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Dosage forms of which bioequivalence studies are waived Injections for intravenous administration discount effexor xr 75 mg fast delivery anxiety 38 weeks pregnant, administered as an aqueous solution 37.5mg effexor xr with visa anxiety symptoms sleep. Ti and Ri show the average dissolutions of the test and reference products at the time point (i) generic 75 mg effexor xr mastercard anxiety symptoms get xanax, respectively, and n is the number of time points at which the average dissolution are compared. Adjusting dissolution curves with lag times The lag time is defined as the time when 5% of the labeled claim of the active ingredient dissolves from the product. A lag time should be determined for respective product by linear interpolation, and then respective dissolution curve is obtained by 22 adjusting dissolution curve with the lag time. Average dissolution curves of the test and reference products are obtained, which can be used for the assessment of similarity and equivalence in dissolution curves. R eference product Testproduct 4)Ifth ereisgeneticpolymorph ism,subjectswith h igh erclearancesh ouldbeemployed. Dissolutiontest Isth ere Isth euseof asignificantdifferencein Y es Y es dissolutionbetweentestand druglimitedto aspecific referenceproductsundera population? N o N o Isth ere asignificantdifferencein B ioequivalencestudyin B ioequivalencestudyinsubjects Y es dissolutionbetweentestand 3,4) from th especialpopulation3,4) ach lorh ydricsubjects reference products atpH 6. N o Innovatordrug G enericdrug Dissolutiontestof3 lots A lotofindustrialscaleornotlessth an1/10 scale R eferenceproduct Testproduct Dissolutiontest A re th e N o dissolutionprofilesbetweentestand referenceproducts similar? Y es Y es Y es A dd-onstudy A regeometricmean N o ratiosofA U C andC max with in90-110%? Th edissolutionfrom referenceproductssh ouldbeover85% with inth e Dissolutiontest specifiedtestingtimeinatleastonetestcondition. Isth ere Isth e Y es Y es alagtimeindissolutionof Y es differenceofaveragelagtimes A redissolutioncurves referenceortest betweentestandreference adjusted with th elag product? N o N o N o N otsimilar N o A djustmentsof dissolutionprofiles with lagtimes Isth e Doesth e Isth e N o differenceof Doeth e Doesth e N o N o N o averagedissolutionof averagedissolutionof averagedissolutionof averagedissolutionof dissolutionswith in 9% atth e referenceproductreach 85% referenceproductbetween specifiedtimeandth etimepointwh ere referenceproductreach 85% referenceproductreach 85% with inth especified 50 and85% atth especified referenceproductdissolution with in15 min? Y es Y es Isth e Isth e A t15 min differenceof Isth e N o differenceof isth eaveragedissolution differenceof Y es dissolutionswith in 15% at N o dissolutionswith in 15% at N o oftestproduct 85%? Y es Y es N otsimilar Y es N otsimilar N otsimilar Y es N otsimilar Similar1) 1) Similar1) Similar1) 1) Similar Similar 1) Ifth eresultsmeetoneofth efollowingcriteria F ig. Y es Y es Isth e Isth e differenceof Y es differenceof dissolutionswith in 12% atth e N o dissolutionswith in 15% at3 time N o specifiedtimeandth etimepointwh ere pointswh erereferenceproduct referenceproductdissolution dissolutionare 30,50 and80%? Y es N otsimilar N otsimilar Y es Similar1 Similar1) N otsimilar 1) ) Similar F ig. Th eaveragedissolutionofreferenceproductssh ouldbeover80% with inth e Dissolutiontest specifiedtestingtimeinatleastonetestcondition. Isth e differenceof Doesth e Isth e N o N o dissolutionswith in 6% atth e No averagedissolutionof averagedissolutionof specifiedtimeandth etimepointwh ere referenceproductreach 80% with in referenceproductbetween50-80% referenceproductdissolution th especifiedtesting atth especifiedtestingtime? Y es Y es Yes Isth e differenceof Isth e dissolutionswith in 8% atth e N o differenceof N o specifiedtimeandth etimepointwh ere dissolutionswith in 10% at3 time referenceproductdissolution pointswh erereferenceproduct isah alfofth atatth especified dissolutionare 30,50 and80%? Y es Y es N otequivalent N otequivalent 1) Equivalent1) 1) Equivalent N otequivalent Equivalent . As we discuss later, the program was designed to correct an unintended consequence of Which Providers Can Participate in 340B? Some lawmakers involved in the covered entity categories, including six hospital categories and ten categories tied to federal grant programs. Summary Points • The 340B Drug Pricing Program lowers drug prices for specifc categories of “covered entity” hospitals and clinics. Covered entities can access 340B drug pricing for all of their eligible patients, including those with insurance. For example, federally qualifed health centers are eligible for 340B Which Drugs Are Covered by 340B? Eligibility in the six hospital covered entity Drugs that are included in bundled payments to hospitals for categories hinges on statutory criteria within 340B and the Social inpatient care are not included. For example, the defnition of “critical access hospi- diseases (“orphan drugs”) were excluded from 340B for the new tal” follows Section 1820(c)(2) of the act. For example, sole community hospitals and tion Drug Rebate Program, manufacturers are able to obtain state rural referral centers are eligible to participate in 340B if they meet Medicaid coverage for their prescription drugs by entering into an the appropriate statutory defnitions and if they are eligible for at agreement with the Centers for Medicare and Medicaid Services least an 8-percent disproportionate share adjustment. While eligibility to participate in the 340B program is defned at the level of the health care facility rather than the individual, not 2 every individual receiving care at a covered entity can receive drugs calculated for each National Drug Code (i. Te Health Resources and tion of active ingredient, formulation, manufacturer, and package). Government Accountability Tere are no patient eligibility criteria based on fnancial need. Te 340B program sets a ceiling on the price that covered entities Figure 1: An Example of a 340B Discount pay for outpatient drugs. All prices and discounts are price 3 related to 340B drugs, including payments from other payers as Figure 2: Two Most Common Approaches to Purchasing well as out-of-pocket payments, in excess of drug-related purchase and Distributing Drugs Under the 340B Program and distribution costs. Covered entities can purchase drugs at 340B prices directly from manufacturers or through drug wholesalers. Regardless of Cost sharing their approach to purchasing drugs, covered entities should never be charged more than the 340B statutory ceiling price. Figure 2 tracks the fow In the second approach, the covered entity purchases and takes of money and drugs under the two most common approaches. Physically, the frst, covered entities purchase drugs directly from manufactur- however, the drugs never reach a covered entity’s facilities. Covered then either dispense drugs through in-house pharmacies or, in the entities contract with these pharmacies to dispense their 340B case of outpatient physician-administered drugs, administer drugs drugs. Patients may also face out- to obtain drugs from covered entities: Te 340B program controls 4 of-pocket cost sharing when they obtain 340B-purchased drugs patients. Te 340B program was enacted as part of the 1992 Veterans Health Care Act,14 which established section 340B of the Public Program Expansion Health Service Act. As a result, safety-net providers and patients saw prices Services Act hospitals, rural referral enacted. Recent 340B program changes have introduced new covered • Meet all patient defnition requirements: Drugs purchased entity compliance requirements. For example, covered entities through 340B can only be distributed to individuals as written with a formal relationship with the covered entity, must receive Figure 5: Number of Contract Pharmacy Agreements a range of services from the covered entity consistent with the 14,000 entity’s scope of services, and must obtain the prescription 12,000 from a health care provider that is employed by the covered entity or under contract or other arrangement with the covered 10,000 entity. In addition, growth in Entity Category the number of contract pharmacies increases the complexity of Title X family plan monitoring and compliance to prevent diversion. Covered entities Children’s Sole community serve diferent numbers of patients and provide diferent volumes of Rural referral services. Using data on hospital outpatient visits,28 we estimate that Free-standing cancer hospitals participating in the 340B program account for approxi- 0 0. It is important to underscore that every federal are equivalent to 4 percent of federal and state resources fun- program needs and requires careful oversight to ensure that the law neled through major health care safety-net fnancing mechanisms, is being implemented correctly. Some 8 manufacturers contend that, under the law, generous discounts on Figure 7: Comparison of Estimated Annual 340B Savings and Payments Through Select Safety-Net Programs prescription drugs are inappropriately used by hospitals to gener- ate revenue outside of Congress’s original intent to serve indigent 20 $17. Conversely, many safety-net providers maintain that any 16 additionally generated revenue contributes to the procurement of 14 $11. As we noted, both motivations— 10 ensuring that indigent and low-income patients have access to 8 $7.

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Goal Attack Strategies Consider a case in which a clinician identifies three semantic relations—agent + action purchase effexor xr uk anxiety symptoms stomach pain, action + object buy effexor xr with a visa anxiety disorder test, and attribute + object—as goals for a preschooler limited to single-word productions buy effexor xr cheap anxiety jelly legs. A key question in this case is “How do I help the child to reach all three of these goals most efficiently, given that each is developmentally appropriate and that development of these three relations could lead to spontaneous facilitation of other multiword constructions? Fey (1986, 1990, 1992) identified three general strategies that provide options in the answer to this question, although there are many possible variations of each, and we know very little about how they affect treatment outcomes. Vertical strategies involve a progression from one goal to another, and advance- ment to the next goal is based on the child’s attainment of a predetermined level of performance on an outcome variable. In our example, the clinician would prioritize the three goals and attack them one at a time, waiting for some criterion on the first goal before attacking the second goal, and so forth. Horizontal strategies involve simultaneous attention to multiple specific goals within a single session. Within this strategy, all three semantic relations would receive focus in each intervention session. This strategy may increase the time it takes for a child to reach criterion for a single target, but it may shorten the time it takes for the child to learn all three relations, and it may hasten the child’s development of other multiword relations and combinations of relations. Cyclical strategies involve clinical focus on one goal for a period of time, followed by movement to another goal whether or not the child makes progress on the first goal. In our example, agent + action might be the focus of the Week 1 ses- sions, followed by attribute + object during Week 2 and action + object during Week 3. Excerpted from Treatment of Language Disorders in Children, Second Edition by Rebecca J. This strat- egy is based on the assumption that the child will continue learning, even when a goal is no longer serving as a focus of treatment (Hodson & Paden, 1991). Thus, over time, the child would be expected to acquire more language forms with the cyclical approach than the more traditional vertical approach. Procedures and Activities Procedures consist of all of the acts performed by the intervention agent that are ex- pected to lead the child directly to the intervention goals. They make up what may be hypothesized to be the “active ingredients” of the intervention and include a variety of acts, such as modeling the child’s target, giving the child structured practice with the target, reinforcement of the child’s use of target behaviors, systematic responses to child utterances or actions, and even explicit description of the target (Fey, 1990). Activities create the social and physical conditions within which the intervention agent may apply the procedures. They fall along a continuum that moves from a high level of adult intrusiveness toward less structure and greater similarity to the child’s life outside of treatment (Fey et al. In the middle of the continuum, we include gamelike interactions that are selected or are structured to provide some emphasis on the child’s specific goals. The least intrusive activities are those that occur outside the context of con- ventional therapy, including play, bath time, and snack time for younger children and art class, group writing assignments, or even reading group for school-age children. Although the activity is virtually the same as the procedure in some cases, such as drill, it is fruitful to keep these constructs distinct. For example, a child may gain no special language or communication benefit from dinnertime or play during the bath. The same activity, however, may provide multiple opportunities for the intervention agent to model the target, for the child to attempt it, and for the adult to respond to the child’s attempts. Language intervention takes place only when special proce- dures, designed to instruct and provide opportunities for use and mastery, are applied during the course of activities, which may in turn require the adult to intrude to varying degrees on the child’s agenda. Activities are the most obvious aspect of treatment because they are the part that can easily be described by an observer with little knowledge of the intervention. Lay observers, and at times even beginning clinicians, can sometimes confuse an activity with an intervention as a whole. That is, the observer recognizes the activity but fails to take note of the procedural steps taken by the interventionist. Selecting or creating the appropriate activity, however, requires considerable skill. It is not easy to create activities that are meaningful and motivating for the child yet provide many opportunities for the application of intervention procedures directed toward specific goals. In fact, successful activity planning requires attention to many other elements of intervention, including the goals of the intervention (at all levels), the assumed mechanism by which learning will take place most efficiently, and the availability of particular agents and materials. Dosage According to Warren, Fey, and Yoder (2007), language intervention dosage relates to dose, or the amount of time the intervention procedures are applied at a single setting Excerpted from Treatment of Language Disorders in Children, Second Edition by Rebecca J. Because group interventions necessarily reduce the number of teacher episodes that are possible in an individual session, we also view consideration of service delivery individually or in groups as a dosage issue. As a topic in communication disorders, an interest in the role of dosage has grown dramatically over the past few decades (e. Anyone who has pursued the acquisition of an unfamiliar skill as an adult, such as playing the piano or learning to golf, has probably developed the suspicion that, at least in general, more attempts at learning result in “better” learning than do fewer efforts: Practice makes perfect, after all. There is a broad literature indicating that learning based on trials that are spaced over time is better, in the sense of more lasting and more likely to generalize, than learning that occurs with massed trials (e. However, although dosage differences have been raised as an explanation for the better results of some treatment approaches over others (Kamhi, 1999; Law & Conti-Ramsden, 2000), there has been very limited systematic study of this aspect of treatment among children with language disorders (see Chapters 3, 5, and 15 for some exceptions and for some evidence that more is not always better). In clinical practice, scheduling the frequency of treatment sessions is often guided by no stronger a principle than the notion that children with more severe impairments are generally seen more frequently than those with less severe impairments (Brandel & Loeb, 2011). Still, clinicians who use the results of published studies to support their intervention choices must attend closely to dosage. They should be concerned when- ever they choose or are forced to select a treatment intensity that differs significantly from that used in published research reports (as is often the case). Intervention Agents Intervention agents are typically individuals who interact with the child for the pur- pose of realizing treatment goals. Intervention Context(s) Contexts are the social and physical environments in which interventions take place. Contexts in which interventions are carried out may be selected on theoretical grounds because of their functional value to the child (Bronfenbrenner & Morris, 1998) or because of increased Excerpted from Treatment of Language Disorders in Children, Second Edition by Rebecca J. Contexts are often se- lected on practical grounds; for example, participation by parents is often feasible only in some settings, such as the child’s home. When the context is forced by such circum- stances, there are often ramifications in other components of intervention. For exam- ple, it may be possible to utilize certain procedures, such as recasts (Chapter 5), within the typical classroom setting or when children are working in small in-class groups. It may not be possible, however, to implement certain procedures, such as imitative drill or observational modeling, in a discreet manner within the classroom setting. Comprehensive Assessment of the Intervention Within the structural model of intervention described thus far, the child’s achievement of subgoals represents an integrated and handy method by which the effects of the inter- vention can begin to be gauged for an individual child. In general, performance-related goals that are more specific and represented more to the right in Figure 1. Because subgoals are so highly particular to specific procedures and outcomes, progress on subgoals may or may not lead to predictable achievement on the higher level goals that prompted intervention in the first place (Fey & Cleave, 1990). Because the intent of intervention is to effect positive change in a child’s life, it is important to determine whether goals that are relatively less abstract and less func- tional (e. Attainment of basic goals should ultimately lead to meaningful changes in the child’s life, and those changes should be (and increasingly are) carefully measured (Bain & Dollaghan, 1991; Bothe & Richardson, 2011; Kazdin, 2001; McCauley, 2001). These include professions such as psychology, social work, physical and occupational therapy, and speech-language pathology.

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A 5 third study that measured time until return to work did not find a statistically significant difference between groups order effexor xr 37.5mg with amex anxiety while pregnant. At one and a half months purchase effexor xr 37.5mg free shipping anxiety 0 technique, the early weight bearing group had no limitation and scored statistically significantly higher on the physical function buy effexor xr visa anxiety 504 plan, social function, vitality, and emotion components of the Rand-36 scale. One study reported that statistically significantly more patients returned to sports at 12 months (see Table 109). However, two other studies reported no statistically significant difference in return to sports at six or twelve months. There was no statistically significant difference in pain, satisfaction, return to work, or footwear restrictions at twelve months (see Table 110 through Table 113). Of the two patients with re-ruptures, one patient did not follow the written rehabilitation protocol and the second patient suffered a fall on ice and forcibly dorsiflexed his ankle. There were no statistically significant differences between groups in complications. Table 108: Description of treatment groups Author Post operative Instructions Early weight bearing group: Bear weight on the tiptoes of the operated leg as tolerated but keep leg elevated for the first two weeks. Non-weight bearing group: No weight bearing and keep leg elevated for first two weeks. Early weight bearing group: Bear weight on the operated leg as tolerated but keep leg elevated for the first two weeks. Early weight bearing group: Two weeks of non-weight bearing followed by weight bearing. The authors state both 56 and 53 as the number of patients enrolled Table 110 Pain Result (months) Author Outcome LoE N 1. Immediate full-weight bearing mobilisation for Less than 10 patients per 2003 repaired Achilles tendon ruptures: a pilot study group Wagnon, et The Webb-Bannister percutaneous technique for No patient-oriented al. Early active motion and weight bearing after cross- evidence - not 1998 stitch Achilles tendon repair comparative Not best available Speck, et al. Early full weight bearing and functional treatment evidence - not 1998 after surgical repair of acute Achilles tendon rupture comparative Solveborn, Not best available Immediate free ankle motion after surgical repair of et al. Non-Weight Bearing Weight Non-Weight Author Outcome LoE Duration N Result Bearing Bearing Suchak, et al Rand-36 Physical 61. Implications: Practitioners should generally follow a Moderate recommendation but remain alert to new information and be sensitive to patient preferences. All five studies randomized the patients into two groups with either six weeks in a cast or early motion with a modified splint device. For all studies, patients in the mobilization group had a splint or modified cast device that limited dorsiflexion to protect the repair. One of three studies found a significantly higher rate in return to sport activities at twelve months, 40, 39 while two found no difference. One study 5 found a significantly higher re-rupture rate in the postoperative mobilization group (2 of 23 patients) compared to the immobilization group (0 of 25 patients). Both patients had documented non-compliance with the use of their postoperative splint and fell during the first 4 weeks after surgery. Although the ultimate level of function achieved after operative repair of an Achilles rupture is similar regardless of the postoperative immobilization protocol, early postoperative mobilization allows the patient to achieve a quicker return to activities during the first six months than those patients treated with immobilization. However, treatment decisions should be made in light of all circumstances presented by the patient. Mutual communication between patient and physician should include a discussion of the importance of patient compliance when a program is prescribed for early mobilization. Patient compliance to protocol is important to aid in protection of the incision during the early post-operative period and is also important to prevent wound healing complications. The post operative mobilization and immobilization regimes are detailed in 116 v1. Please see Table 122 through Table 129 for results of mobilization versus immobilization. Of the forty outcomes reported, seventeen were statistically significant in favor of early motion. Nine of the seventeen statistically significant results measured time until return to activity, sports, walking, stair climbing, work, weight bearing, discharge from physiotherapy, number of physiotherapy sessions, and sick leave (see Table 122). However, another study that reported time until return to sport and work did statistically significantly differ between groups (see Table 122). Patients in the early motion group reported statistically significantly less pain at one month but no statistically significant difference in pain at three, six, or twelve months (see Table 123). One of seven outcome measures found a statistically significant difference in the percent of patients able to return to sports in favor of the motion group. Statistically significantly more patients were able to stand on their toes and walk as far as they could before surgery in the early motion group at three and six months. Patients in the early motion group were more satisfied with their cast at one year. There was no statistically significant difference between groups in regard to: patient opinion of results, footwear restrictions, EuroQoL, E5D, or Ankle Performance Score (see Table 124). Of the two patients with re-ruptures, one patient did not follow the written rehabilitation protocol and the second patients suffered a fall on ice and forcibly dorsiflexed his ankle. Abnormal sensibility was significantly more prevalent in the immobilized group than in the motion group. There were no other statistically significant differences between groups in complications. Description of Treatment Groups Author Post operative Instructions Mobilization group: Immediate weight bearing and mobilization Costa, et al. Mobilization group: Below the knee dorsal plaster splint followed by Mortensen, et al. Below the knee dorsal cast for 6 weeks, this Kangas, et al allowed for free plantar flexion. Below the knee plaster cast Mobilization group: Removable splint and mobilization at 2 weeks. EuroQoL, E5D, Ankle Performance Score Duration (Months) Author Outcome LoE Comparison N 3. Patient opinion of results Author Outcome LoE 3 m 6 m 12m 16m Patient opinion Cetti, et al. Rerupture Statistically Early Immobilizatio Author LoE Duration N Significant Motion n Difference Cetti, et al. Cast - Complications Statistically Early Rigid Cast Author Complication LoE N Significant Motion Group Difference Cetti, et al. Immobilization Quality ● = Yes ○ = No × = Not Reported n/a = not applicable Author Outcome N Treatment(s) LoE Costa, et Mobilization al. Immobilization Study Data Results Author Outcome LoE Duration N Early Motion Cast Results Return to same Cetti, et al. Rationale: A systematic review did not identify any studies that met the inclusion criteria. Supporting Evidence: We searched for any studies addressing post operative physical therapy including supervised and unsupervised physical therapy. The only studies that we identified did not specifically study whether physical therapy was effective.

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This may recommend the involvemenof obstricians buy generic effexor xr line anxiety symptoms blood pressure, radiologists safe 150mg effexor xr anxiety symptoms 5 yr old, physicians P and haematologists cheap 37.5mg effexor xr anxiety 4th breeders. If ultrasound is negative and a high level of clinical suspicion exists, anticoagulantreatmenshould be discontinued buthe ultrasound should be repead on days 3 and 7. The sensitivity of serial compression ultrasonography with Doppler imaging was 94. With Evidence regard to V/Q lung scanning, during pregnancy the ventilation componencan ofn be omitd level 2+ thereby minimising the radiation dose for the fetus. The radiation dose depends on breassize, the chnique used and the age of the woman � the risk of cancer being grear in younger women. The delivery of 10 mGy of radiation to a woman�s breashas been estimad to increase her lifetime risk of developing breascancer by 13. For a 25-year-old whose background Evidence risk of developing breascancer in the following 10 years is 0. Furthermore, Allen and Demetriades48 have suggesd thaven this small risk is an overestima. Nevertheless, breastissue is especially sensitive to radiation exposure during pregnancy because of hormonally induced increased glandular activity. In each of these studies, the authors conclude thaprospective trials are required to valida their fndings. Baseline blood investigations Whabaseline blood investigations should be performed before initiating anticoagulantherapy? Before anticoagulantherapy is commenced, blood should be taken for a full blood count, coagulation D screen, urea and electrolys, and liver function sts. B The use of anticoagulantherapy can be infuenced by renal and hepatic function, and can Evidence infuence the plalecount, and blood should be taken to confrm thathese are normal level 4 before commencing treatment. Levels level 1++ of antithrombin and proin C may fall, particularly if the thrombus is exnsive. In addition, proin S levels fall in normal pregnancy and an acquired activad proin C resistance is found in around 40% of pregnancies. This is of particular relevance in obstric practice where obstric haemorrhage remains the moscommon cause of severe obstric morbidity. This recommendation was based on anti-Xa activity and a paucity of reports on safety and effcacy of once-daily dosing. Initial dose of enoxaparin is dermined as follows: Booking or early pregnancy weighInitial dose of enoxaparin < 50 kg 40 mg twice daily or 60 mg once daily 50�69 kg 60 mg twice daily or 90 mg once daily 70�89 kg 80 mg twice daily or 120 mg once daily 90�109 kg 100 mg twice daily or 150 mg once daily 110�125 kg 120 mg twice daily or 180 mg once daily > 125 kg Discuss with haematologisTable 1b. Initial dose of dalparin is dermined as follows: Booking or early pregnancy weighInitial dose of dalparin < 50 kg 5000 iu twice daily or 10 000 iu once daily 50�69 kg 6000 iu twice daily or 12 000 iu once daily 70�89 kg 8000 iu twice daily or 16 000 iu once daily 90�109 kg 10 000 iu twice daily or 20 000 iu once daily 110�125 kg 12 000 iu twice daily or 24 000 iu daily > 125 kg Discuss with haematologisTable 1c. D Obstric patients who are postoperative and receiving unfractionad heparin should have D plalecounmonitoring performed every 2�3 days from days 4 to 14 or until heparin is stopped. Iis therefore recommended thaobstric patients who are postoperative and receiving unfractionad heparin should have plalecounmonitoring performed every 2�3 days from days 4 to 14 or until heparin is stopped. Collapsed, shocked women who are pregnanor in the puerperium should be assessed by a am of experienced clinicians including the on-call consultanobstrician. P Women should be managed on an individual basis regarding: intravenous unfractionad heparin, thrombolytic therapy or thoracotomy and surgical embolectomy. P Managemenshould involve a multidisciplinary am including senior physicians, obstricians and radiologists. Marnity units should develop guidelines for the administration of intravenous unfractionad heparin. Collapsed, shocked women who are pregnanor in the puerperium should be assessed by a multidisciplinary resuscitation am of experienced clinicians including the on-call consultanobstrician, who should decide on an individual basis whether a woman receives intravenous unfractionad heparin, thrombolytic therapy or thoracotomy and surgical embolectomy. A perimorm caesarean section should be performed by 5 minus if resuscitation is unsuccessful and the pregnancy is more than 20 weeks. Where such problems Evidence are considered to exist, haematologists should be involved in the patient�s management. Imay level 2+ be useful to dermine the anti-Xa level as a measure of heparin dose. With unfractionad heparin, a lower level of anti-Xa is considered therapeutic (targerange 0. Afr thrombolytic therapy has been given, an infusion of unfractionad heparin can be given, buthe loading dose (outlined above) should be omitd. Mosbleeding events occur around cather and puncture sis and, in pregnanwomen, there have been no reports of intracranial bleeding. If the patienis nosuitable for thrombolysis or is moribund, a discussion with the cardiothoracic surgeons with a view to urgenthoracotomy should be had. A randomised controlled trial comparing knee-length with thigh-length hosiery concluded thathigh-length compression elastic stockings do novidence offer betr proction againspost-thrombotic syndrome than below-knee hosiery and are level 1+ less well tolerad. A piloaudiof compliance with graduad compression stockings in pregnancy showed poor levels of compliance relad to discomforand side effects. Outpatienfollow-up should include clinical assessmenand advice with monitoring of blood plalets and peak anti-Xa levels if appropria (see sections 5 and 6. Reducing to an inrmedia dose may be useful in pregnanwomen aincreased risk of bleeding or osoporosis. A review of 91 level 3 pregnancies in 83 women concluded thadanaparoid is an effective and safe antithrombotic in pregnancy for women who are intoleranof heparin. Vitamin K antagonists cross the placenta readily and are associad with adverse pregnancy outcomes including miscarriage, prematurity, low birthweight, neurodevelopmental problems Evidence and fetal and neonatal bleeding. They are also associad with a characristic embryopathy level 2+ following fetal exposure in the frstrimesr. Where possible, anticoagulantherapy should be alred to avoid an unwand anticoagulanffecduring delivery. Women should be advised noto injecany further heparin if they are in established labour or think they are in labour. Subcutaneous unfractionad heparin should be discontinued 12 hours before and intravenous unfractionad heparin stopped 6 hours before induction of labour or regional anaesthesia. If iis markedly prolonged near delivery, protamine sulfa may be required to reduce the risk of bleeding. One approach to the use of anticoagulantherapy in this situation level 4 has been described by McLintock eal. Iis considered thaobstric patients have a lower incidence of spinal haematoma than elderly patients. Measures should be taken to allow drainage of any haematoma, including the use of drains and inrrupd skin sutures. A case�control study has repord an increased incidence of wound Evidence complications in women receiving peripartum anticoagulation. Any woman who is considered to be ahigh risk of haemorrhage, and in whom continued heparin D treatmenis considered essential, should be managed with intravenous unfractionad heparin until the risk factors for haemorrhage have resolved.

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