderate-to-severe psoriasis and the variability in patient response highlight that despite a large range of available treatments, there remains an unmet need for new and effective treatments, as well as improved access to existing treatments. Continued research is needed to develop effective treatments for psoriasis with acceptable safety profiles and convenient administration routes, as well as regimens that will address issues of low treatment satisfaction and poor adherence among patients. Action is also needed to ensure that US treatment guidelines allow decision makers to control costs while providing patients with optimal care, and that such guidelines are followed by providers. Recent advances have led to the discovery of new agents for the treatment of psoriasis, providing broader treatment choices than those available only a few years ago.
Improved education of clinicians and payers in terms of the continually evolving nature of available treatments and their different mechanisms of action, efficacy, potential side effects, and position in treatment algorithms is needed to help inform treatment choices. Treatment plans should be developed in discussion with the patient to enhance adherence to their treatment regimens and to optimize patient outcomes.
The writing and preparation of this article were funded by Pfizer, Inc.
Medical writing support, under direction from the authors, was provided by Carole Evans, PhD, of Complete Medical Communications.
Dr Feldman has received research, speaking and/or consulting support from a variety of companies including AbbVie, Advance Medical, Suncare Research, Anacor, Astellas, Baxter, Boehringer Ingelheim, Janssen, Lilly, Merck, Merz, Mylan, Caremark, Celgene, Cosmederm, Galderma, GSK/Stiefel, Informa, Leo Pharma, National Biological Corporation, National Psoriasis Foundation, Novartis, Pfizer Inc, Qurient, UpToDate, and Valeant. He is founder and majority owner of www.DrScore.com, and founder and part-owner of Causa Research, a company dedicated to enhancing patients' adherence to treatment. Dr Feldman has participated in advisory boards for AbbVie, Boehringer Ingelheim, Merck, Novartis, and Pfizer Inc; has served as a consultant for AbbVie, Amgen, Celgene, Galderma Laboratories, Lilly, Mylan, Novartis, and Pfizer Inc; and is a member of speakers' bureau for Celgene, Galderma, and Janssen. Dr Feldman has received research grant support from Galderma Laboratories, Celgene, Novartis, and National Biological Corporation.
Dr Gottlieb has current consulting or advisory board agreements with Abbott Labs (AbbVie), Actelion, Amgen Inc, Astellas, Akros, Baxalta, Beiersdorf, Inc, Bristol-Myers Squibb Co, Canfite, Catabasis, Celgene Corp, Centocor (Janssen), Coronado, CSL Behring Biotherapies for Life, Dermipsor Ltd, GlaxoSmithKline, Genentech, Incyte, Karyopharm, Kineta One, KPI Therapeutics, Lilly, Novartis, Meiji Seika Pharma Co, Ltd, Mitsubishi Tanabe Pharma Development America, Inc, Novo Nordisk, Pfizer Inc, Takeda, TEVA, UCB, Vertex, and Xenoport; and has received research/educational grants (paid to Tufts Medical Center) from Abbott (AbbVie), Amgen, Baxalta, Celgene, Centocor (Janssen), Dermira, Levia, Lilly, Merck, Novartis, Pfizer Inc, and Xenoport.
Dr Goffe has research, speaking, and/or consulting support from AbbVie, Amgen, Astellas, Celgene, Centocor, Lilly, Novartis, and Pfizer Inc.
Mr Rice has participated in advisory boards for AbbVie, Biogen Idec, Janssen, Novartis, and Pfizer Inc; has served as a consultant for Gilead; and is a member of speakers' bureau for Novartis.
Dr Kaur, Ms Robertson, Dr Sierka, Dr Bourret, and Dr Evans are employees and shareholders of Pfizer Inc.
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PAYERS: Payers have long recognized that psoriasis is a chronic inflammatory disease that affects a significant portion of the US population. The most common form is plaque psoriasis, which affects approximately 2% (ie, 7 million patients) of the population.1 According to Feldman and colleagues, approximately 20% of these patients may have moderate-to-severe disease and are therefore potential candidates for systemic therapies.2,3 Payers also recognize the unmet needs for this patient population. There is no cure for this disease, and many patients are burdened with complex and difficult-to-use topical therapies. In the past 2 decades, systemic biologic therapies began to offer patients new and sometimes remarkably effective treatments for this condition. There are currently 6 approved systemic biologic treatments for psoriasis. The mainstay continues to be anti–tumor necrosis factors; however, newer agents that target interleukins are now also available.
While reading the current article,2 I was particularly struck by the figure of $30,568—the calculated annual healthcare cost per patient between 2007 and 2012 for biologic therapies for patients with moderate-to-severe psoriasis.2 If we agree that 7 million patients have psoriasis, and that 20% have moderate-to-severe disease, then potentially 1.4 million patients are candidates for biologic therapy. If only 50% of those patients were treated with biologics, at a cost of $30,568, the bill would then be an astonishing $21.4 billion, assuming that costs have not risen since this study. This is only 1 example of the staggering fiscal reality that payers deal with on a daily basis while trying to maintain access and affordability for members and their employer customers.
PROVIDERS, PATIENTS: Feldman and colleagues balance perspectives from the patient, the payer, and the physician.2 Patients want better and more affordable treatments; physicians struggle with the burden of payer management; such as prior authorizations and clinical management programs; and payers must find ways to continue to pay for these often-revolutionary treatments. However, we all must deal with the continuing reality of cost.
As noted, the cost potential of treating even one disease, such as psoriasis, could become unsustainable. Payers are left with blunt instruments (eg, prior authorizations, step-therapy, and contracting for best price) to help control costs. Payers recognize the administrative burdens that these approaches create, but these are necessary in today's environment. The challenge will be to bring payers, drug developers, physicians, and patients together to come up with potentially more innovative ways to manage the growing costs. We may need to develop new reimbursement methods, share risk with providers and patients, and find innovative ways to match the best treatment for each patient at the right cost. In the meantime, payers will continue to use the current approaches, while eagerly seeking alternative models in search of new ways to pay for advances in therapy.
1. Langley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology, clinical features, and quality of life. Ann Rheum Dis. 2005;64(suppl 2):ii18-ii23; discussion ii24-ii25.
2. Feldman SR, Goffe B, Rice G, et al. The challenge of managing psoriasis: unmet medical needs and stakeholder perspectives. Am Health Drug Benefits. 2016;9(9):504-513.
3. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
4. QuintilesIMS. IMS Health study: U.S. drug spending growth reaches 8.5 percent in 2015. Press release. April 14, 2016. www.imshealth.com/en/about-us/news/ims-health-study-us-drug-spending-growth-reaches-8.5-percent-in-2015. Accessed December 11, 2016.