text:
Applying Expert System Technology to Code Reuse with Pyke
PyCon 2008, Chicago
|Bruce Frederiksen
|Fri, 14 Mar 2008
|© 2008, Bruce Frederiksen
This paper explores a new approach to code reuse using a backward-chaining rule-based system, similar to prolog, to generate a function call graph before the functions are called. This is compared with current solutions which build the call graph as the functions are called.
This approach is introduced through an open source project called Pyke (Python Knowledge Engine).
Finally, the initial results show that the utility of this approach far exceeds expectations; leading to something more akin to automatic programming rather than adaptable libraries. A call for help is given to explore the capabilities of this approach across different domains.
- Abstract
- The Thinking that Led to Pyke
- Pyke
- Initial Results
- Going Forward
The Thinking that Led to Pyke
The Need for Code Reuse
At one of my contracting jobs, they had many clients running essentially the same program, but each client needed minor code modifications. Their objective was to maximize code reuse.
What is Code Reuse?
The first question is what does "code reuse" mean? And the answer that seems most logical is function reuse. Where code modifications are required, a new function can be created incorporating those modifications.
Then the remaining task is to bring the proper collection of functions together for each client.
This gets more complicated as several versions of many functions will be produced for various clients that are all available for reuse by the next client. So it's not simply the case that there will be one standard default version of each function, and then several one-off customized versions that each only apply to a single client.
The result of this function combination exercise is a function call graph.
Example 1
Let us imagine that we start out with two functions for client1:
And then client2 comes along.
Let us first suppose that we need a new version of function A, but can reuse function B1:
This is easy in any programming language and leads naturally to the idea that the functions to reuse are the lower-level ones, which can be placed into libraries.
But now let us suppose the opposite; that we need a new version of function B, but can reuse function A1:
This is where we need help.
Current Solutions
The current solutions are all run-time solutions that trap the call from function A1 to some function B and figure out which function B to use when the call is made. For example:
- O-O Dynamic Binding
- Zope Adapters
- Generic Functions
Current Solution Limitations
These solutions are all limited for the same reason. Let's look at another example to see why.
Example 2
Real world programs have many more than two functions, but we can start to see the limitations of the current solutions by looking at a three function example.
We start with one client and three functions.
When client2 was added, it could only share function A1 and had to have a new B (B2) that needs a new function with a different call interface than C, so we'll call it D1.
Then along comes client3. This time things are looking up, because all we need is a new version of function D:
Now let's see what happens when we want to call the program for client3. We know we need to start with function A1, since there is only version of function A:
But at this point we have two choices for function B. All we know for client3 is that we're supposed to use function D2, so we're left to guess about function B. So we try the first one, function B1:
It's not until function B1 tries to call some function C that we discover a problem.
This is where the current solutions break down.
Certainly for this example, it is easy to imagine a developer telling the binding system: oh yea and client3 is going to have to use function B2 as well. But more realistic call graphs are much more complicated than this; so the developer would have to specify which functions to use going back many levels.
And then when there is a change in these upper level shared functions later on, it will affect the call graphs for many clients.
So the current solutions don't scale well.
Continuing on with our example; what we need to do at this point is back up and try the other B function:
After doing this, we discover the solution for the final call graph:
What's Needed
By looking at this example, we discover two things about how to solve this problem:
Do function selection prior to calling any of the functions.
We can't wait until one function calls another to figure out what to do, because we may change our minds!
Use a standard backward-chaining rule-based algorithm.
The process of first trying function B1, then backing up and trying function B2 is exactly the process used in backward-chaining rule-based systems like prolog. They call it backtracking.
Applying Backward-Chaining to Code Reuse
The next question is how do we use a backward-chaining system to produce function call graphs?
Let's examine, conceptually, what a set of backward-chaining rules would look like to find a solution to this problem. Then we can determine how to turn this into a function call graph.
The following diagram shows goals as dotted line boxes around the rules that prove that goal. In this example, some goals only have one rule and some have two.
We also see how rules link to other goals. For example, rule Use B1 and rule Use B2 both prove the same goal: Find B. But Use B1 links to the Find C goal, while Use B2 links to Find D.
Now we can follow how these rules would be run by the knowledge engine:
- The whole process is kicked off by asking the knowledge engine for a solution to Find A.
- There is only one rule for Find A: Use A1, so the knowledge engine tries this rule.
- Use A1 needs a solution to Find B.
- The knowledge engine tries the first rule for Find B: Use B1.
- Use B1 needs a solution to Find C.
- The knowledge engine tries the only rule for Find C: Use C1, which fails for client3!
The situation now looks like:
Continuing on:
- Since there are no other rules for Find C, the Find C goal fails.
- Which means that the Use B1 rule fails.
- So the knowledge engine tries the next rule for Find B: Use B2.
- Use B2 needs a solution for Find D.
- The knowledge engine tries the first rule for Find D: Use D1, which fails for client3.
- The knowledge engine tries the next rule for Find D: Use D2, which succeeds for client3!
- The Find D goal succeeds.
- The Find B goal succeeds.
- And the Find A goal succeeds.
When we achieve final success, we have the following situation:
What remains is to translate this into a function call graph.
It becomes obvious that we want to attach our python functions directly to the backward-chaining rules:
Pyke KRB Syntax
How does all of this look in Pyke?
Pyke has its own language for rules, which it compiles into python source modules and then imports. This gives a performance boost by circumventing nearly all of the inference engine interpretation logic. It also makes it very easy to embed short python code snippets directly within the rules to help out with the inferencing. This keeps the inference mechanism simpler as it does not have to deal with things that are already easy in a procedural language (like arithmetic and simple list manipulation).
The Pyke rule source files are called knowledge rule bases and have a .krb suffix.
We'll continue with the previous example here.
First, let's look at the rules before we attach the python functions. Here's three of the rules:
use_B2 use find_B($client) when check_function($client, B, 2) find_D($client) use_D1 use find_D($client) when check_function($client, D, 1) use_D2 use find_D($client) when check_function($client, D, 2)
Note that Pyke uses a $ to indicate pattern variables (anonymous pattern variables start with $_).
The check_function goal checks to see what version of the indicated function should be used for this client. If this is the incorrect version, it fails. If there is no indication for this function, it succeeds to allow guessing.
Attaching Python Functions to Backward-Chaining Rules
Here are the last two rules with the python code added. The rules have the python function attached to them so that the function can be returned from the goal as an additional parameter. Because this parameter does not affect the inferencing process, it is a hidden parameter.
These examples just show one line of python code, but you may have as many lines as you want:
use_D1 use find_D($client) when check_function($client, D, 1) with print "D1" use_D2 use find_D($client) when check_function($client, D, 2) with print "D2"
Pyke calls the function call graphs plans. This terms applies to both the final top-level call graph, as well as intermediate call graphs.
Calling Subordinate Plans
Now we do the same thing to add python code to the use_B2 rule:
use_B2 use find_B($client) when check_function($client, B, 2) find_D($client) with print "B2"
We have code for the B2 function, but how does it call the plan returned from the find_D goal?
The most common way is:
use_B2 use find_B($client) when check_function($client, B, 2) find_D($client) $$() with print "B2"
In general, there may be many goals in the when clause that produce plans. Each would have an indented line of python code under it with $$ indicating the subordinate function. These indented lines are combined with the lines in the with clause to form the complete python function for this rule (with the differences in indenting levels corrected).
But in this case, this would mean that print "Dx" would be executed before print "B2", which seems backwards.
To call the subordinate plan within the with clause, there is an alternate mechanism:
use_B2 use find_B($client) when check_function($client, B, 2) find_D($client) as $d with print "B2" $d()
The as $d clause stores the plan function in pattern variable $d rather than adding a call to it to the with clause. Then you can decide in the with clause whether to call it, when to call it, how many times to call it, etc.
Note that pattern variables in general can be used within the python code. These are replaced by their final bound values (as constants) after the top-level goal has been proven. Thus, the rules can also be used to determine and set constant values within the plan functions to further customize the code. This is the reason that the code for the attached python functions is placed directly in the .krb file rather than in a separate python module.
Some Final Points about Plans
Function parameters are specified at the end of the use clause with an optional taking clause:
use_B2 use find_B($client) taking (a, b = None) ...
A completed plan appears as a normal python function.
Plans may be pickled and reused.
- If you add functools.partial to copy_reg.
You don't need to import all of Pyke to unpickle and run a plan.
- Only one small Pyke module is needed.
Other Capabilities
Pyke also supports forward-chaining rules:
fc_rule_name foreach fact_base_name.fact_name(pattern...) ... assert fact_base_name.fact_name(pattern...) ...
- Pyke runs all of the forward-chaining rules whose foreach clause succeeds prior to running any backward-chaining rules. Thus, forward-chaining rules can not call backward-chaining rules and vice versa. But backward-chaining rules can examine facts asserted by forward-chaining rules.
There are different kinds of knowledge bases:
- Fact Bases:
- simply store facts.
- Rule Bases:
- store both forward-chaining and backward-chaining rules.
- can use rule base inheritance to inherit, and build upon, the rules from
another rule base.
- But only single inheritance.
- Thus each rule base has a unique root rule base.
- All rule bases that share the same root form a rule base category.
- allow selection of which rule base(s) to use through rule base
- But only one rule base per rule base category may be active at one time.
- Extensibility. You can write your own knowledge bases. These might:
- look up facts in a database
- ask users questions
- probe hardware/software settings
- Fact Bases:
Initial Results
After writing Pyke's younger brother, it occurred to me that backward-chaining could be used to automatically figure out how to join database tables together and generate SQL statements.
And if the backward-chaining rules could see which substitution variables are needed by an HTML templating system, it could automatically generate the SQL to get these data and build the code to update the template.
It seemed that it would no longer be necessary to include anything that looks like code in the HTML templates. The graphic designers could just add simple attributes to their tags and the backward-chaining system would figure out the rest. This would mean that the programmers don't need to modify the HTML templates, and the graphic designers could maintain full ownership of the HTML.
I had a WSGI front-end that would simply assert the data passed to it as facts.
The forward-chaining rules took these starting facts, parsed the cookie information, form information, browser information, and url, determined whether the user was logged in, figured out which client the request was for, established all of this as additional facts and activated the appropriate rule base for this client.
Then the WSGI front-end simply asked for a proof of the process() goal and executed the resulting plan function which returned the final HTTP status codes and HTML document.
For a page retrieval (vs. form action), the process goal used two sub-goals:
- A format_retrieval goal that read the HTML template, and built a plan to render the template, given the needed data. This goal also returned a simple descriptor of this needed data as part of its inferencing.
- A retrieve goal then took that descriptor of the needed data, built the necessary SQL statements, and cooked them into a plan to execute those statements and return the needed data as a simple dictionary.
Then the two sub plans were combined in the reverse order, to first retrieve the data and then populate the template, for the final plan that went back to the WSGI front-end.
The Pyke examples/sqlgen and examples/web_framework are simplified examples that you can look at.
Now, as it turned out, the company had been running without a president for quite awhile, and had finally hired a new president.
So just as I finished the SQL generation logic to handle unique data (vs. multi-row data) and was preparing to show some demonstrations; our new president, coming from a java background and apparently never having heard of python, decided to cancel the project.
End of contract!
Code Reuse through Automatic Programming
The fundamental lesson learned was that this technique ends up being far more capable than what I had first imagined.
More than producing adaptable libraries capable of using B1 or B2 at some point in their call graphs, this approach leads to something more akin to the back-end of a compiler -- except that the compiler front-end does not target a textual language that needs to be written and parsed; but is rather a simple observer of already known facts:
Show me your schema, and I'll build your SQL statements.
Show me your HTML templates, and I'll build the code to populate them for you.
This seems to change the whole concept of code reuse; elevating it from the realm of static libraries, to the realm of dynamic automatic programming.
Going Forward
Thinking that others might find this useful, I've re-implemented the underlying knowledge engine from scratch, with numerous improvements gained from the experience of the first attempt, and made it open source.
With the backward-chaining rule base system, many applications are possible:
- Complicated decision making applications.
- Compiler back-ends.
- The .krb compiler uses Pyke.
- Automatic SQL statement generation.
- Automatic HTML generation/template processing.
- The control module for a web framework tool.
- Incorporate new custom functions into a large set of standard functions, which may change the selection or configuration of standard functions in other parts of the program.
- Automatically re-distribute the modules of a system over different programs and computers to meet a wide range of performance and capacity goals.
- Diagnosis systems.
- E.g., Automated customer service systems.
- Program or library customization for specific uses.
- Instantiate, configure, and interconnect networks of objects to meet a specific need or situation.
Up to this point, I've been flying solo. For this project to move forward to fully explore its capabilities, I'm going to need help!
I'd like to see several early adopters run with this and try it out in different domains. Pyke is in alpha status now and is ready to start to lean on.
This paper is licensed under a Creative Commons Attribution 3.0 Unported License.


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text: New drugs 2014, part 1Hussar, Daniel A. PhDNursing2014: February 2014 - Volume 44 - Issue 2 - p 44–54 doi: 10.1097/01.NURSE.0000441875.11512.03 Feature: CE Connection In Brief Author Information Article Outline Be prepared to administer and teach patients about 14 recently approved drugs, including the first in a new class of antidiabetic agents, an anticoagulant that's proven superior to warfarin for certain indications, and new antineoplastic drugs indicated for multiple myeloma, unresectable or metastatic melanoma, and thyroid cancer. Remington Professor of Pharmacy, Philadelphia College of Pharmacy, University of the Sciences, Philadelphia, Pa. The authors and planners have disclosed no potential conflicts of interest, financial or otherwise. SELECTED REFERENCES ANTICOAGULANT Apixaban Several significant advantages over warfarin REFERENCE LIPID-LOWERING DRUGS Lomitapide mesylate Mipomersen sodium Two drugs newly approved for a rare genetic disorder LOMITAPIDE MESYLATE REFERENCE MIPOMERSEN SODIUM REFERENCE ANTIDIABETIC DRUGS Canagliflozin First in its class REFERENCE Alogliptin benzoate New addition to an established drug class REFERENCE DRUG FOR DYSPAREUNIA Ospemifene Pain relief in a convenient oral formulation REFERENCE ANOREXIANT Lorcaserin First prescription weight-loss drug in years REFERENCE DRUG FOR MULTIPLE SCLEROSIS Dimethyl fumarate Another option for patients with relapsing forms of MS REFERENCE ANTITUBERCULAR DRUG Bedaquiline fumarate Effective therapy for multidrug-resistant TB REFERENCES ANTIDIARRHEAL DRUG Crofelemer First drug approved to manage diarrhea in patients with HIV... REFERENCE IN THIS ARTICLE, you'll learn about 14 recently approved drugs, including the first in a new class of antidiabetic agents. an anticoagulant that proved superior to warfarin for certain indications. new antineoplastic drugs indicated for multiple myeloma, unresectable or metastatic melanoma, and thyroid cancer. Unless otherwise specified, the information in the following summaries applies to adults, not children. Consult a pharmacist or the package insert for information about each drug's safety during pregnancy and breastfeeding. Consult a pharmacist, the package insert, or a comprehensive and current drug reference for more details on precautions, drug interactions, and adverse reactions* for all these drugs. Back to Top | Article Outline SELECTED REFERENCES Drug Facts and Comparisons. St. Louis, MO: Facts and Comparisons, Inc.; 2014. Nursing 2014 Drug Handbook. Ambler, PA: Lippincott Williams & Wilkins; 2014. Physicians' Desk Reference. 68th ed. Montvale, NJ: Medical Economics; 2014. Back to Top | Article Outline ANTICOAGULANT Apixaban Several significant advantages over warfarin Apixaban (Eliquis, Bristol-Myers Squibb; Pfizer), a factor Xa inhibitor anticoagulant, is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Evaluated and compared with warfarin in a multinational study of more than 18,000 patients, apixaban was determined to be superior to warfarin for the primary study endpoint of reducing the risk of stroke and systemic embolism. Superiority to warfarin was primarily attributable to a reduction in hemorrhagic and ischemic strokes with hemorrhagic conversion compared to warfarin. Purely ischemic strokes occurred with similar rates with both drugs. Treatment with apixaban resulted in a significantly lower rate of all-cause death than did treatment with warfarin, primarily because of a reduction in cardiovascular death, particularly stroke deaths. As with other anticoagulants, bleeding is the most important concern with apixaban. In clinical trials, however, significantly fewer major bleeding events (such as intracranial and gastrointestinal [GI] bleeding) occurred in patients treated with apixaban than in those treated with warfarin. The rate of major bleeding events was 2.13% per year with apixaban, compared with 3.09% with warfarin. Deaths attributable to bleeding events including hemorrhagic stroke occurred in 0.06% and 0.24% of patients per year, respectively. The bleeding risk increases when other medications that affect hemostasis are used concurrently. Apixaban should be discontinued at least 48 hours before elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. It should be discontinued at least 24 hours before elective surgery or invasive procedures in which the risk of bleeding is low or bleeding can be easily controlled. Apixaban doesn't require routine international normalized ratio (INR) monitoring, an advantage over warfarin. However, no specific antidote reverses an excessive anticoagulant action of apixaban. This represents a disadvantage for the new drug compared with warfarin, for which vitamin K is a specific antidote. A procoagulant reversal agent such as prothrombin complex concentrate may be considered, but this option hasn't been evaluated in clinical studies. Discontinuation of apixaban in the absence of adequate alternative anticoagulation increases the risk of thrombotic events such as strokes, the subject of a boxed warning in the labeling. If treatment with apixaban must be discontinued for a reason other than pathologic bleeding, coverage with another anticoagulant should be strongly considered. Precautions: (1) Contraindicated in patients with active pathologic bleeding. (2) Use cautiously in patients taking other drugs that affect hemostasis, such as other anticoagulants, fibrinolytic agents, aspirin and other antiplatelet drugs, nonsteroidal anti-inflammatory drugs, selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, and serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine. (3) Not recommended for patients with prosthetic heart valves. (4) Not recommended for patients with severe hepatic impairment. (5) Apixaban is a substrate of P-glycoprotein (P-gp), as well as CYP3A4. The concurrent use of a strong dual inhibitor of CYP3A4 and P-gp (such as ketoconazole or clarithromycin) increases the concentration of apixaban and the dosage of the anticoagulant should be reduced or its use avoided. (6) Avoid concurrent use with strong dual inducers of CYP3A4 and P-gp (such as carbamazepine, rifampin, and St. John's wort), which reduce exposure to apixaban. Adverse reactions: bleeding, hypersensitivity reactions such as skin rash Supplied as: 2.5 mg and 5 mg film-coated tablets Dosage: 5 mg twice a day. A lower dosage of 2.5 mg twice a day is recommended in patients with any two of the following characteristics: age 80 years or older; body weight of 60 kg or less; serum creatinine of 1.5 mg/dL or higher. If a patient is also taking a strong dual inhibitor of CYP3A4 and P-gp, the recommended dosage is 2.5 mg twice a day. Avoid concurrent use of a strong dual inhibitor of CYP3A4 and P-gp in patients already being treated with a dosage of 2.5 mg twice a day. Nursing considerations: (1) Teach patients to take the medication as prescribed and to recognize and report signs and symptoms of bleeding. (2) Tell patients that if they miss taking a dose at the scheduled time, they should take it as soon as possible on the same day and resume twice-daily administration. Warn them not to double the dose to make up for a missed dose. (3) Discontinue apixaban as prescribed before invasive procedures. (4) If a patient is switching from warfarin to apixaban treatment, discontinue warfarin and start apixaban when the INR is below 2, as prescribed. Switching a patient from apixaban to warfarin treatment is a challenge; apixaban affects the INR, so determining the appropriate warfarin dosage is difficult. Consult the product labeling for detailed recommendations on discontinuing apixaban or switching therapy from apixaban to another anticoagulant. Back to Top | Article Outline REFERENCE Prescribing information. Eliquis (apixaban) tablets for oral use. http://packageinserts.bms.com/pi/pi_eliquis.pdf. Back to Top | Article Outline LIPID-LOWERING DRUGS Lomitapide mesylate Mipomersen sodium Two drugs newly approved for a rare genetic disorder Homozygous familial hypercholesterolemia (HoFH) is a rare inherited disorder caused by defects in the low-density lipoprotein (LDL) receptor gene. These defects are associated with changes in vascular endothelial function that result in very high serum concentrations of LDL cholesterol. Approximately one in 1 million individuals in the United States (about 300 people) experiences HoFH. These patients are at risk for cardiovascular disorders and death at an early age, even during childhood. Two new drugs were marketed in 2013 specifically to treat HoFH. Although approved for the same indication, they'll be discussed separately because they have different mechanisms of action and administration routes. 1. FDA approves new orphan drug for rare cholesterol disorder. FDA news release. December 26, 2012. Back to Top | Article Outline LOMITAPIDE MESYLATE Lomitapide mesylate (Juxtapid, Aegerion) is indicated to treat patients with HoFH as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL apheresis where available, to reduce LDL-cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apoB), and non-high-density lipoprotein cholesterol (non-HDL-C). Its effectiveness was demonstrated in a clinical study involving 29 patients, 23 of whom completed the study over 78 weeks. The effect of lomitapide on cardiovascular morbidity and mortality wasn't determined, and its effectiveness hasn't been established in patients with hypercholesterolemia who don't have HoFH. The risk of hepatotoxicity is the subject of a boxed warning in its labeling and is the reason the drug is available only through a restricted distribution program. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, and total bilirubin should be determined before the start of treatment, and at least ALT and AST should be determined before each dosage increase or monthly, whichever comes first, during the first year. After the first year, these tests should be performed at least every 3 months and before any dosage increase. Lomitapide increases hepatic fat (hepatic steatosis), which is also a subject of the boxed warning. This may occur with or without elevations in ALT and AST, and may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis. In clinical trials, most patients (93%) experienced GI adverse reactions; 14% experienced GI reactions so severe that treatment was discontinued early. To reduce the risk of GI adverse reactions, the dosage of lomitapide should be increased gradually and patients should adhere to a low-fat diet. The administration of lomitapide with food may increase the risk of GI adverse reactions, so it should be administered apart from food. Because it primarily acts in the small intestine, lomitapide may reduce the absorption of fat-soluble nutrients. The risk of nutritional deficiencies may be increased in patients with chronic bowel or pancreatic diseases that predispose them to malabsorption. Consult the product insert for details about daily dietary supplements recommended for patients taking lomitapide. Lomitapide is classified in Pregnancy Category X and is contraindicated in pregnant women. Precautions: (1) Contraindicated in patients with moderate or severe hepatic impairment or active liver disease. (2) Patients treated with lomitapide should avoid alcohol or consume no more than one alcoholic drink per day. Alcohol may increase concentrations of hepatic fat and induce or exacerbate liver injury. (3) Use with caution in patients who are also being treated with other medications that are associated with a risk of hepatotoxicity, such as amiodarone or methotrexate. (4) Avoid use of lomitapide in patients with rare hereditary problems such as galactose intolerance or glucose-galactose malabsorption because of the increased possibility of diarrhea and malabsorption. (5) Lomitapide exposure is increased by about 50% in patients with end-stage renal disease receiving dialysis or mild hepatic impairment; the dosage shouldn't exceed 40 mg daily for these patients. (6) Lomitapide is extensively metabolized in the liver via the CYP3A4 pathway and is contraindicated for concurrent use with strong CYP3A4 inhibitors, such as ketoconazole and clarithromycin, or moderate CYP3A4 inhibitors such as diltiazem and verapamil. (7) Lomitapide is associated with many potential drug interactions. Consult the product insert for comprehensive warnings and recommended dosage adjustments. Adverse reactions: diarrhea, nausea, dyspepsia, vomiting, abdominal pain Table Supplied as: 5 mg, 10 mg, and 20 mg capsules Dosage: Initially 5 mg/day, increased gradually based on patient tolerance to the maximum recommended dosage of 60 mg once a day. Consult the product insert for detailed recommendations, including monitoring parameters and dosage adjustments for certain patient populations. Nursing considerations: (1) Women of reproductive potential should have a negative pregnancy test before starting treatment and use reliable contraception during therapy. (2) Because of the risk of nutritional deficiencies, teach patients the importance of taking dietary supplements as prescribed. (3) Tell patients on warfarin therapy to get regular INR testing as directed by their healthcare provider. Lomitapide has been reported to increase the plasma concentration of warfarin by about 30% and the INR by 30%. (4) Warn patients that taking lomitapide with food may exacerbate GI problems. Tell them to take each dose with a glass of water at least 2 hours after the evening meal. (5) Instruct patients to avoid grapefruit juice, which is a CYP3A4 inhibitor. (6) Remind patients to swallow capsules whole without opening, crushing, dissolving, or chewing them. Back to Top | Article Outline REFERENCE Prescribing information. Juxtapid (lomitapide) capsules for oral use. http://juxtapid.com/sites/default/files/downloads/Prescribing_Information.pdf. Back to Top | Article Outline MIPOMERSEN SODIUM The primary goal of treatment of patients with HoFH is to reduce the greatly elevated concentrations of LDL-C. Mipomersen sodium (Kynamro, Genzyme) is an oligonucleotide inhibitor of apoB-100 synthesis. ApoB-100 is the principal apolipoprotein of LDL. Administered via subcutaneous injection, this drug has been approved as an adjunct to lipid-lowering medications and diet to reduce LDL-C, apoB, TC, and non-HDL-C in patients with HoFH. It hasn't been evaluated as an adjunct to LDL apheresis and isn't recommended for use in patients receiving this treatment. The effectiveness of mipomersen was demonstrated in a placebo-controlled study in 51 patients. An average reduction in LDL-C concentrations of approximately 25% was found during the first 26 weeks of therapy. As with lomitapide, its effect on cardiovascular morbidity and mortality hasn't been determined, and its effectiveness hasn't been established in patients with hypercholesterolemia who don't have HoFH. As with lomitapide, the risk of hepatotoxicity is the most important concern for patients taking mipomersen, and the contraindications and warnings in the product labeling for the two drugs are almost exactly the same. The risk of hepatotoxicity is the subject of a boxed warning for both drugs and is the reason they're available only through a restricted distribution program. The risk of increased hepatic fat is also a subject of the boxed warning. Before a patient starts treatment, ALT, AST, alkaline phosphatase, and total bilirubin should be determined, and at least ALT and AST should be determined monthly during the first year of treatment. After the first year, these tests should be performed at least every 3 months. Precautions: (1) Mipomersen is contraindicated in patients with moderate or severe hepatic impairment or active liver disease. (2) Avoid concurrent use with other medications that can increase hepatic fat. (3) Patients taking mipomersen should avoid alcohol or consume no more than one alcoholic drink a day. (4) Not recommended for patients with severe renal impairment or clinically significant proteinuria, or for those on renal dialysis. Adverse reactions: injection site reactions (pain, pruritus, inflammation), flu-like symptoms (pyrexia, chills, myalgia, fatigue), nausea, headache, elevated ALT Supplied as: single-use vials and prefilled syringes providing 200 mg/mL Dosage: 200 mg once a week, on the same day every week. Consult the product labeling for recommended dosage adjustments in patients who experience elevations of transaminases. Nursing considerations: (1) For patients who will self-administer the drug at home, the first injection should be supervised by an appropriately qualified healthcare professional. Teach patients how to administer mipomersen subcutaneously into the abdomen, thigh region, or outer area of the upper arm. Instruct them to avoid areas of active skin disease or injury such as sunburns, skin infections, or areas of tattooed skin and scarring, and to alternate injection sites. (2) If patients miss a dose, tell them to take it if at least 3 days remain until the next scheduled weekly dose. (3) Tell patients to refrigerate vials and syringes, keep them in their original cartons until time of use, and protect them from light. Before administration, the drug should be removed from refrigeration for at least 30 minutes so it can warm to room temperature. Back to Top | Article Outline REFERENCE Prescribing information. Kynamro (miposmersen sodium) Injection. http://www.kynamro.com/~/media/Kynamro/Files/KYNAMRO-PI.pdf. Back to Top | Article Outline ANTIDIABETIC DRUGS Canagliflozin First in its class Designated as a sodium-glucose cotransporter 2 (SGLT2) inhibitor, canagliflozin (Invokana, Janssen) is the first drug approved in this new class of antidiabetic drugs. SGLT2 is expressed in the proximal renal tubules and is responsible for the reabsorption of most glucose filtered by the kidney. By inhibiting SGLT2, canagliflozin reduces reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion and lowering blood glucose concentrations. Canagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Its effectiveness has been demonstrated in studies in which it was used as monotherapy, in combination with metformin, a sulfonylurea, metformin and a sulfonylurea, metformin and pioglitazone, and in combination with insulin (with or without other antihyperglycemic agents). It's also been compared with sitagliptin and glimepiride in clinical studies. The use of canagliflozin resulted in reductions in A1C concentrations and fasting plasma glucose concentrations, and, in many patients, weight reduction. Hypersensitivity reactions, including erythema, rash, pruritus, and angioedema, were experienced by 4% of patients in the clinical studies of canagliflozin, with a small number of patients experiencing serious reactions. Canagliflozin increases serum creatinine concentrations and decreases estimated glomerular filtration rate (eGFR); patients with hypovolemia may be more susceptible to these changes. Assessment of renal function is recommended before treatment starts and periodically thereafter. Treatment shouldn't be initiated in patients with an eGFR less than 45 mL/minute/1.73 m2. More frequent renal function monitoring is recommended in patients with an eGFR below 60 mL/minute/1.73 m2. The drug should be discontinued if the eGFR is persistently less than 45 mL/minute/1.73 m2. Canagliflozin causes an osmotic diuresis that may reduce intravascular volume and cause symptomatic hypotension, particularly in patients with impaired renal function (eGFR less than 60 mL/minute/1.73 m2) or low systolic BP, older adults, or patients treated with diuretics or medications that interfere with the renin-angiotensin-aldosterone system, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Although canagliflozin isn't likely to cause hypoglycemia, it can increase the risk of hypoglycemia when used in combination with insulin or an insulin secretagogue such as a sulfonylurea. Dosage reductions for these agents may be warranted for patients on a combination regimen that includes canagliflozin. The concurrent use of drugs such as rifampin, ritonavir, phenytoin, and phenobarbital may require a higher dosage of the new drug because these drugs may decrease canagliflozin's action. In clinical studies, the incidence of pancreatitis and bone fracture was higher in patients treated with canagliflozin than with comparator agents. The FDA is requiring postmarketing studies that will monitor for these events, as well as malignancies, severe hypersensitivity reactions, photosensitivity reactions, liver abnormalities, adverse pregnancy outcomes, and cardiovascular outcomes. Precautions: (1) Contraindicated in patients with a history of a serious hypersensitivity reaction. (2) Contraindicated in patients with severe renal impairment (eGFR less than 30 mL/minute/1.73 m2) and end-stage renal disease, and in patients on dialysis. (3) Periodically monitor serum potassium concentrations for hyperkalemia in patients with impaired renal function and in those who are being treated with an ACE inhibitor, ARB, or potassium-sparing diuretic. (4) Closely monitor patients on digoxin therapy because canagliflozin may increase digoxin's concentration and action. Adverse reactions: female genital mycotic infections such as vulvovaginal candidiasis, urinary tract infections, increased urination, and male genital mycotic infections such as balanitis, hyperkalemia, increased LDL cholesterol, hypermagnesemia, and hyperphosphatemia Supplied as: 100 mg and 300 mg film-coated tablets Dosage: Initially, 100 mg once a day, taken before the first meal of the day. Dosage may be increased to 300 mg/day in certain patients; consult the product insert for dosage adjustment guidelines. Nursing considerations: (1) Teach patients to take canagliflozin before the first meal of the day. This recommendation is based on its potential to reduce postprandial plasma glucose excursions due to delayed intestinal glucose absorption. (2) Teach female patients to recognize and report signs and symptoms of a vaginal yeast infection, such as white or yellowing discharge that may resemble cottage cheese and vaginal itching. (3) Teach male patients to report signs and symptoms of yeast infections affecting skin around the penis, such as redness, itching, or swelling of the penis and pain in the skin around the penis. (4) Educate all patients about signs and symptoms of hypoglycemia, such as headache, drowsiness, irritability, hunger, rapid heart beat, sweating, and feeling jittery. (5) Encourage patients to maintain the prescribed diet and exercise program and to regularly monitor their serum glucose levels as directed. Back to Top | Article Outline REFERENCE Prescribing information. Invokana (canagliflozin) tablets, for oral use. http://www.invokanahcp.com/prescribing-information.pdf. Back to Top | Article Outline Alogliptin benzoate New addition to an established drug class The fourth dipeptidyl peptidase-4 (DPP-4) inhibitor to be approved, alogliptin benzoate (Nesina, Takeda) joins the class of drugs that includes sitagliptin, saxagliptin, and linagliptin. Its properties are very similar to those of its predecessors: By inhibiting the inactivation of incretins, the DPP-4 inhibitors increase and prolong their activity in increasing insulin biosynthesis and secretion. Like the other DPP-4 inhibitors, alogliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It's not indicated to treat patients with type 1 diabetes or those with diabetic ketoacidosis. The effectiveness of alogliptin was demonstrated in placebo-controlled studies in which it was evaluated as monotherapy, and in combination with metformin, glyburide, pioglitazone (either alone or in combination with metformin or a sulfonylurea), and insulin (either alone or in combination with metformin). It hasn't been directly compared with other DPP-4 inhibitors in clinical studies. Like its predecessors, alogliptin is well tolerated by most patients; however, rare but serious hypersensitivity reactions to DPP-4 inhibitors have been reported. In addition, some patients treated with a DPP-4 inhibitor, including alogliptin, have experienced acute pancreatitis. The labeling for alogliptin includes a warning regarding hepatic failure. Conducting liver function tests before initiating treatment is recommended. The DPP-4 inhibitors don't cause hypoglycemia and aren't likely to cause hypoglycemia when used in combination with metformin. However, their concurrent use with insulin or insulin secretagogues such as the sulfonylureas may cause hypoglycemia. Precautions: (1) Contraindicated in patients with a history of a serious hypersensitivity reaction to any drug in this class, such as anaphylaxis, angioedema, and severe cutaneous reactions. (2) Treatment with alogliptin should be promptly discontinued and the patient treated appropriately if pancreatitis is suspected. (3) Treatment with alogliptin should be interrupted if the patient experiences signs and symptoms that may indicate liver injury and/or if liver enzyme concentrations are significantly elevated. Treatment shouldn't resume unless another explanation for liver test abnormalities is found. (4) Closely monitor patients taking alogliptin with insulin or an insulin secretagogue. If indicated, reduce the dosage of insulin or the insulin secretagogue as prescribed. (5) Reduce the dosage as prescribed in patients with moderate or severe renal impairment or end-stage renal disease. Adverse reactions: nasopharyngitis, headache, upper respiratory tract infection Supplied as: 25 mg, 12.5 mg, and 6.25 mg film-coated tablets. Alogliptin is also available in a combination formulation with metformin and in a combination formulation with pioglitazone. Dosage: 25 mg once a day. Consult the product insert for recommended dosage reductions for patients with impaired renal function. Nursing considerations: (1) Assess renal function tests before patients begin therapy and periodically thereafter as prescribed. (2) Tell patients that alogliptin can be taken without regard to food. (3) Educate patients about the risk of acute pancreatitis and tell them to discontinue the drug and contact their healthcare provider immediately if they experience persistent, severe abdominal pain. (4) Warn patients about the risk of hypersensitivity reactions. Tell them to discontinue the drug and seek medical attention immediately if they experience signs of an allergic reaction such as skin rash or hives; swelling of the lips, tongue, or throat; and difficulty breathing. (5) If patients miss a dose, they should skip that dose and take the next one on schedule rather than doubling a dose. Back to Top | Article Outline REFERENCE Nesina (alogliptin) tablets. https://www.takedadiabetes.com. Back to Top | Article Outline DRUG FOR DYSPAREUNIA Ospemifene Pain relief in a convenient oral formulation The reduction in estrogen concentration associated with menopause may make vaginal tissues thinner, drier, and more fragile, resulting in dyspareunia (pain during sexual intercourse). These symptoms of vaginal and vulvar atrophy are among those most frequently reported by postmenopausal women. Ospemifene (Osphena, Shionogi) is an estrogen agonist/antagonist with actions that are mediated through binding to estrogen receptors. It acts like estrogen on vaginal tissues, making them thicker and less fragile. Also designated as a selective estrogen receptor modulator, ospemifene has properties that are most similar to those of raloxifene, a drug used primarily for treatment and prevention of osteoporosis in postmenopausal women. Ospemifene is indicated for moderate-to-severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. It's the first orally administered drug with estrogenic activity to be approved for this indication. The new drug exhibits estrogen agonistic effects in the endometrium; an increased risk of endometrial cancer in women with a uterus who use unopposed estrogens is the subject of a boxed warning in the labeling. Although adding a progestin to postmenopausal estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer, increased risks such as breast cancer are associated with use of progestins. An increased risk of cardiovascular disorders such as stroke and deep vein thrombosis (DVT) is also the subject of a boxed warning in the labeling. Precautions: (1) Ospemifene is classified in Pregnancy Category X and is contraindicated in women who are or may become pregnant. (2) Contraindicated in women with known or suspected estrogen-dependent neoplasia. Appropriate diagnostic measures should be taken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding. (3) Contraindicated in women with known or suspected breast cancer or a history of breast cancer. (4) Contraindicated in women with active DVT, pulmonary embolism, active arterial thromboembolic disease such as stroke or myocardial infarction, or a history of these disorders. (5) Discontinuing ospemifene is recommended at least 4 weeks before any surgery associated with an increased risk of thromboembolism and during prolonged periods of immobilization. (6) Ospemifene shouldn't be used concurrently with an estrogen agonist/antagonist. (7) Not recommended for use in patients with severe hepatic impairment. (8) Ospemifene shouldn't be used concurrently with fluconazole, which inhibits the pathways involved in the metabolism of ospemifene and increases the exposure of the new drug by 2.7-fold. Ketoconazole may also increase exposure of the new drug, but to a lesser extent. Conversely, rifampin induces these metabolic pathways and decreases the exposure of ospemifene by 58%, which is likely to reduce its clinical effect. (9) To reduce the risk of serious adverse reactions that may be associated with long-term use, the drug should be prescribed for the shortest duration that's consistent with treatment goals. Adverse reactions: hot flush, vaginal discharge, muscle spasms, hyperhidrosis, genital discharge Supplied as: 60 mg film-coated tablets Dosage: 60 mg once a day Nursing considerations: (1) Warn patients that ospemifene is likely to cause fetal harm and must not be used by women who are or may become pregnant. (2) Tell patients to take each dose with food, which increases the drug's bioavailability. (3) Teach patients to immediately report unusual vaginal bleeding, changes in vision or speech, sudden new or severe headaches, and severe pain in the chest or legs, with or without shortness of breath, weakness, and fatigue. Back to Top | Article Outline REFERENCE Prescribing information. Osphena (ospemifene) tablets, for oral use. http://www.shionogi.com/pdf/PI/Osphena-PI.pdf. Back to Top | Article Outline ANOREXIANT Lorcaserin First prescription weight-loss drug in years Lorcaserin (Belviq, Arena; Eisai), a new molecular entity, represents the first new prescription weight-loss drug approved by the FDA in 13 years. (Another new weight-loss product, Qsymia [Vivus], is a combination of two older medications, the anorexiant phentermine and the antiepileptic drug topiramate.) A serotonin 2C receptor agonist, lorcaserin is thought to reduce food consumption and promote satiety by selectively activating serotonin 2C receptors on anorexigenic proopiomelanocortin neurons in the hypothalamus. When used in the recommended dosage, the new drug doesn't appear to activate serotonin 2B receptors, the action associated with the heart valve damage that prompted withdrawal of fenfluramine and dexfenfluramine from the market. Lorcaserin is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of 30 or greater (obese), or 27 or greater (overweight) in the presence of at least one weight-related comorbid condition, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. In placebo-controlled studies, about 50% of patients who didn't have type 2 diabetes lost at least 5% of their baseline body weight compared with approximately 25% of those receiving placebo. In patients with type 2 diabetes, approximately 38% of patients treated with lorcaserin and 16% of those receiving placebo lost at least 5% of their body weight. Improved glycemic control was also associated with the use of lorcaserin in patients with diabetes. Because lorcaserin is a serotonergic drug, its use is associated with a risk of life-threatening serotonin syndrome or neuroleptic malignant syndrome-like reactions. The risk of serotonin syndrome is increased by the concurrent use of other drugs with serotonergic activity, including selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine, serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine, tricyclic antidepressants, monoamine oxidase inhibitors, lithium, triptans such as sumatriptan, tramadol, tryptophan, bupropion, dextromethorphan, and St. John's wort. The concurrent use of lorcaserin with any of these is best avoided, but if such therapies are clinically warranted, patients should be monitored even more closely for signs and symptoms of serotonin syndrome, such as mental status changes (agitation, hallucinations), autonomic instability (tachycardia, labile BP, hyperthermia), neuromuscular changes (hyperreflexia, incoordination), and GI effects (nausea, vomiting, diarrhea). The use of serotonergic anorexiants with serotonin 2B receptor agonist activity such as dexfenfluramine has been associated with a risk of heart valve damage. Because lorcaserin is a selective serotonin 2C receptor agonist, it appears less likely to cause such problems and the infrequent reports of valvular effects were at an incidence (approximately 2%) that was similar to that with placebo. However, lorcaserin was not studied in patients with congestive heart failure and it must be used with caution in patients with this condition. Approximately 2% of the patients treated with lorcaserin for at least 1 year in the clinical studies reported impairment of attention and memory, compared with 0.5% of those receiving placebo. Other cognitive adverse events included confusion, somnolence, and fatigue. Lorcaserin has been classified in Schedule IV under the provisions of the Controlled Substances Act because at larger than recommended dosages, it may cause euphoria, hallucination, and dissociation in some patients. Precautions: (1) Contraindicated during pregnancy; lorcaserin is classified in Pregnancy Category X. (2) Monitor patients for signs and symptoms of serotonin syndrome, particularly those taking lorcaserin and another drug with serotonergic activity concurrently. (3) Contraindicated for concurrent use with serotonergic and dopaminergic drugs that are potent serotonin 2B receptor agonists and are known to increase the risk of cardiac valvulopathy, such as cabergoline. (4) Monitor patients for depression and/or suicidal ideation, a potential risk with lorcaserin and other centrally acting drugs. Treatment should be discontinued in patients who experience suicidal thoughts or behaviors. (5) Activation of serotonin 2C receptors may increase the possibility of priapism, so lorcaserin should be used with caution in men with conditions that may predispose them to priapism, such as sickle cell anemia or leukemia, and in men using drugs to treat erectile dysfunction, such as sildenafil. (6) Closely monitor patients with risk factors for these potential problems: decreased heart rate, decreased red and white blood cell counts (periodic monitoring of complete blood cell [CBC] counts may be indicated), increased prolactin concentrations, hypoglycemia in patients with type 2 diabetes treated with insulin and/or insulin secretagogues such as sulfonylureas, and pulmonary hypertension. (7) Use caution in patients with moderate renal impairment or severe hepatic impairment. Lorcaserin isn't recommended for patients with severe renal impairment or end-stage renal disease. Adverse reactions: In patients who don't have diabetes mellitus: headache, dizziness, nausea, fatigue, constipation, dry mouth. In patients with diabetes: hypoglycemia, headache, back pain, cough, fatigue. Supplied as: 10 mg film-coated tablets Dosage: 10 mg twice a day. Nursing considerations: (1) Lorcaserin can be taken without regard to food. (2) Reinforce the importance of diet and exercise in any weight-loss program. (3) Because of the drug's potential cognitive adverse effects, caution patients to avoid driving and other hazardous activities requiring alertness until they determine how the medication affects them. (4) Warn women of childbearing potential that the drug is likely to harm a fetus and tell them to use reliable contraception throughout therapy. (5) Warn men about the potential for priapism. If appropriate, tell them to discuss concurrent use of medications for erectile dysfunction with their healthcare provider. (6) The patient's response to treatment should be evaluated by week 12. If the patient hasn't lost at least 5% of baseline body weight, treatment may be discontinued because it's unlikely that the patient will achieve meaningful weight loss with continued treatment. Back to Top | Article Outline REFERENCE Prescribing information. Belviq (lorcaserin). http://www.belviq.com/documents/Belviq_Prescribing_information.pdf. Back to Top | Article Outline DRUG FOR MULTIPLE SCLEROSIS Dimethyl fumarate Another option for patients with relapsing forms of MS Dimethyl fumarate (Tecfidera, Biogen Idec) is the third oral drug to be marketed in the last 3 years to treat patients with relapsing forms of multiple sclerosis (MS), joining fingolimod and teriflunomide. The effectiveness and safety of dimethyl fumarate (DMF) was evaluated in two placebo-controlled studies. The primary endpoint of one study was the proportion of patients who experienced relapse within 2 years. Only 27% of patients treated with DMF experienced relapse, compared with 46% of those receiving placebo. The drug was also more effective in attaining additional endpoints, including annualized relapse rate and time to confirmed disability progression. In the second study, the primary endpoint was the annualized relapse rate at 2 years, at which time these rates were 0.224 for DMF and 0.401 for placebo. In both studies the drug had a significant effect on the magnetic resonance imaging endpoints, such as a lower number of new or newly enlarging lesions. Precautions: (1) Because DMF decreases mean lymphocyte counts, patients taking it may have an increased infection risk. A CBC count within 6 months of starting therapy is recommended to identify patients with a preexisting lymphopenia. A CBC count is recommended annually during treatment or more often as indicated. (2) Treatment should be interrupted and the patient treated if a serious infection develops. Adverse reactions: flushing (warmth, redness, itching, and/or burning sensation), abdominal pain, diarrhea, nausea Supplied as: 120 mg and 240 mg delayed release capsules. A 30-day starter pack is available that includes a 7-day bottle with 120 mg capsules and a 23-day bottle with 240 mg capsules. A 30-day bottle containing 60 of the 240-mg capsules is available for maintenance treatment. Dosage: Initially, 120 mg twice a day. After 7 days, the dosage is increased to the maintenance dosage of 240 mg twice a day. Nursing considerations: (1) Instruct patients to swallow capsules whole, without crushing or chewing them. (2) Patients are more likely to experience flushing as an adverse reaction soon after starting treatment. Tell them that this usually resolves over time. GI adverse reactions, which are less common, usually resolve over time as well. (3) Although the drug may be taken without regard to food, advise patients that taking it with food may reduce the incidence of flushing. (4) Teach patients to recognize signs and symptoms of infection and report them to the healthcare provider. (5) Tell patients to store capsules in the original container. Once opened, bottles of DMF should be discarded after 90 days. Back to Top | Article Outline REFERENCE Prescribing information. Tecfidera (dimethyl fumarate) delayed release capsules, for oral use. http://www.tecfidera.com/pdfs/full-prescribing-information.pdf. Back to Top | Article Outline ANTITUBERCULAR DRUG Bedaquiline fumarate Effective therapy for multidrug-resistant TB Tuberculous (TB) is relatively rare in the United States, but worldwide it's estimated to affect 9 million people. The CDC reports that 10,528 people in the United States became ill with TB in 2011. Combination regimens of antitubercular drugs that include isoniazid, rifampin, and often other drugs have been the standard of treatment and are usually effective. However, strains of Mycobacterium tuberculosis resistant to isoniazid and rifampin are being reported with increasing frequency. Bedaquiline fumarate (Sirturo, Janssen) is the first antitubercular drug to be approved to treat MDR-TB. Classified as a diarylquinoline antimycobacterial drug, it inhibits mycobacterial adenosine 5'-triphosphate synthase, an enzyme essential for the generation of energy and replication of M. tuberculosis. Bedaquiline is indicated as part of combination therapy in adults with pulmonary MDR-TB. It must be used in combination with at least three other drugs to which the patient's MDR-TB isolate is susceptible based on lab testing. If test results are unavailable, treatment may be initiated with bedaquiline in combination with at least four other drugs to which the patient's MDR-TB isolate is likely to be susceptible. Bedaquiline should be reserved for use in patients for whom an effective treatment regimen can't otherwise be provided. The approval of bedaquiline was based on the analysis of time to sputum culture conversion from two clinical studies in patients with pulmonary MDR-TB. Its effectiveness and safety have not been established in patients with extrapulmonary TB, latent infection due to M. tuberculosis, or drug-sensitive TB. In one of the clinical studies, a higher incidence of death was found in patients receiving bedaquiline (9/79; 11.4%), compared with those receiving placebo (2/81; 2.5%); this is the subject of a boxed warning in its labeling. Because a reason for the imbalance in deaths hasn't been identified, bedaquiline should be used only when another effective treatment regimen can't be provided. Bedaquiline has been reported to prolong the QT interval. Its concurrent use with other medications that prolong the QT interval (such as antiarrhythmic agents, certain fluoroquinolone and macrolide antibacterial drugs, and the antimycobacterial clofazimine) can result in additive QT prolongation and an increased risk of ventricular dysrhythmias. This is the subject of a boxed warning in its labeling. The risk of QT prolongation and subsequent complications is higher in patients with a history of torsade de pointes, hypothyroidism and bradydysrhythmias, uncompensated heart failure, congenital long QT syndrome, or reduced calcium, magnesium, or potassium concentrations. Bedaquiline should be administered by directly observed therapy. Failure to adhere to the prescribed treatment regimen may result in increased antibiotic resistance and treatment failure. Precautions: (1) Because of the risk of ventricular dysrhythmias, an ECG should be obtained before treatment starts and at least 2, 12, and 24 weeks thereafter. Serum potassium, calcium, and magnesium should be determined at baseline and corrected if abnormal. Follow-up monitoring of electrolytes should be performed if QT prolongation is detected. (2) Treatment should be discontinued if the patient develops a clinically significant ventricular dysrhythmia or a heart rate corrected QT interval greater than 500 ms. (3) Because of the risk of hepatic adverse reactions, patients should avoid the concurrent use of alcohol and other hepatotoxic agents. New or worsening hepatic dysfunction (elevated liver function tests and signs and symptoms such as fatigue, anorexia, nausea, jaundice, and dark urine) should be promptly evaluated. Consult the product insert for detailed recommendations about hepatic function monitoring and guidelines for modification or discontinuation of treatment. (4) Use caution in patients with severe hepatic or renal impairment because the drug hasn't been evaluated in these patients. (Dosage adjustment isn't necessary in patients with mild-to-moderate hepatic or renal impairment.) (5) Bedaquiline is metabolized via the CYP3A4 pathway. Avoid concurrent administration with rifampin or another strong CYP3A4 inducer, which significantly reduces exposure to bedaquiline. (6) Avoid concurrent use of ketoconazole, a strong CYP3A4 inhibitor, for more than 14 consecutive days unless the benefit outweighs the risk. Ketoconazole increases exposure to bedaquiline, increasing the risk of adverse reactions. Adverse reactions: nausea, arthralgia, headache, hemoptysis, chest pain, increased serum transaminases Supplied as: 100 mg tablets Dosage: Initially, 400 mg (four tablets) once a day with food for 2 weeks. For weeks 3 to 24, the dosage is 200 mg three times a week with food (for example, Monday, Wednesday, and Friday with at least 48 hours between doses) for a total dosage of 600 mg/week. The total duration of treatment is 24 weeks. Nursing considerations: (1) Educate patients about the importance of adhering to the treatment regimen. (2) Tell patients to take each dose with food, and to swallow tablets whole with water. (3) If a dose is missed during the first 2 weeks of treatment, patients shouldn't make up the missed dose but should continue the prescribed dosing schedule. If patients miss a dose during subsequent weeks of treatment, they should take the missed dose as soon as possible, then resume the three-times-a-week regimen. (4) Bedaquiline tablets should be dispensed in the original container. Tablets dispensed outside the original container should be stored in a tight light-resistant container with an expiration date not to exceed 3 months. Back to Top | Article Outline REFERENCES 1. FDA news release. December 31, 2012. 2. Prescribing information. Sirturo (bedaquiline fumarate) tablets. http://www.sirturo.com/sites/default/files/pdf/sirturo-pi.pdf. Back to Top | Article Outline ANTIDIARRHEAL DRUG Crofelemer First drug approved to manage diarrhea in patients with HIV/AIDS Many patients with HIV/AIDS who are treated with antiretroviral agents experience diarrhea, and some don't respond adequately to conventional antidiarrheal drugs such as loperamide or bismuth subsalicylate. Persistent or severe diarrhea leads some patients to become nonadherent to their antiretroviral regimen. Crofelemer (Fulyzaq, Salix) is a botanical substance derived from the red sap of Croton lechleri, a tree that grows in Central and South America. Administered orally, crofelemer is indicated for symptomatic relief of noninfectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. It's the first drug to be approved to treat diarrhea in patients with HIV/AIDS. The secretion of chloride and fluid by intestinal epithelial cells is regulated by the cyclic adenosine monophosphate-stimulated cystic fibrosis transmembrane conductance regulator chloride ion channel, as well as the calcium-activated chloride channels. Crofelemer inhibits both of these channels. By blocking chloride secretion and accompanying high-volume water loss in diarrhea, it normalizes the flow of chloride and water in the GI tract. The drug's effectiveness was established in a clinical study of 374 HIV-positive patients on stable antiretroviral therapy with a history of diarrhea lasting at least 1 month. The desired clinical response was achieved by 18% of patients taking crofelemer, compared with 8% of those on placebo. The antidiarrheal effect persisted in some patients for 20 weeks. Patients were excluded from the clinical trial if there was evidence that the diarrhea was associated with an infectious cause or if they had a history of a GI disease associated with diarrhea, such as ulcerative colitis or Crohn disease. Crofelemer is being evaluated in patients with conditions such as traveler's diarrhea and irritable bowel syndrome associated with diarrhea, but these aren't labeled indications at present. Following oral administration, crofelemer is absorbed to only a limited extent, so patients aren't likely to experience adverse reactions or drug interactions. Precaution: Infectious causes of diarrhea should be ruled out before therapy with crofelemer begins. Adverse reactions: upper respiratory tract infection, bronchitis, cough, flatulence, increased bilirubin Supplied as: 125 mg enteric-coated delayed-release tablets Dosage: 125 mg twice a day Nursing considerations: (1) Tell patients that crofelemer can be taken without regard to food. (2) Instruct patients to swallow the tablets whole, without chewing or crushing them. Back to Top | Article Outline REFERENCE Prescribing information. Fulyzaq (crofelemer) delayed release tablets, for oral use. http://cdn.salix.com/shared/pi/fulyzaq-pi.pdf.* Common adverse reactions are italicized throughout this article. Cited Here...© 2014 by Wolters Kluwer Health | Lippincott Williams & Wilkins.


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Continental Mechanics Ratify New Contract
Published 8:00 pm, Friday, December 27, 2002
Mechanics and other employees at Continental Airlines have ratified a new four-year contract that includes increased wages and benefits, both sides said.
"This contract underscores the value of working together to reach agreements that are fair to employees and the company," Continental chairman and CEO Gordon Bethune said Friday.
The agreement was struck with the International Brotherhood of Teamsters, which represents more than 3,300 mechanics and other workers at the Houston-based airline. About 1,300 of those are in Houston.
A company spokesman said in a story in the Houston Chronicle's Saturday editions that 73 percent of the ballots cast favored the contract, and that turnout was "substantial."
The union said the agreement provides increased wages and retirement benefits, improved work rules and significantly improved job protection.
For instance, the package increases wages for senior mechanics by 13 percent, to $30.42 an hour retroactive to Jan. 1.
This Jan. 1, wages will increase to $33 an hour; the carrier's top-paid mechanics now make $26.85 an hour.
Continental, the world's 6th-largest airline, has domestic hubs in New York, Houston, Cleveland and Guam. The carrier employs about 48,000 people.
On the Net:
Continental Airlines: www.continental.com


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No, it's not April 1st, but yes, Apple Computer has just released a public beta of their Boot Camp software, which enables users of Intel-based Macs to install and run Windows XP. (Lest you see this as a sign of the apocalypse, remember that Apple sold DOS cards for Macs in the distant past to enable them to run PC software.) If you want to install Boot Camp and Windows XP, you won't need to mess with your Mac data at all, though you will need sufficient disk space for a Windows XP partition.
Boot Camp technology will be a feature of Mac OS X 10.5 Leopard, perhaps under a different name, but for now, you can use this beta to create a dual-boot system, switching between Mac OS X and Windows XP by holding down the Option key at startup and selecting the appropriate partition. The startup choice can also be set through a modified Startup Disk preference pane that Boot Camp installs, as well as a new Control Panel found in Windows XP after Boot Camp installs drivers and extensions.
Clever hackers had already managed to get Windows XP booting on Intel-based Macs - and won nearly $14,000 in private money by figuring it out - but the process is much harder than what Apple developed. Boot Camp provides a graphical assistant that walks the user through creating a second partition for Windows, burning a CD with the required Windows drivers (for your Mac's graphics card, wired and wireless networking, audio, Bluetooth, keyboard Eject button, and Brightness control for built-in displays), and installing Windows from the Windows XP installation CD.
Take special note of the partitioning process: You don't need to back up all the data on your hard disk, reformat the disk, repartition it with appropriately formatted Mac and Windows partitions, and then install Boot Camp. Rather, you simply use the Boot Camp software to create a dynamic logical partition that appears as valid as any previous statically created partition. This is possible only under Mac OS X systems using Intel Core processors using what Apple describes as a GUID Partition Table (GPT) using journaled HFS+ as the filesystem option. Our colleague Dan Frakes noted that "resizeVolume" is now an option for the command line diskutil Unix utility that's part of the Mac OS X 10.4.6 update. Diskutil mirrors the graphical Disk Utility application for most features. In an interview with TidBITS Contributing Editor Glenn Fleishman, Apple product managers wouldn't provide additional detail on this dynamic partitioning, but confirmed that it was new.
Your Mac volumes can be seen by the Windows system and vice-versa. For Windows partitions, you can choose to create either an old-style FAT32 volume, which can't create files larger than 4 GB, or new-style NTFS volume. NTFS has fairly sophisticated capabilities, including journaling - keeping a running record of changes to a volume that can be recovered even after a crash, just as newer versions of Linux, Unix, and Mac OS X 10.3 and later. But only the uglier FAT32 format can be read and written under Mac OS X natively; NTFS volumes mount read-only.
Mac volumes under Windows appear only if you install third-party software, such as MacDrive 6, which the company has already tested and found perfectly good performance with a Boot Camp installation.
Although Boot Camp's dual-boot capability is a first step, virtualization (running Windows within a window, or even running a Windows application as if it were just another program, in the way that Classic runs Mac OS 9 applications) would seem a much more desirable goal, since you wouldn't have to leave Mac OS X to run a Windows application. Virtualization also promises speeds comparable to native operation with the safety of running Windows in its own cage that can be restored to a base point - as in Microsoft's Virtual PC - more easily than a separately bootable Windows partition. Along with the open source Q project, at least three firms are working on virtualization software, including Parallels (whose public beta was released last week) and two others that aren't yet public with their plans. Microsoft may also update Virtual PC for Macintosh, but currently the company has not released any information on its plans. See "WinOnMac Smackdown: Dual-Boot versus Virtualization" later in this issue for a comparison of dual-boot and virtualization options available today.
<http://www.parallels.com/en/products/ workstation/mac/>
Virtualization may be further than Apple is willing to go, though, given that it could conceivably make developing software for Mac OS X less attractive than writing for Windows, which would then be a least common denominator. In particular, game developers would be unlikely to port their games to Mac OS X if there was no downside to writing only for Windows; the companies that would be hurt would be those that actually create the ported versions. I can't see users having any problem running games in Windows given that most games have their own custom interfaces anyway; it's not like anyone would notice if a game running in Mac OS X was really a Windows application as long as its performance didn't suffer. That said, I could easily imagine Boot Camp being built into Leopard in such a way that you could switch between Mac OS X and Windows XP much the way Fast User Switching works now.
To run Boot Camp, you need an Intel-based iMac, Mac mini, or a MacBook Pro with the latest firmware updates; Mac OS X 10.4.6; at least 10 GB of hard disk space; a blank recordable CD; a printer (Apple says about the setup instructions, "You'll want to print them before installing Windows, really."); and a bona fide installation disc for Microsoft Windows XP, Service Pack 2, Home Edition or Professional (multi-disc, upgrade, and Media Center versions won't work). A full copy of Windows XP Home Edition runs nearly $200; Professional, nearly $300. Apple is explicit about how it does not sell or support Windows, and thus you'll not only need your own copy, it's up to you to make sure it's appropriately patched and protected against the panoply of Windows malware. That means installing a robust firewall, anti-virus software, and anti-spyware software. We recommend Zone Alarm by Zone Labs for some of those functions; the company sells a bundle that includes components it doesn't make itself. Google also provides Google Pack, a collection of helpful free software for Windows that Mac users interested in playing with Windows might use as a starting point.
Interestingly, the license for Boot Camp is good until 30-Sep-07, so we can be pretty sure that Leopard will be out before then. The license also says that you're allowed to use Boot Camp purely for evaluation purposes and - amusingly - that it "does not permit the Apple Software to be used in a commercial operating environment where it may be relied upon to perform in the same manner as a final-release commercial-grade product or with data that is not sufficiently and regularly backed up." So what's Apple going to do, sue you if you happen to use Boot Camp in a "commercial operating environment"? You'd be dumb to rely on public beta software in such a situation (and it's perfectly reasonable for a license to warn you that you're using the software at your own risk), but methinks Apple's lawyers were a bit overzealous during some of the writing. But whatever you do, be sure not to use Boot Camp to run your nuclear reactor, airplane navigation system, air traffic control system, or life support machine - the license is clear about how Apple doesn't intend Boot Camp to be used anywhere where a bug could cause death, injury, or severe physical or environmental damage. Playing Solitaire is probably okay, and Outlook will likely cause only the mental part of environmental damage.
Lastly, on our staff mailing list, Apple's choice of the name "Boot Camp" prompted Geoff Duncan to riff on the notion of a stereotypical Army drill sergeant addressing a fresh crop of Windows switchers. We couldn't resist sharing. Enjoy!
"Think you're good enough for this computer, MAGGOTS? You are NOT! Did you HEAR me? You are NOT good enough for this computer. The only way - and I repeat, the ONLY way - you simpering short-haired pencil necks will be good enough is if every REAL computer user on this planet were abducted by aliens!
"WHAT?! You think that's FUNNY, Windows-boy? When I WANT you to laugh, I'll make a cute sound!
"Now then, since you WORMS are all we've GOT - " (Paces the line.) "What does Control-Alt-Delete do?"
"I can't HEEEAR you!"
"Where is the menu bar?"
"What are computers for?"


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Chrysler hasnŌĆÖt cornered the market on comebacks just yet. Mazda is another auto maker that has resurfaced more times than Michael Jordan. In the late 1970s, the Japanese car manufacturer, then known as Toyo Kogyo, teetered on the edge of extinction when the rotary engine on which it had bet heavily suddenly fell out of sync with demands for higher fuel economy and lower emissions. A string of new products ŌĆō including the Miata roadster ŌĆō rescued Mazda in the 1980s, but that momentum ...
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Mocha Yule Logs
Total Time:
Level: Easy
- 2 stick unsalted butter
- 1 package cream cheese
- 1 c. granulated sugar
- 1 large egg
- 4 tsp. instant coffee powder dissolved in 1 Tbsp water
- 2 tsp. vanilla extract
- ¼ tsp. salt
- 3 squares unsweetened chocolate
- 2½ c. all-purpose flour
- 2 squares white chocolate
- ¾ c. slivered almonds
- Heat oven to 350ºF. You'll need a large pastry bag fitted with a star tip that has a 1/2-in. opening.
- Beat butter, cream cheese, sugar and egg in a large bowl with mixer on medium speed until creamy. Add coffee mixture, vanilla and salt. Add unsweetened chocolate; beat until smooth and fluffy. With mixer on low speed, gradually beat in flour until a soft dough forms.
- Fill prepared pastry bag with dough. Pipe long logs (the width of the baking sheet) onto ungreased baking sheet(s), 1 in. apart. Bake 12 minutes or until cookies are golden brown on bottom edges. Cool 2 minutes on pan on wire rack. Cut diagonally into smaller logs with a small serrated knife. Cool completely on wire racks.
- Place white chocolate in a small ziptop bag and seal. Place bag in bowl of hot water until chocolate melts; squeeze bag to blend. Cut tip off one corner. Pipe lines in grooves of cookies. Place a few slivered almonds on chocolate, parallel with the lines in cookie. Refrigerate or leave in a cool place until chocolate sets.
Tips & Techniques
More recipes like this
From: Woman's Day
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At first, Soul was annoyed that he and Glaser had not been considered to reprise the roles that earnt them acclaim 30 years ago. He said: "These guys are good, but they're not Starsky and Hutch." However, he and his erstwhile buddy have since taken a cameo role in the movie, in which they hand over their guns and car keys to their young namesakes.
Re-packaged for 21st-century film-goers in the contemporary goofball "action comedy'' mould, Starsky and Hutch, released next March, is the latest example of Hollywood's obsession with reviving old television shows when it runs out of new ideas.
The actors are different – Ben Stiller and Owen Wilson step into the shoes of Paul Michael Glaser and David Soul to play Dave Starsky and Ken Hutchinson – and no doubt there will more six-pack stomachs, more snogging and bigger explosions, but the most recognisable thing about the show remains: the big, red Ford Gran Torino with the big, white stripe.
When the television series was first aired in 1975 (Saturday nights on BBC1, if I remember correctly), the vast, two-door hardtop would blast out of the opening credits, lurching around grotty LA back streets and careering into conveniently placed piles of cardboard boxes. It was the coolest thing on four wheels. I had a Corgi model of it and my uncle Dave was inspired to paint his Simca 1100 van in the same livery – as did thousands of other British fans, no matter how inappropriate their wheels: Ford Cortinas and Capris, Hillman Avengers and even the odd Mini were given the Starsky and Hutch treatment.
Squealing tyres aside, the show's appeal centred on the relationship between streetwise Starsky (the dark, curly-haired one with the dodgy taste in cardigans, played by Glaser) and the educated, yoga-practising Hutch (the blond one, Soul).
It was The Odd Couple with guns: two young, groovy pin-up law enforcers who engaged in shoot-outs and punch-ups with a weary irony and never took themselves too seriously. Its appeal fizzled out towards the end (it finished its run in 1979 after 88 episodes) as routine violence gave way to schmaltz, but at its peak Starsky and Hutch was essential viewing.
Storylines were of the classic "cops that don't do things by the book'' type. Boss Captain Dobey (played by Bernie Hamilton) shouted a lot and hauled them over the coals every week. Pimp informant Huggy Bear (Antonio Fargas) added the necessary street cred. At the end of every show, everybody got together over a coffee to go over what had happened, epilogue-style, so that American audiences could make sense of it.
One of the running gags was Starsky's anally retentive attachment to the hulking Torino coupé, with its jacked-up back end. A less suitable car for undercover cops was hard to imagine, and the less materialistic Hutch was quite happy to drive a tired and battered Ford Galaxie.
Customiser George Barris (creator of the original Batmobile) conceived the red Torino, building six for the series and the original pilot film. Two of those original cars survive, according to the website for Starsky and Hutch aficionados. But such was the popularity of the show that it also inspired an official factory model. At first, individual Ford dealers painted the cars as one-offs, but eventually Ford bowed to pressure and built a limited production run of about 700 cars between February and May 1976; they were sprayed white initially, then masked-off with a decal made by 3M and painted red before the decal was removed to reveal those distinctive stripes, widening along each flank before leaping over the roof via the C-pillars.
Not everybody loved Starsky and Hutch – the chief constable of Liverpool said it was influencing his officers to wear sunglasses and "drive like bloody maniacs'' – but just about everybody watched it when it was at its peak. Uncle Dave and I were glued to the screen, that's for sure.
Its imagery also made a powerful impression on a nine-year-old called Paul Scarrott. "You had this huge car being slung round corners on massive chrome wheels; it looked the absolute business. It just stuck with me..."
Years later, with the funds to indulge his fantasy, Paul went looking for a Ford Torino just like Starsky's. Trawling the internet, he discovered that Ford had produced an official limited-edition.
After flying to America in March 2001, Paul found himself handing over a large amount of cash to a man in Minnesota for the gleaming, low-mileage example you see here. It even says Starsky and Hutch on the build sheet, although the replicas didn't have the alloy wheels of the television cars; Paul had to find a set and fit them later.
Cruising along the underpasses, flyovers and back streets of London's East End in the Torino, we are in a sort of generic 1970s TV cop world. The car causes jaws to hang open as it burbles past, jacked-up and throaty.
"People love this car," says Paul. "It's nostalgia more than anything; it's not meant to be serious." Along with a handful of other British-based Gran Torinos, Paul's car pays for its keep with occasional promotional appearances, which will no doubt increase among the avalanche of marketing hype that will surely accompany the launch of the new film. Paul's car has already provided the background for the promotion of the new Starsky and Hutch PlayStation computer game.
At heart it's a fairly undistinguished shape from the era when American stylists where beginning to lose the plot. From the side it has an air of MkIII Cortina, whereas the front is big and brutal, with huge bumpers that quiver when the engine fires up.
The 5·8-litre "Windsor'' V8 looks slightly lost in the engine bay and is in a mild and fuzzy state of tune, with a mass of de-smogging pipe-work that brought the power down to a modest 161bhp. No wonder the engines for the film cars were uprated to 460 cubic inches (7·5 litres) to make the action more dramatic. Scarrott has liberated more power by junking the US-spec emissions-control and fitting a large-diameter dual exhaust system.
I wouldn't recommend vaulting over the enormous bonnet as Starsky and Hutch were wont to do at every opportunity (the latter once confessed to doing himself something of an injury as a result of the heavy landing in the show's credit sequence), but jump inside and you find yourself lounging on well-stuffed seats that lack any semblance of side support, gazing upon a facia that looks comprehensive at first glance but lacks the expected rev-counter. There are swirly "Gran Torino'' motifs on the door panels but little else to make the ambience uplifting. But this, don't forget, was a fairly cheap, intermediate model, with wind-down windows; the only luxuries are air-conditioning and cruise control. Engage Drive on the T-handle of the Cruise-o-Matic transmission and an initial prod on the throttle feels quite encouraging as the Torino surges forward; what it lacks in power it makes up for in torque and you suddenly feel the need to don a chunky cardigan and shove a blue light on the roof.
But as for chasing hoodlums through the back streets, forget it. You'd have to be a brave man indeed to attempt nifty manoeuvres in this quivering acreage of steel, which, like most of its ilk, is unwilling to turn in to corners. The air dampers that keep the tail jacked up don't embellish its poise. Cornering antics alarm onlookers as the massive front overhang looks as though it might make contact with the road.
Scarrott accepts that the car is dynamically challenged, but he's as proud of it as Starsky was. And with the new film about to appear, the Gran Torino's profile is rising.
"But what really annoys me," says Paul, "is how many people get it mixed up with the Dukes of Hazzard car."
• You can find out more about the Gran Torino by visiting the website www.starskytorino.com. Paul Scarrott can be contacted about his car on firstname.lastname@example.com.
Unhappy Soul gets a cameo role
FIlming has now finished on the $60 million Starsky and Hutch movie, directed by Todd Phillips (Road Trip, Old School).
Long-time friends Ben Stiller and Owen Wilson play the crime-fighting duo, Stiller as tough guy Dave Starsky (played in the TV series by Paul Michael Glaser) and Wilson as the more sensitive Ken Hutchison, aka Hutch (originally David Soul). Snoop Dogg takes on the Huggy Bear character made famous by Antonio Fargas; Carmen Electra plays his girlfriend. Other stars inlcued Vince Vaughn, Fred "The Hammer" Williamson, Daniel Dae Kim, Raymond Ma, Brande Roderick, Terry Crews, Richard Edson, David Pressman, Chris Penn and Amy Smart.
At first, Soul was annoyed that he and Glaser had not been considered to reprise the roles that earnt them acclaim 30 years ago. He said: "These guys are good, but they're not Starsky and Hutch." However, he and his erstwhile buddy have since taken a cameo role in the movie, in which they hand over their guns and car keys to their young namesakes.


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I am very concerned about my father. He is 59, and has been experiencing sleeplessness, severe itching with no obvious cause, as well as no relief. His vision fails him at times, he has lost weight even though he eats more than enough and has had bouts of anxiety. He gets up almost every night to have a jam sandwich because he craves something sweet, he also sometimes drives to the shop late at night to buy a chocolate. The pharmacist suggested diabetes, so he had is glucose levels tested yesterday. The test revealed nothing out of the ordinary, and indicated normal glucose levels. Are these tests accurate? If not diabetes, what else could it be?
Please help. Any information would be appreciated.
Thank you.


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LANE PR makes Portland Business Journal's 100 Fastest Growing Private Companies list
Posted by: KirstenNieman in: Consumer Lifestyle - Food/Beverage - Financial Services -
Last night, a handful of LANE PR folks attended Portland Business Journal's 100 Fastest Growing Private Companies banquet. Held at the Downtown Hilton Hotel, representatives from 100 different companies walked down the red carpet to receive their award for making the list. Business Journal Publisher Craig Wessel introduced each company, and we are excited to say LANE PR was ranked #88 on the list!More


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Cargill Replaces Trader, Disputes Details of ReportShruti Date Singh
Cargill Inc. replaced a senior trader while disputing some details in a report that said the the largest closely held U.S. company lost at least $100 million in energy trading in recent weeks.
The losses arose mostly from trading in mid-Atlantic power markets amid large price moves caused by unusually cold weather across the U.S. in January, the Wall Street Journal reported, citing industry publication SparkSpread.com.
"We do not provide financial details on our individual business, only at company level, but we do refute the details of the numbers shared" in the report, Pete Stoddart, a spokesman for Minneapolis-based Cargill, said in an e-mail today.
Mike Newman was appointed physical trading manager for North America at Cargill's thermal energy supply chain unit, Stoddart said. His predecessor, David Toole, left the company Feb. 19, the Journal said, citing SparkSpread. Stoddart declined to comment on Toole, who couldn't immediately be reached for comment.
Energy prices soared in January after a polar vortex spread subfreezing arctic air across much of the eastern U.S. Natural gas futures on the New York Mercantile Exchange jumped to their highest in more than three years on Jan. 24 while peak electricity prices were the most in at least a decade.
Proprietary Trading
While Cargill's focus is largely on agricultural markets, through its trading of grains and processing of meat and food ingredients, it also handles non-food commodities. The company's thermal-energy unit is a proprietary trader of oil, gas, coal and power, according to its website. The business also serves clients including utilities, buying transportation and storage capacity and managing supply and distribution assets.
Cargill said Jan. 9 its energy activities had "weak" results in the quarter ended Nov. 30, even as overall net income rose 36 percent to $556 million on sales of $32.9 billion. The segment's performance in the previous quarter was also described as "weak," because of mild weather and "soft" demand.
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A Quiet Storm begins with the sound of a summer shower, a flute, tremulous congas and vibes and Smokey breathlessly caressing the words, "Soft and warm, a quiet storm." As the title tune progresses, the sensuality of its lyrics and the loose, improvisational feel of the backup suggest that the album is going to be Robinson's What's Going On or Innervisions, a formula-defying statement of both personal and social import. But Robinson is moved neither by Marvin Gaye's macho sensibilities nor by Stevie Wonder's semimystical mental images, and he has more pop expertise than either. With 18 years of singing, writing and producing behind him, he naturally passes over both self-celebration and prophecy in favor of love and happiness. And his instincts for the perfect hook, the well-placed quaver and the arresting turn of phrase mean that even his seven-minute songs ("Storm," "Happy") retain the thematic compactness and lustrous patina of Motown singles.
There were no seven-minute songs on Pure Smokey, an album of brilliant singles which produced no hits. Ironically Storm and the first single excerpted from it, "Baby That's Backatcha," took off immediately. The album offers irrepressibly upbeat lyrics, mellow and jazz-tinged instrumental passages, bouquets of sweetness and restrained funk flavorings. Intriguing production touches abound. On "Love Letters," a hesitating fuzz-tone bass pattern is repeatedly undercut by an atempo flute/synthesizer unison. "Wedding Song" is burdened by the sappiest words Robinson has written ("Oh what a beautiful day to take a vow on/Pray that the things we say will last from now on"), but a recurring guitar riff, performed with great sensitivity by Marv Tarplin, redeems it.
In fact, Robinson's much touted abilities as a poetic lyricist aren't very important here, the sexy directness of "Storm" and "Backatcha" notwithstanding. His production and singing carry the album. Even "Happy," a Robinson/Michel Legrand opus from Lady Sings the Blues that fairly oozes sentimentality, succeeds as believable pop because of a soulful, crying vocal and a careful, varied arrangement. It may not represent a very promising direction, but the languid intimacy of "Quiet Storm," the intricate instrumental arrangements on "Backatcha" and "Love Letters," and the prominence given to Tarplin's classy guitar throughout the album are evidence that one of black music's brightest lights is still a dynamic creative force. We can look forward to many more delights from him; if success were going to spoil him, it would have done so long ago.