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The risk reduction in major coronary events was 29% (95% CI discount detrol 1mg without prescription, 13 to 42) in women buy cheap detrol 1 mg on-line, 31% (95% CI, 26 to 35) for men, 32% (95% CI, 23 to 39) in those over age 65, and 31% (95% CI, 24 to 36) in those younger than age 65. Similarly, the Heart Protection 123, 178 Study found that simvastatin reduced cardiovascular events among women generally and particularly in women with diabetes, who benefited dramatically (number needed to treat, 23 to prevent 1 major vascular event). Nine trials of statins that enrolled 16 486 women and 4 additional studies that included 1405 women who used drug therapy other than statins were included in the analysis. For secondary prevention, lipid-lowering therapy reduced risk of coronary heart disease mortality (summary RR 0. In primary prevention studies, there was insufficient evidence of reduced risk of any clinical outcome in women, because of the small number of events in the trials. Sensitivity analyses including only studies using statins did not significantly affect the summary risk estimates. Statins Page 56 of 128 Final Report Update 5 Drug Effectiveness Review Project 193, 194 Two meta-analyses specifically evaluating statins in the elderly confirmed prior findings that these drugs are effective in this population. In particular, a hierarchial bayesian 193 meta-analysis included 9 placebo-controlled trials that enrolled 19 569 elderly patients who had a history of cardiovascular events. The pooled relative risk for all-cause mortality was 0. Coronary heart disease mortality, nonfatal myocardial infarction, need for revascularization, and stroke were all statistically significantly reduced with statins compared with placebo (Evidence Table 8). Of note, the Heart Protection study (which included primary prevention population) was included in the meta-analysis but a sensitivity analysis with and without this trial showed consistent treatment effects. Statins that were included were simvastatin 20-40 mg, pravastatin 40 mg, and fluvastatin 80 mg. African American, Hispanic, and other ethnic groups African Americans had the greatest overall coronary heart disease mortality and the highest out- 4 of-hospital coronary death rates of any other ethnic group in the United States. Other ethnic and minority groups in the United States included Hispanics, Native Americans, Asian and Pacific Islanders, and South Asians. However, these groups are underrepresented in randomized clinical trials reporting reductions in clinical outcomes. As a result there was no evidence to answer whether or not statins differ in their ability to reduce clinical events in the African American, Hispanic, or other ethnic groups. Significant numbers of African American and Hispanic patients participated in AFCAPS/TexCAPS, but the investigators did not analyze events by racial group. In EXCEL, lovastatin 20 mg, 40 mg, and 80 mg daily reduced low-density lipoprotein 195 cholesterol by similar percentages in blacks and in whites. In short-term head-to-head trials, reductions in low-density lipoprotein cholesterol and frequency of adverse events with rosuvastatin 10 to 20 mg and atorvastatin 10 to 20 mg in 23 196 74 Hipanic, South Asian, and African American patients were similar to those observed in studies conducted in primarily white non-Hispanic populations. Safety in demographic subgroups All of the statins used in the major long-term randomized trials were tolerated equally well among men, women, and healthy elderly subjects. These results applied to patients who met the eligibility criteria for the trials: in general, patients with liver disease and other serious diseases were excluded from these trials. Also, most of the patients in the trials took fixed doses of statins that were less than the maximum doses. In a large, observational study of lovastatin, men, women, and the elderly experienced 197, 198 similar rates of adverse effects. The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study was a 4-year study of the tolerability of lovastatin 20 mg, 40 mg, or 80 mg daily in 8245 199-203 patients, including over 3000 women. The rates of myopathy and liver enzyme elevations increased with increasing doses of lovastatin, but did not differ among men, women, and healthy elderly subjects. A meta-analysis of randomized trials of simvastatin 80 mg involving 2819 197 subjects (Worldwide Expanded Dose Simvastatin Study Group) had similar results. These studies were important because they demonstrated that the maximum (80 mg) doses of simvastatin and lovastatin were well tolerated. Similar findings were observed in 3 additional 18, 194, 204 publications. Statins Page 57 of 128 Final Report Update 5 Drug Effectiveness Review Project 195 A subgroup analysis from the EXCEL Study examined the efficacy and safety of lovastatin compared with placebo in 459 African-Americans. The endpoints in the trial were reduction in total cholesterol, low-density lipoprotein cholesterol, triglycerides, and an increase in high-density lipoprotein cholesterol. With regard to safety, there was a significantly higher incidence of creatine kinase elevation in African-Americans compared to white Americans in both placebo and lovastatin treatment groups. However, no cases of myopathy, defined as creatine kinase elevations greater than 10 times the upper limit of normal, occurred in African- Americans. There were no other safety differences between lovastatin and placebo in African- Americans or Caucasians. In premarketing studies, Japanese and Chinese patients living in Singapore had higher 205 levels of rosuvastatin in blood than Caucasians living in Europe. The US Food and Drug Administration asked the manufacturer to perform an appropriately conducted pharmacokinetic study of Asians residing in the United States. The study demonstrated an approximate 2-fold elevation in median exposure in Asian subjects (having either Filipino, Chinese, Japanese, Korean, Vietnamese, or Asian-Indian origin) compared with a Caucasian control group. The rosuvastatin label noted that this increase should be considered when making rosuvastatin dosing decisions for Asian patients.

Identify the round liga- with a big uterus or difficult access you might need ments by asking your assistant to pull the uterus up- a third person to hold additional retractors to im- wards generic 1 mg detrol amex. You will find two folds connecting the uterus prove your view best detrol 4mg. You can conduct the whole to the pelvic brim near the inguinal canal. Put a operation using Vicryl or catgut 0, except for sutur- strong forceps on each around one-third away from ing the fascia of the rectus muscle in the abdominal the uterus. Cut the ligament on the uterine side and wall where you should use Vicryl or catgut 1 or 2. You should always put in a bladder catheter and Leave the suture long after cutting of the needle and give the patient a single shot of antibiotics like ampi- secure them with small forceps. These sutures are cillin and metronidazole before the operation starts. Never omit this intestines upwards with a wet towel, explore the step as it will provide you with access to the retro- abdominal cavity. Check the mobility of the uterus peritoneum and will increase mobility of the uterus by identifying the cervix, putting your fingers easily. Now open the anterior part of the peritone- around it from abdominally and pushing the uterus um on each side by asking your assistant to pull on upwards out of the true pelvis. Cut the peritoneum with dis- fail to reach the cervix put a sharp forceps, e. This tenaculum, in the uterine fundus (do not do this in will help you to identify the ureters if you were not cases where you expect malignancies) and pull the able to visualize them before starting the procedure. Check for adhe- You can identify the ureters at this stage by putting sions in the Douglas space behind the uterus. If ad- your thumb in the retroperitoneal space that you hesions are present carefully remove them with just created and your index finger posterior and cau- your fingers or by using scissors if necessary. Incision and ligation of the round ligaments Put hemo- Incision and ligation of the tubes and utero-ovarian liga- static clamps on both sides of the uterus on the ment or infundibulopelvic ligaments Now put the index tubes, the round ligament and the ligamentum finger of your left hand under the uterine side of the 223 GYNECOLOGY FOR LESS-RESOURCED LOCATIONS Figure 6 Identification of the infundibulopelvic and ovarian ligament Figure 8 Ligation of the adnexal bundle with a Heaney stitch Figure 7 Dissection of the ovarian ligament and the mesosalpinx round ligament to elevate the ovaries. Like this you can see the infundibulopelvic and the utero-ovarian ligament (Figure 6). If you want to leave the ovaries and fallopian tubes inside, put a strong forceps on Figure 9 Dissection of the bladder peritoneum the tube and the utero-ovarian ligament and cut them on the uterine side of the forceps. Alterna- tively you can put a straight forceps on tube and two forceps. Ligate the adnexal bundle under the ligament and make a hole with your index fingers in forceps with a Heaney stitch (Figure 8). It is wise to suture the infundibulo- strong forceps in the hole and cut in between the pelvic ligament twice to prevent bleeding. You will see it ex- tends towards the vesico-uterine fold where the bladder is attached to the anterior uterine wall. Incise the anterior part of the peritoneum by gently pushing closed dissecting scissors under it in the direction of the vesico-uterine fold below its reflection onto the uterus separating the peritoneal lining from its underlying tissue and the uterine body. Pull your scissors back, open them and cut the peritoneum where you have just separated it. Push the bladder gently downwards from the cervix using a sponge on a sponge-holding forceps. Always do this in the midline of the cervix as there Figure 10 Clamping of the uterine arteries are vessels on the sides which will start to bleed once touched with the sponge. Alternatively you can dissect the bladder downwards using scissors. Incision and ligation of the uterine vessels and the broad ligament Ask your assistant to pull the uterus up- wards to the opposite side of your area of prepara- tion using the two straight forceps on the adnexal stumps. This will put tension on the respective broad ligament where the ascending branch of the uterine artery and its vein is running. Place two strong forceps with the tips onto the muscular substance of the uterine body/cervix and let them slip down at right angles to the uterus (Figure 10). Cut the broad ligament between the two forceps right down to the tip of the forceps. This will increase mobility further and reduce bleeding. After you have tied the uterine arteries Figure 11 Clamping of the para-uterine tissue the uterus will become white. Incision and ligation of the para-uterine and paracervical branches of the uterine arteries are ligated on both tissue Now you will cut the para-uterine and para- sides you don’t need to place a contra-forceps any- cervical tissue which are attaching the uterus to the more as there won’t be any important bleeding pelvic wall step by step in nearly the same way as anymore. This is because the ureters are running hysterectomy.

Some fibres from the right crus pass around the lower der of a rib to minimize the risk of injury purchase detrol 2 mg amex. Vascular supply and venous drainage of the chest wall The medial arcuate ligament is made up of thickened fascia which The intercostal spaces receive their arterial supply from the anterior overlies psoas major and is attached medially to the body of L1 and lat- and posterior intercostal arteries cheap 1 mg detrol overnight delivery. The lateral arcuate ligament is • The anterior intercostal arteries are branches of the internal thoracic made up of fascia which overlies quadratus lumborum from the trans- artery and its terminal branch the musculophrenic artery. The lowest verse process of L1 medially to the 12th rib laterally. The median arcuate ligament is a fibrous arch which connects left • The first 2–3 posterior intercostal arteries arise from the superior and right crura. The lower nine posterior inter- •Asternal part: consists of two small slips arising from the deep sur- costal arteries are branches of the thoracic aorta. Openings in the diaphragm The anterior intercostal veins drain anteriorly into the internal thor- Structures traverse the diaphragm at different levels to pass from acic and musculophrenic veins. The posterior intercostal veins drain thoracic to abdominal cavities and vice versa. These levels are as into the azygos and hemiazygos systems (see Fig. Lymph drainage from the: • T10, the oesophageal opening: transmits the oesophagus, vagi and • Anterior chest wall: is to the anterior axillary nodes. The left phrenic nerve passes into the diaphragm as a solitary structure. Only the upper six intercostal nerves run in their inter- • Motor supply: the entire motor supply arises from the phrenic nerves costal spaces, the remainder gaining access to the anterior abdominal (C3,4,5). Diaphragmatic contraction is the mainstay of inspiration. The sensory supply from the • Cutaneous anterior and lateral branches. The thoracic wall II 9 3 The mediastinum Icthe contents of the mediastinum Superior mediastinum Great vessels Trachea Oesophagus Thymus, etc. Middle mediastinum Heart and roots of great vessels Anterior mediastinum Pericardium Thymus Posterior mediastinum Oesophagus Descending thoracic aorta Thoracic duct Fig. The superior mediastinum communicates with the root of the neck The dual drainage of the lower third forms a site of portal-systemic through the ‘thoracic inlet’. The latter opening is bounded anteriorly by anastomosis. In advanced liver cirrhosis, portal pressure rises result- the manubrium, posteriorly by T1 vertebra and laterally by the 1st rib. These veins become distended and fragile (oesophageal varices). They are predisposed to rupture, causing potentially life-threatening • Middle mediastinum: consists of the pericardium and heart. The lower oesophagus also drains into the nodes The contents of the mediastinum (Figs 3. The oesophagus Carcinoma of the oesophagus carries an extremely poor prognosis. In the thorax the oesoph- account for the majority of tumours. The incidence of adenocarcinoma of agus passes initially through the superior and then the posterior medi- the lower third of the oesophagus is currently increasing for unknown astina. Having deviated slightly to the left in the neck the oesophagus reasons. Most tumours are unresectable at the time of diagnosis. The returns to the midline in the thorax at the level of T5. From here, it insertion of stents and use of lasers to pass through tumour obstruction passes downwards and forwards to reach the oesophageal opening in have become the principal methods of palliation. It is situated between the abdom- • A double muscular layeralongitudinal outer layer and circular inal aorta and the right crus of the diaphragm. The muscle is striated in the upper two-thirds and • The thoracic duct carries lymph from the cisterna chyli through the smooth in the lower third. It usually receives • An outer layer of areolar tissue. On trunks, although they may open into the large neck veins directly. After puberty the thymus is gradually replaced by fat. The mediastinum Ibthe contents of the mediastinum 11 4 The mediastinum IIcthe vessels of the thorax Inferior thyroid Inferior laryngeal Superficial cervical Thyroidea ima Suprascapular Costocervical trunk Thyrocervical trunk Vertebral Deep cervical Scalenus anterior Dorsal scapular Superior intercostal Subclavian Upper two posterior Internal thoracic (mammary) intercostals Anterior intercostals Musculophrenic Brachiocephalic Superior epigastric Posterior intercostals (also supply spinal cord) Bronchial Oesophageal branches Mediastinal Subcostal Fig. The internal thoracic artery divides behind the 6th The ascending aorta arises from the aortic vestibule behind the costal cartilage into superior epigastric and musculophrenic branches. It is con- The thyrocervical trunk terminates as the inferior thyroid artery.

Patientsdidreceivediaz epam evening prioraspartof pre-m ed buy detrol 4mg without a prescription. Antiemetics Page 335 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 9 cheap 2mg detrol otc. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear A llow oth er R un-in/ Setting Design Exclusioncriteria Intervention m edication W ash out G an R CT,D B, Ptswereex cludedif they1)hadknownhypersensitivityof G ranisetron0. Ptswerealsoex cludedif they hadex periencednauseaorvom iting of itthey hadtaken antiem etic treatm entinthe48h beforesurgery. Antiemetics Page 336 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 9. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or A ge/ Screened/ W ith drawn/ Y ear G ender/ Eligible/ L ostto fu/ Setting Eth nicity Enrolled A nalyz ed O th erpopulationch aracteristics G an 48years N R /N R /210 34/0/176 M eanweight(kg):72 2005 100% fem ale Sm okers:18. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear Setting R esults A dverse Events G an G ranvsO nd Incidenceof AE s 2005 N ovom iting G ran:37% vsO nd:41% M ulticenter 0-2h aftersurgery:94% vs97% 0-6h aftersurgery:87% vs93% 0-24h aftersurgery:83% vs87% Com pleteresponse 0-2h aftersurgery:75% vs75% 0-6h aftersurgery:59% vs66% 0-24h aftersurgery:46% vs49% R equiredrescuem edication 0-2h aftersurgery:24% vs21% 0-6h aftersurgery:40% vs30% 0-24h aftersurgery:55% vs46% Janicki D olvsG ran N onereportedbysubjectsin 2006 W hileinPACU eithergroup HersheyM edical Incidenceof vom iting orretching:10. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear Setting C om m ents G an 2005 M ulticenter Janicki Alsohasinform ationongenotyping inform ationforCYP2D 6 2006 HersheyM edical Center K h an N E E D TablesandF igures 2005 G eneralhospital N aguib N oprem edicationwasgivenandptsfastedfrom m idnightbeforesurgery. Aftertrachealintubation,allptshadanorogastric tubeplacedto 1996 ensurebaselineem ptying of thestom ach of airandgastric contents. Allorogastric tubeswererem ovedattheendof surgeryandbeforetracheal N R ex tubation. R etching wasnotassessedseparatelyfrom vom iting andnausea. If nauseaorvom iting occurred,rescueantiem etic treatm entof m etoclopram ideiv10m g wasadm inistered. F orpost-operativeanalgesia,m eperidineim 50m g wasadm inisteredif painscorewas ≥ 5. Study alsoincludedam etoclopram idearm (n= 24)andaplaceboarm (n= 29),buttheseresultsarenotincludedinthisdataabstraction. Afterintubation theconcentrationsof thenitrousox ide,ox ygen,carbondiox ide,andisofluraneweredeterm inedcontinuouslybyam ultiple-gasanaesthesia m onitor. Abdom inalinsufflationforthelaparoscopic procedurewasaccom plishedwith carbondiox ide. Antiemetics Page 339 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 9. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear A llow oth er R un-in/ Setting Design Exclusioncriteria Intervention m edication W ash out O ksuz R CT,D B, Thosewith cardiovascular,pulm onary,renal,hepatic or M etoclopram ide10m g R escuem edicationwas N R /N o 2007 Parallel neurologic diseaseswereex cluded. Aswellasthose G ranisetron40m cg/kg perm itted antiem etic within N R receiving drugsknow tohaveantiem etic effects,such as O ndansetron15m cg/kg iv 48hoursof tricyclic antidepressants,scopolam ine,phenothiaz ines, surgery laraz epam ,corticosteroids,andtrim ethobenz am ides;had ex periencednauseaorvom iting,orwhohadreceived antiem etic treatm entinthe48hoursbeforesurgery. W h ite R CT,ACT,Ptswith historyof allergytoanyof thepotentialstudy G ranisteron(1m g) D ex am ethasone4m g N R /N o 2006 D B m edications,pregnancy,breastfeeding,active O ndansetronIV (4m g) IV giventoallafter antiem etic or M ulticenter m enstruation,vom iting orretching within24h beforethe induction psychoactive U SA operation,adm inistrationof antiem etic orpsychoactive m edication m edicationwithin24h beforesurgery,ahistoryof severe Cisatracurium 0. M etocloparm ide10m g IV wasusedasrescue therapy O ndansetron: O DT vs IV Antiemetics Page 340 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 9. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or A ge/ Screened/ W ith drawn/ Y ear G ender/ Eligible/ L ostto fu/ Setting Eth nicity Enrolled A nalyz ed O th erpopulationch aracteristics O ksuz 39. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear Setting R esults A dverse Events O ksuz Incidenceof PO N V (0-3h aftersurgery) N R 2007 M et:12% vsG ran:0% vsO nd:12% N R Incidenceof PO N V (4-24h aftersurgery) M et:44% vsG ran:4% vsO nd:12% (p<0. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear Setting C om m ents O ksuz 2007 N R W h ite Subanalysisof outpatientvsinpatient. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear A llow oth er R un-in/ Setting Design Exclusioncriteria Intervention m edication W ash out Dem iraran R CT,D B Thosewhohadex periencednauseaorvom iting 24hours O D T ondansetron8m g and5 M etoclopram ide10m g N R /N R 2005 beforethestudyorwhoweretaking antiem etic m edication m L norm alsalineIV IV wasusedasrescue SingleSite m edication Turkey IV ondansetron4m g in5m L salineandoralplacebo Placebo:5m lnorm alsalineIV andoralplacebo Pirat R CT,D B Ptswith historyof m otionsicknessorPO N V,preoperative O D T ondansetron8m g and5 IM injectionof N R /N o 2005 pruritus,treatm entwith opioidsorantiem eticswithin48 m L norm alsalineIV diclofenac sodium antiem etic within N R hoursof surgery,hypersensitivitytoondansetron, 100m g wasusedfor 48hoursof m orphine,orbupivacaine,andcontraindicationforor IV ondansetron4m g in5m L postoperativepain surgery refusalorspinalanesthesia. Casesinwhich dural salineandoralplacebo puncturecouldnotbeperform edoropioidswererequired R escuem edicationwas tocontrolintraoperativeorpostoperativepainwerealso Placebo:5m lnorm alsalineIV perm itted ex cluded. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or A ge/ Screened/ W ith drawn/ Y ear G ender/ Eligible/ L ostto fu/ Setting Eth nicity Enrolled A nalyz ed O th erpopulationch aracteristics Dem iraran 47. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear Setting R esults A dverse Events Dem iraran O D T vsIV vsPla O D T vsIV vsPla 2005 Incidenceof nauseaorvom iting (1stm in) Headache:13% vs17% vs15% SingleSite N ausea:28% vs25% vs55% (p<0. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear Setting C om m ents Dem iraran D atapresentedingraphs,num bersareestim atesof thegraphs. Preventionofpostoperative nauseaand vom iting:H ead-to-h ead trials A uth or Y ear A llow oth er R un-in/ Setting Design Exclusioncriteria Intervention m edication W ash out Diem unsch R CT,D B E x clusioncriteriaincludedpregnancy/breastfeeding Aprepitant40m g,orally Prem edication,as N o/no 2007 status,needforanasogastric ororal-gastric tube,useof Aprepitant125m g,orally needed prophylactic M ulticenter neuroax ial-orpropofol-m aintainedanaesthesia,vom iting O ndansetron4m g iv antiem etics within24h beforesurgeryorof anyorganic aetiology, rescuem edication within24h allergytoanym edicationstobeusedbeforeoperationor (chosenby beforesurgery intra-operatively,pre-establishedneedforintensivecare investigator) orstep-downunitcareafteroperation,evidenceof diseaseorhistoryof illnesswhich according tothe investigatorrenderedthepatientinappropriateforthe study,abnorm alpreoperativelaboratoryvalues(aspartate am inotransferase>2. M edicationsknowntoinduceCYP3A4were prohibitedwithin30daysof thestudystartandCYP3A4 inhibitorswereprohibited7daysbeforestartof study. G an R CT,D B Patientswhowerepregnantorbreast-feeding,undergoing Aprepitant40m g orally R escuem edicationwas N o/no 2007 surgeryrequiring routineplacem entof anasogastric or Aprepitant125m g orally perm itted prophylactic M ulticenter oral-gastric tube,orreceiving spinalregionalorpropofol- O ndansetron4m g iv antiem etics m aintainedanesthesia. Ptswhom werevom iting of any within24hours organic etiology,hadvom itedforanyreasonwithin24 beforesurgery hoursof surgery,orhadabnorm allaboratoryvaluesas specifiedbytheprotocol(alanineam inotransferaseof aspartateam inotransferase>2. Thosetaking m edicationsm etaboliz edbyCYP3A4wereex cluded. Dolasetronvs G ranisetronvs O ndansetron Antiemetics Page 348 of 492 Final Report Update 1 Drug Effectiveness Review Project Evidence Table 9.