Improvements in glycemic control

Transcription

1 CLINICAL report Ptient stisfction nd costs ssocited with insulin dministered by pen device or syringe during hospitliztion Improvements in glycemic control hve been shown to gretly reduce the progression of microvsculr complictions in ptients with dibetes. 1,2 Adherence to insulin therpy is mjor fctor in chieving glycemic control. Insulin hs conventionlly been dministered vi the subcutneous route with vils nd syringes. Insulin pen devices were developed nd introduced in the 198s by combining the insulin reservoir nd syringe into single component in n effort to overcome brriers to dherence with insulin self-dministrtion nd to improve convenience nd ese of use for ptients. 3 Despite the vilbility of insulin pens, hospitls continued to use vils nd syringes for subcutneous injections. One reson tht insulin pens were not used in mny hospitls ws tht there ws no utomtic sfety feture tht would prevent ccidentl Estell M. Dv i s, Crl M. Christensen, Ke l ly K. Nystrom, Pmel A. Forl, nd Chris Destche Purpose. Ptient stisfction, sfety nd efficcy outcomes, nd cost svings with insulin pens versus conventionl insulin delivery vi vils nd syringes in hospitlized ptients with dibetes were compred. Methods. Ptients were recruited from two generl medicl surgicl units from July 25 to My 26. Ptients completed survey regrding stisfction with the method in which insulin ws dministered before dischrge. Ptients completed telephone survey pproximtely four weeks fter dischrge to determine home insulin use. Cost svings were determined using the verge wholesle price of insulin vils nd syringes, pens, nd pen needles. Results. A totl of 94 ptients were rndomized to receive insulin dministered vi pen devices (n = 49) or using conventionl vils nd syringes (n = 45). Significntly more subjects in the pen group prepred or self-injected t lest one dose of insulin during hospitliztion, wnted to continue tking insulin t home using the method used during hospitliztion, nd would recommend their method of insulin dministrtion used during hospitliztion to other ptients with dibetes compred with the vil nd syringe group (p <.5). A cost sving of $36 per ptient ws projected if only insulin pens were dispensed during the entire hospitl sty compred to insulin vils nd syringes (p <.5). Conclusion. Incresed ptient stisfction nd continution of the method of insulin dministrtion used in the hospitl t home were reported by ptients who received insulin pens compred with ptients who received conventionl vils nd syringes during hospitliztion. A substntil cost sving ws projected for ptients in the insulin pen group if insulin pens hd been dispensed during their entire hospitl sty. Index terms: Dt collection; Devices; Dibetes mellitus; Drug dministrtion; Hospitls; Injections; Insulin; Insulins; Ptients; Phrmcoeconomics; Toxicity Am J Helth-Syst Phrm. 28; 65: Estell M. Dv i s, Ph r m.d., is Clinicl Phrmcist, Phrmcy Deprtment, Alegent Helth Bergn Mercy Medicl Center (AHBMMC), Omh, NE, nd Assistnt Professor of Phrmcy Prctice, Phrmcy Prctice Deprtment, School of Phrmcy nd Helth Professions, Creighton University (CU), Omh. Crl M. Christensen, Ph r m.d., is Clinicl Phrmcist, Phrmcy Deprtment, AHBMMC, nd Assistnt Professor of Phrmcy Prctice, Phrmcy Prctice Deprtment, School of Phrmcy nd Helth Professions, CU. Kelly K. Nyst rom, Ph r m.d., BCOP, is Clinicl Phrmcist, Phrmcy Deprtment, AHBMMC, nd Associte Professor of Phrmcy Prctice, Phrmcy Prctice Deprtment, School of Phrmcy nd Helth Professions, CU. P m e l A. For l, Ph r m.d., BCPS, is Clinicl Phrmcist, Phrmcy Deprtment, AHBMMC, nd Associte Professor of Phrmcy Prctice, Phrmcy Prctice Deprtment, School of Phrmcy nd Helth Professions, CU. Chr is De stch e, Ph r m.d., FCCP, is Professor of Phrmcy Prctice, Phrmcy Prctice Deprtment, School of Phrmcy nd Helth Professions, CU. Address correspondence to Dr. Dvis t the Phrmcy Prctice Deprtment, School of Phrmcy nd Helth Professions, Creighton University, 25 Cliforni Plz, Omh, NE (edvis@ creighton.edu). Funded by the Internl Reserch nd Development Grnt Progrm of the School of Phrmcy nd Helth Professions, Creighton University. Copyright 28, Americn Society of Helth-System Phrmcists, Inc. All rights reserved /8/ $6.. DOI /jhp7636 Am J Helth-Syst Phrm Vol 65 Jul 15,

2 needle sticks in helth cre workers. The use of insulin pens in the hospitl setting becme more vible option with the introduction of n insulin pen product with sfety needle tht provides pssive sfety feture tht utomticlly engges fter n injection is dministered (NovoFine Autocover 3G disposble sfety needle, Novo Nordisk, Princeton, NJ). The sfety feture prevents ccidentl needle sticks nd needle reuse nd is locked into plce throughout needle disposl. The sfety needle complys with U.S. Deprtment of Lbor Occuptionl Sfety nd Helth Administrtion (OSHA) guidelines nd ppers on OSHA s list of pproved sfety-engineered shrps devices. 4 Administrtion of insulin through pen devices in the mbultory cre setting hs been shown to improve insulin regimen dherence nd ptient stisfction. 5-9 Authors of survey evluting insulin pen use in ptients who previously used vils nd syringes found tht more ptients who used pens reported not missing ny injections nd felt it ws esier to comply with their insulin regimen thn when they used conventionl vils nd syringes. 8 Ptients lso reported strong desire to continue using the pens nd stted tht they would recommend the method to other ptients. Studies in mbultory cre ptients hve lso found tht insulin pens hve similr effects or improve glycemic control compred with insulin dministered using vils nd syringes. In multicenter, rndomized, crossover study in 121 ptients with type 1 or type 2 dibetes mellitus using conventionl insulin dministrtion using vils nd syringes or prefilled, disposble insulin pens, significnt improvement in glycosylted hemoglobin (HbA 1c ) ws observed in both tretment groups fter four-week tretment period, with n verge reduction in men HbA 1c vlues of.3% in the totl popultion (p <.5). 1 Another rndomized crossover study ssessed the efficcy nd sfety of nd ptient complince with insulin dministered from vils nd syringes versus prefilled, disposble pens for n eight-week tretment period in ptients over ge 6 yers. 11 The uthors found reduction of 1.1% ± 1.2% in men ± S.D. HbA 1c vlues for those using insulin pens compred with.6% ± 1.2% reduction with vils nd syringes (men HbA 1c vlue of 8.4% t bseline for both groups) (p <.2). An dditionl study tht evluted the efficcy nd sfety of nd stisfction with insulin pens mong elderly ptients with type 2 dibetes found tht HbA 1c vlues decresed significntly from 7.8% t bseline to 7.6% t three months fter insulin pen use (p <.5). 12 One long-term study followed ptients who were newly initited on insulin pen tretment or insulin tretment dministered from vil with syringe for minimum of two yers to evlute outcomes retrievble through n integrted medicl nd phrmcy clims dtbse contining informtion for ptients enrolled in mnged cre helth plns in the United Sttes (n = 1156). 13 They conducted prenlysis nd postnlysis to evlute the effect of converting ptients from conventionlly dministered insulin to insulin pens on dherence, hypoglycemic events, resource utiliztion, nd the ssocited helth cre costs. Although the uthors did not report findings relted to HbA 1c vlues, they found tht the likelihood of ptients hving hypoglycemic event ws significntly reduced fter switching to insulin pens (odds rtio [OR],.5; 95% confidence intervl [CI],.37.68; p <.5), nd the rte of hypoglycemi in ptients who were considered dherent to insulin decresed by nerly two thirds (incident rte rtio,.35; 95% CI,.11.81; p <.5). There were significnt decreses in hypoglycemi-ttributble emergency deprtment visits (OR,.44; 95% CI,.21.92; p <.5) nd physicin visits (OR,.39; 95% CI,.24.64; p <.5) in ptients receiving insulin pens, wheres the number of hypoglycemi-relted hospitliztions nd outptient visits remined similr fter switching from conventionlly dministered insulin to insulin pens. One survey of 33 physicins found tht 97% of physicins (n = 32) whose ptients switched to insulin pens for six weeks in n outptient setting felt the insulin pen ws better method for insulin delivery overll, 85% felt more confident in their ptients bility to ccurtely deliver dose, nd 91% felt it ws esier to initite insulin therpy with the insulin pen thn with insulin vils to be dministered with syringes. 9 Another study evluted home cre nurse resource utiliztion in 79 mbultory elderly ptients with visul disbilities, motor disbilities, or both who required ssistnce for insulin preprtion nd dministrtion using insulin pens or vils nd syringes. 14 More ptients were ble to independently give themselves injections using insulin pens compred with vils nd syringes (53% versus 2%, respectively). The men ± S.D. time spent by nurses to ssist with injections for those who used pens (4.2 ± 8.1 minutes) ws shorter compred with dministrtion vi vils nd syringes (5.8 ± 8.9 minutes). The sving in time spent ssisting with injections significntly reduced the men dily nursing cost (clculted from nursing visits to ssist ptients with insulin injections) for those who used pens versus vils nd syringes ($114 versus $196, respectively; p <.1). 14 Direct nd indirect costs ttributed to dibetes in the United Sttes were $132 billion in The development of novel insulin technologies tht cn increse ptient dherence, improve ptient nd helth cre worker sfety, nd decrese potentil institutionl nd helth cre costs 1348 Am J Helth-Syst Phrm Vol 65 Jul 15, 28

3 hs driven orgniztions to consider using insulin pen devices for hospitlized ptients. To the best of our knowledge, there re no published rticles tht evlute insulin pen use in hospitlized ptients nd cost svings or ptient stisfction ssocited with insulin pen use in the hospitl setting. Further, it is not known whether ptients who re exposed to insulin pen devices in hospitl setting would continue to use them fter hospitl dischrge or if insurnce nd reimbursement issues would be brriers to their use. The gols of the current study were to evlute ptient stisfction, glycemic control, economic effect, nd postdischrge insulin dministrtion method by compring the use of insulin dministered through pen device with the dministrtion of insulin from vils using syringe in hospitlized ptients. Methods Study design. This prospective, rndomized, controlled, prllelgroup study compred the use of pen devices with conventionl vils nd syringes for the dministrtion of insulin in hospitlized ptients with dibetes mellitus requiring subcutneous injections. A noninferiority study design ws used to evlute ptient stisfction nd cost svings with insulin pens versus vils nd syringes. Ptients were rndomly ssigned (1:1) to receive their insulin using pen devices or vils nd syringes. The study ws conducted in ccordnce with the Declrtion of Helsinki. 16 The procedures for the study were followed in ccordnce with the ethicl stndrds of the investigtionl review bord t Creighton University nd Alegent Helth System. Written informed consent ws obtined from ll ptients prior to ny tril-relted ctivities. Ptients were recruited from two generl medicl surgicl units from July 25 to My 26. Two prefilled, disposble insulin pen devices were used: InnoLet nd FlexPen (Novo Nordisk). Becuse the hospitl hs one preferred formulry mnufcturer for insulin nlogues, orders from prescribers for comprble insulin nlogues were therpeuticlly substituted with n nlogue of the hospitl s preferred mnufcturer whenever possible. Ptients received InnoLet if they were rndomized to the insulin pen group nd prescribed insulin humn regulr, isophne insulin humn (NPH insulin), or the combintion of 7% NPH insulin nd 3% regulr insulin. Ptients received the FlexPen if they were rndomized to the insulin pen group nd prescribed ny rpid-cting insulin (insulin lispro or insulin sprt) or the combintion of 7% insulin sprt protmine with 3% insulin sprt or 75% insulin lispro protmine with 25% insulin lispro. NovoFine Autocover 3G disposble sfety needles were dispensed for ptients enrolled in the pen group. If insulin glrgine ws prescribed, vil ws dispensed regrdless of the tretment group becuse it ws not vilble in pen device t the strt of the study. To prevent the dely of insulin delivery to ptients on the study floors, potentil study ptients who met inclusion criteri were initilly given insulin vils to cover immedite insulin needs. If ptients were ultimtely rndomized to the insulin pen group, the insulin vils were discontinued nd the pproprite insulin pens nd pen sfety needles were used. Ptients rndomized to the vil nd syringe group continued this method during their hospitl sty. Insulin pen trining. Before study initition, registered nurses on the study floors received instruction by study investigtors on both pen devices nd proper use of the sfety needles. Successful completion of competency-bsed insulin pen dministrtion checklist nd successful demonstrtion of mock insulin injection were required by the investigtor before nurse could dminister insulin to ptient using the insulin pen devices. During this trining period, ll phrmcists nd phrmcy technicins were trined how to use, lbel, dispense, nd store the insulin pens. Ptient selection. Ptients were eligible for study inclusion if they hd documenttion of type 1 or 2 dibetes mellitus in their medicl record, required subcutneous insulin for glucose control during hospitliztion, nd were bove the ge of consent (19 yers) in Nebrsk, where the study ws conducted. Ptients were excluded if they were prescribed sole insulin nlogue tht could not be substituted with Innolet or FlexPen. Outcomes mesures. Ptient stisfction. All ptients completed selfdministered, eight-question survey bout their insulin dministrtion experience during their hospitl sty. The first two questions ddressed the number of times tht the ptient withdrew the insulin dose from the insulin vil or used the pen to dil the dose of insulin nd the number of times the ptient self-dministered the insulin dose during the hospitl sty. For the remining questions, ptients were provided sttements nd sked to rte their level of greement with the sttement (i.e., strongly disgree, disgree, unsure, gree, or strongly gree). Any ptients who hd used both insulin pens nd conventionl insulin vils nd syringes before study enrollment were sked to rte their level of greement with three dditionl sttements to compre the two methods of insulin dministrtion. The stisfction survey tools were developed from surveys used in previous studies ssessing ptient nd helth cre provider stisfction with existing insulin delivery methods, stisfction with comprtive types of insulin delivery methods, nd stisfction with novel insulin pen Am J Helth-Syst Phrm Vol 65 Jul 15,

4 devices in the self-cre outptient environment. 6,9,17-21 Two vlidted surveys the Ptient Stisfction with Insulin Therpy questionnire nd the Dibetes Tretment Stisfction Questionnire were used to help develop survey items for the study. Nine questions were identified for inclusion in the survey. The surveys were pilot tested nd modified to finlize the survey items. Clinicl outcomes nd sfety. All ptients were followed to evlute glycemic control during hospitliztion. The primry clinicl outcome ws to compre the initil blood glucose level t dmission nd the finl blood glucose level t dischrge. Secondry clinicl outcomes included the number of hypoglycemic nd hyperglycemic events nd the men rtes of hypoglycemic nd hyperglycemic events. The men rtes of hypoglycemic nd hyperglycemic events for ptients in the vil nd syringe group were clculted using the number of events per length of sty in dys. Hypoglycemic nd hyperglycemic event rtes for ptients in the insulin pen group were clculted using the number of events per length of sty in dys nd the number of events while receiving insulin pens per number of dys using insulin pens. These events were nlyzed in two wys for the pen group becuse ptients could hve been receiving insulin pens for shorter durtion thn their length of sty due to the consent process. Hypoglycemic events were defined per hospitl policy s ny blood glucose concentrtion of <7 mg/dl. Hyperglycemic events were defined s events requiring dministrtion of rpid- or fst-cting insulin for coverge of high blood glucose concentrtions (typiclly >2 mg/dl) vi one-time dose or sliding-scle insulin coverge. Severe hyperglycemi ws defined s blood glucose concentrtions of >4 mg/ dl. During the time of this study, the hospitl did not hve universl sliding-scle order set tht ws utomticlly initited for high blood glucose levels. Helth cre stff were encourged by investigtors to report ny insulinrelted mediction errors using the hospitl s stndrd voluntry reporting method. Insulin-relted needlestick or shrps injury dt were collected by the hospitl s deprtment of infection control. Insulin-relted dverse events, with the exception of hyperglycemic or hypoglycemic events, were recorded on the hospitl s forms for reporting dverse rections. Postdischrge insulin use. Ptients were lso sked to complete followup telephone survey pproximtely four weeks fter they were dischrged from the hospitl. Ptients were sked bout the type of setting they went to fter dischrge; bout the type of insulin they were currently tking, if ny; whether their insulin nd ssocited supplies were covered by insurnce; nd wht their estimted out-of-pocket costs per month were for their insulin nd ssocited supplies. Economic outcomes. A cost-sving nlysis ws conducted during the study period to compre the two insulin dministrtion methods. The cost-sving nlysis evluted the direct insulin mediction nd needle costs using the verge wholesle price (AWP) for the corresponding insulin vils, insulin syringes (Sfety Glide, Becton-Dickinson, Frnklin Lkes, NJ), insulin pens, nd pen sfety needles used by ech ptient (Tble 1). A conversion fctor ws used to more ccurtely estimte the number of insulin vils nd pens used by ech ptient bsed on the totl number of insulin units documented s dministered on the mediction dministrtion record during hospitliztion for both groups. For the vil nd syringe group, if the number of units of insulin dministered per ptient ws 1 or less, this ws equivlent to one vil. For the vil nd syringe group, the totl number of subcutneous injections ws converted to the totl number of syringes used. In the insulin pen group, if the number of units of insulin consumed per ptient ws 3 or less, this ws equivlent to one insulin pen used fter consent ws obtined to convert insulin nlogues to FlexPen or InnoLet. Before consent ws obtined from ptients ssigned to the insulin pen group or for ptients whose order for n insulin nlogue ws not converted Tble 1. Averge Wholesle Price (AWP) Used to Clculte Direct Insulin Costs Insulin Type Insulin humn regulr Isophne insulin humn (NPH) 7% NPH insulin with 3% insulin humn regulr Insulin sprt 7% insulin sprt protmine with 3% insulin sprt Insulin glrgine 75% insulin lispro protmine with 25% insulin lispro Insulin lispro Vil AWP ($) Insulin Pen b c c,d c,d The AWP for ech insulin syringe ws $.41. b The AWP for ech sfety needle used with the insulin pen device ws $.35. c Not dispensed s n insulin pen during the study period. d The AWP ws not included in the projected costs becuse insulin lispro products were not on the hospitl formulry; the AWP of comprble insulin pen devices ws substituted, ssuming tht future ptients would be converted to n insulin pen on the formulry. 135 Am J Helth-Syst Phrm Vol 65 Jul 15, 28

5 to FlexPen or InnoLet, if the number of units of insulin dministered per ptient ws 1 or less, this ws equivlent to one vil. For the insulin pen group, the number of subcutneous injections given before consent for conversion ws obtined or the number of injections given using n insulin nlogue in ptients whose insulin ws not converted to pen device fter consent ws converted to the number of syringes used. After consent ws obtined from ptients ssigned to the pen group, the number of subcutneous injections ws converted to the totl number of sfety needles used. These conversion fctors did not ccount for lost, misplced, or extr vils or needles tht my hve been dispensed to the study floors. The totls for the direct insulin costs for ptients from both groups were determined by multiplying the AWP for insulin nlogues, syringes, nd pen needles by the number consumed during their hospitliztion. The totls for the projected direct insulin costs for ptients in the pen group were determined by evluting the totl number of insulin units given per nlogue nd converting tht number to project how mny insulin pens would hve been dispensed if only insulin pen devices were vilble (i.e., no insulin vils would hve been dispensed for initil insulin orders becuse consent would not be required). The projected totl number of insulin injections for the pen group would remin the sme, but this number would be multiplied by the cost of pen sfety needles to determine costs, since insulin syringes would not be used. The verge direct insulin costs were clculted by dividing the totl direct insulin costs by the number of ptients in ech group. The verge direct cost svings were clculted by subtrcting the verge direct costs of the group with lower verge costs from the verge direct insulin costs for the group with higher verge costs. Sttisticl nlysis. Dt were entered into spredsheet (Microsoft Excel 2) nd imported into the Sttisticl Pckge for Socil Sciences (SPSS-PC, version 14.). All sttisticl nlyses were performed using this softwre. Specificlly, survey stisfction dt, discrete demogrphic outcomes, nd the number of hyperglycemic nd hypoglycemic episodes were nlyzed using Person s chisqure test. Continuous dt (i.e., cost svings nd demogrphic dt) were nlyzed using nlysis of vrince. Results A totl of 94 ptients were eligible for study inclusion nd rndomiztion from July 25 through My 26; 45 were rndomized to the vil nd syringe group nd 49 were rndomized to the insulin pen group. Five ptients dropped out of the vil Tble 2. Demogrphic Chrcteristics of Study Ptients Vrible Age (yr), men ± S.D. Mle, no. (%) Rce, no. (%) Cucsin Africn Americn Other Type 1 dibetes, no. (%) Type 2 dibetes, no. (%) Durtion of dibetes (yr), men ± S.D. Insulin use before dmission, no. (%) Vils nd syringes only Insulin pens only Both vils nd syringes nd pens Currently using vils nd syringes but used pens in the pst Currently using orl ntidibetic mediction but used conventionl insulin in the pst Currently using orl ntidibetic mediction but used insulin pens in the pst Currently using orl nd injectble pen mediction for dibetes Never treted with injectble insulin p >.5 for ll comprisons. nd syringe group (3 were strted on n insulin drip, 1 withdrew consent, nd 1 died of pneumoni during hospitliztion), nd 14 ptients dropped out of the insulin pen group (7 were strted on n insulin drip, 4 trnsferred to nonprticipting study floor during enrollment, 2 withdrew consent, nd 1 hd n dverse event ssocited with pen device nd withdrew from the study). The ptient stisfction survey results were bsed on the responses of the ptients who completed the study: 35 ptients in the pen group nd 4 ptients in the vil nd syringe group. Demogrphic chrcteristics of the 75 ptients completing the study re listed in Tble 2. There ws no significnt difference between groups in resons for dmission. The number of concomitnt diseses including hypertension, hyperlipidemi, Insulin Pen (n = 35) 57.5 ± (46) 3 (86) 4 (11) 1 (3) 6 (17) 29 (83) 14.9 ± (51.4) 4 (11.4) 1 (2.9) 1 (2.9) 1 (2.9) 1 (28.6) Vil nd Syringe (n = 4) 57.1 ± (58) 27 (68) 8 (2) 5 (12) 4 (1) 36 (9) 1.6 ± (45) 3 (7.5) 1 (2.5) 1 (2.5) 3 (7.5) 1 (2.5) 1 (2.5) 12 (3) Am J Helth-Syst Phrm Vol 65 Jul 15,

6 kidney disese, pulmonry disese, nd peripherl vsculr disese, ws similr between tretment groups. Interestingly, more ptients in the insulin pen group hd history of liver disese thn did ptients in the vil nd syringe group (11.4% versus %, respectively). At bseline, both groups hd similr rtes of vision problems, such s dibetic retinopthy, ctrcts, glucom, nersightedness, nd frsightedness. The men ± S.D. length of sty ws similr between tretment groups: 8.9 ± 7.5 dys for the insulin pen group nd 8.1 ± 7.7 dys for the vil nd syringe group. The men number of dys of tretment for the vil nd syringe group ws equl to the group s verge length of sty. The men ± S.D. number of dys of tretment for the insulin pen group ws 5.1 ± 5.7 dys. A totl of 19 ptients in the insulin pen group (54%) nd 18 ptients in the vil nd syringe group (45%) received insulin glrgine during hospitliztion. Eighteen ptients in the insulin pen group (51%) nd 3 ptients in the vil nd syringe group (75%) hd n order for t lest one orl hypoglycemic mediction during their hospitliztion. Ptient stisfction. More ptients in the insulin pen group (77.1%) diled t lest one dose of insulin using the pen device, compred with 5% of ptients who drew t lest one dose using the vil nd syringe method during hospitliztion (p =.2). More ptients in the insulin pen group (77.1%) used the pen to self-inject t lest one dose, compred with only 12.5% of ptients who self-injected t lest one dose using the vil nd syringe method during hospitliztion (p =.1). In both groups, the mjority of ptient responses regrding their stisfction with insulin tretment during hospitliztion were positive ( gree or strongly gree ) (Tble 3). Significntly more ptients using the pen devices thn those using the vils nd syringes responded positively tht they would like to continue dministering insulin t home by the method used during the hospitl sty (74% versus 45%, p <.5) nd would recommend the insulin dministrtion method used during the hospitl sty to other ptients with dibetes (94% versus 73%, respectively; p <.5). Thirty-two ptients (26 in the pen group nd 6 in the vil nd syringe group) indicted hving used both insulin pens nd vils nd syringes before the study. The mjority of responses to the stisfction questions compring insulin pens with vils nd syringes were positive ( gree nd strongly gree ) in fvor of insulin pens. All ptients who hd used insulin pens before the study nd were ssigned to insulin vils nd syringes during rndomiztion felt more confident they were receiving the correct dose of insulin using pens, felt more comfortble using insulin pens, thought it took less time to prepre nd dminister insulin using pens, nd believed insulin pens were Survey Item The method used to give me my insulin in the hospitl ws convenient. The method used to give me my insulin in the hospitl ws simple nd esy. I would like to continue tking insulin t home by the method used during my hospitl sty. I would recommend to other people with dibetes to use insulin by the method I used during my hospitl sty. I ws confident I ws given the correct dose of insulin during my hospitl sty. Overll, I ws stisfied with the method used to give me my insulin in the hospitl. n improvement over dministrtion using vils nd syringes (Tble 4). Further, high percentge of the ptients who hd prior experience using vils nd syringes nd were rndomized to receive insulin vi pen devices during hospitliztion indicted tht they felt more confident they were receiving the correct dose of insulin using pens, felt more comfortble using pens, thought it took less time to prepre nd dminister insulin using pens, nd believed tht pens were n improvement over vils nd syringes (Tble 4). There ws no significnt difference between groups for ech of these comprtive stisfction questions. Clinicl outcomes. The men ± S.D. nonfsting blood glucose concentrtion t the time of dmission ws ± 1.1 mg/dl for the insulin pen group nd ± mg/dl for the vil nd syringe group (p >.5). The men ± S.D. nonfsting blood glucose concentrtion t the time of dischrge ws ± 73.5 mg/dl for the insulin pen group nd ± 76.2 mg/dl Tble 3. Summry of Positive Responses to Survey Items Regrding Ptient Stisfction Asked Before Dischrge from Hospitl Positive responses include responses of gree or strongly gree. b p <.5, chi-squre test. Insulin Pen (n = 35) 33 (94) 31 (89) 26 (74) b 33 (94) b 34 (97) 34 (97) No. (%) Respondents Vil nd Syringe (n = 4) 39 (98) 38 (95) 18 (45) 29 (73) 37 (93) 38 (95) 1352 Am J Helth-Syst Phrm Vol 65 Jul 15, 28

7 for the vil nd syringe group (p >.5). The men ± S.D. number of hypoglycemic events during hospitliztion ws 1.2 ± 2.3 for the insulin pen group nd.8 ± 1.5 for the vil nd syringe group. The men ± S.D. number of hyper glycemic events during hospitliztion ws 19.5 ± 18 for the insulin pen group nd 13.2 ± 11.8 for the vil nd syringe group. The men ± S.D. rtes of hypoglycemic nd hyperglycemic events for the vil nd syringe group were.7 ± 1.5 events dily nd 7.97 ± 7.2 events dily, respectively. The men ± S.D. rte of hypoglycemic events for the pen group for the entire length of sty ws 1.1 ± 2 events dily, nd the men ± S.D. rte of hypoglycemic events while receiving insulin pens ws.4 ±.9 event dily. The men ± S.D. rte of hyperglycemic events for the pen group for the entire length of sty ws 9.1 ± 7.2 events per dy, nd the verge rte of hyperglycemic events while receiving insulin pens ws 5.1 ± 5.7 events per dy. There ws no significnt difference between the number or verge rte of hypoglycemic nd hyperglycemic event Tble 4. Summry of Positive Responses to Survey Items for Ptients with Experience Using Both Insulin Administrtion Methods I felt more confident tht I ws receiving the correct dose of insulin using the FlexPen, InnoLet pen, or other insulin pens thn with insulin vils nd syringes. I felt more comfortble using the FlexPen, InnoLet pen, or other insulin pens thn with insulin vils nd syringes. It took less time to prepre nd give insulin using the FlexPen, InnoLet pen, or other insulin pens thn with insulin vils nd syringes. The FlexPen, InnoLet pen, or other insulin pens re n improvement over vils nd syringes. test. Survey Item rtes between groups. Severe hyperglycemi occurred in 1 ptients in the vil nd syringe group (25%) nd 12 ptients in the insulin pen group (34%). Specificlly, 24 episodes of severe hyperglycemi occurred in the vil nd syringe group, nd 41 episodes of severe hyperglycemi were reported in the insulin pen group, with 16 episodes occurring before the ptients were switched to insulin pens nd 25 episodes occurring while the ptients were receiving insulin from pen devices. One ptient in the insulin pen group experienced 11 episodes of severe hyperglycemi nd hd length of sty of 34 dys. Sfety. No insulin-relted mediction errors or needle-stick injuries were reported in either group. One report of n dverse event of hyperglycemi ws reported nd thought to be relted to the insulin pen device. The ptient nd nurse reported to the investigtor tht insulin ws coming out of the skin fter the pproprite injection technique ws utilized. This ptient chose to withdrw from the study nd switched bck to the conventionl vil nd syringe method. Insulin Pen (n = 26) 21 (81) 21 (81) 23 (88) 23 (88) No. (%) Respondents Vil nd Syringe (n = 6) 6 (1) 6 (1) 5 (83) 6 (1) Positive responses include responses of gree or strongly gree ; p >.5 for ll comprisons, chi-squre Postdischrge insulin use. One ptient in the insulin pen group died, from cuse unrelted to the study, between hospitl dischrge nd the follow-up telephone survey. Followup surveys were completed for 34 ptients in the insulin pen group nd 4 ptients in the vil nd syringe group. The mjority of ptients returned to their home fter dischrge in the insulin pen group (86%) nd vil nd syringe group (82%). In the insulin pen group, 12 ptients (35%) continued to use insulin pens, 14 ptients (41%) switched bck to vils nd syringes, 2 ptients (6%) used both insulin vils nd pens, nd 6 ptients (18%) discontinued insulin use. In the vil nd syringe group, 23 ptients (58%) continued to use vils nd syringes, 4 (1%) switched to insulin pen use, nd 13 (33%) discontinued insulin use. Ptients from both groups who discontinued insulin use t home were switched to orl hypoglycemic gents or the injectble insulin incretin mimetic exntide (Byett, Amylin Phrmceuticls). Forty-one percent of ptients in the insulin pen group used insulin pens fter dischrge, while only 1% of ptients in the vil nd syringe group switched to insulin pens fter dischrge (p =.16). More ptients in the insulin pen group hd insurnce coverge for their insulin nd relted supplies compred with the vil nd syringe group (79% versus 52%, respectively; p =.7). More ptients in the insulin pen group pid for their insulin supplies vi copyment compred with the vil nd syringe group (56% versus 3%, respectively; p =.38). Economic outcomes. Tble 5 provides the ctul number of insulin vils, pens, syringes, nd pen needles used by ll ptients in ech group. Tble 6 provides the projected direct insulin costs for the pen group if no insulin vils were dispensed to the pen group nd only insulin pens nd pen needles were used for those ptients. The totl men ± S.D. direct Am J Helth-Syst Phrm Vol 65 Jul 15,

8 Tble 5. Direct Insulin Costs During Hospitliztion for Study Ptients Insulin Type Insulin humn regulr Isophne insulin humn (NPH) 7% NPH insulin with 3% insulin humn regulr Insulin sprt 7% insulin sprt protmine with 3% insulin sprt Insulin glrgine 75% insulin lispro protmine with 25% insulin lispro Insulin lispro Totl direct costs Insulin Pen (n = 35) No. Vils Dispensed (Totl Cost, in Dollrs) 21 (726.39) 5 (172.95) 2 (69.18) 13 (188.1) 2 (167.4) 19 ( ) 1 (8.35) No. Pens Dispensed (Totl Cost, in Dollrs) 22 (324.6) 9 (132.57) 4 (58.92) 21 (679.14) 2 (64.68) Vil nd Syringe b (n = 4) No. Vils Dispensed (Totl Cost, in Dollrs) 34 (1176.6) 3 (13.77) 3 (13.77) 11 (92.7) 18 (141.3) 3 (241.5) 1 (8.35) 427. A totl of 425 syringes t cost of $ were dispensed to ptients in the insulin pen group before initition of insulin pen therpy; 533 pen needles were dispensed to these ptients t cost of $ The totl cost of insulin, syringes, nd needles for this group ws $ b A totl of 719 syringes t cost of $ were dispensed. The totl cost of insulin nd syringes for this group ws $ Tble 6. Projected Direct Insulin Costs for Ptients in the Insulin Pen (n = 35) Insulin Type Insulin humn regulr Isophne insulin humn (NPH) 7% NPH insulin with 3% insulin humn regulr Insulin sprt 7% insulin sprt protmine with 3% insulin sprt Insulin glrgine 75% insulin lispro protmine with 25% insulin lispro Insulin lispro Totl projected direct costs costs of the insulin vils nd pens nd syringes nd sfety needles per ptient were significntly higher in the pen group ($ ± $91.41) compred with those of the vil nd syringe group ($18.4 ± $62.3) (p =.12). However, once the insulin direct costs per ptient were djusted to project dispensing only the equivlent insulin pen products, the men ± S.D. direct cost per ptient for the pen group ws projected to be $71.85 ± $46.21, yielding cost sv- No. Pens Dispensed (Cost, in Dollrs) 24 (353.52) 1 (147.3) 5 (73.65) 24 (776.16) 3 (97.2) 2 (634.6) 3 (97.2) Reflects costs if ll insulin used by ptients in the pen group were converted to costs of insulin dministered through pen devices. A totl of 958 pen needles would hve been used by the ptients t totl cost of $335.3; the totl cost of insulin in pen devices nd pen needles would hve been $ ing of $36 per ptient for the insulin pen group when compred with the ctul men totl direct costs per ptient in the vil nd syringe group (p =.6). Discussion In this study, significntly more ptients in the insulin pen group prepred nd self-injected t lest one dose of insulin compred with the vil nd syringe group. Ptients with newly dignosed or existing dibetes dmitted to our hospitl hve n eductionl cre pln, with n interdisciplinry eduction record initited nd plced under the ptient eduction section in their permnent medicl chrt. This document is intended to provide n eductionl checklist for vrious helth cre professionls to document ptient s rediness to lern bout multiple spects of dibetes, including n understnding of the disese, signs nd symptoms nd tretments for hyperglycemi nd hypoglycemi, blood glucose monitoring, orl ntidibetic medictions nd injectble insulins, the effects of stress nd exercise on dibetes, preventive cre, nd nutrition therpy. In ddition, helth cre professionls my sk ptients to demonstrte certin skills to ssess the ptient s selfcre technique. One skill ptient my be sked to demonstrte is insulin preprtion nd injection. The ptient my be sked to prepre n insulin injection three times before dischrge, inject the insulin dose, rotte injection sites, dispose of the syringe, nd mix two types of insulin, if necessry. During the study trining sessions for the nurses, the investigtors did not specificlly instruct the 1354 Am J Helth-Syst Phrm Vol 65 Jul 15, 28

9 nurses to educte enrolled ptients in either group on how to prepre or self-inject their insulin. Perhps the difference found between groups could be ttributed to the novelty of the insulin pen devices nd the ptients desire to try using them, or the nurses my hve felt more comfortble letting ptients self-dminister using the pens becuse they were simple nd esy to use. Significntly more ptients in the insulin pen group indicted tht they would like to continue using pens t home nd would recommend this method of insulin delivery to other people with dibetes compred with ptients in the vil nd syringe group. Summers et l. 22 evluted the preference for two insulin delivery methods (insulin pens nd vils nd syringes) when distributed to insulin users nd nonusers. Regrdless of whether the responder used insulin, there ws significnt preference for insulin pens over dministrtion using insulin vils nd syringes. One of the significnt predictors for preference of insulin pens for both groups ws socil cceptbility of the method. The uthors hypothesized tht if responders viewed insulin pens s more socilly cceptble, then this could led to positive clinicl outcomes. A survey of outptient insulin users found tht fewer ptients miss insulin injections when using pen devices versus vils nd syringes. 8 Studies hve lso shown tht the use of insulin pens compred to vils nd syringes results in reduced HbA 1c vlues, lower men fsting blood glucose levels, improved mediction dherence, nd improved helth cre resource utiliztion in outptients. 7,11,13,23 The current study ws not designed to mesure long-term indictors of glucose control, such s HbA 1c vlues or morbidity, or mesure dherence through prescriptionrefill history. We believe tht improved complince nd helth cre resource utiliztion could be relized for ptients who continue using insulin pen devices in the mbultory cre setting due to fewer missed injections, improved dherence, nd incresed stisfction with the pen method. The hospitl hs since dopted the use of insulin pens for ll subcutneous doses. In this study, more ptients in the insulin pen group hd insurnce coverge nd pid copyment for their insulin supplies. Informtion regrding individul prescription drug coverge ws not collected from ech ptient before dischrge to ctively investigte if insulin pens were included in the ptient s prescription benefit provider s drug formulry. It could be tht ptients using the vil nd syringe method for insulin dministrtion who continued or switched bck to this method my hve done so becuse of unequl coverge through their mnged cre pln. During the time of study enrollment, insulin pens could hve been on higher tier, requiring higher out-of-pocket prescription expenses for ptients or prior-uthoriztion criteri to be met before pens would be covered by insurnce. An ttempt to locte publicly ccessible prioruthoriztion criteri for insulin pens or mediction formulries from privte mnged cre compnies proved difficult, s this informtion my be proprietry informtion nd unvilble to the public. Mediction formulries for stte deprtments of Medicre nd Medicid re ccessible online. 24,25 Currently, the mjority of Medicre prescription drug pln formulries cover insulin pens, 24 nd over 5 plns include the InnoLet nd FlexPen devices on their formulry in Nebrsk, usully clssified s tier 2 or 3, which in most cses ws the sme tier s the sme insulin nlogue in vil form. However, insulin pen coverge for mnged cre plns could hve been much different during the time of ptient enrollment. Prior uthoriztion is required for Medicid ptients or for beneficiries of few Medicre plns in Nebrsk; however, specific uthoriztion criteri were not publicly retrievble. One stte s prior uthoriztion criteri for Medicid ptients specified tht insulin pens were considered convenience items unless medicl necessity could be documented nd tht coverge ws limited to ptients with significnt visul impirment or physicl disbility tht prevented the use of conventionl vils nd syringes or to juvenile ptients self-dministering insulin in n eductionl setting. 26 Therefore, the desire to continue or switch to insulin pens cn be gretly influenced by ptient s prescription benefit provider s drug formulry nd the potentil cost to the ptient. Also, the ptient must be willing to switch to different insulin preprtion nd dministrtion method. Two recent studies evluted the impct of insulin pens on helth cre costs from mnged cre perspective. One study exmined mediction dherence nd totl helth cre costs mong ptients with type 2 dibetes who were enrolled in Medicid progrm from 21 to The study evluted ptients initited on or converted to insulin with pen device compred with vil nd syringe s dd-on therpy to orl ntidibetic drugs. Ptients receiving insulin with vil nd syringe who converted to pen therpy were compred with those who continued to use the vil nd syringe method in both unmtched comprisons (n = 56 nd n = 9,988, respectively) nd fter pir mtching using propensity scores (both groups, n = 56). The uthors performed second nlysis compring ptients who initited insulin with vils nd syringes (n = 1,162) with cohort tht initited insulin pen therpy (n = 168) fter controlling for covrites in multivrite regression model. All ptients hd complete enrollment in the progrm for t lest 24 months of follow-up. The uthors found tht dibetes-relted nd overll medi- Am J Helth-Syst Phrm Vol 65 Jul 15,

10 ction dherence were comprble for ptients inititing insulin with pen versus vil nd syringe (53% versus 5% nd 94% versus 94%, respectively). However, totl nnulized helth cre costs were significntly lower for ptients using pen therpy thn for those using syringe ($14, versus $31,764.78, p <.5). Cost reductions with pen therpy were reflected in hospitl costs ($1, versus $4,965.31, p <.5), dibetes-relted costs ($7, versus $13,762.21, p <.5), nd outptient costs ($7, versus $13,13.51, p <.5). However, prescription costs of syringes were significntly lower ($535.7 versus $67.52, p <.5) nd costs of pens were higher ($84.33 versus $, p <.5) in ptients who switched from syringes to pens versus those who continued to use syringes. The uthors concluded tht in stte Medicid setting mong ptients with type 2 dibetes, inititing insulin therpy with pen device ws ssocited with comprble mediction dherence nd significnt reductions in helth cre resource utiliztion nd ssocited costs compred with insulin therpy with vils nd syringes. 23 This study is importnt becuse it sheds some light on the finncil impct of insulin pens from Medicid perspective on helth cre costs tht ffect hospitl, outptient, nd prescription costs. Further, this study documents tht in Medicid ptients, while helth cre costs were lower with insulin pens, prescription costs were significntly higher compred with vils nd syringes. This clerly ffects the potentil for ptients to continue using the insulin pen method fter dischrge since their out-of-pocket costs would be higher nd would ccount for Medicid ptients switching bck to vils nd syringes, s pen devices would be cost prohibitive. Another study evluted ptients enrolled in 1 of 57 mnged cre helth plns in the United Sttes (n = 1,156) nd found tht mediction dherence ws significntly improved, the likelihood of experiencing hypoglycemic event ws significntly reduced, nd the frequency of hypoglycemi in dherent ptients decresed by nerly two thirds fter conversion to insulin pens. 13 There were significnt reductions in emergency deprtment visits nd physicin visits, wheres hypoglycemi-relted hospitliztions nd outptient visits remined similr fter conversion. Totl men ll-cuse nnul tretment costs were reduced by $1,59 per ptient (from $16,359 to $14,769, p <.1). Annul hypoglycemirelted costs were reduced by $788 per ptient (from $1,415 to $627, p <.1), predominntly s result of decresed hospitliztion costs (from $857 to $288, p <.1), nd nnul dibetes-relted costs were reduced by $6 per ptient (from $8,827 to $8,227, p <.1). Similr to the previous study, 23 the uthors found tht mong ptients with type 2 dibetes treted in mnged cre setting, switch from dministrtion of insulin therpy by vil nd syringe to prefilled pen device ws ssocited with improved mediction dherence, fewer clims for hypoglycemic events, reduced emergency deprtment nd physicin visits, nd lower nnul tretment costs. 13 Unlike the previous study, these uthors found tht bsed on refill history, mediction dherence ws significntly improved with insulin pens in mnged cre ptients. A significnt sving of $36 per ptient ws relized for ptients in the pen group compred with the vil nd syringe group. It is importnt to note tht our hospitl s infection control policy did not llow shring of insulin vils for multiple ptients on the floors. The cost svings my not be relized by other institutions if the hospitl uses one vil of insulin nlogue for multiple ptients on hospitl unit. Similr cost svings my lso not be relized if the verge length of sty is considerbly longer thn found in this study, since more insulin my be used during longer stys. The cost svings could be underestimted if the number of insulin-relted needlestick injuries decreses nd cre needed for the tretment of bloodborne pthogen is prevented. It is estimted tht the follow-up for high-risk exposure costs $5 $25 per needle-stick injury, even when no infection occurs. 27 There were some limittions to this study. Some ptients in the insulin pen group received insulin dministered from vils with syringe during the study period becuse investigtors did not wnt to dely the delivery of insulin before obtining consent or if ptient received insulin glrgine. This exposure to insulin vils could hve confused the ptient s to how he or she should respond to the survey questions. Ptients in the insulin pen group who hd experience with the vil nd syringe method during hospitliztion only my not hve completed the subsequent comprtive questions of the stisfction survey. Prescription benefit informtion ws not obtined for ech ptient; therefore, it ws difficult to clerly determine if insulin pens required prior uthoriztion or were on higher tier of coverge in 25 6, which could hve ffected the ptient s bility to switch to or continue using insulin pens fter exposure to this method in the hospitl. Conclusion Incresed ptient stisfction nd continution of the method of insulin dministrtion used in the hospitl t home were reported by ptients who received insulin pens compred with ptients who received conventionl insulin vils nd syringes during hospitliztion. A substntil cost sving ws projected for ptients in the insulin pen group if insulin pens hd been dispensed during their entire hospitl sty Am J Helth-Syst Phrm Vol 65 Jul 15, 28

11 References 1. The Dibetes Control nd Complictions Tril Reserch. The effect of intensive tretment of dibetes on the development nd progression of long-term complictions in insulin-dependent dibetes mellitus. N Engl J Med. 1993; 329: U.K. Prospective Dibetes Study (UKPDS). Intensive blood glucose control with sulphonylures or insulin compred with conventionl tretment nd risk of complictions in ptients with type 2 dibetes (UKPDS 33). Lncet. 1998; 352: [Errtum, Lncet. 1999; 354:62.] 3. D Cost S, Brckenridge B, Hicks D. A comprison of insulin pen use in the United Sttes nd the United Kingdom. Dibetes Educ. 22; 28(1):52-6, Interntionl Helthcre Worker Sfety Center. List of sfety-engineered shrp devices. edu/internet/epinet/sfetydevice.cfm (ccessed 27 My 4). 5. Kdiri A, Chribi A, Mroun F et l. Comprison of NovoPen 3 nd syringes/ vils in the cceptnce of insulin therpy in NIDDM ptients with secondry filure to orl hypoglycemic gents. Dibetes Res Clin Prct. 1998; 41: Dunbr JM, Mdden PM, Gleeson DT et l. Premixed insulin preprtions in pen syringes mintin glycemic control nd re preferred by ptients. Dibetes Cre. 1994; 17: Plevin S, Sdur C. Use of prefilled insulin syringe (Novolin Prefilled) by ptients with dibetes. Clin Ther. 1993; 15: Grff MR, McClnhn MA. Assessment by ptients with dibetes mellitus of two insulin pen delivery systems versus vil nd syringe. Clin Ther. 1998; 2: Bohnnon NJ, Ohnnesin JP, Burdn AL et l. Ptient nd physicin stisfction with the Humulin/Humlog pen, new 3.-mL prefilled pen device for insulin delivery. Clin Ther. 2; 22: Korytkowski M, Bell D, Jcobsen C et l. A multicenter, rndomized, open-lbel, comprtive, two-period crossover tril of preference, efficcy, nd sfety profiles of prefilled, disposble pen nd conventionl vil/syringe for insulin injections in ptients with type 1 or type 2 dibetes mellitus. Clin Ther. 23; 25: Corsi A, Torre E, Coronel G et l. Prefilled insulin pen in newly insulin-treted dibetic ptients over 6 yers old. Dib Nutr Metb Clin Exp. 1997; 1: De Luis DA, Aller R, Cuellr L et l. Effect on qulity of life with new insulin injection device in elderly ptients with dibetes mellitus type 2. J Dibetes Complictions. 24; 18: Lee WC, Blu S, Cobden D et l. Mediction dherence nd the ssocited heltheconomic impct mong ptients with type 2 dibetes mellitus converting to insulin pen therpy: n nlysis of thirdprty mnged cre clims dt. Clin Ther. 26; 28: [Errtum, Clin Ther. 26; 28: ] 14. Shelmet J, Schwrtz S, Cpplemn J et l. Preference nd resource utiliztion in elderly ptients: InnoLet versus vil/ syringe. Dibetes Res Clin Prct. 24; 63: Centers for Disese Control nd Prevention. Ntionl dibetes fct sheet: generl informtion nd ntionl estimtes on dibetes in the United Sttes, ndfs_25.pdf (ccessed 28 Apr 18). 16. World Medicl Assocition Declrtion of Helsinki: ethicl principles for medicl reserch involving humn subjects. JAMA. 2; 284: Mrtin JM, Llewelyn JA, Ristic S et l. Acceptbility nd sfety of new 3. ml reusble insulin pen (HumPen) in clinicl use. Dib Nutr Metb. 1999; 12: Sucic M, Glic E, Cbrijn T et l. Ptient cceptnce nd relibility of new Humulin/Humlog 3. ml prefilled insulin pen in ten Crotin dibetes centres. Med Sci Monit. 22; 8:PI Cppelleri JC, Gerber RA, Kourides IA et l. Development nd fctor nlysis of questionnire to mesure ptient stisfction with injected nd inhled insulin for type 1 dibetes. Dibetes Cre. 2; 23: Bott U, Ebrhim S, Hirschberger S et l. Effect of the rpid-cting insulin nlogue insulin sprt on qulity of life nd tretment stisfction in ptients with type 1 dibetes. Dibet Med. 23; 2: Brdley C, Speight J. Ptient perceptions of dibetes nd dibetes therpy: ssessing qulity of life. Dibetes Metb Res Rev. 22; 18(suppl 3):S Summers KH, Szeinbch SL, Lenox SM. Preference for insulin delivery systems mong current insulin users nd nonusers. Clin Ther. 24; 26: Pwskr MD, Cmcho FT, Anderson RT et l. Helth cre costs nd mediction dherence ssocited with initition of insulin pen therpy in Medicid-enrolled ptients with type 2 dibetes: retrospective dtbse nlysis. Clin Ther. 27; 29: Medicre. Formulry finder for prescription drug plns. finder.medicre.gov/formulryfinder/ selectstte.sp (ccessed 27 My 3). 25. Nebrsk Medicid Progrm Phrmcy Services. Covered drug listing. www. hhs.stte.ne.us/med/phrm/covered.sp (ccessed 28 Mr 1). 26. West Virgini Deprtment of Helth nd Humn Resources. Coverge of insulin pens nd crtridges. org/bms/sprog_instr/pim_files/bms_ pim164.pdf (ccessed 28 Mr 4). 27. Jgger J, Bentley M. Direct costs of follow-up for percutneous nd mucocutneous exposure to t-risk body fluids: dt from two hospitls. Adv Expos Prev. 1998; 3(3):25,34-5. Am J Helth-Syst Phrm Vol 65 Jul 15,